Merkel cell carcinoma: A report of gastrointestinal metastasis and review of the literature

Archives of Pathology & Laboratory Medicine,  Mar 2003  by Idowu, Michael O,  Contos, Melissa,  Gill, Satinder,  Powers, Celeste

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* Merkel cell carcinoma (MCC) is an uncommon, highly aggressive cutaneous neoplasm of neuroendocrine differentiation with a poor prognosis. MCC most often presents as a painless, firm, raised lesion in sun-exposed sites of the head and neck region of the elderly. We report a case of a metastatic MCC to the stomach presenting as upper gastrointestinal bleeding. To our knowledge, this is the second reported case of MCC presenting as upper gastrointestinal bleeding and the first case confirmed by the newer immunohistochemical techniques. The literature is reviewed. (Arch Pathol Lab Med. 2003;127:367-369)

Merkel cell carcinoma (MCC) is an uncommon, highly aggressive cutaneous neoplasm of neuroendocrine differentiation with a poor prognosis.1 The prognosis is reportedly worse than for malignant melanoma.2 MCC is derived from Merkel cells, located at the dermoepidermal junction, which are postulated to be neurotactile cells of epidermal origin with neuroendocrine features.1 MCC most often presents as a painless, firm, raised lesion in sun-exposed sites of the head and neck region of the elderly.3 Their homogenous and uniform, small, round cell appearance is easily confused with lymphoma, leukemia, metastatic small cell of the lung, and poorly differentiated cutaneous malignancies.3 Histopathologic diagnosis frequently requires support by immunohistochemistry.

REPORT OF A CASE

A 79-year-old woman presented to the emergency room with a 2-day history of light-headedness and melena. She denied abdominal pain but had experienced a 27.2-kg weight loss over the past 6 months. The patient's past medical history was remarkable for MCC initially presenting in December 1998, with right-sided groin mass. The tumor was treated with surgery, chemotherapy, and radiation. The malignancy recurred as a mass in the right supraclavicular region in January 2001 and was treated similarly. A physical examination during admission revealed a frail elderly woman with a pulse of 124 beats/min, a blood pressure of 130/ 70 mm Hg (sitting), and a temperature of 37.2 deg C. A firm 1-cm subcutaneous mass in the left supraclavicular region was palpated. In addition, 2 firm subcutaneous masses measuring 2 and 1.5 cm were palpable in the right upper and lower quadrants of the abdomen, respectively. Laboratory values were notable for a decreased hemoglobin measurement of 6.6 g/dL (66 g/L). The patient was stabilized with a blood transfusion and subsequently underwent an esophagogastroduodenoscopy, which showed a 3 x 3-cm irregular mass with a 1-cm ulcer along the lesser curvature of the stomach. The ulcer had a clean base and was not actively bleeding. Multiple cold forcep biopsies were taken of the mass.

The diagnosis of metastatic MCC was rendered on histopathologic examination. The diagnosis was aided by the use of immunohistochemical stains against chromogranin (Dako Corporation, Carpinteria, Calif); cytokeratin 20 (CK20; Dako); thyroid transcription factor-1 (TTF-1; Dako); and CD44 (Dako). The tumor consisted of small, uniform, round cells with neuroendocrine features and had a membranous, dotlike, positive immunohistochemical reaction with antibodies to CD44, CK20, cytokeratin CAM 5.2, and chromogranin. There was a negative immunohistochemical reaction to TTF-1.

The patient had a progressive downhill clinical course and died 4 months after the diagnosis.

COMMENT

Primarily a tumor of the sun-exposed areas of the head and neck region of the elderly, MCC has been reported in non-sun-exposed, non-head and neck areas of the body such as the trunk, upper extremity, thigh, and buttock.A4 The etiology of MCC is unknown, but the tumor is increasingly being recognized because of its unique histologic, ultrastructural, and immunohistochemical findings.2,4 Chances of local recurrence (129/65%), regional lymph node involvement (27%-85%), and metastasis (36%-53%) depend on the site of the primary tumor and the treatment modality. Distant metastases have been reported in various organs, including the gastrointestinal system.1,2,45 Survival is sex but not age related,' and 1-, 2-, and 3-year survival rates are estimated to be 88%, 72%, and 55%, respectively.1,2

Histologically, MCC presents as monotonous, uniform, small, round cells with scant cytoplasm. The nucleus has finely dispersed chromatin without prominent nucleoli (Figure 1). Extensive single-cell necrosis and numerous frequent mitoses are present. Ultrastructurally, the cells have a round or dendritic appearance and characteristically contain numerous cytoplasmic membrane-bound dense-core neurosecretory granules. The cells also have well-developed keratin-type intermediate filaments that sometimes accumulate in the cytoplasm, laterally displacing the nucleus in a characteristic dotlike pattern on immunohistochemistry.6

Although MCC exhibits specific clinical and histologic features, its homogenous morphology can be easily confused with lymphoma, leukemia, metastatic small cell carcinoma, and malignant melanoma. Because of overlapping morphology, the diagnosis often requires support by immunohistochemistry.3 Many broad-spectrum immunohistochemical markers are available to aid in the diagnosis of neuroendocrine neoplasm, including MCC with different specificities and sensitivities, These markers include neuron-specific enolase, chromogranin, synaptophysin, and proconvertases PC1/PC3 and PC2. Neuron-specific enolase, however, has a low specificity and should be used only with other broad-spectrum markers of neuroendocrine cells in the diagnosis of neuroendocrine tumors. Chromogranins A and B (Figure 2) are widespread in their distribution and have a high degree of specificity; they are therefore excellent neuroendocrine markers.7