8% of control tissues (16% of control skin tissues) showed MCV sequences [6, 7].

Merkel cell carcinoma is a rare tumor, but the incidence has tripled over the past two decades. The highest incidence rates are in the elderly population [8, 9]. Mean age at diagnosis is 67.9 years, but reports in the literature range from age 15 to 97 years old [10, 11]. Immunosuppression is a risk factor for developing MCC [12, 13]. MCC is more common in patients with organ transplantation, HIV, B-cell lymphoma, or other immunosuppressed conditions [8, 14]. White individuals are more frequently affected than black individuals [11, 12]. MCC also typically occurs in sun-exposed areas, although the exact role of ultraviolet light exposure in the pathogenesis of MCC remains unknown [10, 15]. Areas of the head and neck are most often affected followed by the trunk and extremities [10, 15–17].

Summary: Diagnosis of Merkel Cell Carcinoma

•Merkel cell carcinoma presents as a rapidly growing nodule on sun-exposed skin of elderly individuals.

•Clinical presentation is nonspecific, and biopsy is necessary to establish a diagnosis.

•Merkel cell carcinoma is characterized by a dense dermal infiltrate of small blue atypical cells, staining positive with CK-20 and negative with TTF-1.

24.2Diagnosis of Merkel Cell Carcinoma

24.2.1 Clinical Features

Patient evaluation should begin with a history of the lesion in question, addressing its duration, evolution, symptoms, and previous treatment. The clinical presentation of MCC is non-specific, and diagnosis requires pathologic evaluation. Typically, MCC presents as a rapidly growing, blue, or violaceous solitary nodule on sun-exposed skin of elderly individuals [11]. The surface is usually smooth but can rarely ulcerate. Most primary tumors are <2 cm on presentation [18].

24.2.2 Pathology

Histologic exam reveals a poorly circumscribed, diffuse dermal infiltrate of densely packed atypical small blue cells with scant cytoplasm. The epidermis is usually not involved, and a grenz zone is often present (see Fig. 24.1). Mitotic figures are common, and vascular/ lymphatic invasion can also be seen. Three pathologic subtypes are described in the literature based on cellular pattern: trabecular (rare, less aggressive), intermediate (more common), small cell (most aggressive, can mimic other small cell tumors) [4, 11].

Immunostains are often helpful in differentiating merkel MCC from other small, round blue cell tumors. The most widely used immunostains for MCC include cytokeratin 20 (CK-20) and thyroid transcription factor 1 (TTF-1). MCC stains positive with CK-20 with a sensitivity ranging from 89% to100% [19]. Staining with TTF-1 is negative in MCC which differentiates it from small cell lung carcinoma (SCLC) which can be very similar histologically (SCLC stains positive with TTF-1) [20]. Other neuroendocrine markers positive in MCC include chromogranin A, synaptophysin, neuron-specific enolase, and neurofilament protein (see Fig. 24.2). Leukocyte-common antigen, S-100, and pancytokeratin are useful markers to rule out other diagnoses such as melanoma, squamous cell carcinoma, and leukemia [20]. Staining with cytokeratin or neurofilament protein produces a pattern of perinuclear dot positivity which is specific for MCC [5, 19]. Electron microscopy is also useful in diagnosing MCC as electron dense granules are noted in the cytoplasm [2].

24.2.3 Differential Diagnosis

Since MCC is rarely suspected on initial evaluation, the clinical differential diagnoses are numerous and include other benign and malignant tumors such as adnexal neoplasms, pyogenic granuloma, keratoacanthoma, squamous cell carcinoma, basal-cell carcinoma, atypical fibroxanthoma, melanoma, leukemia, lymphoma, and metastatic carcinoma to the skin. The histologic differential includes other small, round blue cell processes such as small cell lung cancer, leukemia, lymphoma, Ewing’s sarcoma, melanoma, and neuroblastoma.