inhibitor approved by the FDA for the treatment of metastatic and locally advanced BCC, tumors

deemed not candidates for surgery or radiation therapy. Initial objective response rates approach 30%

for metastatic BCC and 43% for locally advanced BCC. Partial response rates are 30% for metastatic

BCC and 22% for locally advanced disease. No complete responses were noted for metastatic BCC, and

20% complete responses for locally advanced BCC. Unfortunately, tumors may recur during or after

discontinuation of the drug with a median duration of response about 8 months in both metastatic and

locally advanced BCC patients. Adverse events occur in more than 30% of patients, 25% serious, and

include most often muscle spasms, taste disturbances, alopecia, weight loss, and fatigue. Data are still

immature with future study and long-term results needed for definitive conclusions.

Other Tumors of Interest

Hundreds of cutaneous tumors exist, and their description is beyond the scope of this chapter. Tumors

that may be encountered by the surgeon for further management include Merkel cell carcinoma (MCC),

sweat gland carcinoma, and dermatofibromasarcoma protuberans (DFSP).

8 MCC, or primary cutaneous neuroendocrine carcinoma, is an aggressive skin cancer with a higher

overall mortality than melanoma (approximately 33% vs. 15%, respectively).111 The incidence of MCC

is low compared to other cutaneous malignancies (approximately 1,500 annually in the United States),

but the number of cases has at least tripled over the last two decades.112 While UV radiation and

immunosuppression are considered important pathogenetic factors, recent findings suggest a virus

(Merkel cell polyomavirus) as a contributing factor in the pathogenesis of MCC.113 MCC most

commonly occurs in older, white individuals, with only 5% diagnosed before the age of 50 years. The

majority of tumors (90%) are located on sun-exposed skin, equally distributed between the head and

neck and extremities. The remaining 10% are located on the trunk and buttocks. Primary MCC typically

presents as a new-onset, growing, red or purple, dome-shaped or subcutaneous nodule, frequently

mistaken for a cyst, lipoma, or BCC (Fig. 107-11). The most common location of metastasis is the

draining lymph node basin, followed by distant skin, lung, central nervous system, bone, and liver.114

MCC is a dermal small blue cell tumor with positive immunohistochemical staining for cytokeratin-20

(CK-20) in a characteristic paranuclear dotlike pattern. Small cell lung cancer, another neuroendocrine

carcinoma histologically indistinguishable from MCC and occasionally CK-20 positive, expresses thyroid

transcription factor-1, which is consistently absent in MCC.115 Newly established AJCC staging for MCC

distinguishes stage I (primary tumor <2 cm without nodal disease), stage II (primary tumor ≥2 cm

without nodal disease), stage III (microscopic or clinically apparent regional lymph node metastases),

and stage IV disease (distant metastasis). Five-year survival rates for stages I, II, and III are 81%, 67%,

and 52%, respectively. Stage IV disease carries a dismal 11% 2-year survival rate.98 The majority (70%)

of patients with MCC present with clinically localized disease (stage I or II), 25% have palpable

lymphadenopathy (stage IIIB), and 5% present with distant metastases (stage IV).114 Multidisciplinary

management of MCC is encouraged by the NCCN.116,117 Treatment consists of WLE with 1- to 2-cm

margins. Postoperative radiation therapy to the primary tumor bed should be considered and is

recommended for stage II disease.117,118 SLNB with immunostaining using CK-20 is highly recommended

for all primary MCC to stage the nodal basin and guide regional nodal therapy.116,118–120 Regional

lymph node metastases can be treated by regional therapeutic lymphadenectomy and/or radiation

therapy. Adjuvant radiation therapy to the regional nodal basin should be considered if SLNB is not

performed or is thought to be false negative. For nonsurgical candidates, primary treatment of MCC

with radiation therapy may also be considered.121 Chemotherapy has failed to demonstrate a survival

benefit in an adjuvant setting in the treatment of localized or regional MCC and should be reserved for

distant metastatic (stage IV) disease.122

3168

Figure 107-11. Merkel cell carcinoma.

Sweat gland carcinomas represent a broad scope of neoplasms with variable risk for local, regional, or

distant metastasis, most commonly of eccrine or apocrine origin.123 These are rare tumors (0.005% of

skin malignancies) that have multiple histologic subtypes, giving rise to a diverse and confusing

nomenclature. The aggressive types of sweat gland carcinomas have a propensity for both local

recurrence and regional or systemic metastasis. Clinically, these tumors appear as indurated plaques,

papules, or nodules commonly on the head and neck or extremities and are red, blue, pink, or skin

colored. Histologic subtypes that are associated with a risk of regional lymph node or systemic

metastasis include aggressive digital papillary adenocarcinoma, hidradenocarcinoma, and eccrine

carcinoma. Recommended treatments have included wide excision of the primary tumor with

consideration of SLNB for high-risk lesions commonly based on size, mitotic rate, histologic grade of

atypia, or immunosuppression.123 Postoperative radiation therapy may also be considered as adjuvant

treatment.

9 DFSP is a rare soft tissue sarcoma (1% of all soft tissue sarcomas) with a propensity for local

recurrence rather than systemic metastasis. It is a spindle cell tumor that characteristically demonstrates

immunoreactivity to CD34. Adults in their third to fifth decades are most commonly affected, but DFSP

may occur in children or the elderly. These tumors appear as firm flesh-colored to dull red plaques that

may be mistaken for keloids or hypertrophic scars. Although DFSPs may appear discrete, they

characteristically demonstrate extensive subclinical involvement, which makes this sarcoma difficult to

manage. Histologically, these sarcomas are identified by their fingerlike projections of spindle cells that

likely account for the increased risk of tumor recurrence. Standard histologic processing makes it

difficult to track these fingerlike projections. Treatment commonly consists of WLE with more

comprehensive margin assessment or Mohs surgery, depending on patient and tumor factors. A

multidisciplinary approach utilizing the expertise from several fields (surgical subspecialties, pathology,

Mohs surgery) may be needed to achieve the goals of complete tumor extirpation, low local recurrence

rates, and reconstructive repair.124,125 Reconstruction involving extensive undermining should be

avoided and tissue rearrangement should be delayed until negative histologic margins are confirmed to

prevent possible tumor seeding from persistent disease. Radiation therapy is indicated when negative

margins cannot be obtained.123 Imatinib mesylate has shown promising results in the treatment of

unresectable or metastatic DFSP.126,127

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