Khối U Ác Tính Dưới Da: Góc Nhìn Phẫu Thuật (Cutaneous Malignancies)

Fig. 9.15 Paramedian forehead flaps allow
for reconstruction of large nasal defects.
Common Reconstructive Techniques after Facial Skin Cancer Excision
188

vessels. The supratrochlear vessels can be found between 1.7
and 2.2 cm lateral to the midline above the eyebrows.32 The flap
is designed such that the templated aspect is superior to the
supratrochlear vessels. Dissection is performed down to the
level of the frontalis muscle. The flap is then rotated on itself
and sutured in place to cover the defect. Most of the donor site
can be closed primarily; however, areas can be left to heal with
secondary intention with outstanding cosmetic results (see
Forehead section earlier). Flaps with a base of only 1.2 cm are
capable of survival.
One of the largest downsides of the forehead flap for nasal
reconstruction stems from the need to have multiple stages.
Variations to provide the superior aesthetic outcomes of the
forehead flap—due to the similar color and texture—without
Fig. 9.15 (continued)
Common Reconstructive Techniques after Facial Skin Cancer Excision
189

the multiple staged approach have been identified. Authors
have described a single-stage paramedian forehead flap for
nasal reconstruction that initially was utilized for small nasal
defects.33,34,35,36 However, total nasal reconstruction can be
achieved in the single-staged manner ( Fig. 9.16). The flap is
designed and elevated in a manner that is similar to the staged
approach. However, the di erence lies in creating a tunnel
using the glabellar subunit. To decrease the potential for venous
congestion by compression of the pedicle, corrugator muscles
are resected and the flap tissue that is to be inset underneath
the tunnel is de-epithelialized. As with the staged approach, the
forehead donor site can be approximated until the tension is
too great and the residual area can be left to heal with secon-
dary intention. This method of reconstruction can be utilized in
either the pediatric or elderly population as well as those with
many comorbidities.
9.7 Conclusion
Facial reconstruction maintains several principles—mainte-
nance of the aesthetic subunits as well as replacing “like with
like” whenever possible. Following these basic tenets allows for
the majority of wounds due to cutaneous malignancy extirpa-
tion to be reconstructed with cosmetically satisfactory results.
While not an encyclopedic compilation of all flaps or specific
areas of the face that can be performed, these common, work-
horse flaps will allow the reconstructive surgeon to provide
exceptional care for those a icted with these wounds.
Fig. 9.16 Total nasal reconstruction can be performed using a paramedian forehead flap in a single-staged manner.
Common Reconstructive Techniques after Facial Skin Cancer Excision
190

References
[1] Guy GP, Jr, Thomas CC, Thompson T, Watson M, Massetti GM, Richardson LC,
Centers for Disease Control and Prevention (CDC). Vital signs: melanoma inci-
dence and mortality trends and projections - United States, 1982–2030.
MMWR Morb Mortal Wkly Rep. 2015; 64(21):591–596
[2] Guy GP, Jr, Machlin SR, Ekwueme DU, Yabro KR. Prevalence and costs of skin
cancer treatment in the U.S., 2002–2006 and 2007–2011. Am J Prev Med.
2015; 48(2):183–187
[3] Tagliacozzi G. De Curtorum Chirurgia per Insitionem, 1597.
[4] Nadol JB, Galla RJ, Fabian RL, Montgomery WW. Surgical Anatomy of the
Head and Neck. Philadelphia, PA: Lippincott Williams & Wilkins; 2001
[5] Burget GC, Menick FJ. The subunit principle in nasal reconstruction. Plast
Reconstr Surg. 1985; 76(2):239–247
[6] Seline PC, Siegle RJ. Forehead reconstruction. Dermatol Clin. 2005; 23(1):1–
11, v
[7] Trussler AP, Stephan P, Hatef D, Schaverien M, Meade R, Barton FE. The frontal
branch of the facial nerve across the zygomatic arch: anatomical relevance of
the high-SMAS technique. Plast Reconstr Surg. 2010; 125(4):1221–1229
[8] Ebrahimi A, Nejadsarvari N. Upper forehead skin reconstruction with h-flap. J
Cutan Aesthet Surg. 2013; 6(3):152–154
[9] La Trenta GS. Atlas of Aesthetic Face and Neck Surgery. Philadelphia, PA:
Saunders; 2004
[10] Roth DA, Longaker MT, Zide BM. Cheek surface reconstruction: best choices
according to zones. Oper Tech Plast Reconstr Surg.. 1998; 5(1):26–36
[11] Rapstine ED, Knaus WJ, II, Thornton JF. Simplifying cheek reconstruction: a
review of over 400 cases. Plast Reconstr Surg. 2012; 129(6):1291–1299
[12] Mustarde JC. Repair and Reconstruction in the Orbital Region. 2nd ed. Lon-
don: Churchill-Livingstone; 1980
[13] Austen WG, Jr, Parrett BM, Taghinia A, Wolfort SF, Upton J. The subcutaneous
cervicofacial flap revisited. Ann Plast Surg. 2009; 62(2):149–153
[14] Boyette JR, Vural E. Cervicofacial advancement-rotation flap in midface
reconstruction: forward or reverse? Otolaryngol Head Neck Surg. 2011; 144
(2):196–200
[15] Fralick FB. Anatomy and physiology of the eyelid. Trans Am Acad Ophthalmol
Otolaryngol. 1962; 66:575–581
[16] Spinelli HM. Atlas of aesthetic eyelid and periocular surgery. Philadelphia, PA:
Saunders; 2004
[17] Neligan PC. Strategies in lip reconstruction. Clin Plast Surg. 2009; 36(3):477–
485
[18] Boutros S, Thorne CH, Beasley RW, et al. Grabb & Smith’s Plastic Surgery. 6th
ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2007
[19] Ishii LE, Byrne PJ. Lip reconstruction. Facial Plast Surg Clin North Am. 2009;
17(3):445–453
[20] Behmand RA, Rees R. Reconstructive lip surgery. In: Achauer BM, Eriksson E,
Guyuron B, et al., eds. Plastic Surgery: Indications, Operations, and Outcomes.
Philadelphia, PA: Mosby-Year Book; 2000
[21] Sasidaran R, Zain MA, Basiron NH. Lip and oral commissure reconstruction
with the radial forearm flap. Natl J Maxillofac Surg. 2012; 3(1):21–24
[22] Fernandes R, Clemow J. Outcomes of total or near-total lip reconstruction
with microvascular tissue transfer. J Oral Maxillofac Surg. 2012; 70
(12):2899–2906
[23] Abbe RA. A new plastic operation for the relief of deformity due to double
hairlip. Med Rec. 1898; 53:477
[24] Ebrahimi A, Maghsoudnia GR, Arshadi AA. Prospective comparative study of
lower lip defects reconstruction with di erent local flaps. J Craniofac Surg.
2011; 22(6):2255–2259
[25] Degala S, Shetty SK, Monalisha. The karapandzic flap in lower lip reconstruc-
tion. J Maxillofac Oral Surg. 2015; 14 Suppl 1:421–425
[26] Menick FJ. Reconstruction of the nose. In: Baker SR, Swanson NA, eds. Local
Flaps in Facial Reconstruction. St. Louis, MO: Mosby; 1995:305–307
[27] Zitelli JA. The bilobed flap for nasal reconstruction. Arch Dermatol. 1989; 125
(7):957–959
[28] Zoumalan RA, Hazan C, Levine VJ, Shah AR. Analysis of vector alignment with
the Zitelli bilobed flap for nasal defect repair: a comparison of flap dynamics
in human cadavers. Arch Facial Plast Surg. 2008; 10(3):181–185
[29] Rohrich RJ, Muza ar AR, Adams WP, Jr, Hollier LH. The aesthetic unit dorsal
nasal flap: rationale for avoiding a glabellar incision. Plast Reconstr Surg.
1999; 104(5):1289–1294
[30] Levy RM, Hanke CW. The nose: a high risk area for skin cancer.
cancer.org/skin-cancer-information/basal-cell-carcinoma/the-nose. Accessed
May 1, 2015.
[31] Millard DR, Jr. Hemirhinoplasty. Plast Reconstr Surg. 1967; 40(5):440–445
[32] Shumrick KA, Smith TL. The anatomic basis for the design of forehead flaps in
nasal reconstruction. Arch Otolaryngol Head Neck Surg. 1992; 118(4):373–
379
[33] Har-El G. Single-stage paramedian forehead flap for nasal reconstruction.
Oper Tech Otolaryngol–Head Neck Surg. 1999; 10:127–130
[34] Park SS. The single-stage forehead flap in nasal reconstruction: an alternative
with advantages. Arch Facial Plast Surg. 2002; 4(1):32–36
[35] Fudem GM, Montilla RD, Vaughn CJ. Single-stage forehead flap in nasal recon-
struction. Ann Plast Surg. 2010; 64(5):645–648
[36] Park SS. Revisiting the single-stage forehead flap in nasal reconstruction.
JAMA Facial Plast Surg. 2013; 15(5):383–384
Common Reconstructive Techniques after Facial Skin Cancer Excision
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10 Operative Lymphadenectomy
Calvin J. Young, Amrita Pandit, and Deepak Narayan
10.1 Operative Lymphadenectomy
10.1.1 Introduction
Malignant melanoma is the cutaneous malignancy that most
often mandates an operative lymphadenectomy. The presence
or absence of a positive lymph node in the draining basin is one
of the most important prognostic factors in this disease. The
rationale for a sentinel lymph node biopsy (SLNB) is discussed
elsewhere in this text. For melanoma patients with positive
SLNBs, lymph node dissection of the entire nodal basin is cur-
rently the standard of care in the United States. Other cutane-
ous malignancies for which a sentinel node biopsy and
lymphadenectomy may be performed include Merkel’s cell
carcinomas,1,2 high-risk squamous cell carcinomas (SCCs),3
cutaneous apocrine adenocarcinoma,4 and digital papillary
adenocarcinomas.5
10.2 Sentinel Node Biopsy:
Technical Aspects
The concept of SLNB, as a minimally invasive technique to
assess nodal involvement, was developed in 1977 by Cabanas,
for the management of penile SCC.6 In 1992, Morton et al
applied the same concept to the management of cutaneous
melanoma, with the objective to reduce the morbidity related
to lymph node dissection in these patients. The SLNB protocol
is currently applied to other cutaneous malignancies as well.7
The assumption is that early detection of tumor cells in lymph
nodes leads to a better prognosis by assisting in appropriate
management by aiding the expeditious removal of other dis-
eased lymph nodes in the a ected basin. It also hones the indi-
cations for lymphadenectomy, by limiting the procedure only to
those situations where an involved node has been definitively
identified. This helps to limit the number of lymphadenecto-
mies performed, consequently limiting the morbidity that they
entail. In cutaneous melanomas, a completion lymphadenec-
tomy performed for a positive SLN will reveal that only a small
percentage of the dissection specimens examined will harbor
more involved nodes—that is, nodes other than the sentinel
node(s) containing malignant deposits. A representative figure
of 15% was quoted by Elias et al from the Massachusetts General
Hospital.8 Thus, there is scope for further refinement of this
particular intervention. One idea is to use the SLNB as a stand-
alone therapeutic procedure. This concept is currently being
tested out in clinical trials.
10.3 Lymphoscintigraphy
The concept of lymphoscintigraphy began with cadaveric stud-
ies in the 1800s when Cruickshank used intradermal mercury
injections to demonstrate lymphatic drainage patterns.9 It was
later discovered that lymphatic drainage is not as dogmatic and
predictable as once thought. Although it is possible, based on
population studies, to predict which basin a particular cutane-
ous zone will drain into, a great deal of variability exists, espe-
cially in the head/neck and trunk.10
Lymphoscintigraphy allows noninvasive preoperative identi-
fication of the primary nodal basin for cutaneous neoplasms.11
This imaging modality is especially valuable in lesions that have
the potential to drain to several nodal basins. For example,
lesions of the lower extremity can drain to the popliteal, femo-
ral, inguinal, or iliac regions. In a similar fashion, lesions of the
anterior scalp can drain to the intraparotid lymph nodes or lev-
els I to Vof the anterior cervical chain.
In current practice, lymphoscintigraphy is performed by
injecting a radiolabeled substance into the intradermal space
around the tumor site so that the tracer can be taken up into
the lymphatic system. The ideal radiolabeled injectable sub-
stance should have the following characteristics12:
● It locates and demonstrates the sentinel lymph node without
migrating further into the lymphatic chain.
● It rapidly clears from the injection site to optimize ease of
imaging the draining nodal basin.
● The radiotracer should have a high detection rate but a short
half-life and low particulate emission to minimize radiation
dosage to health care personnel.
Radiopharmaceuticals used for lymphoscintigraphy are princi-
pally technetium (Tc)-based labels and include 99m-Tc anti-
mony sulfide, 99m-Tc rhenium sulfur colloid, and 99m-Tc
albumin nanocolloid.
In the United States, 99m-Tc sulfur colloid (50–2,000 nm par-
ticle size) is the most popular radiopharmaceutical. Typically,
the filtered form of the compound is used. The use of a 0.2-µm
filter eliminates particles larger than 200 nm, which allows for
optimal uptake and transmission to the primary nodal basin for
the lesion (Fig. 10.1).
Identification of a sentinel node, however, does not mandate
a lymphoscintigram. Vital dyes (isosulfan blue, methylene blue)
have been used to duplicate the results of their radioactive
counterparts. In this case, however, the identification of the
sentinel lymph node cannot be performed in a noninvasive
manner since the process of identification requires making an
incision and visually identifying the appropriately stained node.
A combination of 99m-Tc sulfur colloid and a blue dye has been
reported to yield the best detection of sentinel nodes.13
A recent innovation has been the use of fluorescent imaging
in the detection of sentinel lymph nodes.14,15,16 Indocyanine
green (ICG), a tricarbocyanine dye with a molecular weight of
751.4 Da, is the most commonly used compound for this pur-
pose. ICG has been widely used for a variety of human studies,
most commonly in ophthalmology, where it helps in delineat-
ing the retinal vasculature. In the context of sentinel node biop-
sies, the dye is injected in a peritumoral fashion analogous to
its radioactive counterpart. The dye track and sentinel node are
subsequently visualized using special imaging devices. The
principle of fluorescence imaging is based on illuminating the
target tissue with light at the excitation wavelength ( 750–
800 nm) while observing it at longer emission wavelengths,
Operative Lymphadenectomy
192

that is, greater than 800 nm. An additional benefit is that the
green color of the dye can provide visual confirmation of the
node ( Fig. 10.2). Further research is warranted to reliably
establish the e cacy and utility of ICG for SLNB.
A variety of other techniques such as quantum dots, receptor
binding agents, and nanospheres have been used to visualize
sentinel nodes on an experimental basis but have not yet been
used routinely in the clinical arena.
Fig. 10.1 The injection site (small arrow) and the uptake in the axilla. Concurrent use of isosulfan blue confirmed the presence of the sentinel node.
Note blue lymphatic vessel leading into node.
Fig. 10.2 The injection site of ICG in front of the ear (held by forceps) and the uptake in the node adjacent to the skin hook. The visualized node is also
stained green.
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193

10.4 Performance of
Lymphoscintigram
As previously mentioned, the sulfur colloid is injected intrader-
mally to mimic lymphatic drainage of the primary lesion. Using a
25-gauge needle, the tracer is injected to surround the lesion or
on both sides of the center of the incisional scar (if the primary
tumor has already been excised) in four to six sites. Dynamic and
static images are then obtained, 1 to 2 hours after injection, such
that all potential nodal basins within the field are visualized. Each
static image collection time should last approximately 5 to
10 minutes so that faintly labeled lymph nodes can be detected.
The static images are obtained in standard views to allow ad-
equate anatomic localization. Markers can be used to identify sta-
ble anatomic landmarks such as the ear canal or clavicle.
The addition of SPECT/CT (single-photon emission computed
tomography/computed tomography) allows tracer imaging to
be superimposed on to the anatomic information obtained by
CT and can be useful in head and neck primary melanomas.17
10.4.1 Timing of the Lymphoscintigram
It is worthwhile to consider the timing of preoperative lympho-
scintigraphy given that it can be obtained either days in
advance of the proposed sentinel node biopsy or on the day of
the procedure. Given the logistical issues described earlier
regarding timing delays of image acquisition, it can be di cult
to schedule lymphoscintigraphy on the day of the procedure.
Obtaining imaging in advance of the operative intervention
allows for review and confirmation with the interpreting nuclear
medicine specialist. The other side of this argument is that a vast
majority of these studies are straightforward and do not require
detailed analysis. The typical practice is to inject the patient with
the radionucleotide on the day of surgery. This obviates loss of
the signal and any false positives that might result from the
migration of the label into secondary or tertiary lymph nodes.
10.4.2 Aberrant or Interval Drainage
Patterns
Drainage patterns that do not conform to the norm are signifi-
cantly more common in the head/neck and trunk.18,19 Interval
nodes refer to the presence of nontraditional nodes situated in
line of the drainage path between the site of the tumor and the
main (traditional) drainage basin.
In the head and neck, these patterns include drainage to the
postauricular nodes from the anterior forehead or drainage to
the occipital nodes from the scalp. Truncal melanomas may
drain to the triangular intermuscular space, interpectoral
nodes, interval nodes over the costal margin, or even retroperi-
toneal nodes. The epitrochlear and popliteal regions are a part
of the normal lymphatic drainage patterns in the upper and
lower limb, respectively, but their involvement is seen in less
than 1% of cases (Fig. 10.3).
10.5 Performance of the Sentinel
Node Biopsy
As with the lymphoscintigram, the radiopharmaceutical is
injected in four to six sites intradermally in a peritumoral loca-
tion. This injection, depending on the institution, is done either
by radiologists in the nuclear medicine suite or in the operating
room by the surgeon. The uptake in the appropriate basin(s) is
confirmed by a Geiger counter prior to the start of the proce-
dure. Occasionally, this may take longer than 5 minutes, espe-
cially in the elderly with lower extremity melanomas. The vital
dye, if used, can be injected in the operating room, after the
induction of anesthesia to prevent unnecessary discomfort to
the patient.
In the interests of patient comfort, our practice is to inject
the dye and the radiopharmaceutical after the induction of
anesthesia. The site of the biopsy is included in the operating
field and is appropriately prepared. If access to the node
Fig. 10.3 A subungual melanoma draining to epitrochlear node (smaller inferior dark circle) and a high axillary node (large dark circle) seen below left
clavicular marker. The epitrochlear node contained metastatic melanoma.
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194

involves nerve stimulation, the anesthesiologist is informed, so
that appropriate short-acting muscle relaxants are used, if indi-
cated. We use prophylactic antibiotics that are administered
immediately prior to the start of the procedure.
The resection of the primary tumor site is carried out first.
This is done in order to minimize background radiation that
might interfere with the location of the sentinel lymph node.
The incision for the SLNB is centered over the node directly or in
a site that gives the best access to other nodes that may be har-
vested as sentinel nodes. Care must be taken to site SLNB inci-
sions appropriately. In general, the incisions are designed such
that they can be extended into a larger access incision, should
an operative lymphadenectomy prove necessary. For analogous
reasons, the SLNB incisions must be placed in such a way so as
not to compromise the flaps that will be raised if a subsequent
lymphadenectomy is to be performed. Using the handheld
gamma probe and a small incision, the bed is explored and the
nodes are harvested. The use of a vital dye and its coloration of
the sentinel node may aid in this process. Some surgeons tabu-
late the baseline counts in a nona ected area as well as a non–
node-bearing area and remove all nodes using the 10% rule (see
later).The appropriate nodal counts are also documented. Care is
taken to ligate the lymphatics to prevent a seroma postopera-
tively. The placement of a drain after this procedure is a matter
of surgical judgment. While we have a low threshold for drain
placement, we do not use antibiotics postoperatively, regardless
of whether a drain is placed or not. The sentinel nodes are
appropriately marked and the pathologist is informed about the
use of radioactivity in the node harvest.
10.5.1 Identification of the True
Sentinel Node
The experience of the last two decades has shown that the
“hottest” node, that is, the node with the highest amount of
radioactivity, does not translate into a guarantee that the
malignant deposit will be found within it. In other words, a less
radioactive lymph node may well be the abode of tumor cells.
In 2008, Chung et al established 10% rule for SLN for breast
cancer.20 These authors suggest that the removal of all the
nodes with >10% of radioactivity of the “hottest node” mini-
mizes the false-negative rate of SLNB. The same criteria have
been applied for SLNB in melanoma. Some other criteria used
include radioactivity of 10 ×background and even 3 ×back-
ground.11 The sensitivity after removal of three “hot nodes” is
93 to 99% and that after removal of four nodes is 100%.21 The
false-negative rate is 1 to 10% using the combined method (dye
plus radionucleotide).22
10.5.2 Di culties in Sentinel Node
Identification
Nonvisualization of sentinel lymph nodes may occur in some
cases. In our experience, this has usually been seen in elderly
men in the head and neck region.
The proximity of the sentinel node site to the primary tumor
may obscure the visualization of the sentinel node (Fig. 10.4).
In this scenario, it may be helpful to excise the primary lesion
(and the principal source of the obscuring radioactivity) before
looking for the sentinel node as mentioned earlier. Another sol-
ution to the problem is to combine the use of vital dye with the
radioactive tracer such that the sentinel lymph node can be vis-
ually confirmed without the distraction of heightened back-
ground radioactivity.
The presence of previous flap surgery may alter the flow pat-
tern of the draining lymph vessels and thus yield false-negative
results. In an analogous problem, the presence of a large scar
(from an ill-advised attempt at an excisional biopsy) can gener-
ate misleading results if the entire length of the scar is included
in the injection of the radiopharmaceutical. Under these cir-
cumstances, injecting the central part of the scar, the presumed
site of the primary lesion, can yield satisfactory results
Fig. 10.4 Intense radioactivity at site of injection of right mandibular melanoma obscuring sentinel node (left). Low-power histological section
depicting resected skin at the 11 o’clock position and the rim of the lymph node (blue) at the 4 o’clock position.
Operative Lymphadenectomy
195

(Fig. 10.5). The presence of tattoos in the catchment area of
the lymph node may lead to confusion with melanoma cells in
the sentinel lymph nodes (Fig. 10.6). The presence of concur-
rent melanomas of di ering prognostic significance, in the
same anatomic region, may mandate the sequential lympho-
scintigraphic assessment to accurately delineate the lymph
nodal basins involved ( Fig. 10.7).
Occasionally, anatomic or surgical constraints may dictate
whether a sentinel node is accessible (Fig. 10.8).
10.5.3 Special Considerations in the
Head and Neck Region
The presence of a rich lymphatic network in and around the
parotid gland complicates the harvest of sentinel nodes in
the head and neck region.23 The preauricular lymph nodes,
situated in the sulcus between the external auditory m eatus
and the parotid gland, are usually sm all and are therefore
di cult to detect. This di culty increases when the sentinel
node is detected within the substance of the parotid gland.
Based on traditional teaching, the recomm ended method of
harvesting these nodes is via a superficial parotidectomy
w ith a formal identification of the facial nerve in order to
m inim ize the chances of damaging it. Another option is to
directly access the sentinel node in the parotid using a clas-
sic facelift incision and carefully dissecting through the sub-
stance of the gland, using a nerve stim ulator if necessary, to
harvest the node.24 At our center, we have used both meth-
ods and currently prefer the technique of directly harvesting
the sentinel node without a form al parotidectomy. In our
series of 58 patients, we did not encounter a single case of
facial nerve palsy. Interestingly, a survey of Head and Neck
surgeons emphasized the w ide variability in approaches to
this problem, w ith as many as 48% of the surgeons surveyed
opting for a superficial parotidectomy.25
It must be emphasized that the parotid sparing approach for
sentinel node harvest should only be undertaken by experi-
enced surgeons, failing which a parotidectomy is always the
safer option.
10.5.4 Frozen Sections in the
Identification of Sentinel Nodes
Frozen sections, in general, are not recommended for the analy-
sis of sentinel nodes in melanomas.26 These require a special
expertise on the part of the examining pathologists which may
not be universally available. The presence of benign nevus cells
in the subcapsular region that may be mistaken for cells of
metastatic melanoma further heightens the degree of uncer-
tainty during such analyses.
A final consideration for lymphoscintigraphy in melanoma
(and other malignancies) is how lymphatic drainage and there-
fore radiotracer localization may be a ected by regional meta-
static disease. There is evidence that micrometastases do not
a ect mapping techniques or SLNB identification. Additionally,
there are some studies that demonstrate normal or near-nor-
mal lymphatic drainage patterns despite lymph node
metastases.
10.5.5 Complications of Sentinel Node
Biopsy
Sentinel node biopsies, generally speaking, are very safe proce-
dures. Seromas and hematomas probably constitute the most
common problems. To limit the occurrence of the former prob-
lem, we are liberal in the use of drains in our practice. Wound-
healing problems such as infection and wound dehiscence are
similarly rare. There have been reports of lymphedema occur-
ring after the harvest of sentinel nodes alone but these situa-
tions, too, are extremely rare.
Fig. 10.5 Previous ill-advised excisional biopsy (8-mm depth melanoma) and scar indicated by the marked double Y on the left chest wall. This is
encircled by the marking that shows presumed area of mobilization for closure. Injection of blue dye and 99m-Tc in the central part of the scar
identified a single axillary sentinel node that was positive for melanoma.
Operative Lymphadenectomy
196

10.6 Operative Lymphadenectomy
Planning for operative lymphadenectomy begins with thor-
ough history and physical exam at the initial encounter w ith
the patient. Neck, groin, or axillary bulges, m asses, or dis-
comfort can be the first presentation of a clinically positive
regional lymph node in a patient with m elanom a and rarely
in other cutaneous cancers. Physical exam should include
exam ination of all possible drainage basins based on tum or
location. Factors in this exam m ight be of considerable
importance in the conduct of these procedures. Some exam -
ples include the presence of previous scars that might m od-
ify placem ent of incisions or impact the vascularity of
poorly placed ones, problem s a ecting the cervical spine or
the shoulder w hich m ight lim it optim al positioning and
exposure of the operative site of the patient, or the presence
of inguinal of fem oral hernias that m ight go unnoticed or
unrecognized leading to possible dam age in the dissections
of this area.
10.6.1 General Considerations
Certain common features apply to the dissection of the major
lymph nodal basins, that is, cervical, axillary, and inguinofem-
oral and pelvic basins.
● Positioning is of utmost importance. A poorly positioned
patient can significantly add to operating time.
● Communication with the anesthesia team is critical if nerve
testing is to be performed so that long-acting paralytic agents
are not administered.
● The resection of large tumor masses that may result in
significant bleeding should necessitate a preoperative type
and cross-match of blood, if this is not routinely performed.
● Along the same lines, if an unusually long or bloody proce-
dure is anticipated, the preoperative placement of a Foley
catheter may be helpful. This is mandatory in patients with
pelvic or groin dissection to prevent inadvertent damage to
the bladder, especially in the elderly.
Fig. 10.6 Top left panel: extensive tattoo on chest wall and melanoma at the midarm. Top right panel: harvested lymph node with multiple dark areas
suggestive of deposits of malignant melanoma. Bottom panel: histological evidence of iron pigment from tattoo stained with Prussian blue.
Operative Lymphadenectomy
197

● Sequential compression devices are routinely used on the
lower extremities to prevent deep vein thrombosis.
● Postoperatively, one must be vigilant about lymphedema,
especially with the lower limb, pelvic, and groin dissection
and to a lesser degree in the upper limb. The importance of
this preoperative discussion cannot be overemphasized. The
prophylactic use of controlled pressure stockings may be of
some benefit in high-risk patients, such as the obese ones.
● The adequacy of the lymphadenectomy can be judged using
the number of nodes harvested during the procedure. Thus,
Spillane and colleagues from the Sydney Melanoma Unit o er
the following benchmarks.27 Axillary dissections should aim
for a minimum of 10 nodes, inguinal and ilioinguinal dissec-
tions for a minimum of 7 nodes, and cervical lymph node dis-
sections involving 4 or more levels should aim for a minimum
of 20 nodes.
10.7 Neck Dissection
The cervical lymph nodes are the most common initial site of
regional metastases for melanomas of the head and neck. As
mentioned previously, patterns of lymphatic spread can gener-
ally be predicted based on the location of the primary tumor.
The anterior scalp, ear, and face typically drain first to the intra-
parotid node. These structures as well as the anterior neck can
also drain to the cervical nodes including levels I to V
(Fig. 10.9). A complete (radical) neck dissection has become
standard of care in patients with melanomas of the head and
neck who have a positive SLNB or those patients with clinically
positive lymph nodes.
The posterior scalp and posterior neck typically drain to level
V cervical nodes as well as the retroauricular and suboccipital
node. The discussion of head and neck lymphadenectomy is
incomplete without a mention of SCCs of the lip and cheek.
SCCs account for nearly 95% of lip cancers. The size of the pri-
mary tumor is one of the most significant predictors for prog-
nosis.28 For example, T2 lesions have a 5-year survival rate of
approximately 90%, while T3 lesions have a 40 to 60% survival
rate at 5 years.
Regional metastases to the lymphatic system seem to occur
less frequently in SCCs of the lip as compared to other SCCs of
the head and neck. Lower lip SCCs metastasize to the subman-
dibular nodes in 70 to 90% of cases of regional spread.28 Isolated
nodal spread is present in 75% of regional metastases for SCCs
of the lip, and 25 to 45% of these cases involved the submental,
Fig. 10.7 Top panel: the location of two concurrent melanomas on the back—the superior melanoma of 1.1-mm depth and the inferior one of 15-mm
depth. Lymphoscintigrams of the lesions on two separate days revealed that the superior lesion (situated on the right of the midline) drained to the
left supraclavicular region (left and central panel), while the lower melanoma drained to both axillae (right inferior panel).
Fig. 10.8 Melanoma (circled) in a patient with history of spinal fusion
with rib harvest from left chest wall and a midline incision over the
spinous processes for Harrington’s rod placement. Lymphoscintigram
revealed drainage to paravertebral nodes. An attempt at biopsy was
abandoned owing to difficulty of access under Harrington’s rods.
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level I nodes. SCCs of the upper lip typically spread to the sub-
mandibular or lower intraparotid nodes.
For SCCs of the lip and cheek, the presence of clinically evi-
dent, metastatic nodal disease mandates an ipsilateral complete
neck dissection. It is possible to preserve structures within the
lateral neck but preservation should not compromise lymphatic
excision.
Some have advocated elective lymph node dissection in a
clinically negative neck for SCCs of the lip and cheek.28 How-
ever, 80% of clinically negative patients will not go on to
develop cervical lymph node metastases during the course of
their disease. This finding has led some to the supraomohyoid
lymphatic dissection as a technique for assessing the lymph
node status of the patient’s neck given that the submandibular
lymph nodes are the most frequently involved level. If the
primary SCC is midline on the lower lip, bilateral levels I and II
lymph nodes will need to be excised and examined.
10.7.1 Terminology
The term “neck dissection” has undergone many permutations
over the last few decades. The classic radical neck dissection
sacrificed the internal jugular vein, the sternocleidomastoid
muscle, and the spinal accessory nerve. Based on the landmark
studies of Bocca et al, the modified radical neck dissection or
the functional neck dissection is now accepted as being onco-
logically equivalent to its more radical predecessor.29 This dis-
section preserves the aforementioned structures and will be
described in the following.
Fig. 10.9 Division of nodal groups by subzones in both lateral (left) and anterior view (right). Level I: Submental and submandibular nodes. This group
includes the lymph nodes located within the submental triangle, bounded by the anterior belly of the digastric muscle and the hyoid bone. The
submandibular group includes the lymph nodes located within the boundaries of the anterior and posterior bellies of the digastric muscle, the
stylohyoid muscle, and the body of the mandible. The submandibular gland, which is located within this cervical space, should be removed when this
nodal group is included in the resection. IA, submental nodes; IB, submandibular nodes. Level II: Upper jugular nodes. This group contains the lymph
nodes located around the upper third of the internal jugular vein and the spinal accessory nerve. It goes from the level of the skull base superiorly to
the level of the inferior border of the hyoid bone and carotid bifurcation inferiorly. The posterior boundary is the posterior border of the
sternocleidomastoid muscle, and the anterior boundary is the lateral border of the sternohyoid and stylohyoid muscles. IIA, upper jugular nodes
anterior to the XI nerve; IIB, upper jugular nodes posterior to the XI nerve. Level III: Middle jugular nodes. This group includes the lymph nodes located
around the middle third of the internal jugular vein. The boundaries of this space are the inferior border of the hyoid bone and the carotid bifurcation
superiorly, the inferior border of the cricoid cartilage, and the junction of the omohyoid muscle with the internal jugular vein inferiorly, the posterior
border of the sternocleidomastoid muscle posteriorly, and the lateral border of the sternohyoid muscle anteriorly. Level IV: Lower jugular nodes. This
nodal group contains the lymphatic structures located around the lower third of the internal jugular vein. Its boundaries are the inferior border of the
cricoid cartilage and the omohyoid muscle superiorly, the clavicle inferiorly, the posterior border of the sternocleidomastoid muscle posteriorly, and
the lateral border of the sternohyoid muscle anteriorly. Level V: Posterior triangle. This group includes the lymph nodes located along the transverse
cervical artery and lower half of the spinal accessory nerve as well as the supraclavicular lymph nodes. The boundaries are the anterior border of the
trapezius muscle posteriorly, the posterior border of the sternocleidomastoid muscle anteriorly, the clavicle inferiorly, and the convergence of the
sternocleidomastoid and trapezius muscles superiorly. VA, lymph nodes in the posterior triangle located above the level of the inferior border of the
cricoid cartilage; VB, lymph nodes in the posterior triangle located below the level of the inferior border of the cricoid cartilage. Level VI: Anterior
compartment. This level contains the pre- and paratracheal nodes, precricoid (Delphian) node, perithyroidal nodes, and the lymph nodes along the
recurrent laryngeal nerves. The boundaries are the hyoid bone superiorly, the suprasternal notch inferiorly, and the carotid arteries laterally.
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10.7.2 Modified Radical Neck Dissection
(Anterior Cervical Chain Levels I–IV,
Posterior Level V)
The following is standard technique for lymphadenectomy of
the anterior and posterior cervical chain and includes levels I to
V.
Access to the cervical group of lymph nodes can be obtained
by means of a variety of incisions ( Fig. 10.10). Our preference
is for the one popularized by Ariyan, which allows the incision
to be hidden by regular clothing, as well as preventing the
placement of a suture line over the major blood vessels.25 The
latter issue a matter of some concern in the face of postopera-
tive radiation (for SCC or Merkel’s cell tumors), which might
result in exposure of the great vessels. A summary of our oper-
ative technique is presented in Fig. 10.11.
The patient is brought to the operating room and placed in
the supine position on the operating room table. The head is
rotated comfortably away from the lesion for exposure. A
shoulder roll is placed to add to the ease of exposure.
The head end is elevated to approximately 20 degrees to col-
lapse the veins and prevent venous oozing. The entire neck
including the lower face to the angle of the mandible and chest
is prepped and draped in a standard sterile fashion. The edge of
the orbit and the modiolus are left visible by means of cover
with a transparent dressing. This enables the visualization of
the muscles innervated by the branches of the facial nerve, if
nerve stimulation is employed. The incision begins by palpating
the anterior border of the trapezius. The incision is made just
behind the border of the trapezius so as not to inadvertently
damage the spinal accessory nerve. This line is marked in a cur-
vilinear fashion such that the inferior extent of the incision
Fig. 10.10 Access incisions for neck dissection.
(This image is provided courtesy of Stephan
Ariyan, MD.)
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moves gradually toward midline (Fig. 10.12). The skin is
incised sharply with a # 15 blade. Electrocautery is used to carry
the dissection through the platysma, the first muscular layer
encountered. The platysma is raised with the medial skin flap
both medially and superiorly. The two heads of the sternoclei-
domastoid muscles are identified, marked with heavy sutures,
and transected, protecting the underlying structures with a
wooden tongue blade. The investing layer of the deep cervical
fascia is incised and the transected sternocleidomastoid is
reflected upward. Thus, the entire lymph nodal packet is
exposed. All lymphatic tissue is resected en bloc encompassing
levels I to V, as shown in Fig. 10.12. This dissection can be
modified according to the preference of the operator.
If alternate incisions, such as the ones shown are used, the
above-mentioned principles are utilized. Classically trained
Head and Neck surgeons may choose to leave the attachment of
the sternocleidomastoid muscle intact and proceed with the
dissection around the muscle.
We prefer to start the dissection inferiorly and move cranially
and medially, since the plane here is easily found and there is a
lesser density of vital structures. The identification of the spinal
accessory nerve is easily accomplished first owing to its very
superficial location. Erb’s point on the middle of the posterior bor-
der of the sternocleidomastoid is a useful landmark for the spinal
accessory and the great auricular nerves. We use the handheld
nerve stimulator for ease of identification of motor nerves.
As this dissection moves medially, the omohyoid and the
transverse cervical vessels are identified and transected. The
carotid sheath is incised and the sheath attached to the lymph
nodal packet is swept underneath the blood vessels. Superiorly,
the dissection always includes the jugulodigastric nodes. If level
I nodes are being dissected, the marginal mandibular nerve is
identified deep to the fascia and the dissection proceeds anteri-
orly. If the nodal involvement of the submandibular gland is
noted, removal of the submandibular salivary gland is recom-
mended for oncologic clearance. The facial artery, which is inti-
mately involved with the gland, is doubly ligated and care taken
to preserve the lingual and hypoglossal nerves. Within the
carotid sheath, the vagus nerve and the sympathetic trunk are
encountered. Careful dissection preserves these vital structures
and allows for adequate resection of all lymphatic tissue. The
phrenic nerve lying on the scalene muscle is identified and pre-
served. Finally, the dissection continues to the inferior-most
aspect of the neck where the thoracic duct is encountered as it
joined the internal jugular vein (predominantly for dissections
of the left neck). Once all the lymphatic tissue is excised and
meticulous hemostasis is achieved, a closed suction drain is
placed in the wound bed and brought out through the skin by a
Fig. 10.11 Steps of neck dissection. See text for details. BP, brachial plexus; CC, common carotid; IJ, internal jugular; SA, spinal accessory; SCM,
sternocleidomastoid; T, trapezius. (This image is provided courtesy of Stephan Ariyan, MD.)
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201

separate stab incision. The wound is then closed in layers with
interrupted absorbable sutures.
Postoperatively, it is vital to initiate range of motion exercises
for the neck. The drain can be removed either as an inpatient or
upon follow-up, depending on the quantity and quality of the
output.
10.7.3 Parotidectomy and Neck
Dissection
The finding of a positive sentinel lymph node in the immediate
vicinity of the parotid or in the substance of the gland mandates
the removal of the parotid gland in continuity (en bloc) with a
modified neck dissection. Failure to remove the parotid gland
results in an unacceptably high recurrence rate. The same is
true of palpable nodes or in-transit metastases in this region.
The description that follows highlights our technique for a
parotidectomy.
The positioning and general comments that apply to a neck
dissection apply in their entirety to a parotidectomy. In most
instances, the operative term refers to the removal of the gland
anterior or superficial to the branches of the facial nerve. Rarely,
an invasive tumor may mandate removal of the deeper part of
the lobe, along with a possible resection of the facial nerve
branch or branches.
In the case of a combined procedure, our preference is to start
with the parotidectomy part since this is the more demanding
half of the surgical exercise. Access to the parotid is obtained by
Fig. 10.12 Neck dissection. Top panel: Patient
with metastatic melanoma lesions in parotid.
Note preauricular incision carried out behind the
neck and thence in a curvilinear fashion across
the supraclavicular region. The dotted line
represents the surface marking of the XI cranial
nerve and the diagonal line the anterior border of
the trapezius. Central panel (left): Completed
superficial parotidectomy with blue arrow point-
ing to main trunk of the facial nerve. Central
panel (right): Green arrow points to spinal
accessory. Blue arrows point to lymph nodes that
are often harvested as sentinel lymph nodes
Black arrow points to reflected sternocleidomas-
toid muscle. Bottom panel (left): Lymphoid
content of neck being removed en bloc. Note
reflected sternocleidomastoid muscle in upper
left corner. Bottom panel (right): Neck dissection
just prior to completion. Note preserved internal
jugular vein with common carotid adjacent to it.
The green sutures (no. 1 Ethibond) at the inferior
end of the incision will be used to resecure the
sternocleidomastoid to its attachments. Blue
arrow shows platysma incorporated in the
reflected flap to improve vascularity. Black arrow
points to lymphovascular packet. Note reflected
sternocleidomastoid muscle in upper left corner
(different case).
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a face-lift incision in the preauricular area. This incision can
easily be extended into the neck as described earlier.
The skin flap is raised using skin hooks for traction. The dis-
section plane anterior to the parotid fascia (which is marked by
a whitish hue) is easily found. The flap is raised to the anterior
border of the parotid gland remembering that the facial nerve
branches emerge immediately under the cover of this land-
mark. Dissection then proceeds in the interspace between the
parotid gland and the external auditory meatus. Small nodes in
this area are included in the final specimen. The use of a head-
light and loupes is invaluable in dissecting this anatomically
constrained area. Small crossing veins are sealed o with the
bipolar cautery. Blunt self-retaining retractors are placed to
maximize exposure. It is important to keep in mind that the
anatomic landmark for intraoperative identification of the facial
nerve (posterior belly of the digastric muscle, mastoid process,
tympanic bone, and external auditory cartilage). The use of the
“tragal pointer” is a very useful and reliable landmark in the
identification of the trunk of the facial nerve. The nerve lies
approximately 1-cm deep and slightly anterior and inferior to
the tip of the external canal cartilage (also called “pointer”).
Alternatively, the nerve can be identified as it lies approxi-
mately 1-cm deep to the medial attachment of the posterior
belly of the digastric muscle to the digastric groove of the mas-
toid bone. In elderly men and those prone to alcohol abuse and
diabetes, the di use enlargement of the parotid gland (sialosis)
may make this tedious. The use of a nerve stimulator cannot be
overemphasized while conducting this dissection. If an in-con-
tinuity dissection is to be performed, the dissection proceeds in
a cranial to caudal direction. The gland is painstakingly dis-
sected o the nerve using a combination of blunt and sharp dis-
section. We use the bipolar cautery at low settings, exclusively,
to obtain hemostasis during this part of the procedure.
10.7.4 Posterior Cervical Chain
Dissection
On occasion, only a posterior chain neck dissection is required if
a pre- or intraoperative localizing study indicates that only the
posterior triangle lymphatic tissue is involved. The following is
an example of a standard technique for posterior cervical chain
lymph node dissection.
The patient is brought to the operating room and placed in
the supine position on the operating room table. The head is
rotated comfortably away from the lesion for exposure of the
posterior cervical chain. The entire neck including the lower
face to the angle of the mandible and chest is prepped and
draped in the standard sterile fashion. The anatomic borders of
this lymphatic dissection are the most superior portion of the
posterior border of the sternocleidomastoid muscle and the
anterior aspect of the trapezius. The clavicle defines the inferior
extent of the dissection. An incision is made 2 cm posterior to
the anterior border of the trapezius. The incision is carried out
inferiorly in a linear fashion such that each border of the dissec-
tion is accessible in the wound. Care is taken inferiorly as the
brachial plexus is identified as it emerged between the anterior
and middle scalene muscles. Once all the lymphatic tissue is
excised and meticulous hemostasis was achieved, a closed suc-
tion drain is placed in the wound bed and brought out through
the skin by a separate stab incision. The wound is then closed in
layers with interrupted absorbable sutures. Postoperatively, the
same considerations mentioned earlier apply.
10.7.5 Complications of Head and Neck
Lymphadenectomy
Complications specific to the location are damage to the major
motor nerves (marginal mandibular branch of the facial nerve,
the phrenic nerve, and the spinal accessory nerves), chylous
leak commonly seen on the left side due to damage of the
thoracic duct, and potential exposure of the great vessels (with
blowout) if working in a patient with compromised circulation
and/or radiation.30
10.8 Selective Nodal Dissections
In general, the concept of selective nodal dissections has been
advocated principally for low-risk SCCs involving the face or
cheek. We have noted that a selective approach sparing level I
nodes may be feasible in melanomas when lymphoscintigraphic
studies do not indicate that the dye traverses a path through
the level I tissue.23 It must be emphasized that this is performed
only in the absence of palpable nodal disease in melanoma, that
is, a completion lymphadenectomy for an SLNB positive for
melanoma. Similar studies have not been performed for Mer-
kel’s cell tumors and other rare cutaneous cancers.
10.8.1 Axillary Node Dissection
Therapeutic lymph node dissection of the axilla is most often
performed in the surgical treatment melanoma metastatic to
the lymph nodes and less frequently for Merkel’s cell tumors or
metastatic SCCs.30 The following is a standard technique for
approach to axillary lymphadenectomy.
The patient is brought to the operating room and positioned
on the operative table in a supine position. The ipsilateral upper
extremity is abducted on an arm board, while close attention is
paid to positioning and padding of bony prominences, such that
position-based neuropathies is minimized. A roll under the
axilla thrusts the contents forward and makes dissection easier.
The axilla is clipped and the chest wall, axilla, and circumferen-
tial arm and hand are prepped and draped in a standard sterile
fashion. We administer preoperative antibiotics.
Several incisions are possible based on physician and patient
preference. One option is to make a transverse incision in the
axillary fold and opposing vertical incisions along the posterior
arm and anterior chest wall near the border of the pectoralis
major, thus opening the axilla in a Z fashion.
Alternatively, the incision is made starting at the superior
and lateral edge of the pectoralis major muscle within the axil-
lary hairline. This incision is continued posteriorly to the border
of the latissimus dorsi in a curvilinear fashion. A final option is
to place the incision in the same position within the axillary
hairline and continue the incision inferiorly along the lateral
border of the pectoralis major muscle.
We prefer to use the Z pattern for exposure of the axillary
contents for the following reasons:
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● It allows excellent access to the deeper reaches of the axilla
with minimal retraction.
● Excision of cutaneous nodules or compromised scars can
easily be incorporated without di culty in subsequent clo-
sure ( Fig. 10.13).
● It minim izes the possibility of axillary contractures by redis-
tributing tension across di erent planes.
This access incision creates medial and lateral flaps which are
sutured to the skin by means of temporary silk sutures, which
provide stable retraction. The flaps are raised in the subcutane-
ous plane, maintaining a thickness compatible with good vascu-
larity. We have found that it is useful to keep the base of these
flaps thick, in order to prevent ischemic compromise at the dis-
tal ends. The use of a lighted retractor (or headlights) and a
handheld nerve stimulator is extremely valuable in this
dissection.
Our practice is to commence the dissection by identifying the
perimeter of the axillary contents to be removed. The superior
border is defined by the length of the axillary vein. The poste-
rior boundary corresponds to the anterior margin of the latissi-
mus dorsi muscle, while the anterior counterpart is the lateral
margin of the pectoralis major muscle. Inferiorly, the dissection
is carried down to the junction of the latissimus dorsi and
serratus anterior muscles, which usually correspond to the fifth
intercostal space.
In this context, it is useful to recollect the conventional
nomenclature of axillary node levels31:
● Level 1 nodes: below (inferior to) the pectoralis minor.
● Level 2 nodes: behind (posterior to) the pectoralis minor.
● Level 3 nodes: above (superior to) the pectoralis minor.
In contrast to the breast lymphadenectomies, removal of
involved nodes for melanomas encompasses all three levels.
The location of the axillary artery is first palpated to orient
the operator to the axillary contents. The axillary vein lies
immediately in front of this important landmark.
We begin the dissection superiorly by sharply incising the
fascia over the axillary vein along its length. The dissection is
kept anterior to the anterior surface of the axillary vein. Smaller
vessels or tributaries are ligated or cauterized. As the dissection
proceeds inferiorly, the subscapular vein (thoracodorsal vein) is
identified on the inferior surface of the axillary vein.
Occasionally, multiple tributaries of the axillary vein are
noted, which may prove confusing (Fig. 10.14). It is important
to dissect out all the tributaries to accurately identify the true
subscapular vein, which helps in identifying the thoracodorsal
artery and nerve.
Following the identification of these structures, the artery
and nerve are dissected down to their point of entry into the
substance of the latissimus dorsi muscle. Once this has been
accomplished, the lateral component of the dissection begins
on the anterior surface of the latissimus muscle. The dissection
is first carried out medially until the previously dissected thora-
codorsal neurovascular bundle is reached. The dissection is
then carried out inferiorly, freeing up the base of the cone of
the axillary contents until the chest wall is reached medially.
The medial aspect of the dissection starts at the lateral border
of the pectoralis major muscle by incising the clavipectoral fas-
cia. It is then carried out along laterally and superiorly until
Fig. 10.13 Involvement of the skin of the axilla, as in the case of this
squamous cell carcinoma metastatic to the lymph nodes, mandates
resection of the overlying skin with tissue rearrangement to prevent
axillary contracture.
Fig. 10.14 Completed axillary dissection showing two tributaries of the
axillary vein in the left axilla. These variants may pose difficulty in
identification of the true thoracodorsal (TD) vasculature, which arises
from the lower of the two tributaries descending into the latissimus
dorsi (LD) muscle.
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connected with the medial end of the superior dissection, that
is, the medial part of the axillary vein. The dissection on the
chest wall is now continued posteriorly. At this point, the inter-
costobrachial nerve is encountered and may be preserved or
transected depending on the preference of the operator. On the
undersurface of the pectoralis major muscle, the medial pec-
toral nerve is identified as it comes through or just medial to
the pectoralis minor muscle. This is preserved to maintain the
innervation of the pectoralis major muscle. The specimen is dis-
sected o the lateral border of the pectoralis minor muscle
incorporating the interpectoral nodes. The lateral pectoral
nerve, which may have a variable course, is generally seen run-
ning along the lateral border of the pectoralis minor muscle.
This muscle may be divided or resected if bulky nodal disease
mandates better exposure or complete oncologic clearance.
At this point, it is mandatory to identify the long thoracic
nerve. This can be done in two ways. In the first, the previously
dissected thoracodorsal vascular bundle is identified. In most, if
not all, cases, a venous branch can be seen extending medially
to the chest wall. This vein is carefully followed to the chest
wall. The long thoracic nerve is usually located posterior to this
branch hugging the chest wall. The second method is to dissect
posteriorly along the contour of the chest wall, putting gentle
downward and lateral traction on the fibrofatty contents. The
long thoracic nerve can be palpated as a taut cord at the upper
end of the axilla or rolled along and/or visualized on the chest
wall. The use of a handheld nerve stimulator can significantly
speed up the process.
Once this structure is identified, the entire base of the cone
representing the bulk of the axillary contents is rendered free.
Dissection now proceeds superiorly toward the axillary apex.
The insertion of the pectoralis minor may be detached to pro-
vide better access. Larger lymphatic trunks may be encountered
which merit careful ligation. Level II lymph nodes are now dis-
sected o the axillary vein and bluntly dissected downward. A
centrally located vein in this fat pad must be identified and
ligated before it causes troublesome bleeding. Removal of the
level III nodes involves completion of the dissection from the
thoracic inlet laterally to the pectorals minor medially.
This dissection technique allows excision of all lymphatic tis-
sue in axillary levels I to III. The wound is then copiously
irrigated and hemostasis is ensured. A closed suction drain is
left in the wound bed and the wound is closed in layers with
interrupted sutures.
Postoperatively, elevation of the extremity and avoidance of
peripheral intravenous catheters on the ipsilateral arm will
reduce edema. An arm sling can be maintained for comfort but
range of motion exercises for the upper extremity should be
started as soon as feasible for the patient.
10.8.2 Inguinofemoral Node Dissection
(Groin Dissection)32
The term groin dissection generally refers to the removal of the
superficial inguinal and femoral nodes. This can be combined
with an iliac node dissection if needed or indicated.
The patient is placed in the supine position with the ipsilat-
eral leg externally rotated and the knee slightly flexed. A Foley
catheter is placed and body hair is clipped from the skin of the
operative field including the groin, upper leg, and lower abdo-
men. The entire abdomen below the umbilicus to the knee,
including bilateral groins, is prepped and draped in a sterile
fashion. A modesty towel is placed. The options of incisions for
inguinal–femoral node dissection are shown in Fig. 10.15. If
the inguinal dissection has been combined with a femoral and
iliac dissection, one can perform the dissection from both inci-
sions (described elsewhere) with an elevated skin bridge by
leaving 4 to 5 mm of subcutaneous tissue. If the inguinal dissec-
tion is to be performed as the sole procedure, a single incision
is made from superior and lateral to the anterior superior iliac
spine and continued inferiorly and medially until 1 to 2 cm
below the inguinal crease ( Fig. 10.16). The borders of the dis-
section include all fatty and lymphatic tissue between Scarpa’s
fascia and the external oblique fascia from the inguinal ligament
to 5 to 6 cm superiorly. A closed suction drain is left in place.
The wound is then closed with interrupted sutures in Scarpa’s
fascia and a running subcuticular suture for the skin.
For the femoral part of the dissection, the lymphoid tissue
and the fat contents of the femoral triangle are removed. The
boundaries of the triangle are the sartorius laterally, the adduc-
tor longus medially, and the inguinal ligament as the base of
the triangle. The femoral vessels within the femoral sheath and
Fig. 10.15 Different access incisions for groin
dissection. VIL, video inguinal lymphadenectomy.
(This image is provided courtesy of Viraj Master,
MD, PhD, FACS, and Keith Delman, MD, FACS.)
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205

the femoral nerve, lateral to the vascular structures, are impor-
tant structures to be preserved in the dissection ( Fig. 10.17).
The removal of these contents can be done en bloc with the
inguinal part regardless of the incisions chosen and is impor-
tant if there is extracapsular spread ( Fig. 10.18).
The course of the femoral artery is palpated and a vertical
incision is marked from two fingerbreadths inferior to the
inguinal ligament inferiorly to the femoral triangle apex. Alter-
natively, a single oblique incision along the inguinal crease can
be used. The borders of this dissection are from level of the
inguinal ligament to the apex of the femoral triangle formed by
the junction of the adductor longus and the sartorius where
they cross inferiorly.
Fig. 10.16 Neglected metastatic melanoma
(right groin). Groin dissection with resection of
involved skin and reconstruction with advance-
ment flap closure. Dressing is at drain site.
Fig. 10.17 Contents of the femoral triangle. (This
image is provided courtesy of Viraj Master, MD,
PhD, FACS, and Keith Delman, MD, FACS.)
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The marked incision is carried out down sharply until Scar-
pa’s fascia is encountered. The fascia is incised and included in
the medial and lateral skin flaps. Dissection is carried out medi-
ally until the femoral vein is identified and preserved. The
medial border—the border of the adductor longus—is then iden-
tified. Our practice then is to identify the lateral border of the
dissection, that is, the sartorius muscle. The dissection is then
carried out on the surface of the muscles, sparing the deep fas-
cia on these muscles (to decrease the chances of lymphedema),
until the apex is reached. Thus, the fat pad and the lymph nodes
to be removed have been outlined. The saphenous vein is trans-
ected and securely ligated.
The saphenous vein and the adjacent tissue are carefully dis-
sected heading cranially. Large lymphatics are seen alongside
this vein and must be securely ligated or coagulated. The vein is
followed superiorly sweeping all lymphatic tissue and the fem-
oral sheath o the femoral vessels until the saphenofemoral
junction is identified on the anterior surface of the femoral
vein. The saphenous vein is ligated here. It is critically impor-
tant to identify the femoral vein prior to ligating the saphenous
for fear of confusing the femoral vein for the saphenous vein.
The dissection is carried out medially from the adductor longus
to the femoral vessels, and laterally from the sartorius to the
same junction. The removal of the lymph node of Cloquet can
be performed while moving from the medial border of the dis-
section to the femoral vessels. The dissection is completed
while sweeping the lymphatic tissue o the femoral vessels.
This dissection allows for the identification and preservation of
the femoral vessels and femoral nerve. A closed suction drain is
placed and the wound is closed in layers with interrupted
sutures. Deep absorbable sutures are placed to obliterate the
dead space (Fig. 10.19). The skin is closed with a running sub-
cuticular suture.
Postoperatively, it is important to stress elevation of the
lower extremity and early ambulation. Lower extremity com-
pression may be required for a short time postprocedure to
alleviate edema.
10.8.3 Variations of Technique
Minimally Invasive Groin Dissections33,34,35
The previously described groin dissection techniques are e ec-
tive for management of regional metastases of malignant skin
neoplasms of the lower extremity, lower abdomen, and peri-
neum. However, these traditional incisions have the potential to
lead to undesired complications such as seroma formation, skin
flap necrosis, wound infection, and wound dehiscence. In fact,
groin lymph node dissection is associated with a 50 to 75%
complication rate in some series. Recently, there has been inter-
est in applying laparoscopic principles to groin dissections in an
e ort to decrease operative morbidity. Indeed, these techniques
can reduce the degree of tissue injury and postoperative pain.
Additionally, laparoscopic techniques can decrease the required
dissection of important structures such as the abdominal wall
musculature or the inguinal ligament.
Finally, there is an improved cosmetic result with minimally
invasive techniques. Minimally invasive techniques generally
use three smaller incisions with one camera port and two
instrument ports (Fig. 10.15). We have described a minimally
invasive method using a small incision used for the sentinel
node biopsy and a lighted retractor (Fig. 10.20). Several
groups, including ourselves, have described laparoscopic iliac
lymphadenectomy either alone or in combination with superfi-
cial groin dissection.
Sartorius Flap
In order to prevent exposure of the femoral vessels, some sur-
geons transpose the sartorius muscle over the vessels
(Fig. 10.21). It is important to remember that the sartorius
has a segmental blood supply (type IV in the Mathes–Nahai
classification). For this reason, we recommend that not more
than two segmental vessels be divided when mobilizing this
muscle in an e ort to maintain its viability.
Fig. 10.18 The presence of extracapsular spread and in-transit
metastases in this case of groin dissection emphasizes the need for en
bloc resection.

Fig. 10.19 Placement of heavy absorbable sutures to obliterate dead
space in groin dissection field to prevent seroma formation.
Operative Lymphadenectomy
207

Removal of the Lymph Node of Cloquet
There is significant variation in practice regarding the removal
of Cloquet’s node in the femoral canal. Some surgeons routinely
remove and use it as an indicator of deeper involvement and a
guide to iliac node dissection if positive for disease (melanoma).
This practice, however, is not universal.
10.8.4 Iliac Node Dissection (Including
Obturator Nodes)36
Based on pre- and intraoperative localization studies, iliac (pel-
vic) lymph node dissection may be required singly or in combi-
nation with other groin dissections for malignant melanoma of
the lower extremity or torso. If combined with a femoral dissec-
tion, the lymph nodal packet can be removed en bloc by incis-
ing the inguinal ligament (followed by its repair) using a single
incision or through a discontinuous incision. Our preference is
for the latter as it avoids the morbidities commonly associated
with these procedures, such as skin flap necrosis. Of note, it is
useful to have muscle relaxants on board during the intra-
abdominal part of the procedure to provide ease of access to
deeper structures. A standard technique for iliac lymphadenec-
tomy is described in the following.
The patient is placed in the supine position on the oper-
ative table w ith the leg ipsilateral to the dissection exter-
nally rotated and the knee slightly flexed. A Foley catheter
is placed and the body hair clipped from the operative field
including the groin, upper leg, and lower abdom en to the
um bilicus. The entire abdom en below the um bilicus to the
knee including bilateral groins is prepped and draped in a
sterile fashion. A m odesty tow el is placed. The dissection
described here ultim ately allows for excision of all fatty tis-
sue and lym phatics from the bifurcation of the com m on
iliac artery to the fascia over the obturator foram en. A cur-
vilinear incision is m ade approxim ately 5 cm above the
inguinal ligam ent from the pubic tubercle to the anterior
superior iliac spine. The external oblique aponeurosis is
bluntly dissected o the subcutaneous tissue until the
inguinal ligam ent is identified. This allow s for easier reap-
proxim ation at the end of the operation as well as facile
access to the fem oral artery should it be required em er-
gently. The fascia of the external oblique is incised along
the length of the incision. The internal oblique m uscle is
split along its fibers, as is the transversalis m uscle. In doing
so, the deep circum flex iliac artery is ligated. Once through
the transversalis fascia, the peritoneum is identified and
bluntly swept cephalad until the com m on iliac vessels are
identified. Care is taken to preserve the peritoneum to pre-
vent the annoying intrusion of bowel loops into the field.
The ureter is also identified and preserved as it crosses the
com m on iliac just superior to the vessels’ bifurcation. This
allow s for safe dissection of all lym phatic tissue from the
level of the bifurcation inferiorly. It m ay be necessary to
ligate the inferior epigastric artery as it com es o the
external iliac artery for ease of dissection. This allows
exposure of the vas and the testicular vessels (round liga-
m ent in fem ales) and aids in placing them out of harm ’s
way.
Fig. 10.20 The use of a lighted retractor as shown here can be used in
the performance of a minimally invasive groin dissection.
Fig. 10.21 Sartorius flap. The first panel shows the harvest of the sartorius muscle after a right groin dissection. Note the relatively short length
mobilized (held by forceps) to preserve the vascularity of the muscle, which is segmental. The second panel shows the muscle transposed over the
femoral vessels and secured to the inguinal ligament.
Operative Lymphadenectomy
208

A self-retaining retractor (Bookwalter) is placed. We prefer
to start the dissection superiorly using sharp dissection over
the vessels. All lymphatic vessels are either clipped or
ligated. The use of sealing devices (Ligasure, Medtronic) can
significantly increase the speed of the procedure. The lymph
nodes are swept o the artery and vein, peeling them o
w ith a sheath over the vessels. This is continued inferiorly
between the vessels to the level of the obturator fascia. The
nodes overlying the obturator fascia are best dissected
bluntly since palpation of the tissue in this area reveals the
obturator nerve as a taut cordlike structure which is pre-
served. At this point, the iliac and obturator nodes are
removed en bloc and the dissection is complete. The retro-
peritoneum is packed and reinspected for hem ostasis No
drain is left in the pelvis. Again, it is important to stress ele-
vation of the lower extrem ity and early ambulation postop-
eratively. Lower extrem ity compression m ay be required for
a short tim e postprocedure to alleviate edem a.
10.8.5 Rare Locations37
There are other less frequently used lymph node dissections
with which the melanoma surgeon should be familiar. These
are the dissections of the epitrochlear basin and the popliteal
fossa.
Epitrochlear lymph node dissection may be required for mel-
anoma of the hand, subungual region, or skin of the forearm to
the elbow (Fig. 10.22). The incidence is infrequent. A rate of
3.7% for clinically apparent metastases to this region has been
quoted. The following is a description of our technique for the
epitrochlear dissection.
The patient is placed in the supine position on the operating
table. An arm board is positioned appropriately. The entire arm
and hand up to and including the axilla are prepped and draped
in a sterile fashion. A curvilinear incision is made from 5 cm
proximal to the medial epicondyle in an inferior and lateral
fashion such that it traverses the antecubital fossa to the bra-
chioradialis muscle. This pattern is critical to avoid a contrac-
ture in the region of the elbow. Skin flaps are raised such that
the biceps and brachioradialis muscles are identified laterally
and the medial head of the triceps and the flexor origin on the
medial epicondyle are identified medially. Any superficial veins
that are encountered are ligated. The borders of this dissection
are the medial head of the triceps, the short head of the biceps,
the musculature overlying the medial epicondyle (the common
flexor origin), and the brachialis muscle. After the skin flaps are
raised, dissection progressed from distal to proximal as out-
lined earlier, such that all adipose tissue is included. The supe-
rior cubital lymph node is encountered in its anatomic position
deep to the biceps aponeurosis where the brachial artery bifur-
cates. This is included in the specimen. Additionally, the median
nerve is identified in its anatomic position deep the biceps ten-
don and is preserved.
Proximally, the dissection is concluded once the intersection
of the brachial artery and the medial intermuscular septum is
reached. The inferior ulnar collateral artery and vein are ligated
and divided and the specimen is delivered from the wound. A
closed suction drain is placed in the wound bed. The wound is
closed in layers and the skin is closed with a running subcuticu-
lar suture.
Postoperatively, it is important to remember arm elevation
and range of motion exercises.
10.8.6 Popliteal Lymphadenectomy38
Involvement of the popliteal lymph node is rare even in
patients with primary lesions of the foot or posterior leg. One
case series demonstrated clinically involved popliteal lymph
nodes at a rate of 0.3%. As such, indications for popliteal lym-
phadenectomy are limited to SLNB-positive lymph nodes in this
area or clinically apparent metastatic disease. A standard
description of popliteal lymphadenectomy is as follows.
The patient is placed in the prone position on the operating
table. The leg and foot are prepped and draped in a sterile fash-
ion to the gluteal fold. To maximize exposure and minimize
future scar contracture across the popliteal fossa, a Z-plasty-
type incision is made within the flexor crease. The interior
angle of the incision can be between 75 and 100 degrees. To
prevent flap ischemia, we routinely raise skin flaps sharply
using a knife, maintaining an even flap thickness. We also advo-
cate the use of bipolar cautery for hemostasis for the same
Fig. 10.22 Incision for access. Epitrochlear nodes shown in blue. (This
image is provided courtesy of Viraj Master, MD, PhD, FACS, and Keith
Delman, MD, FACS.)
Operative Lymphadenectomy
209

reason. Once the flaps are raised, it is useful for the surgeon to
orient himself/herself by palpating the popliteal artery.
The distal perimeter of the dissection is defined by the
medial and lateral heads of the gastrocnemius muscle. Superi-
orly, the dissection is carried out up to the bifurcation of the
common peroneal and tibial nerves from sciatic trunk.
We prefer to start the dissection distally. The lesser saphe-
nous vein is identified, ligated, and divided to improve expo-
sure. The small cutaneous nerve branches that are identified
are preserved if possible. Next, the posterior fascia is incised in
a vertical manner. Dissection of the lymphatic tissue within in
the popliteal fossa is carried out using a combination of blunt
and sharp dissection. The tibial nerve is identified as the most
superficial midline structure and is gently retracted laterally.
The peroneal nerve is identified as it courses along the biceps
femoris and semimembranosus before it turns obliquely and
laterally toward the fibula. It is gently retracted and protected.
All lymphatic tissue from the bifurcation of the sciatic nerve to
the heads of the gastrocnemius is excised en bloc (Fig. 10.23).
In doing so, the popliteal vessels are identified and exposed,
with the artery being medial and deeper than the vein. A drain
is left in the wound bed and placed to self-suction. The wound
is closed with interrupted sutures in layers and a running sub-
cuticular suture is used for the skin.
10.9 Conclusion
While the roles of sentinel node biopsy and completion lymph-
adenectomies in melanomas have been more clearly delineated
and refined in recent years, the situation is far from being set-
tled. The principal controversy has centered on the benefits of
elective versus prophylactic node dissection as guided by the
sentinel node status.
The final report of the MSLT I trial issued in 2014 indicated
that biopsy-based staging of intermediate thickness (defined as
1.20–3.50 mm) or thick melanomas (3.50 mm) provides impor-
tant prognostic information and prolongs disease-free sur-
vival.39
However, in keeping with earlier studies (in the
presentinel node era), the overall survival rates were not
a ected. The MSLT II trial that is currently ongoing should
resolve some of the criticisms leveled against the previous
study.40 This is a phase III, multicenter, randomized trial of sen-
tinel lymphadenectomy and complete lymph node dissection
versus sentinel lymphadenectomy alone, in cutaneous mela-
noma with evidence of metastases in sentinel nodes. Unfortu-
nately, the results of this study will not bear fruit until 2022. In
the interim, the statistics of the low yield of additional positive
lymph nodes, harvested at the time of completion lymphade-
nectomy, has led to carefully controlled ongoing studies in
Europe using the sentinel node harvest alone as a therapeutic
intervention. This minimalist approach resembles the evolution
of treatment in breast cancer.41 The results of these trials are
eagerly awaited by surgeons and patients alike.
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11 Role of Dermatopathology in the Surgical Management
of Skin Cancer
Jennifer S. Ko, Eugen C. Minca, and Klaus J. Busam
11.1 Introduction
The role of derm atopathology in the surgical m anagem ent of
cutaneous malignancy m irrors the role of pathology in the
m anagem ent of m ost cancers. The goal is to establish an
accurate diagnosis, provide prognostic information, and
determ ine the surgical m argin status. Derm atopathology is
somew hat unique in that many tumors are caught at very
early stages; thus, these patients are typically expected to
do well compared to patients with tum ors occurring at vis-
ceral sites. Also unique is the variety of benign and m alig-
nant cutaneous neoplasm s w ith a broad spectrum of
histopathologic features and clinical behaviors. For example,
there is no other type of benign human tumor w hich dis-
plays as great a spectrum in features as melanocytic nevi.
Additionally, there is no other benign tum or, which can be
as di cult to distinguish from its m alignant counterpart as
an atypical nevus from melanom a. This chapter is intended
to highlight the particularities found in the most com mon
types of cutaneous m alignancies as they relate to the vital
diagnostic, prognostic, and predictive inform ation contained
within the pathology report.
The need for improved com pleteness in cancer pathology
reporting to im prove patient care has been recently recog-
nized. In response to this need, pathology organizations
have published recom m ended reporting protocols for vari-
ous tum or types. Much of w hat is included in the pathol-
ogy cancer reports generated in the United States is guided
by the College of Am erican Pathologists (CAP)-produced
cancer Protocols, w hich reflect current updates to the
Am erican Joint Com m ittee on Cancer (AJCC) Cancer Staging
Manual and the m ost recent WHO tum or classification sys-
tem s.1 The CAP cancer protocols serve as a resource for
pathologists to aid in e ective reporting of surgical pathol-
ogy findings necessary to provide quality patient care, and
can additionally include optional cancer biom arker report-
ing templates. Biom arker reporting tem plates establish
reporting guidance for com m only ordered biom arkers (e.g.,
estrogen receptor, progesterone receptor, and hum an epi-
derm al grow th factor receptor 2 in breast cancer) and
im prove consistency and completeness of results reporting.
Currently, there are no such biom arker reporting tem plates
for prim ary cutaneous neoplasm s, yet this m ay change in
the com ing years. The Am erican College of Surgeons Com -
m ission on Cancer (ACS CoC) has recognized the value of
such protocols, and it has been m andated that pathologists
at CoC-approved cancer program s include the scientifically
validated or regularly used data elem ents of the protocols
in their surgical pathology reports on cancer specim ens, as
of January 1, 2004.
11.2 Basal Cell Carcinoma
Basal cell carcinoma (BCC) derives its name from its resem-
blance to the basal layer keratinocytes of the epidermis. It is
thought to originate from the lowest layers of the epidermis or
the outer root sheath of the pilosebaceous unit. This carcinoma
shares many features with follicular matrix epithelium, includ-
ing their immunophenotypic-staining pattern. BCC is the most
common cancer in humans,2 and yet the CAP does not include
specific cancer reporting protocols for BCC, due to its overall
excellent prognosis. That said, appropriate management is nec-
essary to avoid local tissue destruction and tissue disfigurement
while preserving cosmesis and function. To this aim, pathologic
parameters in the biopsy specimen can help determine the
potential for subclinical extension beyond a clinically defined
border, and thus are commented on.
The pathologic risk factors which define high-risk versus
low-risk primary BCC relate to tumor size, depth of invasion,
histologic tumor subtype, perineural invasion, and vascular
invasion (very rarely seen, but unfavorable if present). Studies
have shown that the gross size of tumor impacts the risk for
depth of invasion, subclinical extension, and recurrence-free
survival, with ≥2 cm appearing to confer increased risk to trunk
and extremity lesions; ≥6 mm for face, genitalia, hands/feet;
and ≥10 mm for all other anatomic locations.3 The histologic
tumor subtype of BCC is a predictor of risk of recurrence and
metastasis. Indeed, studies list the strongest predictors for
recurrence to be aggressive histologic tumor type, along with
positive excision margins.4 While there are many types of BCC
recognized, most can be grouped as nonaggressive, aggressive,
or indi erent (Table 11.1), and often there are mixed types
within one tumor. Nodular ( Fig. 11.1a) and superficial
(Fig. 11.1b) BCCs are common forms falling into the nonag-
gressive category. Nodular BCC grows in large dermal tumor
nodules, often with connection to the overlying epidermis.
Table 11.1 Histologic subtypes of basal cell carcinoma according to ag-
gressiveness and risk of recurrence
Aggressiveness/
Risk of recur-
rence
Low/Low

Low/High

High/High
Basal cell carci-
noma histologic
subtype
(most common
in bold)
Nodular
Adenoid
Keratotic
Pleomorphic
(giant cell)
Clear cell
Signet ring
With adnexal
differentiation
Infundibulocys-
tic
Superficial
(multicentric)
Micronodular
Infiltrative
Morpheaform
Metatypical
(basosquamous)
Role of Dermatopathology in the Surgical Management of Skin Cancer
212

Within these nodules, cells can form into trabeculae or pseudo-
glandular spaces. The perimeter of tumor nodules shows
nuclear palisading and often retraction artifact from the sur-
rounding myxoid stroma by a cleft-like space. Superficial BCCs
are multifocal in nature and hang o the epidermis. For this
reason, they show a higher rate of local recurrence compared to
nodular subtype alone. Infundibulocystic BCC is the most indo-
lent variant of BCC, and some argue it may not be a real carci-
noma, thus referring to it as “basaloid follicular hamartoma.”
Micronodular ( Fig. 11.2a), infiltrative (Fig. 11.2b, c), and
morpheaform (Fig. 11.2d) subtypes of BCC are associated with
a higher incidence of positive margins and thus tumor recur-
rence.5,6 For this reason, BCC subtyping is important informa-
tion to be included in the pathology report. The micronodular
pattern shows small tumor nodules (<0.15 mm) and lacks cir-
cumscription. Micronodular BCC (Fig. 11.2e) usually shows at
least focal retraction artifact, stromal mucin, increased mitosis,
and a lack of papillary mesenchymal bodies, as distinguishing
factors from trichoepitheliomas ( Fig. 11.3a–c). Infiltrative
BCCs show thin, linear basaloid tumor strands growing in an
infiltrative pattern. When the same type of growth becomes
even more spiked and associated with a densely sclerotic
stroma, tumors are called morpheaform BCC. Perineural inva-
sion is another important pathologic prognostic feature in BCC,
and BCC tumors with this feature ( Fig. 11.3d) have higher
rates of recurrence and morbidity. While studies on treatment
protocols in this setting are relatively limited, Mohs surgery
appears to confer better outcome, and adjuvant radiotherapy
may be considered.7
The vast majority of BCCs do not require immunohistochemi-
cal (IHC) staining for diagnosis. In rare BCCs, such as the so-
called trichoepitheliomatous types (Fig. 11.2e), or clear cell
types, IHC staining may be required. BCC stains in a pattern
similar to the follicular infundibulum and will be positive for
both high- and low-molecular-weight cytokeratins, BerEP4, Bcl-
2 (di use), and Ki-67 (20–40% proliferative index), and will
show exclusion of CK20 +Merkel’s cells.8 A recent study by
Nedved et al revealed that while there is only fair concordance
between dermatopathologists with regard to specific BCC
typing, there is substantial agreement when tumors were
reclassified into a two-tiered system of high- and low-risk phe-
notypes.9 As such, BCCs often do not require a second patho-
logic opinion.
BCC is typically thought to be a continuously growing tumor;
yet, reports of “skip” lesions still exist, especially with regard to
superficial BCC. For the purposes of surgical and pathologic
margins, however, BCCs can be considered a continuously
growing tumor. Current practice guidelines from the National
Comprehensive Cancer Network suggest a 4-mm lateral clinical
margin for BCCs ≤2 cm diameter treated with elliptical excision,
based on studies which showed a 98% histologic cure rate in
this setting.10 This may not always be desirable given the cos-
metically and functionally sensitive location. As such, Mohs’
micrographic surgery or surgical excision with complete, cir-
cumferential, peripheral, and deep margin assessment
(CCPDMA) or “slow Mohs” is often undertaken.11 Some studies
suggest that traditional para n-fixed serial cross-sectioning
(bread loafing) techniques can miss positive surgical margins in
up to 56% of cases.12 In addition, although the pathology report
will include the positivity or negativity of the surgical margins,
the distance of the margin to tumor may or may not be
reported. Margins can only be partially examined in shave “sau-
cerization” and punch biopsy specimens, and thus are typically
not discussed. In rare circumstances in which surgical treat-
ment is not feasible for BCC, systemic therapy has become avail-
able. Options include vismodegib (BMS-833923), saridegib (IPI-
926), and sonidegib/erismodegib (LDE225), which target the
activating mutations in the hedgehog signaling pathway that
are known to drive BCCs.13
11.3 Squamous Cell Carcinoma
Cutaneous squamous cell carcinoma (cSCC) is the second most
common skin cancer, and is formed from the keratinizing cells
of the epidermis. SCC is typically classified as high risk or low
risk depending on the risk for local recurrence and metastasis.
The tumor size and anatomic location criteria for risk
Fig. 11.1 (a) BCC, nodular. (b) BCC, superficial,
multifocal.
Role of Dermatopathology in the Surgical Management of Skin Cancer
213

stratification are identical to those used for BCC. CAP requires
reporting of invasive squamous cell carcinomas greater than
2 cm in greatest dimension (which are automatically a mini-
mum of pT2 pathologic tumor stage) to be performed in a tem-
plated manner,1 due to the doubled risk for local recurrence
and tripled risk for metastasis in this setting.14 The templated
pathologic report should contain all histopathologic parameters
associated with a worse prognosis, defined as high-risk features
by the AJCC-7 staging criteria. These include tumor size and site
(greatest dimension: >2 cm; ear or non–hair-bearing lip), histo-
logic grade (poor or undi erentiated), maximum tumor thick-
ness (>2 mm), anatomic level (Clark IV or V), and perineural or
vascular involvement (present).14,15 The caliber and location of
the involved nerve is prognostically relevant. Local recurrence
is more likely if the involved nerve is located in the subcutis or
muscle and when the caliber exceeds 0.2 mm.
While various subtypes of squamous cell carcinoma are
recognized, including acantholytic ( Fig. 11.4a), Bowenoid
(Fig. 11.4b), and verrucous ( Fig. 11.4c), such typing is not
necessary to include (though often incorporated) in the report-
ing template. The histologic grade, rather, is the required infor-
mation because decreasing levels of di erentiation are
associated with increasing risk of recurrence. Well-di erenti-
ated cSCC will closely resemble normal epithelium, but often
shows an irregular border of invasive islands with a desmoplas-
tic host response, paradoxical maturation with descent into the
dermis, and subtle nuclear atypia ( Fig. 11.5a). Keratoacantho-
mas ( Fig. 11.5b) appear to represent a unique form of inva-
sive, well-di erentiated squamous cell carcinoma that will
often involute on its own, possibly due to the relatively
increased expression of apoptotic genes.16 As such, well-di er-
entiated SCC and keratoacanthomas perform the best clinically.
Moderately di erentiated cases show less obvious squamous
features (Fig. 11.5c). Poorly di erentiated (Fig. 11.5d, e)
squamous cell carcinoma, which may require IHC staining for
confirmation (Fig. 11.5f), and undi erentiated, sarcomatoid
(Fig. 11.6a-BSCC) squamous cell carcinoma, which requires
clinical correlation, a precursor lesion, or focal IHC staining
Fig. 11.2 (a) BCC, micronodular. (b) BCC, infiltrative (low power). (c) BCC, infiltrative (high power). (d) BCC, morpheaform. (e) BCC,
trichoepitheliomatous (alternative).
Role of Dermatopathology in the Surgical Management of Skin Cancer
214

Fig. 11.3 (a) Desmoplastic trichoepithelioma. (b,
c) Desmoplastic trichoepithelioma (low and high
power, alternative). (d) BCC, infiltrative with
perineural invasion.
Role of Dermatopathology in the Surgical Management of Skin Cancer
215

positivity by definition, have increased risk for recurrence. As
such, both poor and de-di erentiation are histologic features
which upstage a patient from a pT1 to a pT2 tumor.14
Maximum tumor thickness (Breslow’s thickness) is measured
with a calibrated ocular micrometer, which is a glass disk that
fits in the microscope eyepiece. It has a ruled scale used to
measure the size of magnified objects. The physical length of
the marks on the scale varies depending on the degree of mag-
nification. Breslow’s tumor thickness is measured from the
granular layer of the epidermis, or the base of the ulcer in ulcer-
ated lesions, to the deepest extent of tumor. Increasing
Breslow’s thickness is associated with increased risk, as is
increasing Clark’s level of invasion ( Table 11.2). Perineural
invasion is more common in larger tumors (Fig. 11.7a), as is
lymphovascular invasion.
Often, tumors with high-risk features are treated with Mohs
micrographic surgery or resection with CCPDMA. Tumors with
perineural invasion especially benefit from intraoperative mar-
gin control and possibly adjuvant radiation therapy. The size of
the involved nerve should be included in the pathology report,
as diameter 0.1-mm or greater increases risk of recurrence and
metastasis.16
Fig. 11.4 (a) Cutaneous squamous cell carcino-
ma (cSCC), acantholytic. (b) cSCC, Bowenoid. (c)
cSCC, verrucous.
Role of Dermatopathology in the Surgical Management of Skin Cancer
216

Fig. 11.5 (a) Cutaneous squamous cell carcinoma (cSCC), well-differentiated. (b) cSCC, keratoacanthoma. (c) cSCC, moderately differentiated. (d)
cSCC, poorly differentiated (low power). (e) cSCC, poorly differentiated (high power). (f) cSCC, poorly differentiated (CK5/6 and p63).
Fig. 11.6 (a) Cutaneous squamous cell carcinoma (cSCC), sarcomatoid, spindle cell (H&E low power). (b) cSCC, sarcomatoid, epithelioid (high power).
Role of Dermatopathology in the Surgical Management of Skin Cancer
217

Incomplete removal of primary cSCC makes subsequent
therapies much less likely to succeed.17 If a lesion is removed by
elliptical excision, the surgical specimen should be oriented and
bread-loafed sections submitted at 2- to 3-mm intervals with
marginal involvement reported. The best clear indicator of a
positive margin is tumor with either ink or cautery artifact on it
(Fig. 11.7b). If positive margins are found after initial excision,
then Mohs micrographic surgery or resection with CCPDMA is
typically indicated, especially if graft placement is necessary.
Measurement of distance to the margin is not required informa-
tion, but is often reported.
Sentinel lymph node biopsy (SLNBx) is considered in patients
with high-risk cSCC and clinically negative lymph nodes
because approximately 12% of these nodes will be positive.18,19
Sentinel and regional lymph node detection of cSCC is usually
possible using hematoxylin and eosin (H&E) stains alone, due to
the significantly di erent morphology of this carcinoma com-
pared to normal lymph node constituents (Fig. 11.7c). The
size, number, and site (ipsilateral or bilateral) of lymph node
involvement is associated with clinical outcome, with meta-
static deposit size the most important factor.20,21 As such, these
are required components of the templated pathology report.
11.4 Malignant Melanoma
Although malignant melanoma (MM) is much less common
than BCC and cSCC, no other diagnosis lends itself to as much
di culty, subjectivity, and lack of agreement among dermato-
pathologists.22,23,24,25,26 This may be due to the large degree of
histologic overlap of melanoma with various benign mimickers,
and due to the limited spectrum of cytologic atypia in melano-
mas compared to other malignancies. For instance, superficial
spreading (Fig. 11.8a), nevoid (Fig. 11.8b, c), and Spitzoid
(Fig. 11.8d, e) melanomas can show histopathologic overlap
with dysplastic nevi (Fig. 11.9a) or recurrent nevi
(Fig. 11.9b-d) and Spitz nevi (Fig. 11.9e), respectively.21
Meanwhile, the so-called atypical Spitz tumor/nevus is a diag-
nosis that often requires ancillary testing for confirmation due
to the lack of consistent distinguishing histologic features from
melanoma. Farmer et al illustrated that within a panel of eight
expert pathologists, diagnostic discordance between two or
more panel members was observed in 38% of melanocytic
lesions.25 The experimental design and premise of this study
has been questioned by some who insist that the majority of
cases can be accurately classified; and that descriptive reporting
Table 11.2 Risk of recurrence and metastases in cutaneous squamous
cell carcinomas based on Clark’s level of invasion
Clark’s level

cSCC risk of recurrence
and metastases
I Tumor confined to the epidermis (in situ) Low
II Tumor invasion into the papillary dermis
III Tumor at the junction of the papillary and
reticular dermis
IV Tumor invasion into the reticular dermis High
V Tumor invasion into the subcutaneous fat
Abbreviation: cSCC, cutaneous squamous cell carcinoma.
Fig. 11.7 (a) Cutaneous squamous cell carcinoma (cSCC), perineural invasion. (b) cSCC, positive inked margin. (c) cSCC, lymph node metastasis.
Role of Dermatopathology in the Surgical Management of Skin Cancer
218

on the uncertain malignant potential of particular lesions is in
fact permissible.27 Contemporary studies done by Niebling et al
at the Melanoma Institute Australia (MIA) on 5,011 MIA and
non–MIA-matched reports on the same primary melanomas
found significant changes in the diagnosis, AJCC-T classification,
and treatment recommendations after pathology review by
melanoma pathologists, with moderate concordance
demonstrated for various tumor staging parameters. Because of
this, the recommendation that pathology review be considered
for all patients attending specialist melanoma treatment cen-
ters has been made.28,29 Needless to say, it is important to trust
the dermatopathologist diagnosing melanocytic lesions. Like-
wise, it is important that pathology reports of at least border-
line melanocytic lesions document key diagnostic criteria
Fig. 11.8 (a) Melanoma, superficial spreading, arising in a nevus. (b) Melanoma, Spitzoid and nevoid (low power). (c) Melanoma, nevoid (low power).
(d) Melanoma, spitzoid, with epidermal consumption (low power). (e) Melanoma, spitzoid, with epidermal consumption (high power).
Role of Dermatopathology in the Surgical Management of Skin Cancer
219

(microscopic features) on which the diagnosis was based, and
describe any areas of uncertainty.
Clinical information can be crucially important in the diagno-
sis of melanoma. Older patient age, increased signs of solar
damage, and large lesional diameter (>6 mm) will immediately
alter the perspective through which a biopsy is reviewed.
Numerous criteria are considered, both in number and severity,
in the assessment for malignancy. In general, melanomas tend
to show many forms of asymmetry. These include asymmetry
of low power silhouette, lateral border cell distribution, cyto-
logic features, pigmentation, inflammatory host response,
and nesting architecture. Consumption of the epidermis
(Fig. 11.8e) and pagetoid spread of melanocytes ( Fig. 11.10)
are emblematic clues to melanoma.30
Owing to the diagnostic di culty sometimes associated with
melanoma and its capacity to spread relatively early in evolu-
tion, it is our practice that all melanomas diagnosed by outside
pathologists be reviewed by pathologists within our institution
prior to definitive treatment at our institution. For those
surgeons treating patients in the community, it is likely not
practical to have every melanoma reviewed by an outside
Fig. 11.9 (a) Dysplastic nevus (mild melanocytic atypia). (b) Recurrent nevus versus melanoma (nevus), low power. (c) Recurrent nevus versus
melanoma (nevus), high power. (d) Recurrent nevus versus melanoma (melanoma). (e) Spitz nevus.
Fig. 11.10 Melanoma, superficial spreading with pagetoid spread.
Role of Dermatopathology in the Surgical Management of Skin Cancer
220

pathologist. However, there are certain red flags that surgeons
can be aware of which should reflexively lead to a second path-
ologist’s opinion ( Table 11.3). When a second opinion is
sought, it should often be from a dermatopathology group at a
tertiary-care center who more regularly diagnose melanomas,
and who has access to ancillary diagnostic tests which can aid
in the di erential diagnosis.
11.4.1 Diagnostic Aids in Melanoma
Comparative Genomic Hybridization
Ancillary tests that assist in distinguishing potentially lethal mel-
anomas from benign melanocytic nevi with atypical histopatho-
logic features are available. The arguably most robust ancillary
method that has emerged over the past decade is cytogenetic
analysis. Based on the pioneering work by Bastian and col-
leagues, melanomas were found to commonly carry chromoso-
mal copy number changes, while these are absent or rare in
nevi. The preferred cytogenetic method is comparative genomic
hybridization (CGH), because it tests all chromosomes. CGH
determines DNA copy number by the competitive hybridization
of two di erentially labeled DNA populations (tumor DNA and
normal control DNA) hybridized to a substrate (representing the
genome). The ratio of the two di erentially labeled signals is
used to determine increases and decreases in copy number of
tumoral DNA at a given genomic coordinate. Multiple studies
have shown semi-characteristic chromosomal gains and losses
in melanomas that were not seen in nevi.31,32 Isolated 11p gains
were seen in Spitz nevi and not melanomas.32 Higher resolution
array-based CGH studies have allowed for the identification of
recurrent genetic abnormalities more common in unique types
of melanomas arising in various contexts (Table 11.4).33
Fluorescence In Situ Hybridization
Multiprobe fluorescence in situ hybridization (FISH) assays,
w hich were based on existing CGH data, have been tested in
their ability to discrim inate m elanomas and nevi. Of the var-
ious combinations tested, those probes to loci 6p25 (RREB1),
6p23 (MYB), CEP6 (Centrom ere 6, for discrimination of
aneuploidy and polyploidy), and 11q13 (CCND1) proved to
have the highest sensitivity and specificity ( Fig. 11.11 and
Table 11.5).34 This probe set shows a range of reported
sensitivities and specificities depending on the diagnostic
problem and particular study ( Table 11.635). Multiple stud-
ies using the sam e four-probe FISH set have reported
Table 11.3 Common scenarios for requesting a second opinion in the di-
agnosis of melanocytic lesions
Lesions with overlapping or
ambiguous histopathologic
features
Dysplastic nevi
Spitzoid lesions
Obscuring histopathologic features Inflammation
Regression
Melanocytic lesions arising in
association with a previous biopsy
Unusual clinical features

Young age, unusual location
Table 11.4 Recurrent genomic/genetic abnormalities in unique melano-
ma types
Melano-
ma sub-
type
Cutane-
ous non-
chronic
sun dam-
age
Cutane-
ous
chronic
sun dam-
age
Acral

Mucosal Uveal
Chromo-
some
gains/
amplifica-
tion
1q, 6p, 7,
8q, 17q,
20q
1q, 6p, 7,
8q, 11q,
17q, 20q
4q, 6p, 7,
8q, 17q,
20q
5p15,
11q13,
12q14
1q, 6p, 7,
8q,
11q13,
17q, 20q
1q31,
4q12,
12q14
6p, 8q
Chromo-
some
losses
6q, 9p, 10 6q, 9p, 13 6q, 9p,
10, 11q,
15q, 16q,
21q
3q, 4q,
6q, 8p,
9p, 10,
11p, 11q,
21q
1p, 3, 6q,
8p
Gene al-
teration
BRAFmut
NRASmut
PTENdel
NRASmut
KITmut
CCND1mut
KITmut
p16del
CDK4amp
KITmut
p16del
CDK4amp
GNAQmut
GNA11mut
BAP1del
Abbreviations: mut, mutation; del, deletion; amp, amplification.
Fig. 11.11 Melanoma fluorescence in situ hybridization: Most cells
show three red signals (6p), two green (11q), two cyan (CEP6), and
one to two gold (6q).
Table 11.5 Cuto s of four-probe FISH criteria for genomic abnormalities
consistent with melanoma
FISH criteri-
on
6p25
(RREB1) ab-
solute gain
(>2 signals/
cell)
6p25
(RREB1) rel-
ative gain
(6p25/
CEP6 >1)
6q23 (MYB)
relative loss
(6q23/
CEP6 <1)
11q13
(CCND1) ab-
solute gain
(>2 signals/
cell)
Cutoff

>29% tu-
mor cells
>55% tu-
mor cells
>40% tu-
mor cells
>38% tu-
mor cells
Abbreviation: FISH, fluorescence in situ hybridization.
Role of Dermatopathology in the Surgical Management of Skin Cancer
221

diagnostic utility for distinguishing m elanoma from nevi,36,
37,38 and particular utility in various diagnostically di cult
circumstances ( Table 11.6). Of note, pigmented spindle cell
nevi-like39 and desm oplastic m elanom a40 have reduced FISH
sensitivity (73 and 47%, respectively). Hom ozygous loss of
9p21 (CDKN2A) and gains in 8q24 (MYC) are additional FISH
param eters for the diagnosis of cutaneous m elanoma. When
such probes are used in com bination with the previously
m entioned four probes, the sensitivity and specificity of the
test is improved to 94 and 98%, respectively, in unam biguous
lesions.41,42,43,44,45
Additional studies w ill be needed to
determ ine the sensitivity and specificity in am biguous
lesions. Due to the possibility of false-negative or false-posi-
tive cytogenetic test results, CGH and, in particular, FISH
data need to be carefully correlated with clinical and histo-
pathologic findings. A diagnosis should not solely be based
on cytogenetic results.
Myriad MyPath
In addition to FISH, gene expression m icroarray studies have
attempted to distinguish primary cutaneous m elanom as
from various types of nevi. Myriad Genetics, Inc. has devel-
oped a 23-gene expression signature clinically validated to
di erentiate benign nevi from MM with a sensitivity of 89%
and a specificity of 93%.46 The genes in this expression sig-
nature include those involved in im mune function and those
involved in cell di erentiation and cell cycle. However, this
test is currently of unproved value for am biguous lesions,
since the test has so far only been compared to consensus
diagnoses of the diagnostically straightforward nevi and
m elanoma.
Immunohistochemical Stains in Melanoma
Although various investigators have at various tim es claim ed
that imm unohistochem istry can aid in the distinction of
nevus from m elanom a, there are no robust data available,
and we caution against using staining patterns, such as for
HMB-45 and p16 for diagnosis.47 It is also questionable
w hether im m unohistochem istry, such as for p16, has
independent prognostic significance.48 The m ain value of
imm unohistochem istry is to verify the line of di erentiation
of am elanotic tum ors, such as for the distinction of m ela-
noma from sarcom a, and better visualization of melanocytes
in the context of inflamm ation (e.g., lentigo maligna with
lichenoid inflamm atory reaction) or improved detection of
sm all m elanocyte deposits in the sentinel lymph node. More
recently, imm unohistochemistry has also becom e relevant
for a quick assessment of m utation status, such as by using
the antibody VE1 to detect the m ost comm on form of BRAF
gene mutation—BRAFV600E.49
11.4.2 Histologic Subtypes of
Melanoma
The common melanoma histologic subtypes, superficial spread-
ing melanoma, nodular melanoma, and desmoplastic and len-
tigo maligna melanoma, show fairly good clinicopathologic and
molecular concordance, but have no prognostic significance
beyond that a orded by Breslow’s thickness. Their categorically
discrepant clinical presentations and skewed molecular signa-
tures are of interest, however, in so much as they may lead to
variant algorithms for treatment when additional targeted
therapies become available. This histologic subclassification
also brings to light various clinical and histologic mimickers,
and they are included below for interest.
Superficial Spreading Melanoma
MM is typically characterized by a proliferation of malignant
m elanocytes, which begins to grow horizontally along the
derm al–epiderm al junction and within the epiderm is, as
part of the radial growth phase, prior to entering the verti-
cal growth phase characterized by progressively thicker
derm al involvem ent. This relationship shows a broader
intraepidermal component than dermal component. The
m ost comm on of m elanom a subtypes, these lesions are
often characterized by pagetoid spread of m elanocytes above
the dermal–epiderm al junction; irregularly shaped, sized,
and placed m elanocytic nests; and consumption of and cleft-
ing from the epidermis. Superficial spreading m elanoma is
typically found on interm ittently sun-exposed areas as well
as arising from pre-existing nevi. The m ain di erential diag-
nosis is with dysplastic nevi; nevi of special sites such as
scalp, breast, or genitals; traumatized nevi; or persistent/
recurrent nevi. The most comm on genetic driver in superfi-
cial spreading m elanom as is BRAF m utation, which appears
to correlate with more epithelioid cytology in tumor cells
and more pagetoid scatter of tumor cells.50,51,52
Superficial spreading melanoma will typically show mostly
epithelioid cytomorphology. In banal nevi, melanocytes are
often more epithelioid the younger the patient’s age is. Indeed,
Spitz nevi, which occur mostly in children and young adults,
are the most epithelioid of all nevi. Congenital nevi are typically
very epithelioid superficially, often with patchy single cells in
the epidermis. However, their overall architecture is very
orderly with marked maturation upon descent into the dermis.
Epithelioid cytomorphology in older individuals with back-
ground sun damage should cause pause and closer examination
to exclude a nevoid melanoma.
Table 11.6 Utility of FISH in the diagnosis of melanocytic lesions
Diagnostic problem

FISH sensitivity/specificity
Nevus vs. Melanoma

80–95%; 90–98%
Histopathologically ambiguous
melanocytic tumors
43–100%; 50–80%
Subcapsular nodal nevus vs.
metastatic melanoma
Microstaging primary melanomas
arising in precursor nevi
Primary nevus vs. nevus-like
metastatic melanoma
Prognosis of melanoma
Abbreviation: FISH, fluorescence in situ hybridization.
Role of Dermatopathology in the Surgical Management of Skin Cancer
222

Nodular Melanoma
The nodular subtype of melanoma contains, by definition, a
larger, broader, dermal component of malignant melanocytes
than that in the epidermis. It suggests loss of senescence, and
proliferative advantage early on in the neoplastic process. The
main di erential diagnosis in these types of melanoma includes
intradermal or primarily intradermal Spitz nevi and metastatic
melanoma. The diagnosis of intradermal Spitz nevus should
only comfortably be made when the histologic criteria are per-
fect for Spitz nevi, the patient is young (<40 years old), and his-
tologic evidence of significant sun damage is lacking. The
distinction between metastatic melanoma is often a clinical
one, based on patient history. It should be noted, however, that
cutaneous metastases can show significant epidermotropism,
mimicking a primary melanoma.
According to some reports, nodular melanomas are more
common on intermittently sun-exposed areas in patients with
pale skin and few nevi.53 Some reports also suggest a worse
outcome in nodular subtype that is independent of tumor
thickness, ulceration, Clark’s level, and mitotic count.54 The
main genetic drivers of these lesions are NRAS or BRAF muta-
tions, which are mutually exclusive in melanoma in general.55
Lentigo Maligna Melanoma
Lentigo maligna melanomas typically develop on the face or
other sun-exposed areas in elderly patients and are related to a
history of chronic sun exposure. As such, biopsy specimens show
abundant solar elastosis and actinic changes in keratinocytes.
Melanocytes are arranged in a lentiginous or “lining up” pattern
along the dermal–epidermal junction (Fig. 11.12), with fre-
quent involvement of hair follicles and frequent upward migra-
tion in the epidermis. Cytologically, the cells typically show high
nuclear to cytoplasmic ratios, with increased retraction artifact
from surrounding keratinocytes and nuclear hyperchromasia
with irregular nuclear contours. Epithelioid morphology with
vesicular chromatin and enlarged nucleoli can also be seen. The
main di erential diagnosis is with actinic melanocytic hyperpla-
sia, pigmented actinic keratosis, dysplastic nevi, and even lichen-
oid keratosis. Genetic drivers in LMM most commonly include
NRAS mutations, and rarely c-kit mutations.53,55
Because most melanocytic nevi are known to regress as we
age, the diagnosis of an atypical or “dysplastic” junctional lenti-
ginous nevus on sun-damaged skin in elderly patients (espe-
cially when the lesion is clinically at least 6 mm in diameter) is
rarely to be made. Clinicopathologic experience has trained der-
matopathologists to have a low threshold for calling lentigo
maligna in this setting, especially considering the low degree of
cytologic atypical often seen in these lesions, and their propen-
sity to show field e ect, skipping around the dermal–epidermal
junction quite broadly.
Acral Lentiginous Melanoma
Acral lentiginous melanoma (ALM) occurs on the palms, soles,
and nail beds, and is named based on both its location and its
histologic pattern of growth. This melanoma subtype is the
most common type to occur in dark-skinned patients, and is
not thought to be related to sun exposure. As such, biopsy
specimens show a somewhat similar arrangement to that seen
in lentigo maligna, that is, lentiginous growth of atypical mela-
nocytes along the dermal–epidermal junction, with disorgan-
ized nest size and placement, and frequent upward migration
of nests and single cells within the acral epidermis. Cytologi-
cally, the cells typically can resemble those seen in lentigo
maligna with high nuclear to cytoplasmic ratios, increased
retraction artifact, and nuclear hyperchromasia with irregular
nuclear contours. Epithelioid morphology with vesicular chro-
matin and enlarged nucleoli can also be seen (Fig. 11.13). The
main di erential diagnosis is with acral nevi, which notoriously
show overlapping architectural features of melanoma, possibly
related to trauma. Genetic drivers in ALM can include BRAF,
NRAS, and KIT. BRAF mutations were identified in 17% of the
primary ALMs; and both NRAS and KIT mutations were found
at a similar frequency of 15% in a study of 88 ALMs by Zebary
Fig. 11.12 (a) Lentigo maligna melanoma (low power). (b) Lentigo maligna melanoma (high power).
Fig. 11.13 Acral melanoma.
Role of Dermatopathology in the Surgical Management of Skin Cancer
223

et al.56 Similar rates of BRAF mutations were found in a Japa-
nese cohort in a study by Hong et al, where BRAF-positive
tumors showed improved outcome as well.57
Because of the overlapping, particularly architectural, fea-
tures of acral melanoma and acral nevi, the increased fear of
overdiagnosis due to functional location, and the often incom-
plete biopsy sampling of lesions, acral melanomas have
increased potential for misdiagnosis. As such, a low threshold
for a second pathologist’s opinion is prudent, especially in new
lesions in adults.
Desmoplastic Melanoma
Desmoplastic melanomas are the rarest subtype. They are char-
acterized by narrow, spindled melanocytes with subtle nuclear
atypia, associated with a fibrotic stroma (Fig. 11.14). Tumor
cells often extend deeply into the subcutis along fibrous septae,
but can be di cult to delineate without the help of IHC stains,
due to histologic overlap with scar and other neurofibromatous
proliferations. Some reports suggest that these lesions do better
clinically, compared to their similarly staged counterparts, with
increased tendency for local recurrence and decreased ten-
dency for metastatic spread.58
Desmoplastic melanomas need not have an epidermal com-
ponent, but when they do, it is often lentigo maligna, which is
known to frequently invade in a desmoplastic fashion. The main
di erential diagnosis for DM includes atypical neurofibromas,
malignant peripheral nerve sheath tumors, and nonspecific
increases in dermal fibroblasts. Desmoplastic melanomas usu-
ally lack BRAF mutations.59 Rare cases may carry NRAS muta-
tions. Mutations of TP53 and NF1 are common in desmoplastic
melanoma.60
11.4.3 Pathologic Parameters for
Melanoma Management
Beyond general clinical data elements including tumor site, lat-
erality, and specimen type, the pathologic data elements
required or recommended for inclusion in the structured
reporting protocol for cutaneous melanoma are listed in
Table 11.7 and highlighted below. In addition, some have
argued for the presence and amount of desmoplastic melanoma
to be included as core requirements in the reporting of mela-
noma due to the evidence showing this type to have improved
survival and reduced rate of lymph node metastasis.58
11.4.4 Breslow’s Thickness
Of all the parameters reported for cutaneous melanoma, Bre-
slow’s thickness holds the most prognostic significance for
localized melanoma. It is the primary determinant of tumor
stage within the TNM staging system. Breslow’s thickness is
determined by measuring the distance of the deepest invasive
tumor cell across the broad tumor base from the top of the
overlying granular layer of the epidermis. Breslow’s thickness is
only accurate in sections cut perpendicular to the epidermis.
However, in some tangentially sectioned specimens, Breslow’s
thickness can be measured tangentially, given that it can typi-
cally be inferred that the true Breslow’s thickness is not greater
than the tangential measurement. A statement to this e ect can
be included in the report. In the case that the epidermis is
ulcerated in the region overlying the deepest tumor extent, the
measurement is taken from the ulcer base. Deep vertical tumor
extensions perpendicular to the tumor base are assumed to be
periadnexal and are not included in Breslow’s thickness, except
if they are the only invasive focus. In that particular case, the
Breslow’s thickness may be measured from the inner layer of
the outer root sheath of the follicular epithelium or the inner
luminal surface of sweat glands. Microsatellites and areas of
tumor regression without visible tumor are not to be included
in Breslow’s thickness.61,62 Although controversy exists, tumor
regression in melanoma has not consistently proven to have an
independently positive or negative impact on melanoma-spe-
cific disease-free survival or overall survival.62
Fig. 11.14 Desmoplastic melanoma.
Table 11.7 Pathologic data elements included in the structured report-
ing protocol for cutaneous melanomas
Required pathologic data

Recommended pathologic data
● Procedure (e.g., biopsy, excision)
● Specimen laterality
● Tumor site
● Tumor size (required only if
tumor is grossly present)
● Presence of macroscopic satellite
nodule(s) (required for excision
specimens only)
● Histologic type (e.g., superficial-
spreading, nodular, lentigo mali-
gna)
● Maximum tumor thickness
(Breslow)
● Presence of ulceration
● Margins (including distance of
margin uninvolved by invasive or
in situ tumor)
● Mitotic rate (per mm2)
● Presence of microsatellitosis
● Presence of lymph-vascular
invasion
● Lymph nodes (required only if
lymph nodes are present in the
specimen)
● Pathologic staging (pTNM)
● Macroscopic pigmentation
(e.g., none, diffuse, patchy)
● Anatomic level (Clark’s level)
● Presence of perineural invasion
● Presence of tumor-infiltrating
lymphocytes
● Presence of tumor regression
● Growth phase (e.g., radial, ver-
tical)
● Additional pathologic findings
(e.g., nevus remnant)
Abbreviation: pTNM, pathologic, tumor, lymph nodes, metastasis.
Source: Adapted from
Role of Dermatopathology in the Surgical Management of Skin Cancer
224

The Breslow’s thickness is measured with an ocular micro-
meter in millimeters. Tumors less than 1 mm thickness have
traditionally been considered “thin melanomas,” and are Stage
1 by definition (either 1A or 1B depending on additional fac-
tors). Depending on the look of the sampled tumor, the derma-
topathologist may decide to cut deeper levels into the para n
tissue block to ensure the deepest extent of tumor is available
for measuring, permitting accurate staging.
Because of the importance of Breslow’s thickness, punch
biopsy for suspected melanomas has been advocated. From the
dermatopathologists’ perspective, this approach should only be
employed if the diameter of the lesion is smaller than the diam-
eter of the punch biopsy piercing tool. It is important for the
entire breadth of the lesion to be available for examination in
order to evaluate symmetry, nest placement, and many of the
other features that discriminate melanomas from dysplastic
nevi or Spitz nevi. If the lesion is clinically too large, two alter-
native biopsy approaches include a “scoop shave” or sauceriza-
tion biopsy technique, or an excisional biopsy. Scoop shave
biopsies typically allow for complete visualization of the lesion
across the horizontal plane, and allow many di erent cuts into
the tumor, facilitating the evaluation of depth, ulceration, mito-
ses, etc. That said, scoop shave biopsies risk transecting the
tumor at the biopsy base, thus precluding accurate measure-
ment of Breslow’s thickness, and hence tumor staging. When
strong clinical suspicion for melanoma exists, a small excisional
biopsy may be the best method. In this way, the tumor can be
visualized across its entire breadth, and depth, with little
chance of transection at the base. Large primary excisions
should be avoided due to the theoretical risk of lymphatic
drainage disruption with healing and hence impaired accuracy
of SLNBx that may follow. In addition, when larger tissue sam-
ples are submitted, less cuts through the center of the lesion
may be histologically visualized following biopsy bread loafing.
A majority of studies show that melanoma biopsies are sub-
mitted fairly evenly as punch biopsies shave biopsies and exci-
sional biopsies. Published reports appear to show no di erence
in patient outcome based on the biopsy type.63 Often times,
regardless of the biopsy type, and regardless of whether tumor
was present at the peripheral or deep aspects of the biopsy
margins, residual tumor is not found in the wide excision speci-
men. Whether this is a function of residual tumor destruction
by tissue macrophages during wound healing, or of the propen-
sity for bread loafing of large excisional specimens to miss
microscopic residual disease that may remain within the paraf-
fin block, is unclear and has not been studied.
11.4.5 Ulceration
Primary melanoma tumor ulceration, as defined by intraepider-
mal tumor growth which leads to denudation/erosion of the
epidermis with consequent exposure of lesional cells to the
external environment, ranks second to Breslow’s thickness in
primary tumor prognostic factors. Within a given pathologic T
stage, ulceration will upstage a lesion from an A to B, which can
consequently lead to clinical upstaging, and hence worse prog-
nosis. The mechanism behind the conferred worse prognosis is
proposed to relate to an implied increase in tumor proliferative
index.64 Additionally, there is potential for artificial reductions
in Breslow’s thickness, due to erosion of the granular epidermal
layer and the practice of tumor measurement from the ulcer
base in these instances. Finally, ulceration induces a host re-
sponse characterized by the formation of granulation tissue and
wound healing processes also reported to facilitate metasta-
sis.65 Indeed, ulcerated lesions show a relative increase in hem-
atogenous spread compared to nonulcerated lesions.66
While there appears to be agreement among dermatopathol-
ogists for Breslow’s thickness, more subjectivity appears to exist
in the assessment of ulceration. Within the di erential diagno-
sis for tumor ulceration is tumor traumatization. True tumor
ulceration with its prognostic implications should show thin-
ning of the epidermis to the side of the epidermal defect, other-
wise known as “consumption of the epidermis” which leads to
“attenuative ulceration.” Such findings would not be expected
in ulceration resulting from trauma alone.
11.4.6 Mitotic Count
The newest prognostic tumor feature to be included in the AJCC
staging system is tumor dermal mitoses per square millimeter.
The tumor mitotic count should be initiated in the most mitoti-
cally active area or “hot spot” and continued in adjacent fields
until an area corresponding to 1 mm 2 is assessed. Depending on
the type of microscope, 1 mm 2 corresponds to approximately 4
to 6 adjacent high power fields at 400 × –40 ×objective with
10 ×ocular. If no hot spot can be found, then several randomly
chosen areas can be counted and summed. When the intrader-
mal component is less than 1 mm 2, a single mitotic figure is
classified as “at least 1/mm 2.”67
The mitotic rate, according to some studies, has been inde-
pendently associated with outcome in melanoma, with the dif-
ference being most marked with increasing mitotic counts.68
The most important implication to this approach, however, is
that previously staged T1a melanoma tumors with any dermal
mitotic activity (>0 Mit/mm 2) are now classified as stage T1b
tumors according to the 2009 revision of the AJCC staging sys-
tem.65 As such, patients who would not have been previously
considered for SLNBx are now often undergoing this procedure
in many centers.69,70 Some have argued that the evaluation of
mitoses is too subjective and confounded by variability in tissue
processing, number of histologic levels obtained, and time
spent searching, for example, to be bestowed with such impact
on management.71 As such, attempts at standardization of this
procedure have been made which include recommendation for
mitotic figures to be sought in the original two levels obtained
with multiple cuts on each level. Additional sections for the
purpose of mitotic count should not be obtained.67 The impact
that this change ultimately has on primary tumor staging, ma-
nagement, and outcome in thin melanomas will be an interest-
ing area of future investigation.
11.4.7 Lymph Node Biopsy
It is required that the number of sentinel and nonsentinel
lymph nodes received and the number with tumor be reported.
The lymph node status is the strongest pathologic predictor of
outcome for cutaneous melanoma patients. Unfortunately, the
method in which sentinel and nonsentinel lymph nodes are
processed varies between medical centers, with SLNBx process-
ing being one of the most nonstandardized processes.72 Dekker
Role of Dermatopathology in the Surgical Management of Skin Cancer
225

and Duncan found that uniform processing practices included1
processing (for para n) all of the lymph node tissue rather
than submitting representative sections and2 use of IHC stains
if no tumor was identified on the H&E-stained sections. They
found significant variability regarding the method of sectioning
lymph nodes at grossing and in the histology laboratory (e.g.,
thickness in mm of lymph node sections at grossing and num-
ber of cuts into the para n block examined histologically).
Most laboratories bisect nodes longitudinally (94%) and place at
least some deeper levels into the block (67%), but these were
not uniform practices. S-100 was the most commonly used IHC
stain (78%), followed by Melan-A (56%), MART-1 (50%), HMB-45
(44%), tyrosinase (33%), MiTF (11%), and pan-melanoma (6%).73
Interestingly, at least two large studies have shown that the
amount of tumor burden seen in SLNBx following routine proc-
essing (typically two H&E levels, and two to four levels for IHC
staining per LN) tends to underestimate the tumor burden
present in the SL, when the para n block is more thoroughly
sectioned into.74,75,76 This may help explain why rare isolated
melanoma tumor cells found in SLNs retain prognostic signifi-
cance regardless of the minute size of tumor involvement. More
intriguing, perhaps, is the fact that patients with SLNBx positiv-
ity detected with enhance pathologic analysis (EPA) which
included at least 20 sections (250 µM apart), as well as those
with negative SLNs by EPA demonstrated improved recurrence-
free and disease-specific survival compared with patients with
SLN disease detected by routine pathologic analysis (RPA).74
This may be due to the fact that most outcome and manage-
ment studies have been conducted using RPA. Furthermore,
when Li et al re-reviewed the histopathology of negative SLNs
from patients who developed regional node field recurrence
after a negative SLN biopsy (2.7% of cases total in a median fol-
low-up of 35.7 months) via multiple further sections cut from
each block and stained with H&E, S-100, HMB45, and Melan A,
they revealed occult tumor in approximately 25% of the cases
available for examination.76 While this study depicts the inher-
ent inaccuracy in SLNBx evaluation due to the impracticality of
histologically evaluating the entire LN, it also points to the rela-
tive rarity of clinical consequence of this inaccuracy, as well as
additional mechanisms which may lead to nodal recurrence in
this setting.
11.4.8 Additional Prognostic Features
While the type of biopsy technique—scoop shave, punch, or
excisional—used in primary melanoma diagnosis does appear
to impact the rate of residual tumor found in the wide excision
specimen, it does not appear to have any impact on SLNBx accu-
racy, rate of positivity, tumor recurrence, or disease-specific
survival.76 Likewise, the length of time between primary biopsy
and definitive treatment has been shown not to impact overall
survival, disease-free survival, and recurrence-free survival
within a 56-day window for definitive surgery.77,78 The pres-
ence of residual tumor in the wide excision specimen does not
appear to impact survival independently from other poor
pathologic factors. The detection of perineural invasion is asso-
ciated with tumor ulceration, desmoplastic and acral lentigi-
nous histologic subtype, and head/neck/hands/feet tumor
location. Although detection of perineural invasion is enhanced
by the use immunohistochemistry, it does not appear to impact
disease-free or overall survival. Routinely detected (H&E stains)
perineural invasion, but not immunohistochemically detected
perineural invasion, was associated with increased risk of local
tumor recurrence.79 In contrast to perineural invasion, immu-
nohistochemistry-aided detection of lymphovascular space
invasion (LVSI;D2–40 and CD34 antibodies) was found by Rose
et al to be a significant marker of both reduced disease-free sur-
vival and overall survival.80 However, Storr et al did not find sig-
nificant and independent association with clinical outcome
using the same IHC markers, although LVSI was positively asso-
ciated with known markers of aggressive disease, including Bre-
slow’s thickness, ulceration, and mitotic count.81
Distance to the surgical margin is included in pathology
reports to ensure that definitive treatment is achieved. Involve-
ment of the surgical margin is known to result in tumor
regrow th and to poorly a ect patient outcome. Wide excision
margin recommendations are based on the tumor thickness of
the primary cutaneous melanoma, and are derived from the
results of numerous randomized controlled trials done in sev-
eral countries.82,83,84,85
Melanoma is known to be one of the most immunogenic
tumors, and is frequently associated with histologic evidence of
a host immune response. Tumor-infiltrating lymphocytes (TIL)
can be characterized based on their level of tumor infiltration
and disruption. Historically, an infiltrate has been considered
“brisk” if it surrounds and infiltrates the tumor base leaving less
than a 0.3-mm defect in the bandlike infiltrate. An infiltrate that
is “present, non-brisk” has a defect that is greater than 0.3 mm.
Around 50% of tumors will show “absent” TIL. The factors which
dictate such host recognition warrant investigation for two
basic reasons. First, numerous studies have shown that patients
whose tumors are briskly infiltrated by TIL have superior clini-
cal outcome and reduced sentinel lymph node tumor spread,
and that this relationship is independent of other primary
tumor factors.86,87,88,89 Second, the magnitude of immune infil-
tration of tumors is positively associated with programmed
death 1 receptor and its ligand (PD-1 and PD-1L) expression in
the tumor microenvironment, and responsiveness to the newly
approved PD-1 inhibitor therapies, pembrolizumab and nivolu-
mab.90,91 The assessment and grading of TIL currently remains
somewhat subjective. That said, the superior e cacy of immu-
notherapy in melanoma will likely demand the development of
methods for pathologic quantification and characterization of
the tumor-infiltrating immune signature in the future.
Although lymphatic spread at the time of melanoma diagno-
sis can be fairly successfully detected with SLNBx, there is cur-
rently no way to detect whether or not hematogenous spread
has occurred at the time of diagnosis. With improved molecular
techniques to detect circulating, cell-free DNA, it is expected
that hematogenously disseminated tumor cells may one day be
detected and intervention be initiated prior to clinical manifes-
tation. This is an area of ongoing investigation.92,93
Castle Biosciences Inc. (Friendswood, TX) has developed a
prognostic test for melanoma, also known as DecisionDx-Mela-
noma, which is a gene expression–profiling (GEP) test that
looks at the messenger RNA expression profile of 28 genes to
identify patients at risk for tumor spread. The data are reported
as either a class I (low risk) or class II (high risk) signature. This
assay has been shown to be an independent prognostic marker
for cutaneous melanoma in multivariate analysis94 and may one
Role of Dermatopathology in the Surgical Management of Skin Cancer
226

day be adopted as a frontline test to identify Stage I–II patients
who may benefit from adjuvant systemic therapy following
wide excision.
11.5 Merkel’s Cell Carcinoma
Merkel’s cell carcinoma is a primary neuroendocrine tumor of
the skin, derived from Merkel’s cells, which are inconspicuously
distributed among basal keratinocytes in the epidermis and are
involved in discrimination of light touch. Although still rela-
tively rare, MCC appears to be increasing in incidence. The rise
in incidence is thought to be due to the larger population of
patients who are elderly and who are immunosuppressed, and
relates to the mechanistic initiation of carcinogenesis by the
Merkel’s polyomavirus in approximately 80% of cases in the
United States.95 This virus is one of the thirteen known polyo-
maviruses that naturally infect humans,96 and one of six viruses
thus far implicated in human malignancy. While approximately
60% of patients have the MPV in their skin flora, most of these
do not develop MCC.97
Histologically, MCC is typically a dermal-based proliferation
of small to medium-sized cells with scant cytoplasm, high
nuclear to cytoplasmic ratio, finely clumped, salt and pepper
chromatin, and no nucleoli ( Fig. 11.15a, b). The main morpho-
logic di erential diagnosis is with metastatic small cell carci-
noma of the lung, BCC, and lymphoma. As such, confirmation
with IHC staining is almost always required. MCC will stain pos-
itively with pan-cytokeratin markers such as CAM5.2 and AE1/
3, typically in a perinuclear dot-like pattern, and negatively for
the follicular epithelial marker characteristic of BCC (BerEP4),
and the lymphoid marker CD45. To rule out cutaneous involve-
ment by metastatic small cell lung carcinoma, it is prudent to
always stain MCC with TTF-1 and CK20. MCC will be negative
for TTF-1 and CK7, and positive for CK20 in more than 95% of
cases, although rare CK20-negative cases exist. Meanwhile,
small cell lung carcinoma will be positive for TTF-1 and CK7 in
Fig. 11.15 (a) Merkel’s cell carcinoma, nodular (H&E, low power). (b) Merkel’s cell carcinoma, nodular (high power). (c, d) Merkel’s cell carcinoma,
nodular (CK20, synaptophysin). (e) Merkel’s cell carcinoma, infiltrative (low power).
Role of Dermatopathology in the Surgical Management of Skin Cancer
227

more than 80% of cases, and negative for CK20. Perinuclear
staining with CK20 is particularly specific for MCC in this set-
ting, and neuroendocrine markers, such as synaptophysin, will
also be positive ( Fig. 11.15c, d). Indeed, NCCN guidelines call
for confirmatory immunostains to establish the diagnosis of
MCC, preferable with CK20 and TTF-1.98
11.6 Prognostic Features Reported
The only relevant features to be reported for Merkel’s cell carci-
noma beyond the diagnosis include tumor size, the presence or
absence of lymphatic invasion, and margin status.99,100,101,102,103
It is possible that in the future, knowledge of the viral status
and CD8-positive TILs may be clinically relevant and therefore
beneficial to report. Virus-positive tumors tend to be mutation-
poor. Virus-negative tumors often occur in older individuals,
are more common in areas of high UV exposure, such as Aus-
tralia, and are rich in mutations typical of a UV signature. Virus-
negative tumors may be pure or associated with squamous cell
or other carcinomas. Studies mostly suggest that MCPyV DNA-
positive tumors are associated with relatively improved clinical
outcome compared to virus-negative tumors, although not all
studies confirm this.103,104,105 Superior outcome in virus-posi-
tive tumors would seem to parallel data in head and neck squa-
mous cell carcinomas, for instance, where human papilloma
virus–associated tumors have improved outcome. It is postu-
lated that the improved survival in this setting is related to
increased tumor recognition by host immune cells, and there-
fore increased tumor control, and increased synergy with
chemotherapy and radiation.106 As such, further reports have
shown that increasing density of tumor-infiltrating CD8 +T-
lymphocytes (TIL) is associated with improved survival in
MCC.107,108,109 For this reason, viral status testing and TIL quan-
tification may one day become a part of the tumor report. The
tumor growth pattern (nodular or infiltrative) and the presence
of secondary malignancy (typically squamous cell carcinoma)
are other pertinent pieces of information typically reported,
with some reports showing survival advantage with nodular
(Fig. 11.15a) compared to infiltrative ( Fig. 11.15e) growth
pattern.99
11.6.1 SLNBx Evaluation
As with most other tumors, SLNBx has been increasingly uti-
lized in the management of MCC. There have been conflicting
reports as to the utility of this procedure, and the information
gained from it, to direct management decisions or aid in prog-
nostication.110,111,112,113,114,115 There is conflicting evidence on
the prognostic value of the SLNBx in patients with MCC.114,115 A
therapeutic benefit by the procedure has not been proven. For
histopathologic analysis of the SLN status, pathologists often
use CK20116 for best identification of tumor cells in the lymph
node. Recent studies by our group suggest that patients with
microscopic stage III disease may be prognostically stratified
based on a solid versus non-solid pattern of sentinel lymph
node involvement by MCC, among other factors.117 Confirma-
tory studies in a larger cohort are needed.
11.7 Cutaneous Sarcomas
Cutaneous sarcomas vary widely in both their histomorphology
and clinical outcome, and are relatively rare. For this reason,
they are often and should often result in diagnostic consultation
within pathology. Due to the histologic overlap with various
benign and malignant processes, as well as the varied morpho-
logic subtypes within each tumor type, IHC staining may be a
requisite for almost all cutaneous sarcomas for correct identifi-
cation ( Table 11.8). Compared to sarcomas located in the
deep soft tissues, dermal sarcomas can show significant nuclear
pleomorphism and still behave in a relatively indolent
fashion.118
11.7.1 Angiosarcoma
Angiosarcoma is a malignant sarcoma derived from vascular
endothelial cells. Cutaneous angiosarcoma comprises approxi-
mately half of all angiosarcomas, and occurs in two basic set-
tings. Primary angiosarcoma occurs on sun-exposed areas,
primarily head and neck, of older individuals. While primary
angiosarcoma is thought to be related to sun exposure, due to
the strong predilection to a ect sun-exposed skin of older Cau-
casians, this has not been directly proven. Secondary angiosar-
coma occurs following surgery, in the setting of Stewart-Treves
syndrome due to chronic lymphedema, and following radiation,
as postradiation angiosarcoma.119 Up to 100% of secondary
angiosarcomas may show amplification in the MYC onco-
gene.120,121 Angiosarcoma, although always considered biologi-
cally high grade, can show variable degrees of vascular
di erentiation, and the amount of di erentiation in a given
tumor will dictate which other conditions come into the di er-
ential diagnosis. Highly di erentiated tumors can be di cult to
distinguish from unusual benign hemangiomas, because they
Table 11.8 Immunohistochemical stains useful in the diagnosis of cuta-
neous spindle cell lesions and sarcomas
Immunohistochemical stain
Tumor

Cytoker-
atin
S-100 Melano-
cytic
markers
(Melan-
A, HMB-
45)
SMA Des-
min
Endo-
thelial
markers
(CD31,
CD34)
Sarcomatoid
SCC
+

-

-

-

-

-
Spindle cell
melanoma
-

+

-/ +

-

-

-
AFX

-

-

-

-/ +

-

-
Leiomyosar-
coma
-/ +

-

-

+

+

-
Angiosarco-
ma
-/ +

-

-

-

-

+
Abbreviations: AFX, atypical fibroxanthoma; SCC, squamous cell
carcinoma; SMA, smooth muscle actin.
Role of Dermatopathology in the Surgical Management of Skin Cancer
228

form distinct vascular channels lined by mildly atypical endo-
thelial cells which, nevertheless, show an infiltrative pattern of
growth ( Fig. 11.16a). Most angiosarcomas show moderate dif-
ferentiation and consist of irregularly shaped and sized vascular
channels which travel in unique planes and wrap around and
splay collagen bundles. These channels often anastomose in an
irregular, sieve-like fashion and can be filled with erythrocytes
or clear fluid (Fig. 11.16b). Poorly di erentiated tumors may
not be distinguishable from poorly di erentiated carcinomas,
melanoma, or other sarcomas, and may consist of sheets of
highly atypical, epithelioid cells with significant nuclear pleo-
morphism (Fig. 11.16c). In this setting, more well-di erenti-
ated areas may provide diagnostic clues, and IHC staining
specific for vascular endothelial cells, CD31, CD34, and ERG,
provide confirmation (Fig. 11.16d-g). Extravasated erythro-
cytes can be an additional diagnostic clue.
Outcome in angiosarcoma is linked to a number of factors,
including patient age, tumor size, and surgical margin status. In
general, outcome in angiosarcoma may be more closely linked
to clinical factors compared to histologic factors, because the
systems commonly used in tumor grading do not lend them-
selves well to angiosarcoma. The various subtypes of angiosar-
coma, including soft-tissue angiosarcomas, are often grouped
together for study purposes, due to the rarity of the disease,
and this may confound precise prognostic categorization. That
said, older patients have a worse prognosis than their younger
counterparts; tumor size is strongly linked to outcome, clinical
extent of disease, and tumor resectability; and margin status is
Fig. 11.16 (a) Angiosarcoma, well-differentiated (low and high power). (b) Angiosarcoma, moderately-differentiated. (c, d) Angiosarcoma,
epithelioid. (e, f, g) Angiosarcoma, epithelioid, with ERG nuclear staining positivity.
Role of Dermatopathology in the Surgical Management of Skin Cancer
229

an important determinant of outcome, based on several stud-
ies.122,123,124,125 Patients whose tumors are less than 5 cm and
completely excised with negative margins have improved prog-
nosis. As such, the most important part of the pathology report
for angiosarcoma will be histologic margin status (in addition to
tumor size which may be clinically apparent). Margin status
will become more di cult to evaluate with increasing di eren-
tiation of the tumor, especially considering the subtle and far-
reaching manner in which angiosarcomas can travel. For this
reason, Mohs surgery may be technically unsatisfactory, while
CCPDMA is a practical alternative. Due to the known hematoge-
nous, rather than lymphangitic manner in which angiosarcoma
disseminates, lymph node biopsy has not been employed in this
disease.
Atypical Fibroxanthoma
Atypical fibroxanthoma (AFX) is an undi erentiated tumor, typ-
ically occurring in sun-damaged skin, often with some fibrohis-
tiocytic/myofibroblastic features. By definition, the tumor does
not involve the subcutis or deeper structures. Because of the
presence of mesenchymal cell malignant atypia and associated
genomic aberrations, AFX is in essence a sarcoma. That said, the
term “AFX” is preferable to avoid overtreatment, since strictly
defined tumors (no extension beyond the dermis on multiple
levels) tend to be indolent following complete excision. A tumor
with the appearance of an AFX that involves the subcutis or
deeper structures is best reported as pleomorphic dermal-
based sarcoma and is clinically/surgically managed more
aggressively. Histologically, the cells of an AFX are arranged in
fascicles or sheets. Rarely, a storiform pattern is evident. The
cells are spindled to round, with multinucleation, pleomor-
phism, and numerous typical and atypical mitotic figures
(Fig. 11.17a, b). Immunohistochemically, AFX is typically ne-
gative for both S-100 protein and cytokeratins, allowing distinc-
tion from melanoma and spindled squamous cell carcinoma,
respectively. In addition, pleomorphic leiomyosarcoma and
angiosarcoma can be ruled out with desmin and ERG negativity
as needed. Most cases of AFX also show strong expression of
CD10, but this is not specific. Some cases express smooth
muscle actin, although desmin is typically negative, consistent
with myofibroblastic di erentiation. Aside from these afore-
mentioned entities, which can be ruled out using immunohis-
tochemistry, it is important that AFX be distinguished from a
superficial or dermal undi erentiated pleomorphic sarcoma,
due to the risk of recurrence and metastasis in the latter com-
pared with the nearly uniform excellent prognosis in the for-
mer.126 Aside from correct diagnosis and categorization of AFX,
margin status is the most important prognostic variable to be
included in the pathology report.
Dermatofibrosarcoma Protuberans
Dermatofibrosarcoma protuberans (DFSP) is a cutaneous fibro-
histiocytic tumor of intermediate malignant potential which
can recur locally and rarely metastasizes. It typically presents in
early or middle adult life, although it does a ect pediatric
patients. Histologically, the tumor consists of a uniform dermal
proliferation of spindled cells arranged in a storiform pattern
(Fig. 11.18a, b). The tumor typically extends into the subcuta-
neous fat in an infiltrative pattern, imparting a lace or sieve-like
appearance. The most common entity which enters into the
Fig. 11.16 (continued)
Role of Dermatopathology in the Surgical Management of Skin Cancer
230

di erential diagnosis includes benign fibrous histiocytoma (i.e.,
dermatofibroma), especially the cellular variant. Importantly,
DFSPs will stain di usely positive for CD34 (Fig. 11.18c), and
contain a translocation which results in fusion between the col-
lagen gene COL1A1 on chromosome 17 and the platelet-derived
growth factor-beta gene PDGFβ on chromosome 22 [t(17;22)].
This translocation can be detected by FISH studies, and can be
targeted with the drug imatinib.118,127,128,129
Surgical margin status is the most important predictor of out-
come in DFSP, as well as the presence or absence of fibrosar-
comatous transformation.127
Negative margins can be
technically di cult to achieve due to the tendency of this tumor
to infiltrate with multiple irregular extensions. CD34 staining
may be used to aid in the assessment of margin status, espe-
cially in cases where wide margins are less possible due to
cosmetic locations, etc. In addition, Mohs and CCPDMA
approaches have been used for complex cases, especially in cos-
metic areas.129,130,131
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Role of Dermatopathology in the Surgical Management of Skin Cancer
234

12 High-Risk Cutaneous Malignancies
Sashank K. Reddy and Anthony P. Tufaro
12.1 Introduction
While the incidence of cutaneous malignancies has been rising
in the general population, it has been particularly notable in
certain groups, whom we term high-risk patients. Broadly,
these patients can be divided into two categories: (1) those
with genetic syndrom es conferring a predisposition to skin can-
cer and (2) immunosuppressed patients. The types and num-
bers of malignancies acquired, the aggressiveness of tumors,
the age of onset, their management, and their ultimate outcome
di er in important ways in high-risk patients and in the general
population. Here, we review contemporary understanding of
the etiologies of and approaches to cutaneous malignancies in
high-risk patients.
12.2 Genetic Syndromes
Several genetic syndromes increase the risk of developing cuta-
neous malignancies. These include xeroderma pigmentosum
(XP), Gorlin’s syndrome, Fanconi anemia, Bazex’s syndrome,
and Bloom’s syndrome, among others.1 Below we focus on two
of these rare conditions—XP and Gorlin’s syndrome—that confer
a predilection for nonmelanoma skin cancers, and we also con-
sider genetic predisposition to melanoma.
12.2.1 Xeroderma Pigmentosum
XP comprises a group of disorders with autosomal recessive
inheritance and a prevalence in the United States of 1:250,000
individuals. It is characterized by defects in genes involved in
the nucleotide excision repair (NER) pathway of deoxyribonu-
cleic acid (DNA) repair. This pathway is critical for resolving
mutagenic adducts in DNA that result from ultraviolet (UV)
exposure. Since the pathway is defective in XP patients, their
keratinocytes accumulate numerous mutations, leading to
accelerated tumorigenesis.
Clinically, XP patients have normal skin at birth, but most
show extreme photosensitivity with sunburn occurring even in
infancy.2 A ected children develop innumerable freckles and
other areas of hypopigmentation and hyperpigmentation. Such
patients have a 10,000-fold increase in incidence of developing
nonmelanoma skin cancer and a 2,000-fold increase in incidence
of melanoma.2 Nonmelanoma skin cancers mainly occur on sun-
exposed regions, with 80% occurring on the face, head, and
neck.3 By contrast, approximately 45% of melanomas in these
patients occur in the extremities. Not only do cutaneous malig-
nancies occur more frequently in XP patients, but they also occur
at an earlier age. The median age of onset for nonmelanoma skin
cancer and melanoma are 9 and 22 years, respectively.2 Both are
several decades earlier than in the general population.
The most important step in management of XP patients is
vigorous sun protection including avoiding peak sun exposure,
use of UV-protective clothing and sunglasses, and window tint-
ing. This should be complemented by vitamin D supplementa-
tion. If patients develop cutaneous malignancies, they are
managed through disease- and stage-appropriate surgical and
medical therapies. With these measures, some patients with XP
live well into adulthood.4
12.2.2 Gorlin’s Syndrome
Gorlin’s syndrome, or nevoid basal cell carcinoma (BCC) syn-
drome, is a rare autosomal dominant disorder in which patients
develop BCCs, odontogenic keratocysts, and palmar or plantar
pits. A ected patients can also show various bony developmen-
tal defects. Patients with Gorlin’s syndrome develop numerous
BCCs in their lifetime—up to thousands in some cases.5 Gorlin’s
syndrome patients with fairer skin are at particularly high
risk.5,6,7
Alterations in the Hedgehog (Hh) pathway—a developmental
cascade involved in cell growth and di erentiation—underlie
Gorlin’s syndrome in many patients. Specifically, germline
mutations in the pathway inhibitor Patched (PTCH1) are the
most commonly identified molecular lesions in patients with
Gorlin’s syndrome.8 In the absence of PTCH1 activity, the pro-
tein smoothened (SMO) becomes constitutively active, leading
to transcription of Hh pathway e ectors. This is turn leads to
dysregulation of cell growth and tumorigenesis. The recent clin-
ical development of inhibitors of the Hh pathway, including
several small molecule SMO inhibitors, provides hope for more
e cacious treatment of patients with Gorlin’s syndrome.
Indeed, these agents not only reduce BCC tumor burden, but
also remedy the odontogenic keratocysts and palmoplantar pits
characteristic of the disorder.8 Based on early clinical e cacy,
vismodegib became the first SMO inhibitor to gain the approval
of Food and Drug Administration (FDA) for patients with Gor-
lin’s syndrome in 2012. Better handling of treatment-related
adverse events and methods to combat resistance will be
required, however, before these novel agents achieve their full
promise.
12.2.3 Melanoma
Patients with familial atypical multiple mole melanoma
(FAMMM) syndrome are at a greatly increased risk of develop-
ing melanoma and pancreatic cancer. The disease is defined by
(1) melanoma in one or more first- or second-degree relatives,
(2) high total body nevus count, including atypical nevi, and (3)
specific histologic features of the nevi. FAMMM is inherited in
autosomally dominant fashion with variable penetrance. In up
to 40% of a ected patients, mutations can be found in the
CDKN2A gene which encodes the tumor suppressors p16INK4A
and p14ARF.9 These genes are important for establishing cell
cycle arrest or senescence in damaged cells. In the absence of
CDKN2A gene product activity, incipient tumor cells may be
allowed to progress in the evolution to melanoma.
The large number of nevi that FAMMM patients develop
increases the risk of malignant degeneration. Such patients
should be screened at least every 6 months to document evolu-
tion of nevi. Total body photography and self-examination can
High-Risk Cutaneous Malignancies
235

be valuable adjuncts to identifying nevi requiring further inves-
tigation. Nevi whose appearance changes according to the
asymmetry, border irregularity, color variegation, diameter, ele-
vation or evolution (ABCDE) criteria should prompt early
biopsy. Patients and their immediate family members should
also be referred for genetic counseling. As the number of tar-
geted therapies for melanoma increases, genetic sequencing
may become part of the standard of care for such patients as
well. As with spontaneously occurring melanomas, surgical
excision is the mainstay of management when these lesions
occur in FAMMM patients. Novel immunomodulatory agents for
the treatment of aggressive melanomas will be discussed later.
12.3 Immunosuppression
The number of patients who are chronically immunosup-
pressed has increased markedly in recent decades. This reflects
both natural and iatrogenic causes. The emergence and rapid
spread of human immunodeficiency virus (HIV) since the 1980s
has produced millions of people with severe immunosuppres-
sion worldwide. Autoimmune diseases have also increased in
prevalence over the past few decades, particularly in the devel-
oped world.10 This fact, coupled with the use of immunosup-
pressive medications, has left many people relatively
immunosuppressed during the chronic courses of these dis-
eases. The development of e ective immunosuppressive agents
has also heralded a large increase in organ transplantation since
the pioneering operations of the 1960s. While allogeneic trans-
plants have saved or improved thousands of lives, the require-
ment for lifelong immunosuppression has deleterious
consequences. Most notably, patients with long-term natural or
therapeutical immunosuppression show an increased incidence
of cutaneous malignancies and other cancers. Indeed, the spec-
trum of malignancies encountered in patients with HIV/
acquired immune deficiency syndrome (AIDS) parallels that of
patients on chronic immunosuppression. One recent meta-
analysis found an increased incidence of 20 of 28 cancer types
in transplant and HIV/AIDS patients when compared with the
general populace.11 This suggests that immunosuppression
itself can contribute to the development of cancer. Below, we
first consider the mechanisms by which immunosuppression
may promote cutaneous malignancy. Then we review specific
cases of natural and iatrogenic immunosuppression and con-
sider implications for the emergence and management of cuta-
neous malignancies.
12.4 Basic Science
12.4.1 Immune Surveillance
The concept that the immune system may control or eliminate
malignancies was formally proposed by Thomas and Burnet more
than five decades ago.12,13 Burnet argued that since cells of long-
lived animals naturally accumulate mutations, some of which are
tumorigenic, it is evolutionarily advantageous for the immune sys-
tem to eliminate these cells.13 In its strictest form, this tumor sur-
veillance concept remains controversial, in part because of the
di culty of proving a negative—incipient tumors eliminated by
the immune system are not detected in the clinic. However, a
number of lines of evidence at least indirectly support the notion
that the immune system suppresses cancer development.
If the immune system naturally suppresses cancer growth or
spread, one would predict that patients with impaired immun-
ity would be at higher risk of developing malignancy. This is
indeed the case, both in patients with inherited and acquired
immunodeficiency. Patients with common variable immunode-
ficiency (CVID) who have deficits in antibody-mediated
immunity display an increased risk for lymphoma and various
carcinomas.14,15 Patients with X-linked immunodeficiency with
hyper-IgM (immunoglobulin M) and those with selective IgA
(immunoglobulin A) deficiency are at higher risk for a variety of
gastrointestinal malignancies.15,16 These examples demonstrate
that severe, inherited immunodeficiency predisposes patients
to cancer development, but the rarity of these genetic syn-
dromes limits the generalizability of this finding. Just because
some patients with inherited immunodeficiency develop cancer
more frequently, it does not follow that the immune system in
the much larger group of healthy individuals naturally prevents
tumor development.
More persuasive evidence in this regard comes from patients
who are therapeutically immunosuppressed for autoimmune
disease or for transplantation. It is estimated that over half a
million patients have received organ transplants in the United
States and the increased incidence of various malignancies in
these patients has been amply documented. A recent study of
175,000 solid organ transplant recipients in the United States
revealed an increased risk for 32 types of cancer in patients
who had undergone lung, liver, heart, and kidney transplanta-
tion.17 Notably, the risk was increased both for tumors known
to be caused by oncogenic viruses (implying that a decrease in
antiviral immunity may contribute) and for those in which no
viral cause is known (suggesting that impaired immune surveil-
lance may play a role).17 Strikingly, in a prospective trial of kid-
ney transplant patients on cyclosporine, the incidence of
malignancies increased in a dose-dependent fashion and the
majority of these were cutaneous malignancies.18
The increased risk of carcinogenesis in this group is not solely
explained by decreased tumor surveillance, however. Several of
the agents used in immunosuppressive regimens are them-
selves carcinogenic. In experimental studies, cyclosporine was
shown to increase adenocarcinoma invasiveness and tumor
growth even in mice that are already immunocompromised.19
Similarly, in squamous cell carcinoma (SCC) samples from
patients treated with cyclosporine, there was a significant
increase in the level of activating transcription factor 3 (ATF3), a
transcription factor that can impair p53-dependent cellular
senescence and thereby promote tumorigenesis.20 As with
cyclosporine, use of the immunosuppressive drug azathioprine
is associated with an increased risk of malignancy, in this case
SCC.21 It is thought that azathioprine enhances photosensitivity,
leading to a direct increase in mutagenic adducts in the deoxy-
ribonucleic acid (DNA) of keratinocytes.22 In summary, the
greater propensity for tumorigenesis in transplant recipients
likely reflects an interplay between impaired immune
surveillance, long-term exposure to carcinogenic drugs, and
heightened sensitivity to environmental carcinogens such as
UV light and oncogenic viruses.
High-Risk Cutaneous Malignancies
236