Chapter 21: Uncommon Cutaneous Malignancies

INTRODUCTION

The management of uncommon and rare cutaneous malignancies can be challenging due the lack of high-quality evidence for guidance. They include a varied group of skin carcinomas that arise from the epidermis or dermis, as well as cutaneous sarcomas.

MERKEL CELL CARCINOMA

Merkel cell carcinoma (MCC) is an aggressive epidermal malignancy of neuroendocrine origin.¹ While uncommon, affecting only 0.6 per 100,000 in the United States, its incidence appears to be increasing.^2,3

MCC usually presents as a bland nonpigmented nodule on the head, neck, or extremities of older, fair skinned patients. The main risk factors are ultraviolet light exposure, age, and immune suppression.^2,4 Merkel cell polyoma virus is integrated into the tumor genome in 80% of cases.⁵ The mechanism of viral oncogenesis remains the subject of investigation but the virus encodes large and small tumor antigens that are required for viral replication and tumorigenesis.⁶ Histologically, MCC is composed of uniform small round cells with basophilic nuclei and minimal cytoplasm (Fig. 21-1).

MCC is characterized by high rates of local recurrence as well as regional and distant metastatic spread. The first consensus staging system was introduced by the American Joint Committee on Cancer (AJCC) in 2010 and classifies MCC as stage I/II if it is localized to the primary site (stage I ≤2-cm size, stage II >2-cm size), stage III if there are regional node metastases, and stage IV if there is spread to distant sites.^7,8 Overall prognosis is poor with 5-year disease-specific survival for patients with stage I/II disease 64%, stage III 39%, and stage IV 18%.⁸ Primary tumor thickness also correlated with survival in a recent analysis of 95 patients⁹ though results of earlier studies provide conflicting evidence. Fluorodeoxyglucose positron emmission tomography/computed tomography (FDG-PET/CT) is increasingly utilized in the staging of MCC. A retrospective series demonstrated that FDG-PET altered the staging of patients with MCC in 22% of cases and resulted in a management change in 37%.¹⁰

The management of MCC requires a multidisciplinary approach that incorporates surgery, radiotherapy, and chemotherapy, and takes into consideration disease stage, tumor site, and patient fitness.

Management of primary MCC has traditionally been surgical with wide excision to fascia with 1- to 3-cm margins, aiming to obtain histologically clear margins when clinically feasible.^11,12 However, the management of MCC is increasingly controversial because the tumor is highly radiosensitive¹ and there is a growing evidence base for the use of radiotherapy as both adjuvant and definitive treatment.

In the adjuvant setting, a review of the literature demonstrated that local recurrence rates were significantly lower after adjuvant primary site radiotherapy (10.5%, range 0% to 33%) than surgery ...