Dermatology MCQ - Viral Infections - Merkel cell polyomavirus infection

A 75-year-old fair-skinned man with a history of chronic sun exposure presents with a rapidly growing, firm, violaceous nodule on his cheek. Biopsy reveals a dermal tumor composed of small, round blue cells with scant cytoplasm and numerous mitotic figures. Immunohistochemistry shows the tumor cells are positive for cytokeratin 20 (CK20) in a paranuclear dot-like pattern and negative for TTF-1 and leukocyte common antigen (CD45). Which of the following is the most likely viral pathogen associated with this malignancy?

A) Epstein-Barr virus (EBV)
B) Human papillomavirus (HPV)
C) Merkel cell polyomavirus (MCPyV)
D) Human herpesvirus 8 (HHV-8)
E) Cytomegalovirus (CMV)

Correct Answer: C) Merkel cell polyomavirus (MCPyV)

Explanation

This presentation is classic for Merkel cell carcinoma (MCC), a rare but aggressive neuroendocrine carcinoma of the skin, strongly associated with Merkel cell polyomavirus (MCPyV) infection.

Key Clinical Features of Merkel Cell Carcinoma:

• Demographics: Elderly, fair-skinned individuals with significant chronic sun exposure.

• Appearance: A rapidly growing, firm, painless, violaceous or red nodule on sun-exposed areas (head/neck > extremities > trunk).

• Behavior: Highly aggressive with potential for local recurrence, nodal spread, and distant metastasis.

Histopathology and Immunohistochemistry:

• Histology: Small, round blue cells with scant cytoplasm, fine granular chromatin, and high mitotic activity.

• Immunophenotype:

  • CK20 positive in a characteristic paranuclear dot-like pattern (hallmark).

  • TTF-1 negative (helps distinguish from small cell lung cancer).

  • CD45 negative (rules out lymphoma).

• Viral Association: MCPyV DNA is integrated into the tumor genome in ~80% of cases, with expression of viral T-antigens that drive oncogenesis.

Why Not the Other Options?

• (A) Epstein-Barr virus (EBV): Associated with nasopharyngeal carcinoma, Burkitt lymphoma, and Hodgkin lymphoma, not Merkel cell carcinoma.

• (B) Human papillomavirus (HPV): Associated with squamous cell carcinomas (skin, cervix, anus) and verrucous carcinoma, not neuroendocrine tumors like MCC.

• (D) Human herpesvirus 8 (HHV-8): Associated with Kaposi sarcoma (spindle cells forming vascular slits) and primary effusion lymphoma.

• (E) Cytomegalovirus (CMV): Causes opportunistic infections (e.g., colitis, retinitis) in immunocompromised hosts, not cutaneous malignancies.

Management:

• Wide local excision (often with Mohs surgery) and sentinel lymph node biopsy.

• Radiation therapy (MCC is highly radiosensitive).

• Immunotherapy (e.g., avelumab, pembrolizumab) for advanced disease.

Prognosis:
Poor if not caught early; 5-year survival for metastatic disease is <50%. Viral-positive MCC may have a slightly better prognosis than viral-negative MCC.

Note: ~20% of MCC cases are MCPyV-negative, often associated with UV-induced mutations (e.g., TP53, RB1).