Phẫu Thuật Da Liễu: Khía Cạnh Ngoại Khoa (Surgery of the Skin)

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42
Vitiligo Surgery
Niti Khunger MD DNB DDV, Koushik Lahiri MD, and Venkataram Mysore MD DNB DipRCPath(Lond)
Summary box
 Surgical treatment of vitiligo is an effective technique for
treating stable cases resistant to medical therapy.
 While there is no consensus on definitive parameters for
stability, the absence of progression of disease for a period of
1 year is generally regarded as an optimum period for stable
disease. Test grafting may be performed in doubtful cases to
detect stability.
 The patient should be adequately counseled regarding
the limitations of the procedure and the possible future
progression of the disease.
 The selection of technique depends on the extent, site, and
type of vitiligo and experience of the treating physician.
Miniature punch grafts and suction blister grafts can be
utilized for small lesions and by beginners. Thin split-
thickness grafts require more experience and are required for
larger lesions but are limited by the availability of donor areas.
 Thin split-thickness skin or suction epidermal blister
grafting are recommended as the most effective and safest
techniques. Minigrafting is the easiest technique, but has the
highest rate of adverse effects.
 Recent advances include the introduction of non-cultured and
cultured melanocyte suspensions to expand the yield from
donor area and use of erbium:yttrium-aluminum-garnet and
CO2 lasers to prepare the recipient area.
 The simplification and standardization of these techniques in
the future will go a long way in the treatment of vitiligo.
 INTRODUCTION
Vitiligo is a common acquired depigmenting disorder of psy-
chological and cosmetic importance, characterized clinically
by milky white macules and histologically by an absence of
functional melanocytes in the affected areas. It occurs in
localized, generalized, or segmental patterns and can run a
rapidly progressive course or remain stationary. The patho-
genesis of vitiligo is not yet fully understood and results from
a complex interaction of environmental, genetic, and immu-
nologic factors, which ultimately contribute to melanocyte
destruction, resulting in the characteristic depigmented
lesions. In contrast to fair skin types where lesions are not
very apparent, in those with darker skin tones, vitiligo has a
profound psychological impact and affects the quality of life.
It is associated with great social stigma and the depigmented
patches on exposed areas of the skin become photosensitive.
Conventional medical therapies such as topical and sys-
temic corticosteroids, immunomodulators, and phototherapy
take a long time to for pigmentation to return and are not
always effective. The success of medical treatment depends
on the type, extent, and duration of vitiligo. Sites such as the
lips, nipples, genitals, and acral areas are particularly resistant
to medical therapy. The need for active treatment has led to
the evolution of various surgical modalities to treat recalci-
trant stable lesions. The conventional surgical modalities for
vitiligo are miniature punch grafting, suction blister grafting,
and thin split-thickness skin grafting. The recent advances in
the surgical treatment of vitiligo include autologous non-
cultured epidermal cell suspensions and cultured melanocyte
suspensions or sheets.
Historical vignettes and current views on the concept of
stability in vitiligo can be found online under related material
for this chapter.
 TECHNICAL ASPECTS
Rationale for surgery in vitiligo
Surgery is indicated in vitiligo when medical treatment is
unsatisfactory. Despite the many new advances in medical
management, satisfactory repigmentation is achieved in only
60–70% of cases. In particular, all non-hairy areas, mucosal
areas, bony areas, longstanding lesions, lesions with leuko­
trichia, lesions in elderly patients, and segmental vitiligo
respond inadequately. Surgical treatment of vitiligo offers the
potential for rapid and complete repigmentation of lesions.
Vitiligo is an autoimmune disease and, when active, is a
recipient dominant condition. Therefore, the potential for
depigmentation of the grafted skin as well as depigmentation
of the donor area always needs to be considered carefully,
before attempting surgery. Hence, surgical treatment is advo-
cated in stationary, stable, and resistant cases, after failure of
proper medical management.
Basic principles of surgical treatment
The aim of surgical treatment in vitiligo is complete cos-
metically acceptable repigmentation of the vitiliginous areas.
Surgical treatment cannot stop the progression of the disease.
It only provides pigmentation. It is indicated for resistant
stable vitiligo that does not show significant response to
medical therapy. The basic principle in surgical management

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Part 4  Special Procedures
rule out immunosuppressive states that may be a risk for
delayed healing and infection. Other associated autoimmune
disorders such as hypothyroidism, diabetes, pernicious
anemia, etc., should be ruled out. Cutaneous examination
should be carried out on the full body in proper light. Well-
defined and hyperpigmented borders of the lesions indicate
stable disease, whereas ill-defined borders suggest unstable
disease (Fig. 42.1). The presence of follicular or marginal
repigmentation is a favorable indicator (Fig. 42.2).
Lesion site and extent and type of vitiligo should be assessed
to select the appropriate technique and predict surgical out-
comes. Localized vulgaris and segmental vitiligo respond
better to surgery as compared to acral and extensive vitiligo.
The lips and eyelids need special consideration in view of
is transplantation of autologous melanocytes from unaffected
pigmented skin to lesional skin. In skin grafting, normal pig-
mented skin tissue is transplanted from the donor area to the
depigmented recipient site. Graft adherence and vasculariza-
tion is followed by migration of melanocytes from the edge
of the graft to the achromic skin with colonization by func-
tional and active melanocytes.10
Different surgical modalities are available and the choice of
surgical treatment depends on the type of vitiligo, extent, and
site of lesions, the availability of equipment, and expertise of
the treating cutaneous surgeon. Sometimes more than one
procedure may be required. In general, the outcome of surgi-
cal treatment is good in stable, localized disease and poor in
unstable vitiligo, extensive disease, and acral lesions.10
Vitiligo disease activity score and a discussions of current
concepts of disease activity can be found online under related
material for this chapter.
Case selection
Patients with stable, localized, or segmental lesions that do
not respond to medical treatment are ideal candidates for
surgery. A test graft may be considered whenever there is a
doubt about stability, or the patient is unable to give a clear
history on stability. Each case should be considered individu-
ally on its merit.
There is no uniformly accepted age limit for surgery.
However, there are many limitations for performing surgery
in children. Vitiligo surgery is usually performed under local
anesthesia, which would be difficult in children. The risk of
general anesthesia for vitiligo surgery in a young child might
outweigh the benefits. Finally, the progress of the disease is
unpredictable and therefore stability is difficult to predict in
children. Generally, these surgical procedures should not be
performed in children, though it has been shown that results
of surgery are better in adolescents than in older patients.18,19
Patient counseling and information
Proper and adequate counseling is of paramount importance.
The natural disease course, the rationale of the surgery
chosen, expected outcome, need for proper immobilization
after surgery, possible complications, and the need for con-
comitant medical therapy and phototherapy should all be
clearly explained. It should be emphasized to the patient that
surgical treatment only provides a cosmetic pigmentation, but
does not control disease activity. After surgery, pigmentation
may be incomplete, particularly at the edges. Satisfactory
cosmetic outcome and matching with surrounding normal
pigmented skin occurs over a period of time, up to several
months. Lesions may recur even in stable vitiligo. The patient
should be provided with adequate preoperative information
via one-to-one discussions and print and digital resources.
Patient assessment and documentation
Disease stability should be assessed by a detailed history and
examination of lesions. History taking should include specific
information about recent lesion activity, and occurrence of
lesions at sites of injury. A family history of vitiligo should be
sought as patients with such may be more prone to recur-
rences. Physical examination and laboratory studies should be
performed to assess the general condition of the patient to
Figure 42.1  Unstable vitiligo with ill-defined borders.
Figure 42.2  Stable vitiligo on the neck with follicular and
marginal repigmentation.

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Chapter 42  Vitiligo Surgery
planted on the vitiliginous recipient sites. The instruments
required are 1.5- or 1.2-mm punches, which may be custom
ordered, small jeweler’s or graft holding forceps, and small
curved tip scissors.25
The donor and recipient areas are surgically prepared. The
donor area selected is either the upper lateral portion of the
thigh or gluteal area. Punch impressions in the donor area are
made very close to each other so that a maximum number of
grafts can be taken from a small area. In the recipient area,
the punched out chambers are spaced according to the result
of test grafting or at a distance of 5–10 mm from each other.
Same-sized punches are used for both donor and recipient
area. The recipient chambers should be slightly deeper than
the size of the graft, so that it fits snugly and does not pop
out. The grafts are placed directly from the donor to the
recipient areas. This speeds up the procedure and lessens the
chance of infection. It is important to ensure that the graft
edges are not folded, and the tissue is not crushed or placed
upside down. Too low placement or too high placement
should be avoided. The former leads to depressed punches
and the latter leads to cobblestoning. The tip of the needle
or the forceps may be used to aid proper placement of grafts
in the recipient chambers. Hemostasis is achieved by pressing
a saline-soaked gauze over the area. For the recipient area,
three layers of dressing from inside out are paraffin-embed-
ded non-adherent sterile gauze (Jelonet; Smith & Nephew,
plc, London, UK), sterile Surgipad (Johnson & Johnson,
Langhorne, PA), and bio-occlusive Micropore (3M, St Paul,
MN). For the donor area only, Surgipad and Micropore are
used (Fig. 42.3).
Crusts, when they occur, fall off from the recipient site
within 7–14 days. Perigraft repigmentation is expected to
start in about 3–4 weeks. The treated lesion is expected to
be completely repigmented within 3–6 months, depending
on the location of the treated area. Mild superficial scarring
may occur at the donor site after healing with second inten-
tion and is usually acceptable. Pigment spread may occur
spontaneously, though several studies have documented the
efficacy of additional photochemotherapy (psoralen plus
ultraviolet A; PUVA),23 sunlight (PUVAsol),22 and narrow-
their special anatomic features. Vitiligo-associated psychoso-
cial concerns should also be assessed.
A detailed consent form describing the procedure and pos-
sible complications should be reviewed with and signed by
the patient. It should specifically state the limitations of the
procedure, possibility of future disease progression, and the
need for repeated procedures for satisfactory results. Preop-
erative photography is of vital importance; it also helps in
medicolegal situations.
Preoperative blood counts, coagulation studies, hemoglobin
and blood sugar levels, and electrocardiogram might be
obtained if clinically warranted.
Anesthetic techniques
Local anesthesia is adequate in a majority of cases. At the
donor area, topical anesthesia with a eutectic mixture of local
anesthetics, prilocaine 2.5%, and lidocaine 2.5%, under occlu-
sion for 2 hours has been found adequate in many patients.20
If the anesthesia is not satisfactory, a field block with 1%
lidocaine with epinephrine can be given at the margins of the
donor area. Infiltration anesthesia of the entire donor area
should be avoided as it can result in surface irregularities
causing the graft to be of uneven thickness.
At the recipient areas, topical anesthesia applied under
occlusion may be sufficient. Alternatively, infiltration anesthe-
sia with 1% lidocaine with epinephrine can be given. While
operating on multiple lesions, it is important to observe the
dosage of lidocaine administered to avoid systemic toxicity.
For larger areas on the face, a nerve block may be utilized.
For grafting extensive areas, general anesthesia in a hospital
setting is preferable. However, in such cases, detailed coun-
seling with respect to the risk of anesthesia and proper pre-
anesthetic examination by an anesthetist are necessary.
Surgical techniques
Minipunch grafting
In minipunch grafting (MPG),21–24 small punch grafts are
harvested from the pigmented donor skin and directly trans-
A
B
Figure 42.3  (A) Stable vitiligo treated
with minipunch grafting at 7 days
postgrafting after second session and 2
months after first session. (B) Three
months postgrafting after second
session.

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Part 4  Special Procedures
scarring, keloid and hypertrophic scars, koebnerization, and
spread of disease, may occur. Proper selection of cases and
proper technique can minimize these complications.
Cobblestoning is the most common complication, though
it improves with time22 (Fig. 42.4). Resurfacing by electro-
surgery, radiosurgery, or an ablative laser such as CO2 laser
may be used in resistant cases.27 Grafting should not be per-
formed with punches more than 1.5 mm in diameter; on the
face and lips they should be even smaller (1.2  mm or
1 mm).14,24
Suction blister epidermal grafting
Suction blister epidermal grafting (SBEG) is a method of
tissue grafting where epidermal grafts are obtained from the
donor site, using prolonged suction. These grafts are then
directly transplanted over the denuded vitiliginous areas.28
The donor site selected is either the medial upper arm,
flexor aspect of the forearm, or the thigh. No anesthesia is
band ultraviolet B (NB-UVB).24 Phototherapy may be started
any time after 1 week of grafting. The patients are followed
up fortnightly for an initial 2 months and then monthly until
complete repigmentation is achieved. Falabella, while estab-
lishing a relationship between donor graft and the area of
surgical repigmentation, found that a 1-mm donor graft size
can repigment an area 25 times larger than the graft itself.25
A recent study with 1.5-mm grafts and NB-UVB in type IV
and V skin subjects found that an area 56.21 times the graft
area could be repigmented.24 Though repigmentation of
leuko­trichia is generally considered difficult, it has been
observed with both minigrafting and NB-UVB21 and PUVAsol
therapy.26
Complications are common after punch grafting and include
cobblestone appearance, polka-dot appearance, variegated
appearance, color mismatch, static graft (absence of pigment
spread), depigmentation of graft, perigraft halo or achromic
fissure, graft dislodgement or rejection, and hypertrophic scar
and keloid formation at the recipient site. In the donor area,
A
B
C
Figure 42.4  Cobblestoning with minipunch grafting gradually
improving over time. (A) Pretreatment. (B) Prominent
cobblestone effect on the temple 8 weeks after placement.
More recent grafts immediately after placement. (C) Results
5 months later showing improvement in cobblestoning and
repigmentation.

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Chapter 42  Vitiligo Surgery
dressed with a non-adherent dressing, followed by bandaging.
The dressing is removed 1 week after grafting. Pigment
spread takes place gradually in 4–6 months covering the
entire area, as the melanocytes migrate (Fig. 42.7).
Hyperpigmentation, perigraft halo, incomplete pigmenta-
tion, and graft slough are possible complications. The main
advantage of this method is a thin graft that yields excellent
cosmetic results with no scarring at the donor site. It is also
a simple, inexpensive technique not requiring special surgical
skills. Unfortunately, it is time-consuming, only small rounded
grafts are obtained, and only small areas can be treated at a
time. It is useful for small localized lesions, especially on the
lips.32
Information relevant to Figs 42.8–42.13 discussing a variety
of other grafting techniques and tattoing can be found online
under related material for this chapter. Additionally, informa-
tion on tattoing or micropigmentation, dermabrasion, exci-
sion, leukotrichia, and permanent depigmentation can be
found online.
Role of lasers and light therapy systems
(targeted phototherapy)
Targeted phototherapy systems have been developed with
the aim of sparing unaffected skin from UV irradiation. Most
systems use a wavelength of 308  nm, similar to NB-UVB,
while some systems also deliver the UVA range. These
systems deliver energy through a hand-held delivery system
specifically targeted at the lesions and therefore avoid unnec-
essary exposure to unaffected skin. This reduces the risk of
skin cancer in unaffected skin and also allows delivery of
supraerythematogenic dosages, thereby enhancing pigmenta-
tion at a faster rate.45,46
The excimer laser (308  nm) with a fiber-optic delivery
system emits coherent, pulsed light of high-power density.
The advantages claimed include short duration of treatment,
hand-held targeted delivery and therefore enhanced safety
and quicker results. However, subsequent studies have shown
lack of efficacy over acral areas.
The 308-nm excimer lamp has a non-coherent, continuous
emission, with power density lower than the laser but higher
than the TL-01 lamp. Other systems, such as intense pulsed
light systems with wavelength of 315  nm, seek to achieve
similar energy delivery, with a larger hand piece, at a lesser
cost. Many light-based fiber-optic delivery systems have been
introduced (DuaLight; TheraLight, Inc, Calsbad, CA) (Fig.
required at the donor site. Prolonged suction causes a column
of negative pressure, resulting in a split at the dermoepider-
mal junction and blister formation. Previously, machines with
suction pumps were used, though a simplified syringe-assisted
suction has recently become popular. In this modified syringe-
assisted technique, a 20-mL syringe with its piston removed
is inverted and a 3-way connector is attached at the needle
end. Negative pressure of about 300–400 mmHg, monitored
by a pressure gauge, is created by aspiration of air with a
50-mL syringe. Suction is maintained until a single blister of
sufficient size is formed, which is the end point. Multiple
syringes can be used, depending on the size of graft needed
(Fig. 42.5). The required suction pressure to form a blister
varies with the age of the patient, varying between 500 mmHg
in adolescents to 400  mmHg in adults and 300  mmHg in
an elderly patient. The time taken for blister formation
depends on the site of donor area, diameter of the suction
syringe, temperature of the site, and the negative pressure
obtained.29 In general, a 20-mL syringe, with a negative
suction pressure of −400 mmHg requires about 1.5–2.5 hours
to form blisters (Fig. 42.6). The periphery of the blister is
then cut with fine iris scissors, a sterile glass slide is placed
on the blister, and the graft is then gently everted onto the
glass slide with the help of a fine forceps, with the dermal
side facing upwards.
The recipient site is prepared by denuding the area by
dermabrasion using a high-speed motor-driven dermabrader
with a diamond fraise. A manual dermabrader may also be
used, though it is time-consuming and can therefore be used
only for small areas. The end point of dermabrasion is the
appearance of pinpoint bleeding. Other modalities such as
erbium:yttrium-aluminum-garnet (Er:YAG) laser30 or CO2
laser31 have also been used to denude the recipient area.
The grafts are transferred onto the recipient site by evert-
ing the slide and maneuvering the graft with the dermal side
down. The graft is secured with tissue glue at the edges and
Figure 42.5  Harvesting of suction blister grafts by using
multiple syringes on the thigh.
Figure 42.6  Appearance of blisters after 2.5 hours.

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Part 4  Special Procedures
 POSTOPERATIVE CARE
Adequate postoperative care is essential for a successful
outcome. The first 48 hours are the most important for suc-
cessful graft uptake; hence patients should be advised to
restrict activities. Antibiotics are prescribed for 7–10 days,
depending on the location and size of the grafted sites. Pain
relievers such as paracetamol or ibuprofen may be prescribed
but aspirin should be avoided. If large areas are grafted, exu-
dates can build up under the dressing. These sites may be
inspected at 24 hours and, if present, exudates should be
drained by simple manual pressure or by a sterile needle. The
dressings are removed after 7–10 days by moistening ade-
quately with saline. Topical antibiotic ointments should be
applied for the following 7–10 days. Friction and tight clothes
should be avoided and the grafted sites should be exposed to
sunlight or UV light thereafter, such as PUVA or sunlight
(PUVAsol) or NB-UVB, though not in all cases. The patients
are followed up fortnightly for 2 months and then monthly
until complete repigmentation is achieved. Minimal superfi-
cial scarring is expected at graft donor sites after healing with
second intention and is generally acceptable. Perigraft repig-
mentation is expected to start in 3–4 weeks. The entire
depigmented and grafted area is expected to be completely
repigmented within 3–6 months, based on the area of grafting
and sites involved.
 PITFALLS AND THEIR MANAGEMENT
Failure of graft uptake.  The common causes are inad-
equate immobilization of the graft, hematoma formation
under the graft, and secondary infection. It is important to
secure the graft by proper pressure dressings and use of
splints over mobile areas.
Incomplete pigmentation.  Pigment spread may not be
complete, particularly in tissue grafts, leading to perigraft
halo or achromic fissures of depigmented skin between the
grafts. To avoid this complication, split-thickness grafts should
42.14) and these systems are cheaper than excimer lasers.
However, while their safety in delivering targeted photo-
therapy is established, claims of superior efficacy over con-
ventional phototherapy are yet to be established in controlled
studies. Presently their role is in treating small areas, lesions
over difficult areas such as the ear lobes, tip of nose, under-
surface of neck, genitals, etc., and in childern. Treatments are
usually given twice a week on non-consecutive days. The
initial dose is 70% of the minimal erythema dose, with dose
increments of 40% for every alternate treatment from treat-
ments one to four. Subsequent dose increments of 30% are
given every alternate treatment from treatments four to eight
and dose increments of 20% every other treatment thereaf-
ter, until an adequate response is noted (Fig. 42.15).
Overview of surgical procedures
Selection of the correct technique depends on various factors
such as the size, site, and pattern of vitiliginous lesions, the
facilities available, and skills of the surgeon. Different methods
have various advantages and disadvantages, which need to be
considered when choosing the technique for a given patient49
(Table 42.2).
A
B
Figure 42.7  Stable resistant vitiligo treated with suction blister grafts.
Figure 42.14  Targeted non-laser phototherapy system. (Photo
courtesy of Dr Munish Paul.)

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Chapter 42  Vitiligo Surgery
A
B
Figure 42.15  Treatment with targeted phototherapy. (A) Before the procedure. (B) Response after 24 sessions, twice a week for 3
months. (Photo courtesy of Dr Munish Paul.)
Table 42.2  Overview of surgical techniques in stable vitiligo
TECHNIQUE
INDICATIONS
SUCCESS RATE
ADVANTAGES
DISADVANTAGES
Minipunch grafting
Small irregular areas
Acral areas
68–82%
Simple inexpensive office procedure
Scarring is frequent at the
donor site
Cobblestoning is common
Results are not immediate as
it takes 3–6 months for
pigment spread
Suction blister
grafting
Small areas
Lips
73–88%
No scarring at the donor site
Good cosmetic results, particularly
on the lips
Safe and inexpensive technique
Does not require special surgical
skills
Lengthy time-consuming
procedure
Small rounded grafts are
obtained
Thin split-thickness
skin grafting
All areas can be
treated
78–91%
Most successful technique
Provides pigmentary cover to large
areas over a short period of time
Pigmentation is uniform
Systemic PUVA therapy is not
required routinely
Difficult areas such as eyelids,
inner canthus of eyes, areola,
nipples, and genitals are easier
to treat
Does not require elaborate
equipment or laboratory facilities
Hyperpigmentation and
hypertrophy are common,
especially on exposed areas
and in dark-skinned patients
In extensive vitiligo, there is a
limitation of availability of the
donor skin
Autologous non-
cultured epidermal
cell suspension
All areas can be
treated
Larger areas can be treated at a
single session since donor area
can be expanded up to 5–10 times
Repigmentation is uniform
Laboratory facilities are
required
Pigmentation takes up to 3–6
months
Expensive technique
Cultured
melanocyte grafting
All areas can be
treated
22–72%
The melanocytes can be expanded
up to 100 times by culture
methods; hence large areas can
be treated in a single session
Pigmentation is uniform and
cosmetic matching is usually good,
though hyperpigmentation and a
variegated appearance have been
reported
It is an expensive technique
requiring a fully equipped
tissue culture laboratory with
experienced staff
The long-term safety of
culture media and
carcinogenic potential need
further evaluation

690
Part 4  Special Procedures
dressing as described previously and the eye is kept closed
with an eye shield.
Eyebrows and beard area
In these areas, terminal hairs grow quickly and tend to lift up
the graft. Instead of shaving, the hair should be plucked prior
to surgery to delay regrowth. Cellular melanocyte suspen-
sions may be used instead.
Areola
Vitiliginous patches in the areola and nipple are often resist-
ant to medical therapy and surgery is usually the only option.
The difficulty is in obtaining a cosmetic color match with
surrounding normal skin. Hence it is better to treat the entire
areola, even if a small area is involved. An interesting observa-
tion is that the color of the graft is often recipient dominant
and matches with the color of the contralateral areola in a
majority of cases.18 There are probably local factors of dermal
origin that may play a role in regulating melanocyte activity
in this region.
Genitals
Genital leukoderma can cause severe psychosocial stress, and
medical therapy is usually unsuccessful. Hence surgery is
usually required. Apart from vitiligo, other causes of leuko-
derma in the genital region include postinflammatory depig-
mentation due to genital herpes and contact leukoderma due to
condoms. In patients with recent active herpes simplex, pro-
phylactic acyclovir is administered for at least 7–10 days. Long-
term prophylaxis with acyclovir is advised for at least 1 year to
prevent recurrences in the treated site. In view of the thin epi-
dermis of the genital area and difficulty in obtaining proper
postoperative immobilization, ultrathin split-thickness skin
grafts or cellular grafts such as non-cultured melanocyte sus-
pensions are the treatments of choice.51 Suction blister grafts or
miniature punch grafting may also be done for small lesions.
Figure 42.17 is an example of repigmentation of the penis
with minipunch grafting and can be found online under
related material for this chapter.
The main difficulty in the genital area is providing immo-
bility to the tissue graft and avoiding contamination with
urine. Immobilization can be achieved by the use of tissue
adhesive or fine stay sutures with 6-0 Prolene. When using
cellular grafts, a collagen dressing is applied. When grafting
larger areas, catheterization may be needed for the first 3
days, to prevent contamination of the graft with urine. Alter-
native treatments include tattooing or targeted phototherapy.
Acral areas
The acral areas, tips of the fingers and toes, and palms
and soles are the most difficult to treat, both medically and
surgically. Skin grafting is not always successful in palms
and soles, due to the thick epidermis. Dermabrasion of the
recipient area should be carried out to a greater depth to
get an adequate vascular bed for proper take of the graft.
Strict immobilization by finger splints is essential. In the
periungual areas, punch grafting gives better results.
Figure 42.18 is an example of repigmentation of aoral areas
and can be found online under related material for this chapter.
extend 1–2 mm beyond the vitiliginous skin; postoperative
PUVA therapy or NB-UVB therapy is usually corrective.
Poor cosmetic color match.  In dark skin, prolonged
hyperpigmentation over the donor area and also over the
recipient area is common, particularly on sun-exposed areas
and the legs. Topical corticosteroids and retinoids have been
used by some to reduce hyperpigmentation of grafts.
Uneven texture.  This is commonly seen with punch grafts
(cobblestone appearance) and with thin split-thickness grafts
(hypertrophy). It usually improves with time, but persistent
foci may require superficial dermabrasion. This complication
is not seen with cellular grafts.
Scarring at the donor site.  Mild scarring is common
with minipunch grafting. In split-thickness grafting, it can
occur due to improper harvesting techniques, leading to
thicker grafts. It is always preferable to harvest donor grafts
from covered areas such as the gluteal region. Donor scarring
is not observed with suction blister grafting.
Recurrence and reactivation of the disease.  Reac-
tivation of the disease with depigmentation over the grafted
area or donor site can occur at any time. However, it has been
observed that during reactivation of the disease, the split-
thickness grafts tend to retain pigment and depigmentation
develops at the edges of the graft areas and at new sites
(personal observation).
 OPTIMIZING OUTCOMES
Surgery at mobile sites often results in difficulty in immobiliz-
ing grafts. Proper technique allows results to be optimized.49
Lips
Depigmentation of the lips may be due to vitiligo or postin-
flammatory changes such as those following recurrent herpes
simplex. It is important to obtain a detailed history, and give
prophylactic acyclovir, before and after surgery. On the lips,
suction blister grafting for small areas and thin split-thickness
skin grafting (STSG) for larger areas and the entire lips give
the best results. The graft is immobilized by surgical glue or
7-0 Prolene sutures. If the wet inner mucosa is involved, the
lower lip is everted by using a suture tied to the chin. The
patient is preferably hospitalized and eating is avoided for at
least 24 hours to prevent movement of the graft and con-
tamination by food. A liquid diet with a straw is permitted
after 24 hours. Hyperpigmentation and hypertrophy of the
graft are common initially in dark-skinned patients, but
resolve gradually.10,50
Figure 42.16 is an example of repigmentation of the upper
and lower lips with STSG and can be found online under
related material for this chapter.
Eyelids
For the upper eyelid, strict immobilization is essential for at
least 3–5 days. This is achieved by using a surgical glue over
the entire graft, which forms a film and prevents wrinkling
of the graft. An antibiotic eye ointment is applied under a

691
Chapter 42  Vitiligo Surgery
 SUMMARY
Vitiligo is characterized by an absence of functional melano-
cytes and medical therapy is often inadequate, prolonged, and
not always successful. Acral and mucosal areas are resistant
to therapy. A number of surgical techniques have been devel-
oped to treat resistant stable vitiligo. The choice of technique
depends on the extent, site, and type of vitiligo and experi-
ence of the treating physician. Punch grafting and suction
blister grafting can be done by beginners, but have limitations
as compared to thin split-thickness grafts, which require
more experience. The use of a motorized dermatome to
obtain ultrathin grafts has simplified the procedure. Cellular
grafts have many advantages, though they require laboratory
facilities and prolonged postoperative treatment. Targeted
phototherapy systems have been developed to spare the sur-
rounding normal skin from UV radiation. The excimer laser
emitting a wavelength of 308 nm is therapeutically useful in
some patients. CO2 and Er:YAG lasers are being utilized to
abrade graft recipient sites. Until the exact pathogenetic
mechanisms of vitiligo are elucidated and safe and effective
medical therapies are established, surgical techniques are
essential options in cosmetically distressed individuals, suf-
fering from stable resistant vitiligo.
 REFERENCES
1. Falabella R. History and chronology of development of surgical therapies
for vitiligo. In: Gupta S, Olsson MS, Kanwar AJ, Ortonne J-P, eds. Sur-
gical management of vitiligo, 1st edn. Massachusetts: Blackwell 2007;
41–48.
2. Savant SS. Surgical therapy of vitiligo: current status. Ind J Dermatol
Venereol Leprol 2005;71:307–310.
3. Behl PN. Treatment of vitiligo with homologous thin Thiersch grafts.
Curr Med Pract 1964;8:218–221.
4. Falabella R. Epidermal grafting: an original technique and its application
in achromic and granulating areas. Arch Dermatol 1971;104:592–600.
5. Falabella R. Repigmentation of leucoderma by minigrafts of normally
pigmented, autologous skin. J Dermatol Surg Oncol 1978;4:916–919.
6. Falabella R, Escobar C, Borrero I. Transplantation of in-vitro cultured
epidermis bearing melanocytes for repigmenting vitiligo. J Am Acad
Dermatol 1989;21:257–266.
7. Gauthier Y, Surleve-Bazeille JE. Autologous grafting with non-cultured
melanocytes: a simplified method for treatment of depigmented lesions.
J Am Acad Dermatol 1992;20:191–194.
8. Kahn AM, Cohen MJ. Repigmentation in vitiligo patients. Melanocyte
transfer via ultra-thin grafts. Dermatol Surg 1998;24:365–368.
9. Kahn AM, Ostad A, Moy RL. Grafting following short pulse CO2 laser
de-epithelialization. Dermatol Surg 1996;22:965–967.
10. Khunger N. Thin split-thickness skin grafts for vitiligo. In: Gupta S,
Olsson MS, Kanwar AJ, Ortonne J-P, eds. Surgical management of vitil-
igo, 1st edn. Massachusetts: Blackwell 2007; 108–114.
11. Das SS, Pasricha JS. Punch grafting as a treatment for residual lesions in
vitiligo. Ind J Dermatol Venereol Leprol 1992;58:315–319.
12. Boersma BR, Westerhof W, Bos JD. Repigmentation in vitiligo vulgaris
by autologous minigrafting: results in nineteen patients. J Am Acad Der-
matol 1995;33:990–995.
13. Olsson M, Juhlin L. Long-term follow-up of leukoderma patients treated
with transplants of autologous cultured melanocytes, ultrathin epidermal
sheets and basal cell layer suspension. Br J Dermatol 2002;47:893–
904.
14. Falabella R. Surgical treatment of vitiligo: why, when and how. J Eur
Acad Dermatol Venereol 2003;17:518–520.
15. Parsad D, Gupta S. Standard guidelines of care for vitiligo surgery. Ind
J Dermatol Venereol Leprol 2008;74:37–45.
16. Falabella R, Arrunategui A, Barona MI, et al. The minigrafting test for
vitiligo: detection of stable lesions for melanocyte transplantation. J Am
Acad Dermatol 1995;32:228–232.
17. Njoo MD, Das PK, Bos JD, et al. Association of the Koebner phenom-
enon with disease activity and therapeutic responsiveness in vitiligo vul-
garis. Arch Dermatol 1999;135:407–413.
18. Gupta S, Kumar B. Epidermal grafting in vitiligo: influence of age, site
of lesion, and type of disease on outcome. J Am Acad Dermatol
2003;49:99–104.
19. Gupta S, Kumar B. Epidermal grafting for vitiligo in adolescents. Pediatr
Dermatol 2002;19:159–162.
20. Juhlin L, Olsson MJ. Optimal application times of eutectic mixtures of
local anaesthetics (EMLA) cream before dermabrasion of vitiliginous skin.
Eur J Dermatol 1995;5:365–370.
21. Malakar S, Lahiri K. Minigrafting for vitiligo. In: Gupta S, Olsson MS,
Kanwar AJ, Ortonne J-P, eds. Surgical management of vitiligo, 1st edn.
Massachusetts: Blackwell 2007; 87–95.
22. Malakar S, Dhar S. Treatment of stable and recalcitrant vitiligo by autol-
ogous miniature punch grafting: a prospective study of 1000 patients.
Dermatology 1999;198:133–139.
23. Hann SK, Im S, Bong HW, et al. Treatment of stable vitiligo with
autologous epidermal grafting and PUVA. J Am Acad Dermatol
1995;32:943–948.
24. Lahiri K, Malakar S, Sarma N, et al. Repigmentation of vitiligo with punch
grafting and narrow-band UV-B (311  nm): a prospective study. Int J
Dermatol 2006;45:649–655.
25. Falabella R. Repigmentation of stable leucoderma by autologous mini-
grafting. J Dermatol Surg Oncol 1986;12:172–179.
26. Malakar S, Dhar S. Repigmentation of leucotrichia over vitiligo patches
after punch grafting. Ind J Dermatol Venereol Leprol 1998;64:252–
253.
27. Malakar S, Lahiri K. Electrosurgery in cobblestoning. Ind J Dermatol
2000;45:46–47.
28. Kim HV, Yun SK. Suction device for epidermal grafting in vitiligo:
employing a syringe and a manometer to provide an adequate negative
pressure. Dermatol Surg 2001;26:702–704.
29. Mutalik S, Ginzburg A. Surgical management of vitiligo. Dermatol Surg
2000;26:248–254.
30. Sachdev M, Krupashankar DS. Suction blister grafting for stable vitiligo
using pulsed erbium:YAG laser ablation for recipient site. Int J Dermatol
2001;39:471–473.
31. Oh CK, Cha JH, Lim LY, et al. Treatment of vitiligo with suction epi-
dermal grafting by the use of an ultrapulse CO2 laser with a computerised
pattern generator. Dermatol Surg 2001;27:563–568.
32. Gupta S, Sandhu K, Kanwar A, et al. Melanocyte transfer via epidermal
grafts for vitiligo of the labial mucosa. Dermatol Surg 2004;30:45–48.
33. Behl PN, Azad O, Kak R, et al. Autologous thin Thierschs grafts in
vitiligo: experience of 8000 cases and 50 000 grafts (1959–98) with
modIfied technique in 198 cases in the year 1997–98. Ind J Derm Vener-
eol Leprol 1999;65:117–121.
34. Khunger N. Cyanoacrylate adhesive in split thickness skin grafts for
resistant vitiligo – an experience in 50 cases. Presented at the 31st
National Conference of the Indian Association of Dermatologists, Vene-
orologists, and Leprologists, Kolkata, Jan 30–Feb 2, 2003, Book of
Abstracts page 180.
35. Torium DM, Grody K, Desai D, et al. Cyanoacrylate adhesive. Plast
Reconstr Surg 1998;102:2209–2219.
36. Mulekar SV. Long-term follow-up study of segmental and focal vitiligo
treated by autologous non cultured melanocyte-keratinocyte cell trans-
plantation. Arch Dermatol 2004:1211–1215.
37. van Geel N, Ongenae K, de Mil M, et al. Double blind placebo control-
led study of autologous transplanted epidermal cell suspensions for
re­pigmenting vitiligo. Arch Dermatol 2004;40:1203–1205.
38. Chen YF, Yang PY, Hu DN, et al. Treatment of vitiligo by transplantation
of cultured pure melanocytes suspension. Analysis of 120 cases. J Am
Acad Dermatol 2004;51:68–74.
39. Redondo P, del Olmo J, García-Guzman M, et al. Repigmentation of
vitiligo by transplantation of autologous melanocyte cells cultured on
amniotic membrane. Br J Dermatol 2008;158:1168–1171.
40. Lontz W, Olsson MJ, Moellman G, et al. Pigment cell transplantation of
cultured autologous melanocytes: a progress report. J Am Acad Dermatol
1994;30:591–597.
41. Mahajan BB, Garg G, Gupta RR. Evaluation of cosmetic tattooing in
localized stable vitiligo. J Dermatol Treat 2002;29:726–730.
42. Spear SL, Arias J. Long-term experience with nipple–areola tattooing.
Ann Plast Surg 1995;35:232–236.
43. Savant SS. Therapeutic spot and regional dermabrasion in stable vitiligo.
Ind J Dermatol Venereol Leprol 1996;62:139–145.
44. Sethi S, Mahajan BB, Gupta RR, et al. Comparative evaluation of the
therapeutic efficacy of dermabrasion, dermabrasion combined with
topical 5% 5-fluorouracil cream, and dermabrasion combined with topical
placentrex gel in localized stable vitiligo. Int J Dermatol 2007;46:875–
879.
45. Passeron T, Ostovari N, Zakaria W, et al. Topical tacrolimus and the
308-nm excimer laser: a synergistic combination for the treatment of
vitiligo. Arch Dermatol 2004;140:1065–1069.

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46. Hofer A, Hassan AS, Legat FJ, et al. The efficacy of excimer laser
(308 nm) for vitiligo at different body sites. J Eur Acad Dermatol Vener-
eol 2006;20:558–564.
47. Agrawal K, Agrawal A. Vitiligo: surgical repigmentation of leukotrichia.
Dermatol Surg 1995;135:1305–1307.
48. Thissen M, Westerhof W. Laser treatment for further depigmentation in
vitiligo. Int J Dermatol 1997;36:386–388.
49. Khunger N. Recent advances in the surgical treatment of vitiligo. In:
Ghosh S, ed. Recent advances in dermatology, vol 2. India: Jaypee
Medical 2007; 319–340.
50. Gupta S, Goel A, Kanwar AJ. Surgical management of lip vitiligo. In:
Gupta S, Olsson MS, Kanwar AJ, Ortonne J-P, eds. Surgical management
of vitiligo, 1st edn. Massachusetts: Blackwell 2007; 211–219.
51. Mulekar SV, Al Issa A, Al Eisa A, et al. Genital vitiligo treated by
autologous, noncultured melanocyte–keratinocyte cell transplantation.
Dermatol Surg 2005;31:1737–1740.

693
43
Management of Dysplastic Nevi
and Melanomas
Ashfaq A Marghoob MD, Ivanka Kovalyshyn BA, and Allan C Halpern MD
Summary box
 Atypical nevi share many of the clinical features of
melanomas.
 Atypical mole syndrome can occur sporadically or can be
inherited.
 Both genetics and ultraviolet light exposure appear to be
involved in the phenotypic expression of atypical moles.
 The total number of melanocytic nevi and the presence
of atypical moles are independent risk factors for the
development of melanoma.
 Patients with even one atypical mole have an elevated risk
for developing melanoma. Although the degree of risk may
fluctuate, it remains elevated even after excision of atypical
nevi; indicating that atypical moles serve as markers of
increased risk as well as potential precursors of melanoma.
 Although melanomas developing in patients with atypical
moles may arise in dysplastic nevi, most develop de novo.
 Avoidance of unnecessary sun exposure, sun protection, and
lifelong skin surveillance via periodic self-examination and
physician-based examination are important in the prevention
and early detection of melanoma.
 Baseline photography and digital dermoscopy may be utilized
to monitor patients for the development of new lesions and
detection of changes in existing nevi, thereby improving
specificity and sensitivity for melanoma detection.
 Any outlier lesion (e.g. ugly duckling), new lesion, changing
lesion, or symptomatic melanocytic neoplasm should be
examined closely and biopsied if warranted.
 Lifelong follow up is crucial in patients with melanoma
because recurrences can occur as long as 20 years after
initial diagnosis and treatment. Patients also have an
increased risk of developing a second primary melanoma.
 Most recurrences or metastases of melanoma are detected
on physical examination or during a review of systems.
Laboratory and imaging studies are of low yield and should
be directed based on symptoms and physical findings.
 INTRODUCTION
Clinical features and presentation
Atypical moles or dysplastic nevi – the two terms will be used
interchangeably in this chapter – are generally diagnosed on
the basis of their clinical and histologic features.1 Clinically,
atypical moles share many of the features of melanomas, such
as those described in the ABCD mnemonic (Asymmetry,
Border irregularity, Color variability, and Diameter > 6 mm)
(Fig. 43.1).2–4 Histopathologic characteristics of dysplastic
nevi include variable degrees of architectural disorder, cyto-
logic atypia, and lymphocytic infiltrate.2 Table 43.1 compares
the features of common acquired nevi, atypical nevi, and
melanomas.
Atypical moles frequently display border irregularity and
often exhibit color variability, with various shades of tans
and browns, and sometimes hues of pinks and reds, black,
and even white. Blue is usually not seen in atypical moles on
clinical examination (Fig. 43.2A), but may be seen on der-
moscopy (Fig. 43.2B). The surface of atypical moles is often
slightly raised and mamillated, but occasionally may appear
papular, nodular, or sessile. A frequently encountered clinical
clue to the diagnosis of atypical moles is the presence of a
macular lightly pigmented area or ‘shoulder’ surrounding the
centrally elevated portion of the nevus (Fig. 43.3). Atypical
moles are often over 6 mm in diameter, but it is not uncom-
mon for them to be smaller. Although atypical moles can
occur on any anatomic region, they are most commonly found
on the trunk and legs (Figs 43.4 and 43.5).3 The reason, for
the occurrence of dysplastic nevi in locations protected from
the sun, such as the buttocks, breasts, scalp, and pubic region,
remains to be explained (Figs 43.6 and 43.7).4,5 It is interest-
ing to note that dysplastic nevi rarely occur on the chronic
sun-exposed skin of the face or hands.
Approximately 7% of Caucasians have clinically atypical
(dysplastic) nevi. However, the prevalence of clinically atyp-
ical nevi among patients with melanoma is higher, ranging
from 34% to 59%.6,7 People with atypical moles can exhibit
a wide range of phenotypic expressions (Figs 43.8 and 43.9).
In addition, a recent article by Huynh et al.8 introduced the
‘cheetah phenotype’ in which patients do not have clinically
atypical moles, but have numerous (>100) similar-appearing,
dark brown, <4 mm in diameter melanocytic nevi that are
uniform in color. These individuals are also at increased risk
of melanoma (Fig. 43.10).
It is interesting to note that an individual’s nevi resemble
each other clinically and dermoscopically – a concept known
as ‘moles breed true’ or ‘signature nevus pattern.’9,10 The
ability to detect outlier lesions (e.g. ugly ducklings), some of
which may be melanomas, is in part contingent upon this
observation that moles breed true (Figs 43.11 and 43.12).9,10
Patients with multiple atypical moles and common nevi have
what has come to be known as the atypical mole syndrome

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Part 4  Special Procedures
A
B
C
D
Figure 43.1  Each of these lesions
exhibits some of the ABCD features.
(A) Asymmetry and variable colors.
(B) Asymmetry and border irregularity.
(C) Different colors with shades of dark
brown and red. (D) Asymmetry, variable
colors, and diameter greater than 6 mm.
Table 43.1  General features of common acquired nevi, dysplastic nevi (atypical moles), and melanomas
FEATURE
COMMON ACQUIRED NEVI
ATYPICAL MOLES
MALIGNANT MELANOMAS
Asymmetry
Symmetric
Variable
Usually asymmetric
Border
Regular
Variable; indistinct
Irregular, often sharp
Color
Uniform tan/brown
Often variegated tan/brown/black/red
Often variegated tan/brown/black/
red/white/blue
Diameter
<6 mm
Often >5 mm
Often >5 mm
Clinical change
Slow then stable, many will regress
Slow then stable, some will regress
Faster (over months)
Surface
Macular or nodular (not both)
Often elevated with peripheral macular ‘shoulder’
Macular to nodular
A
B
Figure 43.2  Blue color is better
appreciated in the dermoscopic image
in (B), as compared to the clinical
image (A).

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Chapter 43  Management of Dysplastic Nevi and Melanomas
Figure 43.3  The center of the lesions are raised with a macular
lightly pigmented periphery.
Figure 43.4  Numerous dysplastic nevi on the trunk.
Figure 43.5  Numerous dysplastic nevi on the lower legs in a
patient with atypical mole syndrome.
Figure 43.6  Several dysplastic nevi on the sun-protected buttocks.
Figure 43.7  Dysplastic nevi on the mons pubis.
Figure 43.8  A person with fewer dysplastic nevi than shown
in Figure 43.9 but within the spectrum of people with dysplastic
nevus syndrome.

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Part 4  Special Procedures
of life, with a subsequent decrease in the total number of
melanocytic nevi with age.15–17 It is fairly well established that
nevogenesis and the density of nevi present in an individual
is under strong genetic control, which is modified by environ-
mental exposures.18–28
The natural progression of some atypical melanocytic nevi
appears to differ from that of common melanocytic nevi. Like
common acquired melanocytic nevi, atypical moles may
first begin to appear during early childhood; however, most
will not become fully clinically manifest until puberty. Both
genetics and ultraviolet (UV) light exposure may be involved
in the phenotypic expression of atypical moles. However,
or dysplastic nevus syndrome. There are several definitions
for atypical mole syndrome (Table 43.2).4,11–14 Atypical mole
syndrome can occur sporadically, but in many individuals it
appears to be an inherited disorder in which the affected
individuals begin to develop atypical nevi during childhood
and continue to develop multiple nevi over their lifetime.
Natural history and progression
The natural history of common acquired melanocytic nevi is
characterized by infrequent occurrence before 1 year of age
and a gradual increase in number, peaking in the third decade
Figure 43.9  This person with numerous, variably sized
dysplastic nevi is on the other end of the spectrum (compared
with Fig. 43.8) of dysplastic nevus syndrome.
Figure 43.10  ‘Cheetah phenotype’ with numerous, dark brown,
similar-appearing nevi.
Three different clinical scenarios in which outlier lesions prompt suspicion
A
B
C
Figure 43.11  This schematic represents three different clinical scenarios in which outlier lesions (‘ugly ducklings’) prompt suspicion.
The rectangles denote a body area such as the back. (A) This scenario shows one dominant mole pattern with slight variation in
size. The outlier lesion (arrow) is clearly darker and larger than all other moles. (B) This scenario shows two predominant nevus
patterns: larger nevi and small, darker nevi. The outlier lesion (arrow) is small but lacks pigmentation. (C) This scenario shows only
one lesion on the back. If this lesion is changing, symptomatic, or deemed atypical by the clinician, it should be removed.

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Chapter 43  Management of Dysplastic Nevi and Melanomas
A
B
C
D
Figure 43.12  Example of an ‘ugly duckling’ in the background of multiple similarly appearing moles. (A) The lesion in the mid-back
indicated by the black arrow stands out as different because it is, in this case, larger and darker than all the other moles. This lesion
was surgically removed and proved to be a melanoma. (B) A close-up image of the melanoma (the lesion labeled with a black arrow
in A) and (C,D) two of the benign moles on the patient’s back (those labeled with white arrows in A). The melanoma (B) is larger,
has an irregular, scalloped border, and displays multiple colors; it is clearly different than the two nevi (C, D), which are smaller and
display only brown color.
although most acquired nevi develop on skin that receives
intermittent sun exposure (e.g. the back), it is not uncommon
for atypical moles to also develop in relatively sun-protected
areas, such as the scalp and groin.25 In fact, in prepubertal
children, the scalp is often the first place where dysplastic
nevi appear.29
Halpern et  al.30 prospectively followed a cohort of 153
dysplastic nevus patients over a minimum of 5 years, and
concluded that atypical moles were dynamic in behavior,
regardless of the age of the patient. Unlike individuals with
common nevi, it is not unusual for persons with atypical nevi
to continue to develop new lesions throughout life (Fig.
43.13).1,12 Over 50% of the patients studied had changes
within their atypical moles throughout an average follow up
of 89 months. The changes included decreased clinical atypia
(35%), the appearance of new atypical moles (33%), increased

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Part 4  Special Procedures
develop de novo (not in association with a dysplastic nevus),
in these patients the removal of all dysplastic nevi will not
eliminate the risk for developing melanoma. In addition,
many of these patients have hundreds of atypical moles, such
that removing all the lesions would be impractical and disfig-
uring (Fig. 43.19). The alternative to wholesale prophylactic
excision of nevi is periodic skin surveillance examinations
aimed at finding new or changing lesions, some of which may
in fact be early melanomas. Guidance during periodic assess-
ment of nevi is provided by dermoscopic evaluation. Melano-
mas usually display at least one of the 10 melanoma-specific
dermoscopic features listed in Table 43.3.
Additional information on prophylactic excising of nevi and
techniques for observation of nevi can be found online under
related material for this Chapter.
 TECHNICAL ASPECTS
Early detection and prevention
The diagnosis and removal of a melanoma when it is early in
its evolution is paramount to ensure a favorable prognosis.
Thus, the goal in the management of individuals with atypical
moles is to ensure that any evolving melanoma is caught as
early as possible. The important elements in the management
of patients who have atypical moles are discussed below (and
online) and listed in Box 43.1.
Visual aids for physician surveillance
Certain tools are helpful in aiding the naked eye in the eval-
uation of suspicious lesions. The simplest is a magnifying glass.
By enlarging the lesions, details can be better appreciated. A
Wood’s light can help visualize areas of regression, by enhanc-
Table 43.2  Atypical mole syndromes
SYNDROME NAME
CLINICAL FEATURES
Sporadic syndromes
Atypical mole syndrome4
Three or more of the following characteristics:
1.  Two or more clinically atypical nevi
2.  >100 nevi >2 mm diameter or >50 nevi if <20 or >50 years of age
3.  Nevi abnormally distributed (buttocks or dorsum of foot)
4.  Nevi in the anterior scalp
5.  Iris pigmented lesion(s)
‘Classic’ atypical mole syndrome11
1.  >100 melanocytic nevi
2.  One or more nevi >8 mm diameter
3.  One or more nevi with atypical features
B-K mole14
≥10 mm diameter; irregular outline; haphazard mixture of tan, brown, black, and pink; small palpable
dermal component
B-K mole syndrome14
Fewer than 10 B-K moles to more than 100 moles prominent on the upper trunk and extremities;
variability of mole size (5–15 mm diameter), outline, and color
Familial syndromes
Familial atypical mole syndrome12
1.  Two or more family members with atypical moles
2.  One or more family members with melanoma
Familial atypical multiple mole–
melanoma syndrome13
1.  Melanoma in two or more first- or second-degree relatives
2.  Many atypical nevi (often more than 50)
clinical atypia (15%), and complete disappearance of atypical
moles (7%) (Fig. 43.14).
Additional material about the dynamic characteristics of dys-
plastic nevi can be found online under related material for
this Chapter.
Risk of melanoma
Melanocytic nevi are risk markers for, and potential precur-
sors of, melanomas. Patients with atypical mole syndrome
have varying degrees of risk for developing melanoma. The
magnitude of the risk depends on factors such as the number
of nevi, personal or family history of melanoma, and family
history of dysplastic nevi. Individuals with dysplastic nevi
who have at least two blood relatives with melanoma have a
lifetime risk for developing melanoma of greater than 80%.28
The penetrance of melanoma in their ‘familial melanoma’
kindreds varies by geography, supporting the role of UV
exposure.
Additional material about the risk of developing melanoma
can be found online under related material for this Chapter.
Prophylactic excision of nevi and
techniques for observation of nevi
Some have advocated for the prophylactic excision of all
dysplastic nevi as a means of ensuring that clinically incon-
spicuous melanomas are removed and all potential precursors
to melanoma are eliminated.68 However, although atypical
moles may be precursors to melanoma, the risk of any given
nevus developing into melanoma is quite small.42,69,70 As a
result, most would agree that the prophylactic excision of all
atypical moles is not a practical method for detecting or
preventing melanomas. Furthermore, since most melanomas

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Chapter 43  Management of Dysplastic Nevi and Melanomas
Figure 43.13  Increasing number of nevi
with increasing age.
Figure 43.14  Change in clinical
appearance with lightening of color
showing regression of this nevus over
time.

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Part 4  Special Procedures
Figure 43.19  Scars on a patient who underwent excision of
multiple dysplastic nevi.
Table 43.3  Dermoscopic structures and their histopathologic correlates commonly seen in melanomas
DERMOSCOPIC
STRUCTURE
DESCRIPTION
HISTOPATHOLOGIC CORRELATE
Atypical pigment network
Reticulated grid of brown lines with
broadened, thickened, or darkened areas that
may end abruptly at the periphery
Atypical lentiginous or nested melanocytic
proliferation along the dermoepidermal junction
Streaks
Linear, radially oriented pigmented
projections at the periphery of a lesion
Confluent junctional nests of pigmented
melanoma cells at the periphery (radial growth
phase)
Negative pigment network
The ‘negative’ of the pigment network,
consisting of hypopigmented lines making up
the grid, and dark areas filling up the ‘holes’
Thin, elongated rete ridges and large tubular
melanocytic nests within a widened papillary
dermis
Chrysalis
Fine, white, shiny streaks within a lesion,
visible only under polarized light dermoscopy
Remodeled or new dermal collagen
Atypical dots and globules
Dark, punctate, or round to oval structures
of varying shape, size, color, and distribution
within a lesion
Junctional or dermal nests of melanocytes;
dots can also represent pagetoid nests
Irregular blotches
Dark areas of diffuse pigmentation with
irregular shapes, sharp margins, or eccentric
locations
Melanin pigmentation throughout the epidermis
or dermis or both
Blue–white structures over
raised areas
White areas, blue areas, or both, overlying
raised or thick portions of a lesion
Compact orthokeratosis overlying
melanophages, melanocytes, or free melanin
in the papillary dermis
Blue–white structures over flat
areas
White areas, blue areas, or both, overlying flat
or thin portions of a lesion
Fibrosis within the papillary dermis and
melanosis (melanophages and free melanin
‘dust’ within the dermis)
Atypical vascular structures
Milky red areas, dotted, linear, or twisted red
structures with differing sizes
Tumor-induced neoangiogenesis
Peripheral brown structureless
areas
Peripherally arranged light brown or tan
areas of variable shape lacking perceptible
structures
Flattening of the rete ridges with pagetoid
spread of atypical melanocytes
Box 43.1  Elements for early detection and
prevention of melanoma
 Periodic routine dermatologic examinations.
 Regular self-examinations.
 Ophthalmologic, oral, and genital examinations.
 Imaging technology (dermoscopy, confocal microscopy).
 Ultraviolet precautions.
 Biopsy and histologic evaluation of suspicious lesions.
ing depigmented areas. Dermoscopy (epiluminescence micro-
scopy) is a non-invasive technique that permits visualization
of subsurface structures not discernible to the unaided eye
by rendering the epidermis translucent. This is accomplished
by reducing light reflection, refraction, and diffraction (Figs
43.25 and 43.26).105,106 In experienced hands, dermoscopy
helps in the diagnosis of both pigmented and non-pigmented
(amelanotic or hypomelanotic) skin lesions.107 The use of
dermoscopy improves the diagnostic accuracy, specificity,
and sensitivity for the detection of melanoma.108,109
Information about UV precautions can be found online
under related material for this chapter. See also Table 43.4.
Additional material about dermoscopy may be found online
under related material for this chapter and contains Figures
43.22 and 43.23, and information about physician screening,

701
Chapter 43  Management of Dysplastic Nevi and Melanomas
A
B
Figure 43.25  (A) Clinical picture of a
dysplastic nevus. (B) Dermoscopic image
with better visualization of areas of
regression.
A
B
Figure 43.26  (A) Clinical picture of a
dysplastic nevus. (B) Dermoscopic
image with more well-defined
reticulated pigment networks and color
contrast.
self-examination, ophthalmologic examination, scan protec-
tion, examination and biopsy of changing or symptomatic
pigmented lesions, and chemoprevention.
Management of melanoma
Optimal management of patients diagnosed with melanoma
requires consideration of multiple factors regarding the man-
agement of the primary site, staging procedures, adjuvant
therapy, and follow up. Treatment should be tailored to the
needs of each individual patient. This section presents a gen-
eralized approach to the surgical management (excision
margins) for melanoma, the diagnostic and staging work-up,
follow-up recommendations, and adjuvant treatment options.
Diagnosis
Diagnosis of melanoma begins with a biopsy of a suspected
lesion.150 Once the diagnosis has been established via histopa-
thology, the staging work-up and treatment options are con-
sidered, taking into account the prognostic attributes such as
thickness of the tumor, location, and overall medical condi-
tion of the patient (Box 43.2). The 2002 revised American
Joint Committee on Cancer (AJCC) staging classification is
listed in Table 43.5.151
It is also of great importance to provide psychological
support for patients diagnosed with melanoma. Melanoma is
a serious, potentially fatal cancer that can be a source of great
anxiety and fear for the patient and his or her family members.
Frequent follow-up visits in the period immediately after
diagnosis can provide reassurance and comfort.
Staging
Staging of melanoma patients begins with a thorough history
and physical examination. Accurate staging is important since
it provides prognostic information (Table 43.6). A problem-
oriented physical examination should include a complete skin
and lymph node examination and assessment of any abnor-

702
Part 4  Special Procedures
Table 43.4  Ultraviolet precautions
PRECAUTION
DETAIL
Minimize sun exposure
Between 10 am and 4 pm
Wear protective clothing in
the sun
A wide-brimmed hat, long-sleeved shirt, and long pants. Choose tightly-woven materials for greater
protection from the sun’s rays
Apply a sunscreen when
exposure is unavoidable
At least 1 hour before every exposure to the sun, and reapply frequently and liberally, at least every 2
hours while in the sun. Reapply after swimming or sweating heavily. Use broad-spectrum (UVA plus UVB)
sunscreen with an SPF of 30 or more
Use a sunscreen
During high-altitude activities such as mountain climbing, hiking, or skiing. Also, the sun is stronger near the
equator
Do not forget to use
sunscreen on overcast days
The sun’s rays are as damaging to skin on cloudy, hazy days as they are on bright sunny days
Apply sunscreens every day
Individuals at high risk for skin cancer (outdoor workers, fair-skinned individuals, persons who have already
had skin cancer, and persons with the atypical mole syndrome)
Beware of reflective surfaces!
Sand, snow, concrete, and water can reflect more than half the sun’s rays onto the skin. Sitting in the shade
does not guarantee adequate protection from the sun
Avoid tanning parlors
The UV light in tanning booths can cause sunburn and premature aging of the skin, and increases the risk for
skin cancer
Keep infants out of the sun
before 6 months of age
Protect children 6 months of age and older with clothing and sunscreens
Teach children sun protection
Sun damage occurs with each unprotected sun exposure and accumulates over the course of a lifetime.
Childhood behaviors strongly impact lifelong attitudes and behaviors
malities detected on a thorough review of systems. Suspicious
signs, symptoms, and physical findings (e.g. in-transit metas-
tases, satellite lesions, and palpable lymph nodes) warrant
additional laboratory studies, imaging studies, and possible
biopsy for histological analysis.
Patients with thin melanomas (<1.0 mm) do not require
routine blood work or imaging studies directed at a search for
occult metastases. For patients with melanomas over 1.0 mm,
baseline laboratory values including complete blood count,
lactate dehydrogenase (LDH), liver function tests, and chest
radiography have been suggested by some, but the yield on
these studies is very low.152 Although routine imaging and
blood work studies are not generally indicated in asympto-
matic patients with stage I or II disease, there may be a
benefit to obtaining them in patients with more advanced-
stage disease. For example, an elevated LDH level on
two separate occasions, at least 24 hours apart, may be an
indication of metastatic disease.153 In addition, LDH levels
can also be monitored as a marker for disease activity. Radio­
Table 43.5  New American Joint Committee on
Cancer staging
CLINICAL
STAGE
DESCRIPTION (ALL SIZES ARE
BRESLOW THICKNESSES)
0
In situ
IA
≤1.0 mm, no ulceration, Clark level II or III
IB
≤1.0 mm, with ulceration, Clark level IV, V
1.01–2.0 mm, no ulceration
IIA
1.01–2.0 mm, with ulceration
2.01–4.0 mm, no ulceration
IIB
2.01–4.0 mm, with ulceration
>4.0 mm, no ulceration
IIC
>4.0 mm, with ulceration
IIIA
Any primary melanoma with one nodal metastasis
IIIB
Any primary melanoma with 2–3 regional nodes or
intralymphatic regional metastasis without nodal
metastasis
IIIC
Any primary melanoma with metastasis to 4 or
more nodes or in-transit metastasis or satellites
with metastasis in regional nodes
IV M1a
Distant skin, subcutaneous, or nodal metastases
with normal lactate dehydrogenase (LDH)
IV M1b
Lung metastasis with normal LDH
IV M1c
All other visceral metastasis with normal LDH or
any distant metastasis with elevated LDH
Box 43.2  Prognostic factors
 Gender.
 Location.
 Age.
 Thickness.
 Ulceration.
 Lymphovascular invasion.
 Regression.
 Mitotic index.
 Lymphocytic infiltrate.
 Angiogenesis.
 DNA ploidy.
 Nuclear volume.
 Microscopic satellitosis/in-transit metastases.
 Recurrent disease.
logic and nuclear imaging studies may be useful in the evalu-
ation and guiding the management of stage III and IV patients
who have nodal or distant metastatic disease. Finally, com-
puted tomography (CT) and positron emission tomography
(PET) are commonly used to evaluate symptoms or abnor-
malities detected during follow-up examinations.

703
Chapter 43  Management of Dysplastic Nevi and Melanomas
lentigo maligna melanomas coupled with their common
occurrence on the face of elderly patients warrants consid-
eration of radiation therapy, cryotherapy, topical immuno-
therapy, or observation in some cases (Fig. 43.27).
For patients with stage IA disease (i.e. thin melanomas
(<1.0  mm) without negative prognostic attributes such as
ulceration, dermal mitoses, or Clark’s level IV–V or lym-
phovascular invasion), wide local excision is sufficient treat-
ment. For patients with stage IB–II disease (i.e. intermediate
and thick lesions (>1.0  mm) without clinical evidence of
nodal involvement), wide local excision with or without sen-
tinel lymph node biopsy (SLNB) should be considered.
Sentinal lymph node biopsy
Few would dispute the fact that the SLNB status provides
important prognostic information.151,156–159 However, whether
a positive SLNB followed by complete lymph node dissection
with or without adjuvant therapy provides a survival advan-
tage remains to be proven.160–162 Patients with metastatic
melanoma found on SLNB typically undergo therapeutic
‘completion’ lymphadenectomy of the affected basin (Fig.
43.28). Those without evidence of melanoma in the sentinal
lymph nodes (SLNs) are spared additional surgery.
Additional material about SNLB can be found online under
related material for this chapter.
Recent results from the first Multicenter Selective Lym-
phadenectomy Trial (MLST-I), designed to evaluate the
effectiveness of intraoperative lymphatic mapping (LM), sen-
tinel lymphadenectomy (SL), and selective complete lymph
node dissection (CLND) for the management of early-stage
melanoma, has shown increased disease-free survival and less
disease recurrence in regional nodes in the LM/SL group as
compared with wide excision followed by nodal observation
(WEO) group.179 Unfortunately, the results from MLST-I did
not reveal melanoma-specific survival benefits; however, it
In patients who have metastatic melanoma with an unknown
primary, a complete skin examination focused on finding
the site of the primary melanoma should be undertaken.
The examining clinician needs to be cognizant of the possi-
bility that the primary melanoma may have regressed from
the cutaneous surface. Both Wood’s light examination and
dermoscopic evaluation may help augment the physical
examination and help highlight areas of regression.154,155
Besides a thorough cutaneous examination, an ophthalmo-
logic, gynecologic, rectal, and nasopharyngeal examination
can be considered.
Surgical management
Surgical excision with margins based on Breslow thickness
is the cornerstone of treatment for primary cutaneous
melanoma. The proposed lateral margins of excision from the
National Comprehensive Cancer Network (NCCN) are
listed in Table 43.7.152 These recommended margins of exci-
sion may need to be modified to accommodate individual
anatomic or cosmetic considerations. For example, it may not
be feasible or necessary to excise a microinvasive melanoma
on the eyelid with a 1-cm margin. In addition, certain cir-
cumstances may require a non-surgical approach to the treat-
ment of melanoma. For example, the large size of some
Table 43.6  Survival data for melanoma
STAGE
1-YEAR
SURVIVAL
(%)
5-YEAR
SURVIVAL
(%)
10-YEAR
SURVIVAL
(%)
IA
95
88
IB
90
80
IIA
78
65
IIB
65
50
IIC
45
32
IIIA
65
60
IIIB
50
40
IIIC
25
20
IV M1a
59
19
16
IV M1b
57
7
3
IV M1c
41
10
6
Stage I, II: worse prognosis with ulceration, increasing thickness, age, axial location,
being male.
Stage III: worse with increasing number of nodes, macrometastasis, ulceration of
primary tumor.
Stage IV: depends on site, but differences are minimal – metastases to the lung only
has 1-year survival advantage over other visceral metastases.
Table 43.7  Surgical margins
BRESLOW
THICKNESS
PROPOSED SURGICAL
MARGINS FROM THE NCCN
In situ
0.5 cm
≤1.0 mm
1.0 cm
1.0–2 mm
1–2 cm
2.01–4 mm
2.0 cm
>4 mm
2.0 cm
Figure 43.27  A lentigo maligna covering the entire nose. An
excisional biopsy or complete surgical treatment would not be
feasible.

704
Part 4  Special Procedures
melanoma patients in the adjuvant setting is interferon (IFN)-
α-2b. Interferon therapy has shown increased disease-free
survival in a few studies, and in one controlled study showed
increased overall survival.184 In this one study, high-dose
interferon-α given for 1 full year in patients with stage IIB
and III disease resulted in a median increase in overall survival
from 2.8 to 3.8 years.184 However, this improved survival
came at the cost of considerable toxicity.185 Other trials using
high-dose IFN have shown improvements only in disease-
free survival without showing any difference in overall
survival.161,186–188
Additional information or adjuvant therapy can be found
online under related material for this chapter.
Treatment of metastatic disease
In spite of many advances in treatment, metastatic melanoma
remains a challenging disease to manage. The treatment
approaches include surgical resection, radiation therapy, sys-
temic chemotherapy, biological therapy, immunotherapy,
targeted therapy, and combination therapy. Unfortunately,
most of these treatments have shown limited success.
In patients with metastatic melanoma distant to the local/
regional site, curative resection of relatively stable remote
nodal and soft tissue lesions as well as isolated visceral lesions
should be considered (Fig. 43.29). In symptomatic patients,
palliative resection may also be appropriate. The lung is the
most common visceral site of metastasis that is potentially
curable with the resection of isolated lesions. Prolonged sur-
vival among some patients treated with surgical resection of
limited liver, pulmonary, or brain metastases has been
reported.193–195 Palliative radiation therapy is an option in the
setting of inoperable brain metastases.
Additional information or treatment of metastatic disease can
be found online under related material for this chapter.
 POSTOPERATIVE CARE
Follow up
Periodic skin examinations are important for patients with
melanoma since they are at risk for developing skin recur-
rence and are at risk for developing subsequent new primary
has been suggested that longer follow up may be necessary
to accurately assess the overall survival in the two groups.180
Additional advantages about SLNB can be found online under
related material for this chapter.
Adjuvant therapy
Adjuvant therapy should be considered for patients at high
risk for recurrence and metastases. Multiple approaches to
adjuvant therapy including chemotherapy, immunotherapy,
or vaccine therapy have been studied. Randomized studies of
adjuvant treatment using bacillus Calmette–Guérin (BCG),
Corynebacterium parvum, dacarbazine (DTIC), levamisole,
vitamin A, and megestrol acetate alone or in combination
have generally failed to show any significant benefit in disease-
free or overall survival.
Adjuvant therapy should be considered for patients at high
risk for recurrence and metastases. Currently the only Food
and Drug Administration (FDA)-approved therapy for
A
B
Figure 43.29  (A) Melanoma recurrence at the surgical site more then 1 year after initial excision. (B) Soft tissue and nodal
metastases.
Figure 43.28  A blue node seen on sentinel lymph node biopsy.

705
Chapter 43  Management of Dysplastic Nevi and Melanomas
 SUMMARY
Compared to the general population, individuals with many
nevi and with atypical moles are at increased risk for develop-
ing melanoma. The management of these patients consists of
strategies aimed at lowering this risk for developing melanoma
and in instituting strategies to help detect this cancer while
it is early and curable. Patients with atypical moles or
melanoma should be educated about the potential hazards of
sun exposure and instructed on methods of sun protection
for themselves and their family members. They should also
be taught the warning signs of melanoma such as the ABCDE
and ‘ugly duckling’ sign together with the technique of cuta-
neous self-examination. All patients with many nevi or with
atypical nevi should have their skin screened at least once a
year by a professional. Cutaneous photography creates an
objective baseline that can help in lesion assessment during
follow-up examinations.
Wide local excision with margins based on Breslow thick-
ness is the cornerstone of melanoma management. Increasing
tumor thickness, presence of ulceration, high mitotic index,
lymphovascular invasion and Clark level greater than III are
predictive factors for regional node metastasis. Currently,
SLNB has no proven survival benefit and is mainly used as a
prognostic and staging procedure. In spite of many advances
in the treatment approaches, advanced melanoma remains a
melanomas. Previous studies report the incidence of a second
primary melanoma to range from 0.2% to 8.6% in patients
with a history of melanoma.64,211,212
Patients with invasive primary melanoma should periodi-
cally be assessed for the development of metastatic disease.
A thorough review of systems and physical examination,
including lymph node examination, will help to identify most
patients with metastatic melanoma.
Risk factors that increase the chance of developing new
primary melanoma(s) include male sex, older age, having
atypical moles, family history of melanoma, and family history
of atypical moles.57,64 In a large prospective study of patients
with multiple primary melanomas, Ferrone et al.64 reported
the 5-year cumulative risk of developing a second primary
melanoma of 11.4%, with more than half of cases detected
in the first year of follow up.
Patients with invasive primary melanoma should periodi-
cally be assessed for the development of metastatic disease.
A thorough review of systems and physical examination,
including lymph node examination, will help to identify most
patients with metastatic melanoma. A focused review of
systems aimed at patients with melanoma should include
queries about weight loss, fatigue, headache, numbness, diz-
ziness, shortness of breath, cough, abdominal pain, and bone
pain. This focused review of systems is based on the knowl-
edge that the first site of metastasis is most commonly the
skin and subcutaneous tissue, followed by lymph nodes, lung,
liver, brain, and bone.213 In addition to the complete cutane-
ous and lymph node examination, auscultation of the lungs,
palpation of the liver and spleen, and a focused neurologic
examination may be warranted in selected patients.
Initially, patients with melanoma should be followed at a
frequency of every 3–6 months. Although recurrences can
occur at any time, even 10–20 years after the primary, the
greatest risk is in the first 1–5 years following the diagnosis.
After the fifth year, the frequency of the follow-up visits can
be spaced out to between 6 months and 1 year, depending
on individual risk factors. It is important to note that the time
to recurrence for patients with node-negative disease varies
inversely with the thickness of the primary tumor.214 Thus,
thin melanomas can potentially recur many years after the
initial diagnosis.
Follow-up laboratory and imaging studies are usually guided
by history, review of systems and symptoms, and findings on
a complete skin examination and lymph node evaluation.215
Most recurrences are found on physical examination or are
found based on symptoms revealed on the review of systems.
A smaller percentage of metastases are found on imaging
studies such as chest radiography or CT and magnetic reso-
nance imaging (MRI) scans.216 The current recommendations
state that most imaging studies are not indicated in patients
with stage I and II disease, since the likelihood of distant
metastasis in these patients is low. Recently, PET with fluor-
odeoxyglucose (FDG-PET) has been introduced as a radio-
logical staging modality for patients with advanced melanoma.
Although non-invasive, PET has the disadvantages of using
ionizing radiation, being a costly procedure, and having a
high false-positive rate. The high false-positive rate can be
lowered somewhat by combined PET with CT, which has
been shown to be more precise than PET alone.217 The current
recommendation of PET is mainly as an adjunctive imaging
modality, particularly for detecting soft tissue and visceral
metastasis.
Pitfalls and their management
 Failure to perform a total body skin examination can be
viewed as a missed opportunity to identify individuals at
high risk for developing melanoma such as those with many
nevi and atypical nevi. This is precisely the segment of the
population that may benefit most from targeted screening
efforts.
 Failure to perform a total body skin examination can also
be viewed as a missed opportunity to find cases of curable
melanoma.
 Although many melanomas manifesting the features
described in the ABCDE mnemonic can be identified via
simple inspection, some may escape recognition if one were
to rely only on this mnemonic as a means of finding potential
melanomas. Differential (e.g. ‘ugly duckling’ sign) and
comparative recognition (e.g. comparison to baseline images)
can facilitate in the identification of many of these otherwise
difficult to diagnose melanomas.
 Partial biopsies have a higher likelihood of resulting in the
false-negative diagnosis of melanoma. To avoid sampling
errors, all suspect lesions should be removed in their entirety
(if feasible) and the submitted pathology specimens should
be step-sectioned. This helps to maximize the chances that a
focus of melanoma will not be missed.
Prognostic factors related to melanoma are listed in Box
43.2. In general, men and older patients have a worse prog-
nosis than women and younger patients. The guidelines for
treatment and follow up from the National Comprehensive
Cancer Network, American Academy of Dermatology, and
the British Association of Dermatologists are summarized in
Table 43.8.152,218,219
 PITFALLS AND THEIR MANAGEMENT

706
Part 4  Special Procedures
very challenging disease to manage with modest response
rates to current regimens. Most recurrences or metastases of
melanoma are detected via a thorough review of systems and
physical examination. Patients with melanoma are at risk for
developing recurrences and subsequent primary melanomas.
Thus, lifelong surveillance of melanoma patients is strongly
recommended.
 REFERENCES
1. Consensus Conference on Precursors to Malignant Melanoma. J Der-
matol Surg Oncol 1985;11:537–542.
2. Elder DE, Murphy GF. Melanocytic tumors of the skin. Atlas of tumor
pathology. Washington, DC: Armed Forces Institute of Pathology 1991;
95.
3. Kraemer KH, Greene MH. Dysplastic nevus syndrome. Familial and
sporadic precursors of cutaneous melanoma. Dermatol Clin 1985;3:225–
237.
4. Newton JA, Bataille V, Griffiths K, et al. How common is the atypical
mole syndrome phenotype in apparently sporadic melanoma? J Am
Acad Dermatol 1993;29:989–996.
5. Newton JA. Familial melanoma. Clin Exp Dermatol 1993;18:5–11.
6. Halpern AC, Guerry DT, Elder DE, et al. Dysplastic nevi as risk markers
of sporadic (nonfamilial) melanoma. A case-control study. Arch Derma-
tol 1991;127:995–999.
7. Tucker MA, Halpern A, Holly EA, et al. Clinically recognized dysplastic
nevi. A central risk factor for cutaneous melanoma. JAMA
1997;277:1439–1444.
8. Huynh PM, Glusac EJ, Alvarez-Franco M, et al. Numerous, small,
darkly pigmented melanocytic nevi: the cheetah phenotype. J Am Acad
Dermatol 2003;48:707–713.
9. Grob JJ, Bonerandi JJ. The ‘ugly duckling’ sign: identification of the
common characteristics of nevi in an individual as a basis for melanoma
screening. Arch Dermatol 1998;134:103–104.
10. Scope A, Burroni M, Agero AL, et al. Predominant dermoscopic patterns
observed among nevi. J Cutan Med Surg 2006;10:170–174.
11. Kopf AW, Friedman RJ, Rigel DS. Atypical mole syndrome. J Am Acad
Dermatol 1990;22:117–118.
12. Greene MH, Clark WH Jr, Tucker MA, et al. High risk of malignant
melanoma in melanoma-prone families with dysplastic nevi. Ann Intern
Med 1985;102:458–465.
13. Lynch HT, Frichot BC 3rd, Lynch JF. Familial atypical multiple mole-
melanoma syndrome. J Med Genet 1978;15:352–356.
14. Clark WH Jr, Reimer RR, Greene M, et al. Origin of familial malignant
melanomas from heritable melanocytic lesions. ‘The B-K mole syn-
drome’. Arch Dermatol 1978;114:732–738.
15. MacKie RM, English J, Aitchison TC, et al. The number and distribution
of benign pigmented moles (melanocytic naevi) in a healthy British
population. Br J Dermatol 1985;113:167–174.
16. Garbe C, Buttner P, Weiss J, et al. Risk factors for developing cutaneous
melanoma and criteria for identifying persons at risk: multicenter case-
control study of the Central Malignant Melanoma Registry of the
German Dermatological Society. J Invest Dermatol 1994;102:695–699.
Table 43.8  Published guidelines for managing patients with melanoma
MARGINS
WORK-UP
FOLLOW UP
AAD
In situ
0.5 cm
H&P*; CXR, LDH
(optional)
General recommendations not stage
specific, should be based on individual risk
H&P 1–4×/year for 2 years then 1–2×/year
Directed laboratory and imaging studies
<2 mm
1 cm
>2 mm
2 cm
Stage III
Not discussed
Not discussed
Not discussed
Stage IV
Not discussed
Not discussed
Not discussed
NCCN
In situ
0.5 cm
None
Not discussed
<1 mm
1 cm
None
H&P every 6 months for 2 years, then yearly
1–4 mm
1–2 cm
Consider SLNB; CXR,
LFT (optional)
H&P 3–6 months for 3 years, then 6–12
months for 2 years. CXR, LFT every 6–12
months (optional)
>4 mm
≥2 cm
Stage III
Excision and lymph node dissection
LFT, CXR; pelvic and
other CT if indicated
H&P 3–6 months for 3 years, then 4–12
months for 2 years, then yearly CXR, CBC,
LFT every 3–12 months (optional), CT scans
as indicated
Stage IV
Excision of primary melanoma and
focal resection of internal organs
involved with metastatic melanoma
(if feasible)
LFT, CXR; CT scans if
indicated
Not discussed
BAD
In situ
0.2–0.5 cm
None
Self-examination, no follow up required
<1 mm
1 cm
None
H&P every 3 months for 3 years
1–2 mm
1–2 cm
Stage II; consider SLNB
H&P every 3 months for 3 years, then every
6 months for 2 years
2.1–4 mm
2–3 cm
Stage IIB and up; LFT,
LDH, CBC, CXR, liver
ultrasound, CT chest,
abdomen, pelvis
>4 mm
2–3 cm
Stage III
Excision and lymph node dissection
Not discussed
Stage IV
Excision of primary melanoma and
focal resection of internal organs
involved with metastatic melanoma
(if feasible)
Not discussed
*H&P includes review of systems, symptoms-directed exam, full skin examination, and lymph node examination.
AAD, American Academy of Dermatology; BAD, British Association of Dermatologists; CBC, complete blood count; CXR, chest X-ray; LDH, lactate dehydrogenase; LFT, liver
function tests; NCCN, National Comprehensive Cancer Network; SLNB, sentinel lymph node biopsy.

707
Chapter 43  Management of Dysplastic Nevi and Melanomas
44. Holly EA, Kelly JW, Shpall SN, et al. Number of melanocytic nevi as a
major risk factor for malignant melanoma. J Am Acad Dermatol
1987;17:459–468.
45. Grob JJ, Gouvernet J, Aymar D, et al. Count of benign melanocytic
nevi as a major indicator of risk for nonfamilial nodular and superficial
spreading melanoma. Cancer 1990;66:387–395.
46. Roush GC, Nordlund JJ, Forget B, et al. Independence of dysplastic
nevi from total nevi in determining risk for nonfamilial melanoma. Prev
Med 1988;17:273–279.
47. Garbe C, Kruger S, Stadler R, et al. Markers and relative risk in a
German population for developing malignant melanoma. Int J Dermatol
1989;28:517–523.
48. Augustsson A, Stierner U, Rosdahl I, et al. Common and dysplastic naevi
as risk factors for cutaneous malignant melanoma in a Swedish popula-
tion. Acta Derm Venereol 1991;71:518–524.
49. Marghoob AA. The dangers of atypical mole (dysplastic nevus) syn-
drome. Teaching at-risk patients to protect themselves from melanoma.
Postgrad Med 1999;105:147–148, 151–142, 154 passim.
50. Rigel DS, Rivers JK, Kopf AW, et al. Dysplastic nevi. Markers for
increased risk for melanoma. Cancer 1989;63:386–389.
51. Sagebiel RW. Melanocytic nevi in histologic association with primary
cutaneous melanoma of superficial spreading and nodular types: effect
of tumor thickness. J Invest Dermatol 1993;100:322S–325S.
52. Black WC. Residual dysplastic and other nevi in superficial spreading
melanoma. Clinical correlations and association with sun damage.
Cancer 1988;62:163–173.
53. MacKie RM, McHenry P, Hole D. Accelerated detection with prospec-
tive surveillance for cutaneous malignant melanoma in high-risk groups.
Lancet 1993;341:1618–1620.
54. Marghoob AA, Kopf AW, Rigel DS, et al. Risk of cutaneous malignant
melanoma in patients with ‘classic’ atypical-mole syndrome. A case-
control study. Arch Dermatol 1994;130:993–998.
55. MacKie RM, Freudenberger T, Aitchison TC. Personal risk-factor chart
for cutaneous melanoma. Lancet 1989;2:487–490.
56. Sober AJ, Burstein JM. Precursors to skin cancer. Cancer 1995;75(2
Suppl):645–650.
57. Marghoob AA, Slade J, Kopf AW, et al. Risk of developing multiple
primary cutaneous melanomas in patients with the classic atypical-mole
syndrome: a case-control study. Br J Dermatol 1996;135:704–711.
58. Tucker MA, Fraser MC, Goldstein AM, et al. Risk of melanoma and
other cancers in melanoma-prone families. J Invest Dermatol 1993;
100:350S–355S.
59. Halpern AC, Guerry DT, Elder DE, et al. A cohort study of melanoma
in patients with dysplastic nevi. J Invest Dermatol 1993;100:346S–
349S.
60. Rigel DS, Rivers JK, Friedman RJ, et al. Risk gradient for malignant
melanoma in individuals with dysplastic naevi. Lancet 1988;1:352–
353.
61. Rhodes AR, Weinstock MA, Fitzpatrick TB, et al. Risk factors for cuta-
neous melanoma. A practical method of recognizing predisposed indi-
viduals. JAMA 1987;258:3146–3154.
62. Tiersten AD, Grin CM, Kopf AW, et al. Prospective follow-up for
malignant melanoma in patients with atypical-mole (dysplastic-nevus)
syndrome. J Dermatol Surg Oncol 1991;17:44–48.
63. Schneider JS, Moore DH 2nd, Sagebiel RW. Risk factors for melanoma
incidence in prospective follow-up. The importance of atypical (dysplas-
tic) nevi. Arch Dermatol 1994;130:1002–1007.
64. Ferrone CR, Ben Porat L, Panageas KS, et al. Clinicopathological fea-
tures of and risk factors for multiple primary melanomas. JAMA
2005;294:1647–1654.
65. Goldstein AM, Chaudru V, Ghiorzo P, et al. Cutaneous phenotype and
MC1R variants as modifying factors for the development of melanoma
in CDKN2A G101W mutation carriers from 4 countries. Int J Cancer
2007;121:825–831.
66. Cuellar F, Puig S, Kolm I, et al. Dermoscopic features of melanomas
associated with MC1R variants in Spanish CDKN2A mutation carriers.
Br J Dermatol 2009;160:48–53.
67. Lipoff JB, Scope A, Dusza SW, et al. Complex dermoscopic pattern:
a potential risk marker for melanoma. Br J Dermatol 2008;158:821–
824.
68. Cohen MH, Cohen BJ, Shotkin JD, et al. Surgical prophylaxis of malig-
nant melanoma. Ann Surg 1991;213:308–314.
69. Clark WH Jr, Elder DE, Guerry DT, et al. A study of tumor progression:
the precursor lesions of superficial spreading and nodular melanoma.
Hum Pathol 1984;15:1147–1165.
70. Elder DE, Clark WH. Developmental biology of malignant melanoma.
In: Elder DE, ed. Pathobiology of malignant melanoma. New York:
Karger 1987; 1–28.
71. Halpern AC. The use of whole body photography in a pigmented lesion
clinic. Dermatol Surg 2000;26:1175–1180.
17. Garbe C, Buttner P, Weiss J, et al. Associated factors in the prevalence
of more than 50 common melanocytic nevi, atypical melanocytic nevi,
and actinic lentigines: multicenter case-control study of the Central
Malignant Melanoma Registry of the German Dermatological Society.
J Invest Dermatol 1994;102:700–705.
18. Harrison SL, MacLennan R, Speare R, et al. Sun exposure and melano-
cytic naevi in young Australian children. Lancet 1994;344:1529–1532.
19. Stefanato CM, Romero JB, Kopf AW, et al. Solar nevogenesis: a sur-
rogate for predicting a rise in incidence of malignant melanoma because
of ozone depletion. J Am Acad Dermatol 1993;29:486–487.
20. Kopf AW, Lazar M, Bart RS, et al. Prevalence of nevocytic nevi on lateral
and medial aspects of arms. J Dermatol Surg Oncol 1978;4:153–158.
21. Kopf AW, Lindsay AC, Rogers GS, et al. Relationship of nevocytic nevi
to sun exposure in dysplastic nevus syndrome. J Am Acad Dermatol
1985;12:656–662.
22. Kopf AW, Gold RS, Rogers GS, et al. Relationship of lumbosacral
nevocytic nevi to sun exposure in dysplastic nevus syndrome. Arch
Dermatol 1986;122:1003–1006.
23. Stierner U. Melanocytes, moles and melanoma – a study on UV effects.
Acta Derm Venereol Suppl (Stockh) 1991;168:1–31.
24. Rivers JK, MacLennan R, Kelly JW, et al. The eastern Australian child-
hood nevus study: prevalence of atypical nevi, congenital nevus-like nevi,
and other pigmented lesions. J Am Acad Dermatol 1995;32:957–963.
25. Abadir MC, Marghoob AA, Slade J, et al. Case-control study of melano-
cytic nevi on the buttocks in atypical mole syndrome: role of solar
radiation in the pathogenesis of atypical moles. J Am Acad Dermatol
1995;33:31–36.
26. Wachsmuth RC, Gaut RM, Barrett JH, et al. Heritability and gene-
environment interactions for melanocytic nevus density examined in a
UK adolescent twin study. J Invest Dermatol 2001;117:348–352.
27. Cockburn M, Hamilton A, Mack T. The simultaneous assessment of
constitutional, behavioral, and environmental factors in the development
of large nevi. Cancer Epidemiol Biomarkers Prev 2007;16:200–206.
28. Slade J, Marghoob AA, Salopek TG, et al. Atypical mole syndrome: risk
factor for cutaneous malignant melanoma and implications for manage-
ment. J Am Acad Dermatol 1995;32:479–494.
29. Fernandez M, Raimer SS, Sanchez RL. Dysplastic nevi of the scalp and
forehead in children. Pediatr Dermatol 2001;18:5–8.
30. Halpern AC, Guerry DT, Elder DE, et al. Natural history of dysplastic
nevi. J Am Acad Dermatol 1993;29:51–57.
31. Tucker MA, Fraser MC, Goldstein AM, et al. A natural history of
melanomas and dysplastic nevi: an atlas of lesions in melanoma-prone
families. Cancer 2002;94:3192–3209.
32. Gray-Schopfer VC, Cheong SC, Chong H, et al. Cellular senescence in
naevi and immortalisation in melanoma: a role for p16? Br J Cancer
2006;95:496–505.
33. Florell SR, Bowen AR, Hanks AN, et al. Proliferation, apoptosis, and
survivin expression in a spectrum of melanocytic nevi. J Cutan Pathol
2005;32:45–49.
34. Altamura D, Avramidis M, Menzies SW. Assessment of the optimal
interval for and sensitivity of short-term sequential digital dermoscopy
monitoring for the diagnosis of melanoma. Arch Dermatol 2008;144:502–
506.
35. Fuller SR, Bowen GM, Tanner B, et al. Digital dermoscopic monitoring
of atypical nevi in patients at risk for melanoma. Dermatol Surg
2007;33:1198–1206, discussion 1205–1196.
36. Banky JP, Kelly JW, English DR, et al. Incidence of new and changed
nevi and melanomas detected using baseline images and dermoscopy in
patients at high risk for melanoma. Arch Dermatol 2005;141:998–1006.
37. Robinson JK, Nickoloff BJ. Digital epiluminescence microscopy moni-
toring of high-risk patients. Arch Dermatol 2004;140:49–56.
38. Haenssle HA, Vente C, Bertsch HP, et al. Results of a surveillance
programme for patients at high risk of malignant melanoma using digital
and conventional dermoscopy. Eur J Cancer Prev 2004;13:133–138.
39. Menzies SW, Gutenev A, Avramidis M, et al. Short-term digital surface
microscopic monitoring of atypical or changing melanocytic lesions.
Arch Dermatol 2001;137:1583–1589.
40. Kittler H, Pehamberger H, Wolff K, et al. Follow-up of melanocytic
skin lesions with digital epiluminescence microscopy: patterns of mod-
ifications observed in early melanoma, atypical nevi, and common nevi.
J Am Acad Dermatol 2000;43:467–476.
41. Kittler H, Seltenheim M, Dawid M, et al. Frequency and characteristics
of enlarging common melanocytic nevi. Arch Dermatol 2000;136:316–
320.
42. Tsao H, Bevona C, Goggins W, et al. The transformation rate of moles
(melanocytic nevi) into cutaneous melanoma: a population-based esti-
mate. Arch Dermatol 2003;139:282–288.
43. Swerdlow AJ, English J, MacKie RM, et al. Benign melanocytic naevi as
a risk factor for malignant melanoma. Br Med J (Clin Res Ed)
1986;292:1555–1559.

708
Part 4  Special Procedures
100. Greene MH, Sanders RJ, Chu FC, et al. The familial occurrence of
cutaneous melanoma, intraocular melanoma, and the dysplastic nevus
syndrome. Am J Ophthalmol 1983;96:238–245.
101. Abramson DH, Rodriguez-Sains RS, Rubman R. B–K mole syndrome.
Cutaneous and ocular malignant melanoma. Arch Ophthalmol
1980;98:1397–1399.
102. Rodriguez-Sains RS. Ocular findings in patients with dysplastic nevus
syndrome. An update. Dermatol Clin 1991;9:723–728.
103. Leow YH, Tham SN. UV-protective sunglasses for UVA irradiation
protection. Int J Dermatol 1995;34:808–810.
104. Bataille V, Pinney E, Hungerford JL, et al. Five cases of coexistent
primary ocular and cutaneous melanoma. Arch Dermatol 1993;129:198–
201.
105. Steiner A, Binder M, Schemper M, et al. Statistical evaluation of epilu-
minescence microscopy criteria for melanocytic pigmented skin lesions.
J Am Acad Dermatol 1993;29:581–588.
106. Stoltz W, Braun-Falco O, Bilek P, et al. Basis of dermatoscopic and skin
surface microscopy. Color atlas of dermoscopy. Cambridge: Blackwell
1994; 7–10.
107. Binder M, Schwarz M, Winkler A, et al. Epiluminescence microscopy.
A useful tool for the diagnosis of pigmented skin lesions for formally
trained dermatologists. Arch Dermatol 1995;131:286–291.
108. Kittler H, Pehamberger H, Wolff K, et al. Diagnostic accuracy of der-
moscopy. Lancet Oncol 2002;3:159–165.
109. Bafounta ML, Beauchet A, Aegerter P, et al. Is dermoscopy (epilumi-
nescence microscopy) useful for the diagnosis of melanoma? Results of
a meta-analysis using techniques adapted to the evaluation of diagnostic
tests. Arch Dermatol 2001;137:1343–1350.
110. Pellacani G, Guitera P, Longo C, et al. The impact of in vivo reflect-
ance confocal microscopy for the diagnostic accuracy of melanoma and
equivocal melanocytic lesions. J Invest Dermatol 2007;127:2759–2765.
111. Friedman RJ, Gutkowicz-Krusin D, Farber MJ, et al. The diagnostic
performance of expert dermoscopists vs a computer-vision system on
small-diameter melanomas. Arch Dermatol 2008;144:476–482.
112. Perrinaud A, Gaide O, French LE, et al. Can automated dermoscopy
image analysis instruments provide added benefit for the dermatologist?
A study comparing the results of three systems. Br J Dermatol 2007;157:
926–933.
113. Elwood JM, Williamson C, Stapleton PJ. Malignant melanoma in rela-
tion to moles, pigmentation, and exposure to fluorescent and other
lighting sources. Br J Cancer 1986;53:65–74.
114. Armstrong BK. Epidemiology of malignant melanoma: intermittent or
total accumulated exposure to the sun? J Dermatol Surg Oncol
1988;14:835–849.
115. Jung EG, Bohnert E, Boonen H. Dysplastic nevus syndrome: ultraviolet
hypermutability confirmed in vitro by elevated sister chromatid
exchanges. Dermatologica 1986;173:297–300.
116. Richard MA, Grob JJ, Gouvernet J, et al. Role of sun exposure on nevus.
First study in age-sex phenotype-controlled populations. Arch Dermatol
1993;129:1280–1285.
117. Kelly JW, Rivers JK, MacLennan R, et al. Sunlight: a major factor asso-
ciated with the development of melanocytic nevi in Australian school-
children. J Am Acad Dermatol 1994;30:40–48.
118. Menter JM, Hollins TD, Sayre RM, et al. Protection against UV pho-
tocarcinogenesis by fabric materials. J Am Acad Dermatol 1994;31:711–
716.
119. Naylor MF, Boyd A, Smith DW, et al. High sun protection factor sun-
screens in the suppression of actinic neoplasia. Arch Dermatol
1995;131:170–175.
120. Thompson SC, Jolley D, Marks R. Reduction of solar keratoses by
regular sunscreen use. N Engl J Med 1993;329:1147–1151.
121. Whitmore SE, Morison WL. Prevention of UVB-induced immunosup-
pression in humans by a high sun protection factor sunscreen. Arch
Dermatol 1995;131:1128–1133.
122. Gallagher RP, Rivers JK, Lee TK, et al. Broad-spectrum sunscreen use
and the development of new nevi in white children: a randomized
controlled trial. JAMA 2000;283:2955–2960.
123. Garland CF, Garland FC, Gorham ED. Rising trends in melanoma. An
hypothesis concerning sunscreen effectiveness. Ann Epidemiol 1993;3:
103–110.
124. Pathak MA. Sunscreens: topical and systemic approaches for protection
of human skin against harmful effects of solar radiation. J Am Acad
Dermatol 1982;7:285–312.
125. Westerdahl J, Olsson H, Masback A, et al. Is the use of sunscreens a
risk factor for malignant melanoma? Melanoma Res 1995;5:59–65.
126. Wolf P, Donawho CK, Kripke ML. Effect of sunscreens on UV radia-
tion-induced enhancement of melanoma growth in mice. J Natl Cancer
Inst 1994;86:99–105.
127. Koh HK, Lew RA. Sunscreens and melanoma: implications for preven-
tion. J Natl Cancer Inst 1994;86:78–79.
72. Kelly JW, Yeatman JM, Regalia C, et al. A high incidence of melanoma
found in patients with multiple dysplastic naevi by photographic surveil-
lance. Med J Aust 1997;167:191–194.
73. Feit NE, Dusza SW, Marghoob AA. Melanomas detected with the aid
of total cutaneous photography. Br J Dermatol 2004;150:706–714.
74. Marghoob AA, Korzenko AJ, Changchien L, et al. The beauty and the
beast sign in dermoscopy. Dermatol Surg 2007;33:1388–1391.
75. Roesch A, Burgdorf W, Stolz W, et al. Dermatoscopy of ‘dysplastic
nevi’: a beacon in diagnostic darkness. Eur J Dermatol 2006;16:479–
493.
76. Guitera P, Pellacani G, Longo C, et al. In vivo reflectance confocal
microscopy enhances secondary evaluation of melanocytic lesions. J
Invest Dermatol 2009;129:131–138.
77. Marghoob AA, Scope A. The complexity of diagnosing melanoma. J
Invest Dermatol 2009;129:11–13.
78. Argenziano G, Mordente I, Ferrara G, et al. Dermoscopic monitoring
of melanocytic skin lesions: clinical outcome and patient compliance
vary according to follow-up protocols. Br J Dermatol 2008;159:331–
336.
79. Schiffner R, Schiffner-Rohe J, Landthaler M, et al. Long-term dermo-
scopic follow-up of melanocytic naevi: clinical outcome and patient
compliance. Br J Dermatol 2003;149:79–86.
80. Marghoob AA, Halpern AC. Biopsy rates in patients with and without
total body photography. J Am Acad Dermatol 2008;58:894–895.
81. Kittler H, Binder M. Risks and benefits of sequential imaging of melano-
cytic skin lesions in patients with multiple atypical nevi. Arch Dermatol
2001;137:1590–1595.
82. Rigel DS, Friedman RJ, Kopf AW, et al. Importance of complete cuta-
neous examination for the detection of malignant melanoma. J Am Acad
Dermatol 1986;14:857–860.
83. Tucker MA, Greene MH, Clark WH Jr, et al. Dysplastic nevi on the
scalp of prepubertal children from melanoma-prone families. J Pediatr
1983;103:65–69.
84. Benmeir P, Baruchin A, Lusthaus S, et al. Melanoma of the scalp: the
invisible killer. Plast Reconstr Surg 1995;95:496–500.
85. Geller AC, Koh HK, Miller DR, et al. Use of health services before the
diagnosis of melanoma: implications for early detection and screening.
J Gen Intern Med 1992;7:154–157.
86. Weinstock MA, Risica PM, Martin RA, et al. Melanoma early detection
with thorough skin self-examination: the ‘Check It Out’ randomized
trial. Am J Prev Med 2007;32:517–524.
87. Berwick M, Begg CB, Fine JA, et al. Screening for cutaneous melanoma
by skin self-examination. J Natl Cancer Inst 1996;88:17–23.
88. Lee KB, Weinstock MA, Risica PM. Components of a successful inter-
vention for monthly skin self-examination for early detection of
melanoma: the ‘Check It Out’ trial. J Am Acad Dermatol 2008;58:1006–
1012.
89. Marks R, Dorevitch AP, Mason G. Do all melanomas come from
‘moles’? A study of the histological association between melanocytic
naevi and melanoma. Australas J Dermatol 1990;31:77–80.
90. Masri GD, Clark WH Jr, Guerry DT, et al. Screening and surveillance
of patients at high risk for malignant melanoma result in detection of
earlier disease. J Am Acad Dermatol 1990;22:1042–1048.
91. Friedman RJ, Rigel DS, Kopf AW. Early detection of malignant
melanoma: the role of physician examination and self-examination of
the skin. CA Cancer J Clin 1985;35:130–151.
92. Novakovic B, Clark WH Jr, Fears TR, et al. Melanocytic nevi, dysplas-
tic nevi, and malignant melanoma in children from melanoma-prone
families. J Am Acad Dermatol 1995;33:631–636.
93. Goldstein AM, Fraser MC, Clark WH Jr, et al. Age at diagnosis and
transmission of invasive melanoma in 23 families with cutaneous malig-
nant melanoma/dysplastic nevi. J Natl Cancer Inst 1994;86:1385–
1390.
94. Crijns MB, Vink J, Van Hees CL, et al. Dysplastic nevi. Occurrence in
first- and second-degree relatives of patients with ‘sporadic’ dysplastic
nevus syndrome. Arch Dermatol 1991;127:1346–1351.
95. Albert LS, Rhodes AR, Sober AJ. Dysplastic melanocytic nevi and
cutaneous melanoma: markers of increased melanoma risk for affected
persons and blood relatives. J Am Acad Dermatol 1990;22:69–75.
96. Bergman W, Palan A, Went LN. Clinical and genetic studies in six Dutch
kindreds with the dysplastic naevus syndrome. Ann Hum Genet
1986;50:249–258.
97. McCarthy JM, Rootman J, Horsman D, et al. Conjunctival and uveal
melanoma in the dysplastic nevus syndrome. Surv Ophthalmol
1993;37:377–386.
98. Vink J, Crijns MB, Mooy CM, et al. Ocular melanoma in families with
dysplastic nevus syndrome. J Am Acad Dermatol 1990;23:858–862.
99. Friedman RJ, Rodriguez-Sains R, Jakobiec F. Ophthalmologic oncology:
conjunctival malignant melanoma in association with sporadic dysplastic
nevus syndrome. J Dermatol Surg Oncol 1987;13:31–34.

709
Chapter 43  Management of Dysplastic Nevi and Melanomas
128. Autier P, Dore JF, Lejeune F, et al. Cutaneous malignant melanoma and
exposure to sunlamps or sunbeds: an EORTC multicenter case-control
study in Belgium, France and Germany. EORTC Melanoma Coopera-
tive Group. Int J Cancer 1994;58:809–813.
129. Ting W, Schultz K, Cac NN, et al. Tanning bed exposure increases
the risk of malignant melanoma. Int J Dermatol 2007;46:1253–1257.
130. Berwick M. Are tanning beds ‘safe’? Human studies of melanoma.
Pigment Cell Melanoma Res 2008;21:517–519.
131. Rossi JS, Blais LM, Redding CA, et al. Preventing skin cancer through
behavior change. Implications for interventions. Dermatol Clin 1995;13:
613–622.
132. Grob JJ, Guglielmina C, Gouvernet J, et al. Study of sunbathing habits
in children and adolescents: application to the prevention of melanoma.
Dermatology 1993;186:94–98.
133. Somach SC, Taira JW, Pitha JV, et al. Pigmented lesions in actinically
damaged skin. Histopathologic comparison of biopsy and excisional
specimens. Arch Dermatol 1996;132:1297–1302.
134. Marghoob AA, Changchien L, DeFazio J, et al. The most common
pitfalls in melanoma diagnosis and how to avoid them. Australas J Der-
matol 2009;50:1–13.
135. Duray PH, Livolsi VA. Recurrent dysplastic nevus following shave exci-
sion. J Dermatol Surg Oncol 1984;10:811–815.
136. Bondi EE, Clark WH Jr, Elder D, et al. Topical chemotherapy of dys-
plastic melanocytic nevi with 5% fluorouracil. Arch Dermatol
1981;117:89–92.
137. Edwards L, Jaffe P. The effect of topical tretinoin on dysplastic nevi. A
preliminary trial. Arch Dermatol 1990;126:494–499.
138. Halpern AC, Schuchter LM, Elder DE, et al. Effects of topical tretinoin
on dysplastic nevi. J Clin Oncol 1994;12:1028–1035.
139. Edwards L, Meyskens F, Levine N. Effect of oral isotretinoin on dys-
plastic nevi. J Am Acad Dermatol 1989;20:257–260.
140. Wolf IH, Smolle J, Binder B, et al. Topical imiquimod in the treatment
of metastatic melanoma to skin. Arch Dermatol 2003;139:273–276.
141. Cotter MA, McKenna JK, Bowen GM. Treatment of lentigo maligna
with imiquimod before staged excision. Dermatol Surg 2008;34:147–
151.
142. Mahoney MH, Joseph MG, Temple C. Topical imiquimod therapy for
lentigo maligna. Ann Plast Surg 2008;61:419–424.
143. Hopson B, Richey D, Sajben FP. Treatment of lentigo maligna with
imiquimod 5% cream. J Drugs Dermatol 2007;6:1037–1040.
144. Shistik G, Prakash AV, Fenske NA, et al. Treatment of locally meta-
static melanoma: a novel approach. J Drugs Dermatol 2007;6:830–832.
145. Spenny ML, Walford J, Werchniak AE, et al. Lentigo maligna (melanoma
in situ) treated with imiquimod cream 5%: 12 case reports. Cutis
2007;79:149–152.
146. Dusza SW, Delgado R, Busam KJ, et al. Treatment of dysplastic nevi
with 5% imiquimod cream, a pilot study. J Drugs Dermatol 2006;5:56–
62.
147. Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2008. CA Cancer J
Clin 2008;58:71–96.
148. Purdue MP, Freeman LE, Anderson WF, et al. Recent trends in inci-
dence of cutaneous melanoma among US Caucasian young adults. J
Invest Dermatol 2008;128:2905–2908.
149. Rigel DS, Carucci JA. Malignant melanoma: prevention, early detection,
and treatment in the 21st century. CA Cancer J Clin 2000;50:215–236,
quiz 237–240.
150. Tran KT, Wright NA, Cockerell CJ. Biopsy of the pigmented lesion –
when and how. J Am Acad Dermatol 2008;59:852–871.
151. Balch CM, Buzaid AC, Soong SJ, et al. Final version of the American
Joint Committee on Cancer staging system for cutaneous melanoma. J
Clin Oncol 2001;19:3635–3648.
152. Houghton A, Coit D, Bloomer W, et al. NCCN melanoma practice
guidelines. National Comprehensive Cancer Network. Oncology (Willis-
ton Park) 1998;12:153–177.
153. Aloia TA, Gershenwald JE. Management of early-stage cutaneous
melanoma. Curr Probl Surg 2005;42:460–534.
154. Paraskevas LR, Halpern AC, Marghoob AA. Utility of the Wood’s light:
five cases from a pigmented lesion clinic. Br J Dermatol 2005;152:1039–
1044.
155. Bories N, Dalle S, Debarbieux S, et al. Dermoscopy of fully regressive
cutaneous melanoma. Br J Dermatol 2008;158:1224–1229.
156. Cascinelli N, Bombardieri E, Bufalino R, et al. Sentinel and nonsentinel
node status in stage IB and II melanoma patients: two-step prognostic
indicators of survival. J Clin Oncol 2006;24:4464–4471.
157. Balch CM, Soong SJ, Gershenwald JE, et al. Prognostic factors analysis
of 17 600 melanoma patients: validation of the American Joint Com-
mittee on Cancer melanoma staging system. J Clin Oncol 2001;19:3622–
3634.
158. Gershenwald JE, Thompson W, Mansfield PF, et al. Multi-institutional
melanoma lymphatic mapping experience: the prognostic value of sen-
tinel lymph node status in 612 stage I or II melanoma patients. J Clin
Oncol 1999;17:976–983.
159. Balch CM, Buzaid AC, Soong SJ, et al. New TNM melanoma staging
system: linking biology and natural history to clinical outcomes. Semin
Surg Oncol 2003;21:43–52.
160. Wong SL, Morton DL, Thompson JF, et al. Melanoma patients with
positive sentinel nodes who did not undergo completion lym-
phadenectomy: a multi-institutional study. Ann Surg Oncol 2006;13:
809–816.
161. McMasters KM, Ross MI, Reintgen DS, et al. Final results of the Sunbelt
Melanoma Trial. Paper presented at: ASCO Anuual Meeting; May 20,
2008.
162. Eggermont AM, Suciu S, Ruka W, et al. EORTC 18961: Post-operative
adjuvant ganglioside GM2-KLH21 vaccination treatment vs observation
in stage II (T3-T4N0M0) melanoma: 2nd interim analysis led to an early
disclosure of the results. Paper presented at: ASCO Annual Meeting;
May 20, 2008.
163. Amersi F, Morton DL. The role of sentinel lymph node biopsy in the
management of melanoma. Adv Surg 2007;41:241–256.
164. Bedrosian I, Faries MB, Guerry DT, et al. Incidence of sentinel node
metastasis in patients with thin primary melanoma (< or = 1 mm) with
vertical growth phase. Ann Surg Oncol 2000;7:262–267.
165. Morton DL, Wen DR, Wong JH, et al. Technical details of intraopera-
tive lymphatic mapping for early stage melanoma. Arch Surg 1992;
127:392–399.
166. McMasters KM, Swetter SM. Current management of melanoma: ben-
efits of surgical staging and adjuvant therapy. J Surg Oncol 2003;82:209–
216.
167. Reintgen DS, Cruse CW, Glass F, et al. In support of sentinel node
biopsy as a standard of care for patients with malignant melanoma.
Dermatol Surg 2000;26:1070–1072.
168. Prieto VG, Clark SH. Processing of sentinel lymph nodes for detection
of metastatic melanoma. Ann Diagn Pathol 2002;6:257–264.
169. Blaheta HJ, Schittek B, Breuninger H, et al. Lymph node micrometas-
tases of cutaneous melanoma: increased sensitivity of molecular diagno-
sis in comparison to immunohistochemistry. Int J Cancer 1998;79:
318–323.
170. Cascinelli N, Belli F, Santinami M, et al. Sentinel lymph node biopsy in
cutaneous melanoma: the WHO Melanoma Program experience. Ann
Surg Oncol 2000;7:469–474.
171. Clary BM, Brady MS, Lewis JJ, et al. Sentinel lymph node biopsy in the
management of patients with primary cutaneous melanoma: review of
a large single-institutional experience with an emphasis on recurrence.
Ann Surg 2001;233:250–258.
172. McMasters KM, Wong SL, Edwards MJ, et al. Factors that predict the
presence of sentinel lymph node metastasis in patients with melanoma.
Surgery 2001;130:151–156.
173. Wagner JD, Gordon MS, Chuang TY, et al. Predicting sentinel and
residual lymph node basin disease after sentinel lymph node biopsy for
melanoma. Cancer 2000;89:453–462.
174. Chao C, Martin RC 2nd, Ross MI, et al. Correlation between prognos-
tic factors and increasing age in melanoma. Ann Surg Oncol 2004;11:259–
264.
175. Berk DR, Johnson DL, Uzieblo A, et al. Sentinel lymph node biopsy for
cutaneous melanoma: the Stanford experience, 1997–2004. Arch Der-
matol 2005;141:1016–1022.
176. Wong SL, Brady MS, Busam KJ, et al. Results of sentinel lymph node
biopsy in patients with thin melanoma. Ann Surg Oncol 2006;13:302–
309.
177. Nowecki ZI, Rutkowski P, Nasierowska-Guttmejer A, et al. Sentinel
lymph node biopsy in melanoma patients with clinically negative regional
lymph nodes – one institution’s experience. Melanoma Res 2003;13:35–
43.
178. Baisden BL, Askin FB, Lange JR, et al. HMB-45 immunohistochemical
staining of sentinel lymph nodes: a specific method for enhancing detec-
tion of micrometastases in patients with melanoma. Am J Surg Pathol
2000;24:1140–1146.
179. Morton DL, Thompson JF, Cochran AJ, et al. Sentinel-node biopsy
or nodal observation in melanoma. N Engl J Med 2006;355:1307–
1317.
180. Thompson JF, Shaw HM. Benefits of sentinel node biopsy for melanoma:
a review based on interim results of the first Multicenter Selective
Lymphadenectomy Trial. A NZ J Surg 2006;76:100–103.
181. Cascinelli N, Morabito A, Santinami M, et al. Immediate or delayed
dissection of regional nodes in patients with melanoma of the trunk: a
randomised trial. WHO Melanoma Programme. Lancet 1998;351:793–
796.
182. Gimotty P, Yoon F, Hammond R, et al. Sentinel lymph node biopsy
(SLNB) improves survival among SEER patients with melanoma. Paper
presented at: ASCO Annual Meeting; May 20, 2008.

710
Part 4  Special Procedures
183. Miliotes G, Albertini J, Berman C, et al. The tumor biology of melanoma
nodal metastases. Am Surg 1996;62:81–88.
184. Kirkwood JM, Strawderman MH, Ernstoff MS, et al. Interferon alfa-2b
adjuvant therapy of high-risk resected cutaneous melanoma: the Eastern
Cooperative Oncology Group Trial EST 1684. J Clin Oncol 1996;14:7–
17.
185. Cole BF, Gelber RD, Kirkwood JM, et al. Quality-of-life-adjusted sur-
vival analysis of interferon alfa-2b adjuvant treatment of high-risk
resected cutaneous melanoma: an Eastern Cooperative Oncology Group
study. J Clin Oncol 1996;14:2666–2673.
186. Creagan ET, Dalton RJ, Ahmann DL, et al. Randomized, surgical adju-
vant clinical trial of recombinant interferon alfa-2a in selected patients
with malignant melanoma. J Clin Oncol 1995;13:2776–2783.
187. Kirkwood JM, Ibrahim JG, Sondak VK, et al. High- and low-dose
interferon alfa-2b in high-risk melanoma: first analysis of intergroup trial
E1690/S9111/C9190. J Clin Oncol 2000;18:2444–2458.
188. Eggermont AM, Suciu S, Santinami M, et al. Adjuvant therapy with
pegylated interferon alfa-2b versus observation alone in resected stage
III melanoma: final results of EORTC 18991, a randomised phase III
trial. Lancet 2008;372:117–126.
189. Hersey P, Coates AS, McCarthy WH, et al. Adjuvant immunotherapy
of patients with high-risk melanoma using vaccinia viral lysates of
melanoma: results of a randomized trial. J Clin Oncol 2002;20:4181–
4190.
190. Wallack MK, Sivanandham M, Balch CM, et al. Surgical adjuvant active
specific immunotherapy for patients with stage III melanoma: the final
analysis of data from a phase III, randomized, double-blind, multicenter
vaccinia melanoma oncolysate trial. J Am Coll Surg 1998;187:69–77,
discussion 77–69.
191. Bystryn JC, Zeleniuch-Jacquotte A, Oratz R, et al. Double-blind trial
of a polyvalent, shed-antigen, melanoma vaccine. Clin Cancer Res
2001;7:1882–1887.
192. Kirkwood JM, Ibrahim JG, Sosman JA, et al. High-dose interferon
alfa-2b significantly prolongs relapse-free and overall survival compared
with the GM2-KLH/QS-21 vaccine in patients with resected stage
IIB-III melanoma: results of intergroup trial E1694/S9512/C509801. J
Clin Oncol 2001;19:2370–2380.
193. Leo F, Cagini L, Rocmans P, et al. Lung metastases from melanoma:
when is surgical treatment warranted? Br J Cancer 2000;83:569–
572.
194. Essner R. Surgical treatment of malignant melanoma. Surg Clin North
Am 2003;83:109–156.
195. Wronski M, Arbit E. Surgical treatment of brain metastases from
melanoma: a retrospective study of 91 patients. J Neurosurg 2000;93:9–
18.
196. Falkson CI, Ibrahim J, Kirkwood JM, et al. Phase III trial of dacarbazine
versus dacarbazine with interferon alpha-2b versus dacarbazine with
tamoxifen versus dacarbazine with interferon alpha-2b and tamoxifen
in patients with metastatic malignant melanoma: an Eastern Cooperative
Oncology Group study. J Clin Oncol 1998;16:1743–1751.
197. Young AM, Marsden J, Goodman A, et al. Prospective randomized
comparison of dacarbazine (DTIC) versus DTIC plus interferon-alpha
(IFN-alpha) in metastatic melanoma. Clin Oncol (R Coll Radiol)
2001;13:458–465.
198. Middleton MR, Grob JJ, Aaronson N, et al. Randomized phase III study
of temozolomide versus dacarbazine in the treatment of patients with
advanced metastatic malignant melanoma. J Clin Oncol 2000;18:158–
166.
199. Kaufmann R, Spieth K, Leiter U, et al. Temozolomide in combination
with interferon-alfa versus temozolomide alone in patients with
advanced metastatic melanoma: a randomized, phase III, multicenter
study from the Dermatologic Cooperative Oncology Group. J Clin
Oncol 2005;23:9001–9007.
200. Hwu WJ, Krown SE, Menell JH, et al. Phase II study of temozolomide
plus thalidomide for the treatment of metastatic melanoma. J Clin
Oncol 2003;21:3351–3356.
201. Atkins MB, Lotze MT, Dutcher JP, et al. High-dose recombinant inter-
leukin 2 therapy for patients with metastatic melanoma: analysis of 270
patients treated between 1985 and 1993. J Clin Oncol 1999;17:2105–
2116.
202. Rosenberg SA, Restifo NP, Yang JC, et al. Adoptive cell transfer: a
clinical path to effective cancer immunotherapy. Nat Rev Cancer
2008;8:299–308.
203. Phan GQ, Yang JC, Sherry RM, et al. Cancer regression and autoim-
munity induced by cytotoxic T lymphocyte-associated antigen 4 block-
ade in patients with metastatic melanoma. Proc Natl Acad Sci USA
2003;100:8372–8377.
204. Sanderson K, Scotland R, Lee P, et al. Autoimmunity in a phase I trial
of a fully human anti-cytotoxic T-lymphocyte antigen-4 monoclonal
antibody with multiple melanoma peptides and Montanide ISA 51 for
patients with resected stages III and IV melanoma. J Clin Oncol
2005;23:741–750.
205. Attia P, Phan GQ, Maker AV, et al. Autoimmunity correlates with
tumor regression in patients with metastatic melanoma treated with
anti-cytotoxic T-lymphocyte antigen-4. J Clin Oncol 2005;23:6043–
6053.
206. Ribas A, Camacho LH, Lopez-Berestein G, et al. Antitumor activity in
melanoma and anti-self responses in a phase I trial with the anti-
cytotoxic T lymphocyte-associated antigen 4 monoclonal antibody
CP-675,206. J Clin Oncol 2005;23:8968–8977.
207. Eisen T, Ahmad T, Flaherty KT, et al. Sorafenib in advanced melanoma:
a Phase II randomised discontinuation trial analysis. Br J Cancer
2006;95:581–586.
208. Lorigan P, Eisen T, Hauschild A. Systemic therapy for metastatic malig-
nant melanoma – from deeply disappointing to bright future? Exp Der-
matol 2008;17:383–394.
209. Curtin JA, Busam K, Pinkel D, et al. Somatic activation of KIT in dis-
tinct subtypes of melanoma. J Clin Oncol 2006;24:4340–4346.
210. Bedikian AY, Millward M, Pehamberger H, et al. Bcl-2 antisense (oblim-
ersen sodium) plus dacarbazine in patients with advanced melanoma:
the Oblimersen Melanoma Study Group. J Clin Oncol 2006;24:4738–
4745.
211. Goggins WB, Tsao H. A population-based analysis of risk factors for
a second primary cutaneous melanoma among melanoma survivors.
Cancer 2003;97:639–643.
212. Cascinelli N, Fontana V, Cataldo I, et al. Multiple primary melanoma.
Tumori 1975;61:481–486.
213. Balch CM, Soong SJ, Murad TM, et al. A multifactorial analysis of
melanoma. IV. Prognostic factors in 200 melanoma patients with distant
metastases (stage III). J Clin Oncol 1983;1:126–134.
214. Romero JB, Stefanato CM, Kopf AW, et al. Follow-up recommenda-
tions for patients with stage I malignant melanoma. J Dermatol Surg
Oncol 1994;20:175–178.
215. Huang CL, Provost N, Marghoob AA, et al. Laboratory tests and imaging
studies in patients with cutaneous malignant melanoma. J Am Acad
Dermatol 1998;39:451–463.
216. Mooney MM, Kulas M, McKinley B, et al. Impact on survival by method
of recurrence detection in stage I and II cutaneous melanoma. Ann Surg
Oncol 1998;5:54–63.
217. Krug B, Crott R, Lonneux M, et al. Role of PET in the initial staging of
cutaneous malignant melanoma: systematic review. Radiology 2008;249:
836–844.
218. Sober AJ, Chuang TY, Duvic M, et al. Guidelines of care for primary
cutaneous melanoma. J Am Acad Dermatol 2001;45:579–586.
219. Roberts DL, Anstey AV, Barlow RJ, et al. UK guidelines for the manage-
ment of cutaneous melanoma. Br J Dermatol 2002;146:7–17.

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44
Mohs Micrographic Surgery and
Cutaneous Oncology
Hubert T Greenway MD, Kurt L Maggio MD, and Robert Lane BS
Summary box
 Mohs micrographic surgery is a specialized surgical
procedure indicated for basal cell carcinoma, squamous cell
carcinoma, melanoma, and other malignancies of the skin
and mucous membranes.
 Mohs micrographic surgery provides complete microscopic
margin control through the use of horizontal frozen histologic
sections of the entire periphery of the excised tumor.
 Mohs surgery is cost-effective and provides the highest cure
rate for tumors that spread by direct extension.
 Mohs surgery requires a physician trained in surgery and
pathology to accurately excise and map tumor extensions.
 Mohs surgery entails a series of precise steps that lead to
tumor extirpation and allow for immediate wound repair.
 Mohs surgery has few complications with proper preoperative
planning, but can be a time-intensive procedure.
 INTRODUCTION
Mohs micrographic surgery is a method of excision that pro-
vides complete microscopic control of tumor margins and
offers cure rates superior to those of other treatment options.
It is most commonly used for cutaneous malignancies, and
can be used for benign neoplasms in special situations. It is a
meticulous technique performed by a physician skilled in
cutaneous surgery and pathology, in which horizontal frozen
histologic sections of the surgical margins of the excised
tumor are generated for the most complete microscopic
examination possible. Residual malignant extensions of the
margins are mapped and excised selectively until the tumor
is removed. It is designed primarily to answer the question
‘Is it all out?’ as opposed to ‘What is it?’1 Mohs micrographic
surgery is usually performed in an outpatient facility over
several hours using local anesthesia. The resulting defect is
minimized by the procedure’s inherent conservation of
normal tissue adjacent to the tumor, and may be repaired
immediately, allowed to heal by second intention, or undergo
delayed reconstruction. Training programs for performing
Mohs micrographic surgery are available throughout the
United States via a 1- or 2-year fellowship after completion
of residency. In 2003, the US Accreditation Council for
Graduate Medical Education approved procedural dermatol-
ogy fellowships in which Mohs surgery is the backbone.
Cutaneous tumors have been successfully treated in a
number of ways. These include standard fusiform excision,
cryotherapy, radiation therapy, curettage and electrodesic-
cation, intralesional interferon,2 topical and intralesional
5-fluorouracil,3 and ablative laser treatment.4 Recently, imi­
quimod, a novel immune response modifier thought to stim-
ulate interferon-α, has been used for cutaneous tumors.5
These methods can provide excellent results in many circum-
stances. However, none of them determine that the borders
are completely tumor free and offer the patient the satisfac-
tion of immediately knowing that their tumor has been com-
pletely removed. Mohs micrographic surgery offers this
information, along with a superior cure rate, and is often the
method preferred by both patient and physician. Mohs
surgery, in both the original form using a fixative on the skin
prior to excision (Fig 44.1) and as now practiced without the
fixative, consistently shows the lowest 5-year recurrence rates
compared to all other modalities.6
History
 1930s: Frederic E Mohs, a general surgical trainee,
developed a technique of excisional surgery in which a
complete margin of skin cancer was plotted in three
dimensions7 and named it ‘chemosurgery’ because it
involved chemical fixation in situ before excision as follows:
n Zinc chloride (as fixative), combined with stibnite (as
permeant) and bloodroot powder (Sanguinaria
canadensis) (as agglutinant) (see Fig. 44.1) was applied to
achieve in-vivo tissue fixation while maintaining cytological
detail for microscopic evaluation of the excised specimen.
n One day later the tumor and saucer-shaped specimen
containing a narrow margin of normal-appearing tissue
were excised painlessly in a bloodless surgical field;
frozen sections were generated from the specimen with
the deep portion and peripheral margin of the excised
tissue in a single horizontal plane, and residual tumor was
precisely mapped based on the microscopic findings.
n Overnight, zinc chloride was reapplied (if indicated) and
the procedure was repeated to remove another saucer-
shaped tissue specimen in the precise location of any
residual tumor.
n The process was repeated until all residual tumor was
removed.

712
Part 4  Special Procedures
to accurately locate residual tumor and selectively excise it
with the next layer (Fig. 44.2).
Mohs micrographic surgery was conceptualized to address
the inadequacy of conventional means of surgical excision
with margins. Vertically cut serial sections of an entire exci-
sional specimen require an excessive number of sections to
be examined. Step sections, representative vertical sections
taken at 2–4-mm intervals as in the breadloaf method (Fig.
44.3), are customarily obtained when excisional specimens
are sent to the pathology laboratory. However, this method
leaves marginal areas between the sections that are not micro-
scopically visualized, and allows examination of less than 1%
of the tumor’s margin.11,12 The quadrant method similarly
fails to identify residual tumor between sampled areas. Failure
to detect subclinical microscopic tumor foci is often respon-
sible for recurrence of the tumor despite ‘clear’ margins on
the pathology report.
Figure 44.1  On the right, the zinc chloride fixative originally
used by Dr Mohs in chemosurgery. Note its dark color. A
similar bloodroot extract currently commercially available from
homeopathic sources for patient self-application (‘black salve’)
is not recommended because of the inherent risks in self-
application in an unsupervised setting.
Superior view
Extension of tumor
represented in Mohs
histology sections
Extension of tumor represented in Mohs
histology sections
Layer I
Surface
Deep
Layer I
Layer II
Layer II
I1
I1
II1
II1
I2
I2
I3
I3
I4
I4
Deep and peripheral margins
Tumor
Mohs surgical
margin
Layer I
Mohs surgical
margin
Layer II
Excision for Mohs micrographic surgery
Figure 44.2  Mohs micrographic surgery technique.
n The wounds were usually left to heal by second intention.
Mohs demonstrated significantly higher cure rates than
conventional excision, but this technique had limitations,
including the time taken (1 day for each surgical layer)
and the delay in wound reconstruction as a result of the
postoperative fixed tissue slough.
 1953: Mohs and others demonstrated that the zinc chloride
fixation could be replaced by local anesthesia and frozen
section processing while still maintaining high cure rates,
making the technique simpler and quicker.
 1985: The official name of this procedure was changed to
Mohs micrographic surgery to reflect the shift away from
chemical fixation toward a fresh tissue fixation technique,
while maintaining reliance on microscopic evaluation of a
layer-by-layer pictorial representation of tumor. This allows
most tumors to be removed in 1 day, permits immediate
wound repair, eliminates preoperative fixative discomfort, and
has a cure rate comparable to that of the chemosurgical
technique.8,9 It is now used almost exclusively by most Mohs
micrographic surgeons.
 1986: American College of Chemosurgery, founded by Mohs,
renamed American College of Mohs Micrographic Surgery.
 Subsequently: College renamed American College of Mohs
Micrographic Surgery and Cutaneous Oncology to reflect
changes in the clinical scope of the practice as the procedure
enjoyed increasingly widespread application.10 It was recently
renamed again as the American College of Mohs Surgery.
Mohs micrographic surgery is predicated on the observation
that skin cancers generally grow through direct extension
without ‘skip’ areas. Tumor cells can be found a significant
distance from the clinically visible and palpable neoplasm, yet
are in continuity with the tumor itself as a result of the
tumor’s microscopic spread. Thus, the tumor can be traced
to its termination by excising it layer by layer and examining
the entire margin of each layer under the microscope. Criti-
cal in this process is that the skin edge and deep surface are
visualized in one plane on the glass slide, and thus the entire
margin can be analyzed. A map is constructed for each layer

713
Chapter 44  Mohs Micrographic Surgery and Cutaneous Oncology
rent tumors or those at high risk for recurrence, those with
clinically indistinct margins, and for those tumors that are
anatomically located where tissue conservation is important
(Table 44.1). It can be used for virtually any neoplasm that
spreads by contiguous growth along cutaneous or mucosal
surfaces.
One additional advantage of the Mohs technique is that
it is tissue sparing. In specific cosmetic or functional areas,
this may allow a more cosmetically acceptable or functional
result after surgery. Frequently it also can simplify the
There are many advantages of using the Mohs technique:
• First, with its improved method of evaluating the
margin, the Mohs technique has significantly improved
cure rates. The 5-year cure rate for primary cancers
treated by Mohs surgery is 99%, compared with 93%
for conventional excision.13 For recurrent cancers, the
5-year cure rate is 95%, compared with 80% for
excision or any other treatment modality.14
• Second, Mohs surgery compares favorably in cost-
effectiveness to other modalities of treatment of
non-melanoma skin cancer.15,16
Mohs surgery is indicated in situations where other treatment
modalities have failed. The Mohs technique is used for recur-
Superior view
Tumor
Elliptical excision margin
Extension of tumor beyond
surgical margin
Extension of tumor not
represented in histology
sections (A–F)
Breadloaf sectioning
Breadloaf section on histologic slides
A
A
B
B
C
C
D
D
E
E
F
F
Surface
Deep
Conventional excision
Figure 44.3  Limitation of breadloaf method of examining the
margin of conventional excision. In this example, excisional tip
sections A and F are clear of tumor and sections B, C, D, and E
demonstrate tumor. No extension to the peripheral margins is
detected, and the excision is technically clear on margins.
However, this is not an accurate margin assessment. Extension
of tumor to the surgical margin between sections D and E is
missed because it is not sampled.
Table 44.1  Indications for Mohs micrographic surgery
TYPE OF TUMOR
EXAMPLES
Recurrent
Positive margin after simple
excision
At high risk for local recurrence
and/or metastasis
Sclerosing (morpheaform),
infiltrative, micronodular,
metatypical subtypes of basal
cell carcinoma
Perineural basal cell carcinoma
or squamous cell carcinoma
Keratoacanthoma
Bowen’s disease
Malignant melanoma
Merkel cell carcinoma
Dermatofibrosarcoma
protuberans
Atypical fibroxanthoma
Malignant fibrous histiocytoma
Microcystic adnexal carcinoma
Sebaceous carcinoma
Extramammary Paget’s disease
Angiosarcoma
In an area where tissue
conservation is important
Eyelids
Ears
Nose
Lips
Digits
Nails
Genitalia
Facial – in area of embryonic
fusion planes
Periorbital, especially medial
canthus
Nasal
Lips
Ears
Retroauricular sulcus
Melolabial folds
Poorly defined clinical margins
Perineural spread
Greater than 2 cm in diameter
Immunosuppressed patient
Skin previously treated with
ionizing radiation
Demonstrated biological
aggressiveness

714
Part 4  Special Procedures
involving the melolabial folds may be particularly deep and
extensive. The Mohs technique should be considered for
virtually any malignant neoplasm of the nose.
Tumors of the skin of the upper lip are usually basal cell
carcinomas, while those of the cutaneous lower lip are most
commonly squamous cell carcinomas. The latter type is
highly capable of regional and metastatic spread, especially if
over 2 cm in diameter. Larger and more aggressive tumors
may require wider excision with lymph node evaluation (i.e.
sentinel lymph node mapping), and involvement of a head
and neck surgeon may be helpful.
Tumors of the digits may be advanced at the time of pres-
entation. Mohs surgery is useful and often avoids the amputa-
tion of a digit, thus maintaining function. Treatment of
subungual or periungual tumors is particularly challenging to
maintain function, avoid infection, and allow for adequate
cosmesis. The nail matrix in particular is extremely vulnera-
ble to tissue loss resulting in visible deformity of the nail plate
with loss of function.
The treatment of tumors of the genitalia may also benefit
from Mohs micrographic surgery.22 Patients may require
penectomy for advanced stages of malignancy; Mohs surgery
may provide the necessary tissue conservation to avoid this
outcome. Larger and more aggressive tumors may require
wider margins of excision and regional lymph node examina-
tion. The precise location and size of the tumor can greatly
influence prognosis. Higher cure rates can be obtained when
tumors involve only the glans or prepuce of the penis, and
when lesions are less than 1 cm in diameter.
 PREOPERATIVE PREPARATION
Patient consultation is provided before the procedure. Criti-
cal in this process is the accurate localization of the tumor,
which can be obtained using photographs, sketches, and
descriptions, often from the referring physician. Physical
examination should include contiguous areas and assessment
for pre-existing cosmetic and functional deficits. Draining
regional lymphatics should be palpated and documented for
all patients. Histologic proof of diagnosis is generally required,
and the histologic slide is reviewed to confirm the tumor type
and pattern. The patient’s health history and review of
systems should be focused, but comprehensive to minimize
complications (Box 44.1). Any history of previous cutaneous
procedures (especially those involving the operative site),
ultraviolet exposure, and radiation therapy should be elicited.
A detailed medication history must include dietary supple-
ment use. In one study, 49% of patients undergoing Mohs
surgery reported taking at least one dietary supplement.23
Patients are instructed to avoid aspirin-containing products,
antiplatelet agents, vitamin E, ginkgo biloba, and garlic, which
have demonstrated anticoagulation properties. Cessation of
warfarin is controversial because of the well-documented
risks of abruptly discontinuing therapy perioperatively.24 It is
our practice to consult with the treating physician, if possible,
when the patient is on a prescribed aspirin-containing product,
antiplatelet agent, or anticoagulant. Improving hypertensive
control and optimizing other medical conditions are impor-
tant to ensure operative success. Preoperative anxiolytic
agents, usually administered sublingually or orally, can be
considered in patients with a high level of apprehension. It
may be advisable for the patient to come for the procedure
after having a light meal and being well rested and with a
reconstruction both by tissue conservation within critical cos-
metic units as well as by allowing the reconstructing surgeon
to be as confident as possible that the entire tumor has been
removed.
Mohs surgery is not limited to the skin – treatment of
mucosal cancers of the head and neck can benefit from its
many advantages.17 The face (especially the eyelids, ears, lips,
and nose), the digits, the genitalia, and the scalp are specific
anatomic locations in which Mohs micrographic surgery can
be most helpful in obtaining clear tumor margins while
sparing as much uninvolved tissue as possible. These are loca-
tions in which tumors can spread along nerves, cartilage,
periosteum, bone, and embryonic fusion planes, making them
high risk for recurrence.
Mohs micrographic surgery should be considered for
virtually all cutaneous malignancies of the face. The face
has multiple unique anatomic structures which must be
preserved in reconstruction, making tissue conservation
critical.18
Lesions on the eyelids present special challenges. It was
with eyelid tumors that Dr Mohs had his earliest successes
with extremely high cure rates.19 Ninety percent of malignant
tumors of the periorbital area are basal cell carcinomas. If the
tumor involves the tarsal plate, levator muscle, or lacrimal
apparatus, especially the canaliculus, oculoplastic repair is
frequently required. Intraocular mucosal spread of basal cell
carcinoma has been documented.20 When operating on the
free eyelid margin, layers may be taken in succession so that
the canaliculus is sacrificed only if involved. The postopera-
tive size of medial canthal lesions can be minimized with the
Mohs technique, allowing for second intention healing in
selected cases. Regardless of the size and extent of the defect,
repair of the Mohs defect can commence immediately, saving
the patient great anxiety and days of non-productive time
while awaiting repair.
Lesions on the ears may also present significant challenges
to the cutaneous surgeon. Making up only 6% of all skin
cancers, those that occur on the ear account for a dispropor-
tionate number of recurrences. The difficulty in eradication
likely stems from the many embryonic fusion planes in the
periauricular area. Tumors of the ear may have a predictable
pattern of spread. Tumors that arise in the postauricular area
tend to spread to the ear itself. Tumors that arise in the
preauricular area spread toward the tragus and the medial and
superior aspects of the helix. Once at the tragus, the tumor
can spread down the external part of the tragus between
tragal cartilage and the parotid gland to involve deeper struc-
tures such as the facial nerve.21 Neuropathic pain in this area
is frequently an indicator for such involvement. Treatment of
tumors involving deep structures, the mastoid, or extending
from the concha into the external auditory meatus may
require sedation or general anesthesia and consultation with
other specialists. Tumors extending beyond the outer third
of the ear canal may be difficult to access, requiring special-
ized surgical expertise and skills. Tumor extirpation can
involve significant morbidity to the patient.
The nose is the the most common site for recurrence of
basal cell carcinoma on the entire integument. Like the peri-
auricular area, embryonic fusion planes may offer the path of
least resistance and facilitate tumor spread along contiguous
anatomic areas. In particular, the alar rim and nasal tip
are two areas where tissue conservation is critical and size
can affect reconstruction possibilities dramatically. Lesions

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Chapter 44  Mohs Micrographic Surgery and Cutaneous Oncology
history is updated, and informed consent is obtained in
writing. The execution of Mohs micrographic surgery requires
several precise steps.
First, the site of the tumor is identified with the aid of
high-intensity lighting, magnification, and/or Wood’s light
(Fig. 44.4). Cross-polarized light sources may be helpful in
this process. Note that the patient cannot always be counted
on to confirm the location with precision. The exact location
of the tumor is confirmed and its size is recorded on an ana-
tomic diagram, which functions as a surgical map. A 1–5-mm
surgical margin, depending on tumor type, is drawn around
the clinically apparent tumor with a surgical marking pen
(Fig. 44.5A). Because local anesthesia can distort the anatomy,
landmarks and borders of cosmetic subunits may also be
outlined at this time. The lesion may be photographed preop-
eratively before or after marking (and at subsequent stages of
the procedure as deemed necessary for documentation).
Local anesthesia is obtained with 1% or 2% lidocaine with
epinephrine 1 : 100 000 or 1 : 200 000 in most situations. A
slow anesthetic technique is most comfortable, and injecting
as the needle is withdrawn is helpful. Topical 20% benzocaine
or lidocaine preparations may alleviate the discomfort of the
injection. It is advisable to wait several minutes to allow for
complete anesthesia and vasoconstriction to occur before pro-
ceeding. Occasionally, regional nerve blocks may be helpful
for large tumors. This may be supplemented with a longer-
acting anesthetic agent such as bupivacaine to enhance patient
comfort between layers.
The tumor and surrounding area is then prepped with
povidone iodine or chlorhexidine gluconate and draped. If the
tumor is large or thick, it may be debulked using a curette or
surgical razor blade with or without the use of electrodesic-
cation (Fig. 44.5B). This may further delineate margins and
reduce the number of layers necessary to obtain clear margins.
A small specimen of this material may be obtained for a
vertical transverse section for documentation and to identify
specific tumor growth pattern within the tissue, especially
family member or friend. Warm layered clothing is advisable
in most operating room environments.
The cutaneous surgeon must successfully alleviate the
patient’s anxieties about their surgery. Many patients present
with closely held perceptions about their aesthetic ideal, and
some have unrealistic expectations. It may be useful to obtain
preoperative digital photographs to document both tumor
location and specific anatomic features. A number of patients
have researched their cutaneous neoplasm on the Internet or
by other sources of information, but the cutaneous surgeon
should still take this opportunity to educate the patient to
ensure the transmission of accurate information. Patient edu-
cation can take many forms, including websites, morphing
software, brochures, pictures, and wax models. However,
none is a total replacement for the direct consultation
between the physician and patient.
A thorough discussion of risks, benefits, alternatives, and
complications of the proposed surgical procedure must take
place. Specific alternatives to surgery such as radiation therapy
and other modalities of treatment (perhaps even observation)
should be discussed. An explanation of the Mohs technique
with respect to anesthesia, stages, waiting periods, and repair
options should be tailored to the patient’s specific case. The
possibility of tumor spread to infiltrate contiguous soft tissue
and cartilaginous and bony structures should be anticipated
and discussed with the patient before or during the operation
before proceeding further. The extent of tumor involvement
may be assessed by computed tomography (CT), magnetic
resonance imaging (MRI), or other diagnostic aids, although
a negative test result may be misleading.
The reconstruction of large tumors that infiltrate widely
may benefit from the expertise of plastic, oculoplastic, and
head and neck surgeons, or other specialists, and their evalu-
ation should be incorporated into the preoperative evaluation
of the patient. Medical oncologists may provide useful input
and therapeutic options in certain cases. In essence, a team
approach may serve the patient best in challenging cases.
 TECHNICAL ASPECTS
Before surgery can commence, vital signs including blood
pressure and pulse are recorded, the patient medication
Figure 44.4  Correct selection of tumor site is critical in Mohs
micrographic surgery. Correct lighting and magnification are
helpful. In this case, a lentigo maligna involving the periorbital
region is being excised in a staged fashion. The area for
excision as determined by visual inspection is outlined;
however, examination using a Wood’s light revealed significant
subclinical extension of visually evident tumor.
Box 44.1  Preoperative evaluation
Medical/surgical history
 Hepatitis
 AIDS
 Herpes simplex virus
 Medications
 Vitamins
 Nutritional supplements
 Allergies to medicines, anesthetics, topical creams, adhesive
tape
 Immunosuppression
 Concurrent malignancies
 Concurrent cutaneous disorders
 Prosthetic joints and valves
 Pacemaker/defibrillator
 Bleeding diathesis
 Smoking history
 Other medical illnesses (e.g. gout)

716
Part 4  Special Procedures
trocautery unit if avoidance of electrical interference with
implanted devices is required.
A two-dimensional map is then created while the patient
is still in the operating suite to document the exact tumor
location. It may be helpful to transpose the map onto a digital
photograph of the lesion.25 The specimen is then divided into
sections small enough to fit on a microscope slide (0.5–
1.5  cm), and its non-epidermal edges are stained to allow
proper orientation (Fig. 44.7C and Fig. 44.8A,B). Two to
three colors are used for each specimen to allow for adequate
orientation.26 The number of specimens depends on the size
of the tumor, but the numbering sequence of the tissue
specimens should be consistent from patient to patient. The
clockwise numbering pattern is the one historically and most
commonly used, starting at the 1 o’clock position. When large
if the biopsy was not definitive. Immediately thereafter, the
incision is made along the outlined margin with a scalpel with
a #15 or #15c blade and the tumor is sharply excised to an
appropriate depth. A #10 blade can be useful for larger
tumors overlying thick skin. A saucer-shaped specimen with
30° beveled edges is ideal so that the specimen may be flat-
tened (Fig 44.6). Flattening means that the bottom and
margins can be sectioned by the histotechnician in the same
plane. Surgical reference marks are made on the specimen
and adjacent tissue with gentian violet or the scalpel for
precise orientation of the specimen before its removal. Once
removed, maintaining proper orientation of the specimen is
critical to the integrity of the entire procedure (Fig. 44.5C,D
and Fig. 44.7). Hemostasis is achieved with direct pressure
or electrocoagulation, or a hand-held battery-operated elec-
Mohs micrographic surgery:
preparation and stage 1 excision
A
B
C
D
Figure 44.5  Preparation and
excision. (A) Preoperative
view of right nasal alar basal
cell carcinoma. (B)
Debulking with curette.
Tumor debulking may be
helpful in delineating
subclinical extensions of
tumor that are not grossly
visible. (C) Stage 1 excision.
Note the 30–45° angle of the
knife blade and the 2-mm
margin of normal-appearing
skin around the debulked
area. (D) Stage 1 excision
completed with specimen
removed. Note scoring of
epidermis at medial and
lateral margins of operative
site corresponding to division
of specimen into sections
appropriate for processing.
(Adapted with permission
from Grekin RC. Mohs
micrographic surgery. In:
Robinson JK, Arndt KA,
LeBoit PE, Wintroub BU, eds.
Atlas of cutaneous surgery.
Philadelphia: WB Saunders;
1996.)

717
Chapter 44  Mohs Micrographic Surgery and Cutaneous Oncology
area after the placement of a pressure dressing. Occasionally,
patients remain in the Mohs operating suite during tissue
processing if their mobility is limited or if they require con-
tinuous monitoring.
Once in the laboratory, rather than being cut vertically,
each specimen is placed bottom-side up on the microtome
stage so that horizontal sections can be taken from the deep
surface. This process requires many precise steps27–30 with
attention to detail to avoid mapping errors. First the speci-
men is embedded in optimal cutting temperature (OCT; or
similar agents) compound (Tissue-Tek, Miles, Inc, Diagnos-
tics Division, Elkhart, IN) and a forceps or flat portion of a
scalpel handle is used to ensure the specimen is completely
flat. If the specimen contains cartilage or fat, this can be more
difficult. A variety of devices and maneuvers is available to
assist in tissue flattening if the histotechnician finds them of
value.
The tissue is immediately frozen with tetrafluoroethylchlo-
ride or liquid nitrogen and then transferred to the cryostat
for thorough freezing (see Fig. 44.8C). Obtaining a complete
section is critical to prevent errors in tissue interpretation
through missing sections. It requires great skill and practice.
Training and certification information is available through
several organizations, including the American Society for
Mohs Histotechnology (Milwaukee, WI). Flattening the spec-
imen, raising its peripheral margins, and cutting through the
tissue block with the microtome blade before representative
sections are obtained are all helpful techniques to avoid
missing skin edges on portions of the microscope slide. Slides
are identified and prepared with the patient’s name, date, and
layer/specimen sequence number, with attention to detail to
avoid mapping errors.
specimens have central portions, the sequence is initiated at
the skin edges and then continued into the central portions
(Fig. 44.9). Ideally, the layer of tissue should be cut into as
few blocks as possible to minimize the risk of false-positive
and false-negative margins that increase with each additional
subdivision.25a
When specimens contain cartilage or bone, or subcutaneous
tissue without any skin edge, this should be indicated on the
map. At this point, the tissue is handed to the histotechnician
for further processing. Patients are advised that each layer
may require 1–2 hours, and they may proceed to the waiting
Figure 44.6  Mohs surgery involving the left lateral forehead/
brow region. The center has been debulked. Layer I removal/
excision with 30–45° angle of #15 scapel blade. Note marking
of the medial margin with gentian violet for orientation.
A
B
C
Mohs micrographic surgery:
mapping and division of specimen
Figure 44.7  Mapping and division of the specimen. (A) Division of specimen using scalpel and forceps. Maintenance of orientation
is critical to the procedure. (B) Divided specimen showing orientation. (C) Map orienting tissue specimen and denoting dye marking
of non-epidermal margins. Note that the map is specific to the anatomic area and whether the tumor is on the left or right. (Adapted
with permission from Grekin RC. Mohs micrographic surgery. In: Robinson JK, Arndt KA, LeBoit PE, Wintroub BU, eds. Atlas of
cutaneous surgery. Philadelphia: WB Saunders; 1996.)

718
Part 4  Special Procedures
tics. Ber-EP4 is one such widely available cytokeratin stain
used for this purpose. Toluidine blue can also be used for
basal cell carcinomas, favored by some for its optical clarity.
Special immunostains can be obtained for other tumor types.
However, due to reagent cost, unavailability of automated
staining equipment, additional processing time, and addi-
tional technician and physician time, the process is impracti-
cal for routine use.32 For melanoma, rapid HMB-45 staining
is used by some to increase the accuracy of interpretation of
frozen sections. Menaker et al.33 found that frozen sections
using HMB-45 stained comparably with paraffin-embedded
permanent sections at each stage of resection in a study of
20 cases of melanoma treated with Mohs micrographic
surgery. Albertini et al.34 found MART-1 to be superior in
sensitivity to both HMB-45 and S-100 for frozen sections.
Smith et al.35 found S-100 staining useful for tracking
perineural extension of granular cell tumor not evident with
hematoxylin and eosin. Harris et al.36 described the use of
carcinoembryonic antigen (CEA) rapid staining in the treat-
ment of extramammary Paget’s disease treated by Mohs
surgery. Similarly, the CD-34 immunostain has been studied
in dermatofibromasarcoma protuberans. When these stains
are used, permanent sections are usually obtained, as in our
practice.
The first section obtained is the truest margin and in our
practice is placed furthest from the frosted edge of the slide,
and then one to three additional sections are obtained at 4–8-
mm intervals and placed on the slide sequentially closer to
the frosted edge (Fig. 44.10A). The process is repeated for
each tissue specimen. Once all tissue has been processed, the
slides are stained, usually with hematoxylin and eosin, though
toluidine blue is also popular in many practices. In high-vol-
ume laboratories, they are placed in an automatic slide stainer
such as the Shandon Linistat automated system (Thermo
Electron Corporation, Waltham, MA) to decrease processing
time by about one-third (Fig. 44.10B). Finally, the slides are
rinsed, a clear mounting medium such as Cytoseal-60 (Richard
Allen Scientific, Kalamazoo, MI) or similar medium is applied,
and cover slips are placed to facilitate microscopic review
(Fig. 44.10C).
Most Mohs micrographic surgery laboratories use routine
hematoxylin and eosin staining for all specimens. In a com-
parison study with a cytokeratin marker, Smeets et al.31
found there was a greater than 99% sensitivity in the identi-
fication of basal cell carcinoma with hematoxylin and eosin
on Mohs sections. However, adjuvant cytokeratin staining
may be useful in selected cases of basal cell carcinomas exhib-
iting aggressive or poorly circumscribed growth characteris-
A
B
C
D
Figure 44.8  Mohs laboratory specimen processing. (A) Tissue dyes. (B) Dye marking of non-epidermal margins with black ink.
(C) Sectioning of frozen specimens. (D) The histotechnician cuts serial sections through specimen block as it passes over the
cryostat blade. The thin, cold tissue adheres directly to the room temperature microscope slide applied to it.

719
Chapter 44  Mohs Micrographic Surgery and Cutaneous Oncology
thus the surgical margin) could be incomplete as a result of
technical error.37,38 Technical errors are the most common
cause of local recurrences after Mohs surgery.39
The vertical specimen is first examined because it may
provide more complete information than the biopsy, and may
be the only view of the tumor if the first Mohs layer is clear.5
By examining the slides in numerical order corresponding to
the map, residual tumor can be identified and its exact loca-
tion determined based on the colors of the margins on the
slide. It is noted on the map with red marking ink (Fig.
44.11). Additionally, areas of calcification, perineural spread,
inflammation, and other incidental skin neoplasms such as
actinic and seborrheic keratoses can be identified. Sections
need to be carefully examined because rete ridges, hair fol-
licles, and other adnexal structures can mimic tumor cells.
Dense inflammation may mask small collections of tumor
cells. Patients with chronic lymphocytic leukemia and solid
organ transplant recipients have a 36% and 13% incidence,
respectively, of prominent inflammatory foci on Mohs sec-
tions compared with controls (1%), making slide interpreta-
tion more difficult.40 However, the presence of dense
inflammation on Mohs sections of basal cell carcinoma does
not necessarily obscure the presence of any residual tumor,41
and may not indicate the need for an additional layer. Simi-
larly, although an intense infiltrate may surround squamous
cell carcinoma, any residual tumor can be visualized if it is
present without the use of special stains.42 In our practice,
each case is approached uniquely because we have seen tumor
masked by inflammation.
If the pathology on frozen sections is not clear, permanent
tissue specimens can be obtained for improved resolution or
increased depth of tissue evaluation through levels to trace
specific anatomic structures of concern. If any of the speci-
mens examined are missing epidermis, dermis, or subcutane-
ous tissue, a recut can be obtained after the specimen has
been reoriented in the OCT medium. In cases with an
extremely large number of specimens, the surgeon may have
every other one processed first to give an initial view of the
tumor extent.
If residual tumor is identified or a segment of the margin
cannot be fully visualized even after recuts have been obtained,
the patient is brought back to the operating room for removal
of another layer. In this way, the Mohs practitioner functions
as both surgeon and pathologist. In a manner similar to the
first layer, but avoiding complete re-excision unless all margins
are positive, a specimen containing the area of residual
tumor and a small amount (2–5 mm) of surrounding tissue is
removed after careful marking with gentian violet (see Fig.
44.11). These layers are successively numbered on the Mohs
map using Roman numerals. This cycle is repeated until no
residual tumor is identified on any slides of a particular layer.
Proper interpretation of Mohs micrographic frozen sections
is thus critical in the training and practice of the Mohs micro-
graphic surgeon.
Once the tumor has been completely removed, the patient
is evaluated for reconstructive options. Cosmetic and func-
tional issues must be considered with each wound before a
decision is made to allow second intention healing or cover
the wound with a graft or flap. If tumor recurrence is possi-
ble, second intention healing or split-thickness skin grafting
should be considered. In these situations, flaps are to be
avoided because they may mask recurrence. Extensive under-
mining and tissue advancement, rotation, or transposition
Specimen interpretation
At this point, the histotechnician hands the stained slides to
the Mohs surgeon for histologic examination. Each micro-
scope slide is examined under light microscopy, carefully
noting the slide sequence numbers. Specimens should be
superimposed on the Mohs map if there is any uncertainty
about the origin or orientation of the specimen. There is a
predictable 10–20% tissue shrinkage that occurs during frozen
section processing, but any larger size discrepancy (or large
holes) should alert the Mohs surgeon that the specimen (and
A
B
C
D
E
2
1
1
2
3
4
1
2
3
1
2
3
4
5
1
2
3
4
5
6
7
8
9
10
11
12
13
14
Mohs micrographic surgery: specimen
markings and sequence numbering
Figure 44.9  Representative numbering sequences of various
specimens. A clockwise pattern is most commonly used, with
number 1 starting at 1 o’clock. Skin edges are numbered first,
followed by interior pieces. Coloured lines represent different
tissue dyes. Minimal division of the primary specimen results in
less risk of false-positive or false-negative margins. The limiting
size of a specimen is a combination of the skill of the
histotechnician and the size of the cryostat specimen object
disc and can range from a few millimeters to more than 2 cm in
one dimension in some laboratories. Small lesions up to 2 cm
in diameter are often halved (A) or trisected (B) if irregularly
shaped. Larger lesions may be divided into more pieces (C). If
the specimen is too large to contain epithelium on all pieces,
single (D) or multiple (E) central specimens might be mapped.

720
Part 4  Special Procedures
A
B
C
Figure 44.10  Specimen slides. (A) Unstained slide: the first section, representing the true surgical margin, is furthest from the
frosted edge of the slide. The histotechnician is able to visually assess for the presence of a complete section. (B) An automatic
slide stainer can greatly improve the efficiency of the Mohs laboratory; a large number of slides can be batched to improve slide
processing and reduce the time between stages of surgery. (C) The slide cover slip has been applied and slides are ready for
examination.
A
B
C
D
E
F
STAGE
STAGE
STAGE
STAGE
Mohs micrographic surgery:
stage II and III excision
Figure 44.11  Stage II and III excision. (A) Residual tumor in the specimen margins noted by coloring the area red on the map.
(B) Excision of stage II includes 2-mm margin of all positive areas. (C) Stage II specimens and map. (D) Residual tumor after stage II
noted on map after prepared specimens have been interpreted by the surgeon. (E) Stage III specimens and map. (F) Postoperative
defect after stage III. (Adapted with permission from Grekin RC. Mohs micrographic surgery. In: Robinson JK, Arndt KA, LeBoit PE,
Wintroub BU, eds. Atlas of cutaneous surgery. Philadelphia: WB Saunders; 1996.)

721
Chapter 44  Mohs Micrographic Surgery and Cutaneous Oncology
facilitate making the incision with the desired bevel.48 Tumors
involving perichondrium, periosteum, and the nail can be
dissected more easily using a periosteal elevator. For aggres-
sive tumors that involve the skull, facial bones, or sinuses, the
deep margin can be cleared by chiseling with a mallet. Bone
specimens require decalcification in ethylenediaminetetra-
acetic acid (EDTA) or similar softening reagent before they
are sectioned the next day, necessitating a surgical delay to
confirm tumor-free margins. For large tumors, a double-
bladed scalpel can be used to allow for maximum tissue
conservation and enhance mapping accuracy in peripheral
may facilitate tumor growth along the path of least resistance.
Second intention healing may allow recurrent tumor to be
visualized more easily. Similarly, split-thickness skin grafts
may allow increased visualization of the defect to detect
recurrent tumor.43 Definitive repair may be delayed to allow
for histologic reconfirmation of clear margins at a future time,
or to increase the success of a full-thickness skin graft.44 If
tumor recurrence is unlikely, repair can proceed with linear
closures, flaps, or grafts.45–47
The use of Mohs micrographic surgery provides the maximal
assurance that residual tumor cells do not remain in adjacent
normal-appearing skin and tissue.
 OPTIMIZING OUTCOMES
Figure 44.12  Typical patient-specific Mohs tray set up that
functions as both surgery and repair tray. Instruments included
in this set, from left to right, are 4-mm Fox dermal curette, #3
knife handle with ruler (with #15 blade attached), Webster/
Halsy needle holder, Adson Brown forceps 7 × 7, Castro-Viejo
fixation forcep with suture platform, Carmault splinter forcep,
Hartman mosquito curved hemostat, Kaye scissors (tungsten
carbide handle), iris scissors, Deaver (sharp blunt) suture
scissors. Also present are a basin for sterile saline, surgical
razor blade, sterile towels, one eye pad, 10 sterile 4 × 4 gauze,
non-adherent dressing, and 10–20 cotton-tipped applicators.
Figure 44.13  Additional supplies recommended for patient-
specific Mohs tray. Brown hypoallergenic tape with patient label
affixed on which allergies/other warning information can be
recorded (i.e. to use battery-operated electrocautery if patient
has a pacemaker), alcohol pads, povidone iodine, 4 × 4 gauze,
surgical marking pen, surgical light holders, electrosurgical
apparatus, and dental syringe.
Optimizing outcomes
 Ensure appropriate instrumentation and equipment are
available (e.g. special instruments for infiltrating tumors that
involve deeper structures; curved ophthalmic blades for
perioral and perinasal areas).
 Ensure all staff, including nurses and technicians, have
special Mohs surgery training.
 Recognize potential complications and plan for the
unanticipated (e.g. perioperative bleeding or emergencies).
Proper instrumentation, equipment, organization, and set up
in the Mohs surgery area are essential to a successful opera-
tive outcome (Figs 44.12 and 44.13). Mohs surgery requires
a qualified practitioner functioning as both a surgeon and
pathologist, as well as well-trained nursing staff and skilled
histotechnician. It also requires patient cooperation in waiting
while the time- and labor-intensive layers are performed.
Recognizing potential areas of complication allows the
surgeon to be proactive in primary prevention and risk man-
agement. Whenever surgery is being performed in the perior-
bital region, caution must be observed to prevent inadvertent
injury to the eye. The eyes can be protected by taping cotton
gauze over the eyelids, which also limits the intensity of the
operating room lights. If the tumor involves the eyelid margin,
a lubricated plastic eye shield may be inserted onto the cornea
after topical anesthesia with tetracaine or a similar fast-acting
anesthetic solution. The external auditory canal can be pro-
tected from undesirable blood by placing gauze into the
meatus. Appropriate restraining belts on the operating room
table are helpful if the patient is at risk of falling for any
reason. A smoke evacuator should be readily available to
remove malodorous electrosurgical plume. Suction should
always be available in case of unanticipated perioperative
bleeding. A plan for handling emergencies or unanticipated
events is necessary. An efficient outpatient surgical area and
laboratory are critical in ensuring overall patient satisfaction.
The removal of infiltrating tumors involving deeper struc-
tures requires special instrumentation to harvest the speci-
men without injuring adjacent structures. A spring-loaded
Castro-Viejo needle driver and Westcott scissors are fre-
quently used for periorbital excisions, allowing the cutaneous
surgeon superior fine control (Fig. 44.14). In our practice, an
operating room microscope may be used to further enhance
precision. Ophthalmic mini-blades on cylindrical handles may
be useful around the eye as well as for the ear and nose, to

722
Part 4  Special Procedures
 PITFALLS AND THEIR MANAGEMENT
margin control.49 Confocal mosaicing microscopy is a tech-
nique which may provide more rapid surgical observation of
large areas of excised tissue with magnification. Mosaics are
produced more quickly than frozen histology sections and
could potentially expedite and assist surgery.50
 POSTOPERATIVE CARE
Immediately after the procedure, the patient’s skin is cleaned
of all blood, antiseptic, and markings, and a pressure dressing
is secured with skin adhesive, to be left undisturbed for 48
hours in our practice. For difficult facial concavities, such as
the melolabial fold, dental rolls may be helpful to secure
pressure. Wound care generally consists of cleansing with 3%
hydrogen peroxide solution, followed by the application of
antibiotic ointment, and then the wound is covered with a
non-adherent dressing. This procedure is carried out twice
daily. Patients should receive explicit instructions on when
and how to call the Mohs surgeon in the event of unexpected
problems.
Postoperative pain is usually easily managed after Mohs
micrographic surgery. Patients should be instructed to take
non-aspirin-containing analgesics for their discomfort. Ana-
tomic locations subject to movement or tension such as
the mid-chest, shoulders, and lips, may be more likely to be
uncomfortable postoperatively. Procedures involving large
tumors or patients with low pain thresholds may require
narcotic analgesics. Patients experiencing pain several days
postoperatively may have a wound infection or hematoma
and should be evaluated.
Mohs surgery patients should be seen at least once in the
6-week postoperative period after suture removal to ensure
proper wound healing and contraction. Patients may have an
unexpected outcome such as a spitting suture, flap tip necro-
sis, partial graft slough, hypertrophic scar, or other event
requiring the surgeon’s intervention to optimize the ultimate
outcome of the surgical procedure. An additional visit 3
months postoperatively is used to monitor for recurrence and
for patient education. Patients should receive regular skin
examination, and be aware of their increased risk for addi-
tional cutaneous malignancies.
Figure 44.14  Castro-Viejo needle holder (top) with Westcott
tenotomy scissors (bottom) can be helpful for excisions around
the orbits.
Pitfalls and their management
 Careful preoperative planning minimizes complications.
 Take an anesthetic history to identify allergy to lidocaine,
which is rare but can cause anaphylaxis.
 Monitor patients for procedural or needle anxiety, using
sedation if necessary, and take appropriate precautions for fall
risk.
 Meticulous surgical technique and patient education help to
reduce postoperative infection.
 Assess whether cutaneous and sensory nerves are at risk and
take precautionary measures (e.g. injection to tumesce tissue
before removal, upward traction, and use of a nerve stimulator
with an alarm).
 In the periorbital region, take care to avoid direct eye injury –
where the eyelid is not directly involved, protect the eyes with
taped gauze pads or drapes.
 Advise patients on wound care and give explicit instructions
on when to contact the surgeon if unexpected problems
occur.
Complications of Mohs micrographic surgery are relatively
infrequent. They may be minimized with careful preoperative
planning. Cook & Perone, in a prospective study of 1358
cases, had a complication rate of 1.64%, most involving dif-
ficulties with hemostasis.51 Office-based Mohs surgical units
provide a safe environment for the patient. A log book should
be maintained to detail complications, to establish trends, and
to prevent recurrences as far as possible. A complete set of
vital signs, including blood pressure and pulse, should be
taken before the procedure.
Of the more serious complications, anaphylaxis to anes-
thetic agents or other administered medications is the most
grave. Use of supplementary oxygen and administration of
emergency medical care may be required. Training in
Advanced Cardiac Life Support is a required component of
fellowship training in Mohs micrographic surgery. Allergy to
lidocaine, the most commonly used of the amide local anes-
thetics, is rare, but can result in anaphylaxis. This agent does
not cross-react with the ester class of local anesthetics which
are more commonly responsible for untoward effects. When
a patient gives a history of ‘allergy’ to local anesthetics, an
episode of epinephrine sensitivity is most commonly elicited.
In these patients and in the elderly with labile hypertension,
the concentration of epinephrine used may be reduced while
still maintaining the hemostatic effect. Some patients may
need an allergy work-up to better characterize their precise
sensitivity. Diluting the anesthetic agent with plain 1% lido-
caine to achieve an epinephrine concentration of 1 : 300 000
can be used to provide sufficient hemostasis.
Patients may faint because of anxiety about the procedure
or a fear of needles. Precautions must be undertaken to avoid
the risk of a fall, including patient monitoring and observa-
tion, maintaining the surgical table as low as possible to the
floor during non-operative periods, and light patient restraints.
Syncopal patients should be placed in the reverse Trendelen-
burg position. Patients should be encouraged to eat a light
meal before surgery to prevent hypoglycemic episodes except
when a nil per os (NPO) status is indicated.

723
Chapter 44  Mohs Micrographic Surgery and Cutaneous Oncology
nerves. Knowledge of the anatomy will enable the cutaneous
surgeon to advise the patient pre- and perioperatively of the
risk of injury and assess for any neurological deficits present.
Nerve injury may be avoided in several ways:
• First, an injection of dilute local anesthetic or 0.9%
saline can be used to tumesce the tissues immediately
before removal of the layer and thus makes it unlikely
to inadvertently encounter vital structures including
nerves.
• Second, gentle traction upward on the tissue as it is
dissected minimizes the risk to underlying nerves. A
nerve stimulator with auditory alarm may be used in
conjunction with the dissection.
• Third, electrocoagulation-induced nerve injury can be
minimized in critical locations such as the periorbital
area by the use of Teflon-coated bipolar forceps.
Mohs micrographic surgery in the periorbital area must be
performed with care to avoid direct eye injury. For surgery
of the eyelid, the eye can be anesthetized with two drops of
local anesthetic (i.e. tetracaine) and a lubricated plastic
corneal shield can be inserted during the procedure. In cases
not directly involving the eyelid, the eyes can be protected
by taped cotton gauze pads or drapes over the eyelids. This
will protect the eyes from inadvertent injury from surgical
instruments, and prevent eye irritation by the bright operat-
ing room lights.
Unrealistic expectations, poor surgical planning, interven-
ing infection or hematoma, and other factors interfering with
healing may result in wound cosmesis that is unacceptable to
the patient. Although the main goal of Mohs micrographic
surgery is complete extirpation of the tumor, the cosmetic
and functional results are frequently of paramount impor-
tance to the patient.
Smokers have a higher rate of graft failure and delayed
wound healing. Wounds closed under sustained tension fre-
quently develop superficial necrosis, which can adversely
affect the cosmetic result. Occasionally a delayed repair is
necessary and the ultimate result may not be realized for a
year or longer, requiring patience on the part of the physician
and patient. Surgical repairs may need refinement in a series
of steps for optimal cosmesis and functionality. However,
most post-Mohs surgical wounds regain their texture, colora-
tion, and sensation eventually.
Tumors that have extended to a free anatomic margin, such
as the eyelid or lip, require additional surgical planning to
prevent functional and cosmetic impairment. Ectropion may
develop if tension is placed on the lower eyelid free margin.
Xerophthalmia and impaired vision may result when the lac-
rimal apparatus of the eye is compromised. Chondritis may
occur when the integrity of the cartilage is disturbed, par-
ticularly if perichondrium is lost and second intention healing
is used. Air flow through the naris can be compromised when
the lateral ala is unsupported after loss of cartilage, requiring
composite flap reconstruction. Consultation with other spe-
cialists may be helpful pre-, peri-, and postoperatively in
these situations.
In some situations, complete clearance of the tumor is not
achievable, even with the Mohs technique.52 Occasionally,
involvement of deep structures means that there is a great
risk of functional injury. Sometimes the layers reveal
perineural tumor or invasion into bone that cannot be cleared
without sacrificing vital structures. In recurrent tumors,
Procedural anxiety may be managed first by a caring staff
attitude and interactions with comfortable, soothing sur-
roundings, and soft, relaxing music and lighting. A surgeon’s
expression of confidence in a favorable outcome is also helpful
in alleviating anxiety. If anxiety is excessive, the patient may
be sedated with an oral or sublingual benzodiazepine, usually
diazepam at a dose of 5–10  mg 1 hour preoperatively.
Diazepam can reduce blood pressure, so careful monitoring
is necessary before further administration. Important causes
of patient anxiety are a fear of needles and pain with injec-
tion. The patient may recall biopsy-related pain, and fear a
commensurate increase in pain with the excision. Slow injec-
tions of anesthesia through a small-bore needle (30-gauge)
are critical. Advancing the needle through previously anesthe-
tized sites and injecting upon withdrawal can greatly mini-
mize discomfort.
Bleeding is the most common complication to be avoided.
Despite the use of epinephrine and meticulous electrocoagu-
lation to aid hemostasis, other measures may be required to
limit blood loss. Suture ligation of large transected blood
vessels may be necessary, especially of the superficial tempo-
ral artery, which is not infrequently encountered in excisions
on the temple. If the field is large or bleeding persists despite
appropriate hemostatic measures, bovine thrombin or hemo-
static gauze (e.g. Seasorb soft alginate dressing, Coloplast
Corp, Marietta, GA) may be helpful. Pressure dressings
between layers are important to minimize bleeding. Upon
repair of the Mohs defect, closure of underlying dead space
in layers is critical to prevent hematomas from small arteri-
oles or capillary beds. Postoperatively, pressure dressings for
24–48 hours are helpful. Dental rolls and other bolster mate-
rials placed on the skin and secured with tape augmented
with skin adhesive (e.g. Mastisol, Ferndale Laboratories, Inc,
Ferndale, MI) are particularly helpful in the mid-face and
periauricular areas.
Infection may develop in the setting of any cutaneous
surgery. Tumors treated with Mohs surgery that have required
multiple layers to clear or prolonged exposed periods of time
may have an increased risk of infection. The risk of infection
is also increased if there is abraded or crusted skin and in
immunocompromised patients. Patients who allow their
wounds to desiccate or lack diligence in their postoperative
care are also more likely to develop an infection. Risk can be
minimized by meticulous surgical technique, including the
removal of hair from the wound, preferably by clipping pre-
operatively, and ensuring appropriate eversion of skin edges
and minimizing dead space. Patients who have a tendency to
develop infections postoperatively can be placed on a course
of antibiotics, but antibiotics are otherwise not routinely
administered prophylactically except for subacute bacterial
endocarditis prophylaxis. Total hip and knee replacement
patients may need prophylaxis during the initial 90-day
inflammatory phase. In our practice, we consult with the
orthopedic surgeon in this group of patients.
Wound necrosis may occur when the repair places the
wound under significant tension. Poor flap design resulting in
vascular compromise may result in wound edge necrosis,
requiring a portion to heal by second intention. Full-thickness
or split-thickness grafts may be lost, again resulting in second
intention healing. Sharp wound debridement may be required
in some situations where eschar covers the wound.
Large or recurrent tumors in high-risk locations may be so
deeply invasive that they may involve cutaneous and sensory

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Part 4  Special Procedures
Cryotherapy with liquid nitrogen is optimally performed
with a thermocouple to ensure lesional tissue temperature is
−50°C or below to ensure adequate cellular destruction.
Alternatively, clinical assessment of halo thaw times using
one of a variety of methods can be used – for an extensive
bibliography, see the American Academy of Dermatology
Committee on Guidelines of Care for Cryosurgery.56
Radiation therapy, when used as a primary modality of
treatment, is limited in use because it is often more expensive
and inconvenient, and can induce subsequent secondary
malignancies within the treatment field.
Greenway et al.2 demonstrated complete clearance of
basal cell carcinoma in eight patients with recombinant
interferon-α-2, using a regimen of injections three times per
week for 3 weeks without any significant side effects. Intra­
lesional interferon-α is efficacious in basal cell carcinoma
through the upregulation of expression of CD95 on tumor
cells, which induces apoptosis, recruitment of CD4+ T cells,
and enhanced secretion of cytokines such as interferon-γ and
interleukin-2.57
Imiquimod, through the upregulation of interferon-α, has
emerged as a novel primary treatment for basal cell carci-
noma, and it is currently approved for the treatment of super-
ficial basal cell carcinoma. It offers the dual convenience of
patient self-treatment using a topical formulation. It appears
that once-daily topical application for 12 weeks is most effi-
cacious.58 However, the response rate can vary, with a com-
plete response rate of 87% for superficial basal cell carcinoma,
but only 65% for more invasive types.59 At least one author
(Greenway) is concerned that both physicians and patients
may overuse new topical therapies, resulting in an increase of
recurrent and residual tumors presenting at a later date.
Mohs surgery may be reserved for those basal cell carcino-
mas exhibiting one or more indications of biologic aggressive-
ness. It can also be used for the basal cell nevus syndrome,60
in which a multiplicity of frequently aggressive tumors creates
the need for conservation of the greatest possible amount of
normal tissue.
Histologic forms of basal cell carcinoma
The most common histologic forms of basal cell carcinoma
are superficial, nodular, ulcerative, metatypical, morphea-
form, and infiltrative.
A superficial basal cell carcinoma appears as an erythema-
tous scaly plaque with well-defined borders, and histologically
is composed of small nests of cells with oval and basophilic
nuclei with scant cytoplasm along the basal layer of the epi-
dermis. A nodular basal cell carcinoma appears as a translu-
cent papule with telangiectasias, and histologically is composed
of basaloid cells with peripheral palisading of the nuclei and
stromal proliferation. An ulcerated basal cell carcinoma
appears as a nodular lesion with central ulceration, and histo-
logically contains foci of epidermal ulceration. Metatypical
basal cell carcinoma is not distinctive clinically, but histologi-
cally contains features of basal cell carcinoma in addition to
foci of squamous differentiation resembling squamous cell
carcinoma. Morpheaform basal cell carcinoma appears as a
yellow–red firm plaque and histologically contains tumor
nests and cords enmeshed in a fibrous, sclerotic stroma. Infil-
trative basal cell carcinoma is not distinctive clinically, but
histologically contains islands of tumor cells with a spiked
appearance in narrow cords within a hyalinized stroma.
unpredictable growth patterns may occur as a result of fibro-
sis from previous radiation or excision. Tumor may spread far
beyond the original site of recurrence along areas of previous
surgery that were undermined for previously used flaps or
grafts, and on rare occasions may be too extensive to clear
completely. In these situations, postoperative radiation
therapy is indicated to enhance local cure rates.53 On occa-
sion, a combined approach is chosen after discussion with the
patient midway during the procedure (i.e. between layers).
A multidisciplinary approach is helpful in the management of
these advanced malignancies.
Radiation therapy can have a primary or adjunctive role in
cutaneous malignancy. The Mohs surgeon should be familiar
with its capabilities and limitations. Radiation therapy has
advanced greatly because of the wide availability of linear
accelerators that generate electrons with energy that can be
varied so that the physician can treat to different depths.
Customization of the beam delivered to the patient through
the use of cerrobend cutouts, blocks, contoured aquaplast
masks, and lead shielding, and refined dose fractionation
schemes that optimize treatment and limit side effects have
also advanced the field. Electron beam radiation penetrates
deeply into the tissue, in contrast to the superficial X-ray
treatments of the past with their diffuse energy scattering
and unpredictable, superficial tissue penetration.
 CUTANEOUS ONCOLOGY
Mohs micrographic surgery has been used most widely and
extensively in the extirpation of basal cell and squamous cell
carcinomas using the fresh tissue technique. More recently,
its use has expanded to include the removal of many other
tumor types that have proved challenging to control locally.
In most situations, this has involved a permanent tissue tech-
nique involving the Mohs technique with slides being gener-
ated using formalin fixation. Mohs surgery thus modified by
the use of tangential, formalin-fixed, paraffin-embedded his-
tologic specimens ensures accurate interpretation of histo-
logic specimens while maintaining the tissue conservation of
the Mohs technique.54 There is a resultant delay in the repair,
but for many of these tumor types the wait is beneficial for
patients, with higher cure rates than with traditional surgical
techniques. The rest of this chapter discusses selected tumor
types and how Mohs surgery can be used in their treatment.
Basal cell carcinoma
Basal cell carcinoma is the most common malignancy. Tumors
are most frequent on the head and neck, where they are more
likely to be biologically aggressive and invade vital structures.
Brodkin et al.55 found that of 840 basal cell carcinomas
studied, over 90% were on the head and neck. The biologic
behavior of a basal cell carcinoma depends on its histologic
subtype and clinical features, including its precise anatomic
location, size, and duration, and whether it is primary or
recurrent. All these factors must be taken into consideration
when employing a particular treatment.
Non-surgical treatment
Non-surgical treatments of basal cell carcinoma include cryo-
therapy, radiation therapy, and immunotherapy with topical
and intralesional interferon and topical imiquimod.

725
Chapter 44  Mohs Micrographic Surgery and Cutaneous Oncology
margins difficult clinically and histologically.
A large prospective randomized controlled trial comparing
the effectiveness of Mohs micrographic surgery and surgical
excision in the treatment of primary and recurrent facial basal
cell carcinoma with 5-year follow up revealed a significantly
lower number of recurrences in those cases treated with
Mohs micrographic surgery (2.4% vs 12.1% for surgical exci-
sion). In terms of primary facial basal cell carcinomas, the
recurrence rate was 2.1% for cases treated with Mohs micro-
graphic surgery compared with 4.4% for those treated with
surgical excision.66
Basosquamous carcinomas (metatypical basal cell carci-
noma), because of their nature, may require special consid-
eration. An Australian prospective multicenter case series
reported on the effectiveness of Mohs micrographic surgery
for basosquamous carcinoma: the local recurrence rate was
4.1% after 5 years for those patients with basosquamous
carcinoma treated with Mohs micrographic surgery, which is
lower than the range of 12–45% reported for wide excision.67
Metastatic basal cell carcinoma occurs in less than 0.5% of
cases. The mean time from the appearance of the primary
basal cell carcinoma of the skin and distant metastasis is 9
years.68 Risk factors include tumor invasion into cartilage,
bone, skeletal muscle, or parotid gland, previous radiation
therapy, and previous treatment with any modality.68 Ana-
tomic locations on the face, scalp, and genitalia are at higher
risk; the ear is the most common site from which metastatic
spread occurs.68 The histologic subtype is not correlated with
metastatic diathesis. Metastasis can occur both hematoge-
nously (to lungs, bone, and skin) and through lymphatics.
Treatment options include combinations of surgery, radia-
tion, and chemotherapy; of the latter, cisplatin is the most
effective agent.69
Squamous cell carcinoma
Squamous cell carcinoma is the second most common cutane-
ous malignancy. It can be treated with multiple modalities,
including surgery, cryotherapy, radiation therapy, and intra­
lesional interferon.
Squamous cell carcinomas commonly present as erythema-
tous scaly plaques in sun-damaged locations. They are also
seen in areas of previous burn scar or irradiation. The bio-
logical behavior depends on many factors, including histologic
subtype, anatomic location, duration, previous injury, previ-
ous therapy, and immune status of the patient.
Histologically, squamous cell carcinomas consist of irregu-
lar proliferating nests of neoplastic keratinocytes arising from
the epidermis, with nuclear hyperchromasia, increased
mitotic activity, cytoplasmic eosinophilia, and varying degrees
of nuclear atypia. Biologically aggressive subtypes include
cystic squamous cell carcinoma, adenoid squamous cell car-
cinoma, clear cell carcinoma, and spindle cell carcinoma.
Squamous cell carcinoma presenting as verrucous plaques is
referred to as verrucous carcinoma, and demonstrates little
epithelial atypia. Bowen’s disease (squamous cell carcinoma
in situ) presents clinically as ill-defined scaly red patches and
demonstrates abnormal keratinocytes confined to the epider-
mis. Cutaneous horns or areas of hyperkeratusis may be on
the surface of squamous cell carcinoma. Squamous cell car-
cinomas may arise in burns, scars, or other injuries. Tumors
arising in immunocompromised patients tend to be more
aggressive and have higher metastatic rates.
The more commonly aggressive subtypes of basal cell car-
cinoma are the ulcerative, metatypical, morpheaform, and
infiltrative forms. Recurrent basal cell carcinomas, even if
originally of a less aggressive subtype, tend to exhibit one or
more of these features. These tumors are frequently found
to extend well beyond their clinical margins when on the
head and neck. Lateral spread of subclinical disease may be
several centimeters beyond that visualized on gross examina-
tion. The tumors have an affinity for fascial planes and other
natural barriers to tumor growth. They can penetrate to the
perichondrium and periosteum and then spread along them
widely. Tumor invasion of nerves may also occur, with tumor
cells either spreading along the perineurium or directly invad-
ing the endoneurium. In 1% of basal cell carcinomas,61
perineural spread may be several centimeters distant from
any involved soft tissues. Perineural spread most commonly
involves the supraorbital, infraorbital, and mental nerves.
Neurotropic basal cell carcinomas may present with symp-
toms of pain, paresthesias, or motor loss in the affected nerve
distribution.62 Radiation therapy may be considered as an
adjunctive therapy in these situations.
Clinical features
The clinical features of a basal cell carcinoma accurately
predict its biological behavior. Many patients are unable to
recall or discern when their tumors appeared, making cor-
relation of tumor duration and invasion difficult. However,
lesions present for longer periods of time do have a greater
chance for deeper invasion into nerves, muscle, cartilage, and
bone, and their extirpation can be extensive. In a series of
434 Mohs cases, tumors with perineural invasion required an
average of 5.3 Mohs layers for clearance, in contrast to those
without perineural invasion, which required only 2.2.62
Tumors with aggressive histology require more Mohs layers
to achieve tumor-free margins.62 The size of the tumor is also
critical in predicting tumor extent. In a large series of 1131
Mohs cases, the most important indicator of extensive sub-
clinical spread in addition to aggressive histology was preop-
erative size greater than 2.5 cm in diameter.63 These larger
tumors require a wider surgical margin. For tumors with a
diameter less than 2 cm, a minimum margin of 4 mm would
be expected to clear the tumor in more than 95% of cases.64
Tumor size is also important for prognosis. In the largest
series to date, 5-year cure rates after Mohs surgery for tumors
involving the nose decreased commensurately with increased
lesion size – for basal cell carcinomas under 1 cm in diameter,
99.9%; for tumors between 1 and 2 cm in diameter, 99.3%;
for tumors between 2 and 3 cm in diameter, 98.3%, and for
tumors greater than 3 cm in diameter, 84.3%.1
Larger tumors in many cases tend to be recurrent tumors,
with discontinuity of tumor foci. They may contain interven-
ing scar or radiation changes, which interrupt tumor growth
patterns. Recurrent tumors have a much lower cure rate with
any form of therapy. Mohs reported a recurrence rate of 7.9%
in a large series of recurrent basal cell carcinomas.1 Robins
et al.65 reported a recurrence rate of 3.4% in a slightly larger
series. Recurrences after radiation treatment can be particu-
larly challenging. These tumors, originally with less aggressive
histologic features, frequently have morpheaform or metatyp-
ical patterns after radiation therapy. In addition, the radiation
therapy itself may induce fibrosis and scar formation, enmesh-
ing individual tumor cells and making interpretation of the

726
Part 4  Special Procedures
oic acid and interferon-α-2a have been used with a similar
response rate, but dose-related side effects have significantly
limited therapy.75 An interdisciplinary approach in caring
for these patients is required. For advanced head and neck
squamous cell carcinoma (which may have a cutaneous
origin), cetuximab is a monoclonal antibody inhibitor of
epidermal growth factor receptor that has been shown to
have an effect both alone and in combination with radiation.
This effect of combination therapy includes a decreased
risk of loco-regional progression by 32% and a decreased risk
of death by 26%, thus improving progression-free and overall
survival.76,77 Induction chemotherapy with a three-drug re­
gimen (docetaxel, cisplatin, and fluorouracil) offered an
increased median time survival for locally advanced squamous
cell carcinoma of the head and neck when combined with
concurrent chemoradiotherapy.78
Actinic keratoses are precancerous epidermal lesions that
are found most frequently on sun-exposed areas. Squamous
cell carcinoma may arise within these lesions as the atypical
squamous proliferation invades into the dermis, and effective
treatment is frequently sought for multiple lesions concur-
rently. Currently, controversy exists regarding the nomencla-
ture for these lesions, because some feel they should be called
stage 0 squamous cell carcinoma.79–88 Surgical approaches
include curettage alone, curettage followed by light cautery,
and cryotherapy. A variety of non-surgical modalities of treat-
ment have been used, including topical immune response
modifiers, and photodynamic therapy. A chemopreventive
strategy was developed in the 1970s using topical 5-fluoro­
uracil after reports that actinic keratoses cleared in patients
on intravenous 5-fluorouracil chemotherapy for internal
malignancies.89 There are currently three topical preparations
widely available – 5% fluorouracil cream, 1% fluorouracil
cream, and 0.5% fluorouracil cream in a microsphere prepara-
tion. Comparable in efficacy, they cause varying degrees of
irritation of perilesional skin that can greatly limit their use.
Imiquimod (Aldara, Graceway Pharmaceuticals, Bristol, TN)
has also been used for the destruction of actinic keratoses,
using a two to three times per week application regimen over
several months with rest periods according to patient response,
but this is also limited by inflammatory response.90 Photody-
namic therapy has shown promise for treating actinic kera-
toses.91 Following the administration of a photosensitizer
topically, it is selectively accumulated and retained in cancer-
ous lesions. Delta-aminolevulinic acid (Levulan Kerastick,
DUSA Pharmaceuticals, Inc, Wilmington, MA), a precursor
of protoporphyrin IX, is most commonly used as the photo-
sensitizer. It is inactive until irradiated by light. Following
administration of light of the appropriate wavelength in the
absorption spectrum of the photosensitizer, cellular destruc-
tion occurs through the generation of toxic oxygen and other
reactive species. This treatment is limited by pain, cost, con-
venience, and photosensitivity issues, but has demonstrated
efficacy and is widely available.
Melanoma
Malignant melanoma, consisting of nests of atypical melano-
cytes with abnormal morphology, should be considered a
systemic disease and remains a serious life-threatening entity.
Patients may benefit from a multispecialty evaluation involv-
ing a dermatologic and/or Mohs surgeon, medical oncologist,
and surgical oncologist. The American Joint Commission on
Squamous cell carcinomas that are more likely to recur or
metastasize should be considered for treatment with Mohs
micrographic surgery. Preoperatively or concurrently, senti-
nel node dissection can be performed for the lesions at par-
ticular risk for metastatic spread, although most practitioners
would consider this additional step to be a research tool and
not a standard of care. There is an increased risk for meta-
static spread for lesions that are histologically moderately to
poorly differentiated, and for facial lesions, particularly
temple, nose, lip, periocular, or periauricular lesions. Lesions
that are larger than 2 cm in diameter may be more prone to
recurrence and metastasis. Squamous cell carcinomas occur-
ring in burn or irradiation scars are also more likely to recur
or metastasize, and squamous cell carcinomas demonstrating
perineural invasion histologically have an increased risk of
recurrence.69 In our experience, 50% of metastatic cases of
squamous cell carcinoma showed perineural spread. There is
a risk of neurotropic spread by lesions overlying large sensory
or motor nerves, such as the supraorbital, infraorbital, mental,
and facial nerve branches. Perineural invasion has been
reported in only 11% of squamous cell carcinomas less than
2.5 cm in diameter, but in 64% of those greater than or equal
to 2.5 cm.70 Patients who are immunocompromised tend to
have more extensive tumor spread, as do those whose tumors
are recurrent. Currently recommended surgical margins for
primary cutaneous squamous cell carcinoma are from 4 to
6 mm, depending on the risks delineated above.71 Mucosal
lesions may have extensive subclinical spread; in one study,
for 70% of lesions there was microscopically identified tumor
1 cm away from the initial tumor’s visible border.17 As for
basal cell carcinoma, tumor spreads to fascial planes and can
involve perichondrium and cartilage, and periosteum and
bone.
Mohs micrographic surgery for recurrent squamous cell
carcinoma can provide local cure rates of 94% or greater.72
Mohs surgery may also be useful in the treatment of less
aggressive forms of disease, including Bowen’s disease and
verrucous carcinoma, in which tumor-free margins are impor-
tant to prevent recurrence but metastatic rates are very low.
Erythroplasia of Queyrat (squamous cell carcinoma in situ
involving the glans penis) and bowenoid papulosis (squamous
cell carcinoma in situ of the penis) may be treated effectively
with a variety of modalities, but Mohs surgery may provide
the tissue conservation advantage required to preserve vital
structures. Mohs surgery for verrucous carcinoma involving
the genital and plantar surfaces improves cure rates to as high
as 98% compared to 80% for standard surgical excision while
avoiding radical surgery.73 Radiation therapy is contraindi-
cated for verrucous carcinoma because of its propensity to
become more aggressive from this treatment.
Therapy for advanced and metastatic squamous cell carci-
noma can be difficult. At our institution, a significant propor-
tion of metastatic neck disease arises from squamous cell
carcinoma of the skin. Neck dissection can result in significant
morbidity for the patient. Surgery and radiation in a com-
bined approach is favored in many cases. In advanced disease,
systemic chemotherapy has been used. Sadek et al.74 reported
the use of combination chemotherapy consisting of cisplatin,
5-fluorouracil, and bleomycin. In 14 patients, all with locally
recurrent squamous cell carcinoma, and nine patients with
nodal involvement, an overall response rate of 79% was
achieved. Doxorubicin, retinoids, and interferon have also
been used in metastatic disease. Combinations of 13-cis retin-

727
Chapter 44  Mohs Micrographic Surgery and Cutaneous Oncology
Cancer (AJCC) issued newly revised guidelines for the
staging of melanoma in 2003, placing greater emphasis on
Breslow depth of spread into the dermis, presence or absence
of ulceration in the epidermis, number of involved lymph
nodes, nodal macro- or micrometastases, metastases, and
measurement of serum lactate dehydrogenase (LDH).92,93
In the upcoming 7th edition of the AJCC staging system,
the measurement of mitotic rate activity/index will be
given increased emphasis, replacing the value of the former
Clarke’s Level measurement in prognostic staging (personal
communication).94,95 Melanoma-in-situ and lentigo maligna
lesions have atypical melanocytes confined to the epidermis,
and thus are not assigned a Breslow depth. Several variants
of invasive melanoma have been described, including super-
ficial spreading, nodular, desmoplastic, amelanotic, and
acrolentiginous.
Surgical excision with clear margins remains the predomi-
nant treatment modality for cutaneous melanoma. Melanoma
patients should be staged by assessing for metastatic disease
using chest radiography, and CT or MRI scanning when
appropriate. Additionally, the recently available positron
emission tomography (PET) scan is being used at some
centers for staging and follow up. By imaging glucose metab-
olism, PET pinpoints areas of increased metabolic activity –
an indicator highly correlated with malignant tissue growth.
Before surgical extirpation of a melanoma, additional
staging information may be obtained by using the sentinel
node biopsy technique. Rapidly increasing in use and availa-
bility, the technique provides additional prognostic informa-
tion for the patient, but has not yet demonstrated any survival
benefit. Because the incidence of nodal metastasis greatly
increases with Breslow depth, it is normally used for those
invasive melanomas intermediate in depth, between 1 and
4 mm. The technique relies on the theory that the sentinel
lymph nodes are the first lymph nodes that drain a primary
cancer site. Thus, a sentinel lymph node biopsy would be
expected to determine the overall status of the regional
lymph nodes. The location of the sentinel node is predictable,
but not invariable, and can be located contralateral to the
tumor. Lymphoscintigraphy using technetium-99 radiola-
beled sulfur colloid injected perilesionally enables precise
localization of the sentinel node(s) through the use of a hand-
held gamma radiation probe. Additionally, a vital blue dye
injected perilesionally provides a visual guide because it is
taken up by the lymphatics within minutes. Lymph node
excision and examination with special stains (i.e. S-100) is
then performed in lieu of frozen section to decrease false-
negative rates (Figs 44.15–44.18). If positive for nodal
disease, a complete nodal basin excision would ordinarily be
performed. The technique, usually performed under general
anesthesia, has improved the staging accuracy of melanoma.96
However, it does require additional steps, can lead to surgical
delays, and does not always yield a sentinel node. Lymphatic
drainage of the head and neck is particularly complex with
multiple drainage patterns. Melanomas of the head and neck
are thus technically more difficult to evaluate using sentinel
node technology, particularly if the site is directly overlying
a nodal basin. At our institution, sentinel lymph node dissec-
tion for head and neck lesions is performed by a head and
neck surgeon, and for trunk and extremity lesions by a general
surgeon, who often work closely together.
Over the years, as survival data have become refined and
focused, recommendations for the margins for width of exci-
sion have been steadily reduced from 5 cm to between 1 and
3  cm, depending on Breslow depth, with only 5  mm for
melanoma-in-situ.97,98 Nevertheless, Mohs micrographic
surgery can offer a means of achieving clear margins while
sparing normal tissue around critical anatomic structures.
Reported rates of local control are comparable to standard
Figure 44.15  A hand-held gamma probe (arrow) registers
counts in vivo. The lymph node of interest usually has focal
significantly elevated counts that register with application of the
gamma probe directly to tissue. In addition, the node should be
visually blue, having taken up the vital blue dye injected earlier.
Negative control (background counts) can be obtained from a
distant site, while the lesion injection site is the positive control
(maximum counts).
A
C-Trak probe
B
Figure 44.16  (A) C-Trak Surgical Guidance System (Care-Wise Medical Products Corporation, Morgan Hill, CA). (B) Probe.

728
Part 4  Special Procedures
the obvious invasive portion of the melanoma. Interpretation
of the degree of atypia of these melanocytes is difficult and
subjective. There are published reports of complete correla-
tion between frozen section tissue margins and permanent
section controls;100 however, for melanoma-in-situ lesions at
least, frozen sections alone may be insufficient for margin
control.101
Cutaneous melanomas of the head and neck may offer
special challenges and may be candidates for Mohs micro-
graphic surgery. In one review of 625 patients, 331 of those
had melanoma-in-situ with a recurrence rate of 0.3%. Inva-
sive cases (294) also had a 0.3% recurrence rate. Mean follow
up was 58 months, demonstrating a significantly lower metas-
tasis rate for both in-situ and invasive disease as compared to
conventional surgery.102
The use of melanocyte-specific immunohistochemical
stains can greatly enhance the accuracy of margin interpreta-
tion.103 Several immunostains that can be used on frozen
sections have been studied extensively, including MART-1,
S-100, MEL-5, Melan-A (A-103), and HMB-45.103 Albertini
et al.34 found MART-1 to be superior in sensitivity to both
HMB-45 and S-100 for Mohs surgery with the fresh tissue
technique. Zalla et al.103 found Melan-A to be superior in
clarity and ease of interpretation of specimens. Positive and
negative control specimens from the tumor and distant skin
can be used for comparison of staining patterns.103 Finally, it
is critical to review vertical sections of the main portion of
the specimen, assessing the presence of and depth of invasion,
because this can change the diagnosis (i.e. from melanoma-
in-situ to melanoma) and staging of the patient. Some pro-
ponents follow in the footsteps of Dr Mohs himself and have
found that chemosurgery can be an effective treatment for
melanoma,104 an approach that appears to have an immuno-
logic basis behind it.105
Advanced stages of melanoma or unresectable lesions can
benefit from cryotherapy, radiation therapy, or immuno-
therapy, all of which have significant limitations in their effi-
cacy. Topical imiquimod, acting presumably through its
effects on interferon-α, has recently been reported to result
in clearance of lentigo maligna106 and cutaneous metastases
of melanoma,107 but insufficient data preclude its recommen-
dation. Intravenous and subcutaneously injected interferon-α
regimens, vaccines, and other immunomodulatory treatments
have been used. There is now overwhelming evidence that
high-dose (20 million units/m2 intravenously for 4 weeks fol-
lowed by 10 million units/m2 subcutaneously three times
weekly for 48 weeks) interferon-α improves relapse-free sur-
vival after surgery for high-risk melanoma,108 and strong evi-
dence that it improves overall survival in a select subset of
patients.109 Lower doses of interferon for longer durations,
biochemotherapy (concurrent interleukin-2 and interferon-
α-2b), and vaccines (particularly dendritic cell-based vac-
cines) are undergoing trials in the treatment of advanced-stage
melanoma. For a further discussion of melanoma, see Chapter
43. In hereditary melanoma, a mutation in the CDKN2A
gene may be a factor in a number of cases.110
Merkel cell carcinoma
Mohs micrographic surgery has been used successfully to
treat Merkel cell carcinoma, a neuroendocrine tumor of the
skin. Clinically, Merkel cell carcinoma is manifest as a skin-
colored or bluish nodular lesion that is firm to palpation,
Figure 44.17  Tissue removed during axillary sentinel lymph
node dissection. The surgeon confirms the presence of the
node visually and by measuring counts with the gamma probe.
Figure 44.18  S-100 immunostain used on the sentinel node.
Note the islands of S-100-positive cells within lymphoid
aggregates that may have been missed with routine frozen
sections not using immunostains.
margin excision. However, the margins required to clear the
tumors in 95% of cases have been reported to be 15 mm for
melanoma-in-situ and 26  mm for invasive melanomas.99
These findings suggest that margins wider than those cur-
rently recommended may be required to ensure tumor clear-
ance. Melanoma treatment with this technique requires the
Mohs surgeon to be either expert in the histologic interpreta-
tion of melanocytic lesions or to adopt the technique to
directly involve the dermatopathologist or pathologist in their
interpretation. Clinical photographs of gross lesions and sec-
tioned tissue may be helpful in orientation. Excellent techni-
cal support is also required, with additional resources to
section tissue with the Mohs technique compared to conven-
tional excision.
Histological interpretation of malignant melanoma with the
fresh technique may be problematic and has been the source
of some controversy. While assessing histologic margins, atyp-
ical single melanocytes may be present at the periphery of

729
Chapter 44  Mohs Micrographic Surgery and Cutaneous Oncology
Mohs surgery has been used to address the subclinical
contiguous growth pattern of dermatofibrosarcoma protuber-
ans with micrographically controlled excision.122 Tumors less
than 2 cm in diameter can be cleared with a 1.5-cm surgical
margin, whereas larger tumors can be cleared with a 2.5-cm
surgical margin.123 In one review, 221 cases had been treated
with Mohs surgery, with only five (2.3%) recurrences.124 Sub-
sequently, a later review revealed a recurrence rate of 1.3%
(6 of the 463 cases reported worldwide).120 Mohs surgery is
particularly helpful in conjunction with special immunostains.
The presence of scattered dermal spindle cells in the dermis
of normal skin makes it difficult to differentiate residual
tumor from normal dermis in Mohs layers.125 Dermatofibro-
sarcoma protuberans stains positively with CD34,124 and this
can be used to achieve greater accuracy of margin control
when used in conjunction with either frozen or permanent
section Mohs surgery.
Mohs surgery is the treatment of choice for dermatofibro-
sarcoma protuberans; in a recent review of our cases at
Scripps Clinic over the past 20 plus years, 25 patients treated
with Mohs micrographic surgery had no recurrences (100%
cure rate) with a follow-up time of 101 months, with perma-
nent section technique, with postoperative defect sizes 27%
less than those from wide local excision.126 If immunostains
are unavailable, a biopsy of normal skin can be useful as a
control to improve histologic accuracy for comparison pur-
poses.125 A selective platelet-derived growth factor receptor
(PDGFR) tyrosine kinase inhibitor, imatinib, may induce
regression in patients with unresectable or metastatic der-
matofibrosarcoma protuberans and also has been used for
partial remission.120
Atypical fibroxanthoma
Atypical fibroxanthoma usually presents as an ulcerated, ery-
thematous nodule or plaque on heavily actinically damaged
skin of the head and neck in older men. This fibrohistiocytic
tumor with bizarre histology has a favorable prognosis, and
metastases are rare. When the tumor does spread, it generally
spreads through regional lymphatics. Treatment consists of
wide surgical excision with a 1-cm margin. Mohs surgery may
be used for large, recurrent tumors or in areas where tissue
conservation is important,127 and can improve cure rates. In
a series of five patients with atypical fibroxanthoma treated
by Mohs surgery, there were no local recurrences and no
metastases after a mean follow-up period of 3 years.128
Malignant fibrous histiocytoma
Malignant fibrous histiocytoma, a deeper and more invasive
tumor with some shared features of atypical fibroxanthoma,
can also be treated successfully with Mohs micrographic
surgery. It is a soft tissue sarcoma with a less favorable prog-
nosis than atypical fibroxanthoma. Mohs surgery can improve
the cure rate. In a series of 17 patients with malignant fibrous
histiocytoma treated by Mohs surgery, there was only one
local recurrence and no metastatic disease after a mean fol-
low-up period of 3 years.128 Special stains may be of value
with CD74 positive in 90% of patients.129
Microcystic adnexal carcinoma and other
sweat gland neoplasms
Varying in clinical presentation from a flesh-colored papule
to a firm subcutaneous nodule, microcystic adnexal carci-
which most commonly occurs on the head and neck of elderly
men. Histologically, monomorphous sheets of basaloid cells
are seen. The pathogenesis in at least some cases has been
linked to a previously unknown virus, now named the Merkel
cell polyomavirus, with viral DNA integrated into the tumor
genome.111 This is the first example of a polyomavirus genome
naturally integrated into cellular DNA.112
Merkel cell carcinoma is an aggressive tumor with reported
local recurrence rates of 30%, regional node involvement
rates of up to 50%, and metastatic rates of 40%.113 Survival
rates statistically correlate with nodal status. Because of high
local recurrence rates after excision, a 3-cm margin is cur-
rently recommended for the primary excision of this tumor,
but because the tumor occurs on the head and neck in 60%
of individuals, this is not always possible without sacrificing
vital structures. Mohs surgery successfully limited the
required margin to 1.5 cm (1.2 cm on the face and 1.9 cm
on the extremities) in one study.114
Although the optimal treatment of Merkel cell carcinoma
is unknown, radiation therapy is a commonly used adjunct to
surgery to improve local control, with several series reporting
improved overall survival, relapse-free survival, and disease-
free survival with its use.113,115 The largest series to date,
consisting of 45 cases treated with Mohs surgery with and
without adjuvant radiation, was unable to find such improve-
ment.116 Adjuvant radiation is recommended for large, recur-
rent, or incompletely excised tumors which are at high risk
for recurrence. In our institution, we have found a combined
approach of Mohs surgery and radiation oncology consulta-
tion for adjunctive treatment helpful. Brissett et al., based on
a retrospective analysis of 22 cases, found that wide local
excision and dissection of the lymphatic drainage basin pro-
vided the best overall survivial.117 Adjuvant chemotherapy has
been used for metastatic disease, but no chemotherapy pro-
tocol has been shown to improve survival. Recent advances
in sentinel lymph node technology have been applied to
Merkel cell carcinoma, using sentinel lymph node dissection
and Mohs surgery simultaneously.118 Bleomycin, via direct
antiviral effectiveness, demonstrated no evidence of recur-
rence or metastasis after 5 years in a series of four patients
with localized disease treated intralesionaly.119
Dermatofibrosarcoma protuberans
Dermatofibrosarcoma protuberans is characteristically a slow-
growing, locally aggressive malignant tumor of the skin with
a characteristic spindle cell morphology histologically. It is
most common on the trunk, upper thighs, and groin, fre-
quently consists of multiple discrete nodular lesions, and
clinically may resemble a keloid. Although well-circum-
scribed, dermatofibrosarcoma protuberans can extend widely
from its base. Histologically it frequently invades the fat, and
tumor-free margins are difficult to obtain with certainty
because of its resemblance to normal fibroblasts on hema-
toxylin and eosin staining. Recurrence rates after wide exci-
sion can be as high as 60%, but years may pass before they
are noted because of the tumor’s slow growth. In a recent
review, recurrences after wide local excision were noted to
be in the range of 20.7% (288 of the 1394 cases reported
worldwide).120 Wide local excision plus radiation therapy may
offer lower recurrence rates. In more than 90% of patients,
specific chromosomal aberration is described involving chro-
mosomes 17 and 22.121 Metastases are rare.

730
Part 4  Special Procedures
biopsies to further delineate tumor involvement.139 The value
of sentinel node biopsy has not been established, owing in
part to possible false-negative findings in the difficult head
and neck area as compared to other locations.140
Extramammary Paget’s disease
Extramammary Paget’s disease is a rare cutaneous malignancy
characterized by scaly red patches that are sometimes pruritic
in apocrine-bearing areas such as the axillae and groin. It may
be multifocal and usually extends beyond clinically apparent
margins. Wide excision is followed by a high recurrence rate
as a result of subclinical tumor spread. Mohs surgery has been
successfully used for extensive cases of extramammary
Paget’s disease and tissue sparing of critical anatomic struc-
tures can be achieved.141 Radical excision is not required for
most cases, but monitoring for recurrence is important. In
one series, two of six cases treated with Mohs surgery recurred
locally.142 Scouting biopsies of multiple surrounding areas
may offer valuable information prior to Mohs micrographic
surgery.143 A larger case series demonstrated recurrence rates
of 16% in primary lesions and 50% in recurrent lesions treated
with Mohs micrographic surgery, but felt this to be the best
treatment because of the extensive subclinical spread and
poor recurrence rates with standard surgical excision.144
Recently, imiquimod has been shown to have potential
value in the treatment of this condition.145,146 Consideration
has also been noted for advocating imiquimod as an initial
treatment, followed by surgery if complete resolution was not
obtained.147
Angiosarcoma
Angiosarcoma is a rare, highly aggressive malignant neoplasm
characterized by solitary or multicentric violaceous papules
or plaques on the head and neck and has a poor prognosis.
Surgical management for lesions less than 10 cm in diameter
is the treatment of choice.148 Wide excision results in a high
recurrence rate, and treatment is challenging because of
extensive subclinical spread beyond the tumor’s visible
margin. Local control can be achieved with peripheral biop-
sies to assess tumor extent and Mohs surgery followed by
adjunctive radiation therapy.149 Newer novel therapeutic
agents such as paclitaxel, avastin, and taxotere may offer clear
palliative effects but prolonged survival with angiosarcoma is
rare. Avastin may play an important role because of its inhibi-
tion of the biologic activity of vascular endothelial growth
factor. Taxotere may offer some promise in treating patients
resistant to conventional therapy.150,151
Other benign and malignant neoplasms
Mohs micrographic surgery is playing an increasingly impor-
tant role in the surgical management of a wide variety of
cutaneous tumors. Rarely encountered tumors such as apo-
crine adenocarcinoma,152 malignant cylindroma,153 syringoid
eccrine carcinoma,154 adenoid cystic carcinoma,155 leiomyosar­
coma,156 and malignant trichoepithelioma157 have been suc-
cessfully treated with the Mohs technique. More recent
reports of its use in erosive adenomatosis of the nipple,158
infantile digital fibroma,159 spiradenocarcinoma,160 rhabdomyo­
sarcoma,161 and granular cell tumor35 illustrate its versatile
application to virtually any neoplasm with contiguous growth
characteristics. Clinicians increasingly recognize and value its
utility for patients in the management of their malignancies.
noma is a rare, locally aggressive malignant tumor that most
commonly occurs on the upper lip in middle-aged women.130
Previous radiation therapy may be an important predisposing
factor. The tumor infiltrates deeply by local invasion within
the dermis and subcutaneous tissues, and frequently invades
skeletal muscle; perineural invasion may be seen. Metastases
were noted in seven of 300 reported cases in the world lit-
erature (2.1% metastatic rate).131 Histologically, microcystic
adnexal carcinoma can resemble basal cell carcinoma and
adnexal neoplasms such as desmoplastic trichoepithelioma
and syringoma. It contains ductal and glandular structures,
keratin cysts, follicular structures, and a desmoplastic stroma.
Superficial shave biopsy may not be diagnostic, with many of
these features found deep in the dermis.
Microcystic adnexal carcinoma has a high local recurrence
rate with standard surgical excision, whereas Mohs surgery
has been used successfully. The local recurrence rate by
standard excision is almost 50%, whereas that with Mohs
surgery is almost 10%.107 In two recent series of a total of
24 cases with a mean follow-up of 5 years, there were no
recurrences.132,133
Mohs surgery has also been advocated for the treatment of
primary eccrine adenocarcinoma of the skin. Also known as
eccrine porocarcinoma, this rare malignant tumor of the
eccrine sweat gland displays a tendency for local recurrence,
and regional lymphatic spread may occur. The tumor is
radioresistant, and skip areas may occur between the tumor
nodules.
Primary mucinous carcinoma is another rare sweat gland
malignancy with locally aggressive behavior that frequently
involves the face, for which the Mohs technique results in an
improved cure rate and tissue conservation.134
Mohs surgery has also been used for benign sweat gland
neoplasms, such as the papillary eccrine adenoma. More
aggressive lesions on the digits and volar surfaces of the palms
and soles are ideal for Mohs surgery, because of the need for
tissue conservation and preservation of sensory and motor
function.135
Sebaceous carcinoma
Sebaceous carcinoma is an aggressive malignant tumor that
most frequently occurs on the eyelids, and has a tendency for
local invasion and metastases. It is characterized histologically
by lobules of atypical sebaceous glands and large cells with
mitoses. It has a high local recurrence rate, sometimes requir-
ing orbital exenteration. A pagetoid pattern of intraepithelial
tumor spread has been described,136 making clinical discern-
ment of tumor margins problematic. Mohs surgery has been
successfully used for the treatment of this neoplasm.137 It
appears that it does not always spread by direct contiguous
extension, and as one would expect there are several reports
of recurrences after Mohs surgery. In certain cases with
pagetoid spread, because the tumor may be multifocal, it is
possible to obtain a tumor-free margin without actually
removing the entire tumor. Additionally, recognition of the
pagetoid pattern of spread can be difficult with frozen sec-
tions; paraffin-embedded sections are recommended.138 Oil
red O stain aids in visualization of the tumor. Some authors
have advocated taking an additional Mohs layer after a tumor-
free margin has been obtained, citing the presence of multifo-
cal disease or discontinuity on excisional histologic specimens
in 6% of cases.138 Others also recommend conjunctival map

731
Chapter 44  Mohs Micrographic Surgery and Cutaneous Oncology
12. Abide JM, Nahai F, Bennett RG. The meaning of surgical margins. Plast
Reconstr Surg 1984;73:492–497.
13. Rowe DE, Carroll RJ, Day CL Jr. Long-term recurrence rates in previ-
ously untreated primary basal cell carcinoma: implications for patient
follow-up. J Dermatol Surg Oncol 1989;15:315–328.
14. Rowe DE, Carroll RJ, Day CL Jr. Mohs surgery is the treatment of
choice for recurrent (previously treated) basal cell carcinoma. J Derma-
tol Surg Oncol 1989;15:424–431.
15. Cook J, Zitelli JA. Mohs micrographic surgery: a cost analysis. J Am
Acad Dermatol 1998;39:698–703.
16. Bialy TL, Whalen J, Veledar E, et al. Mohs micrographic surgery vs
traditional surgical excision: a cost comparison analysis. Arch Dermatol
2004;140:736–742.
17. Davidson TM, Haghighi P, Astarita R, et al. Microscopically oriented
histologic surgery for head and neck mucosal cancer. Cancer 1987;60:
1856–1861.
18. Scotto J, Fears TR, Fraumeni JF. Incidence of non-melanoma skin
cancer in the United States (NIH publication No. 83-2433). Washing-
ton, DC: Public Health Service; 1983.
19. Mohs FE. Micrographic surgery for the microscopically controlled exci-
sion of eyelid cancers. Arch Ophthalmol 1986;104:901–909.
20. Fosko SW, Gibney MD, Holds JB. Basal cell carcinoma involving the
lacrimal canaliculus. A documented mechanism of tumor spread. Der-
matol Surg 1997;23:203–206.
21. Roenigk RK, Roenigk HH. Dermatologic surgery: principles and prac-
tice, 2nd edn. New York: Marcel Dekker 1996; 703–729.
22. Mohs FE, Snow SN, Larson PO. Mohs micrographic surgery for penile
tumors. Urol Clin North Am 1992;19:291–304.
23. Collins SC, Dufresne RG Jr. Dietary supplements in the setting of Mohs
surgery. Dermatol Surg 2002;28:447–452.
24. Alam M, Goldberg LH. Serious adverse vascular events associated with
perioperative interruption of antiplatelet and anticoagulant therapy.
Dermatol Surg 2002;28:992–998.
25. Lin BB, Taylor RS. Digital photography for mapping Mohs micrographic
surgery sections. Dermatol Surg 2001;27:411–414.
25a. Ellis JI, Khrom T, Wong A, et al. Mohs math – where the error hides.
BMC Dermatol 2006;6:10.
26. Mikhail GR. Mohs micrographic surgery. Philadelphia: WB Saunders
1991; 1–60.
27. Dogan MM, Snow SN, Lo J. Rapid skin edge elevation using the
OCT compound droplet technique to obtain horizontal microsections
in Mohs micrographic surgery. J Dermatol Surg Oncol 1991;17:857–
860.
28. Motley RJ, Holt PJ. A simple device for optimal tissue preparation for
Mohs micrographic surgery. Br J Dermatol 1992;126:57–59.
29. Leshin B, Cook SR, Frye DW. Cryomold: a device for tissue embedding
for Mohs micrographic surgery. J Dermatol Surg Oncol 1991;17:234–
236.
30. Honda NS, Friedman DH. A simple method of tissue embedding for
Mohs micrographic surgery. J Dermatol Surg Oncol 1989;15:502–
504.
31. Smeets NW, Stavast-Kooy AJ, Krekels GA, et al. Adjuvant cytokeratin
staining in Mohs micrographic surgery for basal cell carcinoma. Derma-
tol Surg 2003;29:375–377.
32. Robinson JK. Current histologic preparation methods for Mohs micro-
graphic surgery. Dermatol Surg 2001:27:555–560.
33. Menaker GM, Chiang JK, Taliba B, et al. Rapid HMB-45 staining in
Mohs micrographic surgery for melanoma in situ and invasive melanoma.
J Am Acad Dermatol 2001:44:833–836.
34. Albertini JG, Elston DM, Libow LF, et al. Mohs micrographic surgery
for melanoma: a case series, a comparative study of immunostains, an
informative case report, and a unique mapping technique. Dermatol
Surg 2002;28:656–665.
35. Smith SB, Farley MF, Albertini JG, et al. Mohs micrographic surgery
for granular cell tumor using S-100 immunostain. Dermatol Surg
2002:1076–1078.
36. Harris DW, Kist DA, Bloom K, et al. Rapid staining with carcinoembry-
onic antigen aids limited excision of extramammary Paget’s disease
treated by Mohs surgery. J Dermatol Surg Oncol 1994;20:260–264.
37. Grabski WJ, Salasche SJ, McCollough ML, et al. Interpretation of Mohs
micrographic frozen sections: a peer review comparison study. J Am
Acad Dermatol 1989:670–674.
38. Gardner ES, Sumner WT, Cook JL. Predictable tissue shrinkage during
frozen section histopathologic processing for Mohs micrographic surgery.
Dermatol Surg 2001;27:813–818.
39. Hruza GJ. Mohs micrographic surgery local recurrences. J Dermatol
Surg Oncol 1994;20:573–577.
40. Mehrany K, Byrd DR, Roenigk RK, et al. Lymphocytic infiltrates and
subclinical epithelial tumor extension in patients with chronic leukemia
and solid-organ transplantation. Dermatol Surg 2003;29:129–134.
 SUMMARY
Mohs micrographic surgery is a technique with broad applica-
tions for malignancies of the skin, soft tissues, and mucous
membranes. Through a series of precise, reproducible steps,
a high rate of cure can be achieved in a predictable fashion
for even the most complex tumors. It has benefited numerous
patients immensely. The presently used technique has been
modified over the years, with perhaps the most significant
advance being the use of the fresh tissue technique. The
future for Mohs surgery is bright. Optical coherence tomog-
raphy or polarized light imaging may be used to determine
skin cancer margins and to guide surgical excision during
Mohs surgery.162 Fast confocal reflectance microscopic exam-
inations of excisional material may augment or replace histo-
logic slide reading.163 Advances in the use of dynamic
telepathology may allow the technique to be brought to
remote sites, as demonstrated by Nehal et al.164 In spite of
modifications to the technique, the two basic principles
guiding Mohs surgery since its inception will remain the same
– precise margin control and tissue conservation.
In the field of cutaneous oncology, the use of biological
response modifiers, photodynamic therapy, and other innova-
tive treatment modalities is expanding. The future of non-
surgical treatment of cutaneous malignancies is also bright.
Recent advances in confocal microscopy enable real-time
imaging of skin in vivo. Using this technology, Goldgeier et
al.165 demonstrated that basal cell carcinoma could be non-
invasively diagnosed, treated, and cleared with topical imi­
quimod. Physicians and surgeons as cutaneous oncologists
must become familiar with the use, applications, and limita-
tions of these new modalities of treatment that are becoming
available.
The opinions or assertions contained herein are the private
views of the authors and are not to be construed as official
or as reflecting the views of the Department of the Army or
the Department of Defense.
 REFERENCES
1. Weisberg NK, Becker DS. Potential utility of adjunctive histopathologic
evaluation of some tumors treated by Mohs micrographic surgery. Der-
matol Surg 2000;26:1052–1056.
2. Greenway HT, Cornell RC, Tanner DJ, et al. Treatment of basal cell
carcinoma with intralesional interferon. J Am Acad Dermatol
1986;15:437–443.
3. Miller BH, Shavin JS, Cognetta A, et al. Nonsurgical treatment of basal
cell carcinomas with intralesional 5-fluorouracil/epinephrine injectable
gel. J Am Acad Dermatol 1997;36:72–77.
4. Wheeland RG, Bailin PL, Ratz JL, et al. Carbon dioxide laser vaporiza-
tion and curettage in the treatment of large or multiple superficial basal
cell carcinomas. J Dermatol Surg Oncol 1987;13:119–125.
5. Gupta AK, Browne M, Bluhm R. Imiquimod; a review. J Cutan Med
Surg 2002;6:554–560.
6. Thissen MR, Neumann MH, Schouten LJ. A systematic review of treat-
ment modalities for primary basal cell carcinomas. Arch Dermatol
1999;135:1177–1183.
7. Mohs FE. Chemosurgery, microscopically controlled surgery for skin
cancer. Springfield, IL: Charles C Thomas 1978; 1–29.
8. Mohs FE. Cancer of the eyelids. Bull Am Coll Chemosurgery 1970;3:
10–11.
9. Tromovitch TA, Stegman SJ. Microscopically controlled excision of skin
tumors: chemosurgery (Mohs): fresh tissue technique. Arch Dermatol
1974;110:231–232.
10. Mohs FE. Mohs micrographic surgery: a historical perspective. Derma-
tol Clin 1989;7:609–611.
11. Rapini RP. Comparison of methods for checking surgical margins. J Am
Acad Dermatol 1990;23:288–294.