What is Merkel Cell Carcinoma
Merkel cell carcinoma (MCC) is a rare, highly aggressive cutaneous neuroendocrine tumor that carries a worse prognosis than melanoma, with mortality rates exceeding melanoma and 5-year survival ranging from only 30-64%. 1, 2
Clinical Characteristics and Epidemiology
MCC presents as a rapidly growing skin tumor that combines the aggressive local behavior of infiltrative non-melanoma skin cancer with the metastatic potential of thick melanoma. 1 The disease demonstrates particularly concerning patterns of spread:
- Local recurrence occurs in 25-30% of all cases 1, 2
- Regional lymph node metastases develop in 52-59% of cases 1, 2
- Distant metastatic disease appears in 34-36% of patients 1, 2
The typical patient profile includes older Caucasians (≥65 years of age) with tumors appearing on sun-exposed skin, particularly the head and neck region. 1, 2 Extensive sun exposure represents a major risk factor for disease development. 1
High-Risk Populations
Immunosuppressed individuals face disproportionately higher risk, including those with: 1, 2, 3
- Solid organ transplants
- Lymphoproliferative malignancies (especially chronic lymphocytic leukemia)
- HIV infection
These immunocompromised patients generally experience worse survival outcomes. 3
Pathophysiology
Merkel cell polyomavirus (MCPyV) is detected in 43-100% of MCC tumor samples and plays a significant role in pathogenesis. 2, 3 The virus appears to have increased oncogenic potential in immunocompromised hosts. 3 In MCPyV-negative tumors (approximately 20% of cases in the northern hemisphere), ultraviolet radiation-induced DNA damage is implicated as the causative mechanism. 4
Diagnostic Challenges
The diagnosis is rarely suspected clinically because the primary tumor lacks distinguishing characteristic features and can present with innocuous appearance on examination. 1, 5 The most challenging histologic differentiation is between primary MCC and metastatic small cell lung cancer. 1
Diagnosis requires immunohistochemical staining with cytokeratin 20 (CK-20) and thyroid transcription factor-1 (TTF-1) to differentiate from small cell lung cancer. 1, 2 CK-20 is positive in 89-100% of MCC tumors, while TTF-1 is consistently absent in MCC but expressed in 83-100% of small cell lung cancer. 1
Critical Pathology Elements
The pathology report should include (preferably in synoptic format): 1
- Tumor size
- Peripheral and deep margin status
- Lymphovascular invasion
- Extracutaneous extension to bone, muscle fascia, or cartilage
Common Pitfalls
Failure to perform sentinel lymph node biopsy may miss regional metastases, which occur frequently in MCC. 2 Given the high rate of regional disease (52-59%), thorough surgical staging is essential for appropriate treatment planning. 2