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Merkel cell carcinoma is an uncommonly encountered neuroendocrine malignant skin tumor that has an aggressive behavior. This tumor is derived from specialized nerve endings within the skin. The tumor promoting Merkel cell polyomavirus has been implicated in its pathogenesis. The prognosis of Merkel cell carcinoma is worse than that of melanoma. This tumor has a high rate of recurrence and often has spread to the regional lymph nodes by the time of diagnosis.

Detail of a Merkel disc nerve ending

Clinical Findings: Merkel cell carcinoma is a rare cutaneous malignancy with an estimated incidence of 1 in 200,000. Merkel cell carcinoma is much more common in Caucasian individuals. The tumor has a slight male predilection. The average age at onset is in the fifth to seventh decades of life. The lesions occur most often on the head and neck. This distribution is consistent with the notion that chronic sun exposure is a predisposing factor in the development of this tumor. These tumors also occur more commonly in patients taking chronic immunosuppressive medications. The tumors often appear as red papules or plaques that quickly increase in size. They can also appear as rapidly enlarging nodules. On occasion, the tumor ulcerates. The clinical differential diagnosis is often between Merkel cell carcinoma and basal cell carcinoma, inflamed cyst, squamous cell carcinoma, or an adnexal tumor. These tumors are so rare that they are infre- quently in the original differential diagnosis.
It has been estimated that up to 50% of all patients diagnosed with a Merkel cell carcinoma will develop lymph node metastasis. Other notable areas of metastasis include the skin, lungs, and liver. The staging of this tumor is based on its size (<2 cm or >2 cm), the involvement of regional lymph nodes, and the presence of metastasis. Patients with higher-stage disease have a progressively worse prognosis. Patients with metastatic disease (stage IV) have a 5-year survival rate of 0%. In contrast, the 5-year survival rate for local stage I or II disease is 65% to 75% and approximately 50% to 60% for stage III (lymph node involvement). Grouping all stages together, one third of the patients diagnosed with Merkel cell carcinoma will die from their disease.
Pathogenesis: Merkel cell carcinoma is derived from a specialized cutaneous nerve ending. The normal Merkel cells function in mechanoreception of the skin. Merkel cells, like melanocytes, are embryologically derived from the neural crest tissue. Chronic immuno- suppression is believed to be one of the largest risk factors. Patients taking immunosuppressive medica- tions after organ transplantation are at much higher risk than age-matched controls. Chronic sun exposure and its effect on downregulating local immunity in the skin have also been theorized to play an etiological role. The Merkel cell polyomavirus has been studied to assess its role in the development of Merkel cell carcinoma.
Polyomaviruses are similar in nature and structure to the better-known papillomaviruses. There are at least five polyomaviruses that cause human disease. Most of them affect patients who are chronically immunosuppressed at a higher rate than healthy matched controls. Researchers have implicated the Merkel cell polyomavirus as a potential cause of Merkel cell carcinoma. This virus has been isolated from a high percentage of Merkel cell tumors, but not from all of them. It is likely to be a player in the pathogenesis of a subset of patients with Merkel cell carcinoma, but it is unlikely to be the only explanation. The discovery of this virus may lead to therapeutic options in the future.
Histology: Merkel cell carcinoma is a neuroendocrine tumor. The tumor is composed of small, uni- formly shaped, basophilic-staining cells. The tumor is poorly circumscribed and grows in an infiltrative pattern between dermal collagen bundles and subcutaneous fat lobules. The cells have a characteristic nuclear chromatin pattern. These tumors can be stained with various immunohistochemical stains. The most helpful one is the cytokeratin 20 stain. It has a characteristic, if not pathognomonic perinuclear dot, staining pattern.
Treatment: Surgical excision with wide (2-3 cm) margins is still the standard therapeutic treatment. Sentinel node sampling has been helpful in staging. Those patients with localized disease often undergo postoperative irradiation of the surgical removal site. Those with widespread metastatic disease are often treated with cisplatin-based chemotherapeutic regimens.