Dermatology MCQ - Viral Infections - Human polyomavirus 6

A 70-year-old man with a history of chronic lymphocytic leukemia (CLL) presents with multiple, flat-topped, violaceous papules and plaques on his trunk and extremities. The lesions are asymptomatic and have developed over several months. A skin biopsy shows a dense lymphoid infiltrate in the dermis with atypical lymphocytes. Immunohistochemistry reveals the cells are positive for CD3 and negative for CD20. Further testing detects human polyomavirus 6 (HPyV6) DNA within the lesions. Which of the following is the most likely diagnosis?

A) Mycosis fungoides
B) Primary cutaneous CD30+ lymphoproliferative disorder
C) Merkel cell carcinoma
D) Viral-associated trichodysplasia
E)de novo cutaneous T-cell lymphoma not otherwise specified

Correct Answer: A) Mycosis fungoides

Explanation

This presentation is suggestive of mycosis fungoides (MF), the most common type of cutaneous T-cell lymphoma, with an emerging association with human polyomavirus 6 (HPyV6) in some cases.

Key Clinical Features:

• Presentation: Flat-topped, violaceous, scaly patches or plaques that may progress to tumors. Chronicity and progression over months to years are characteristic.

• Population: Often older adults; may be associated with immunosuppression (e.g., CLL in this case).

• Symptoms: Often pruritic, but can be asymptomatic.

Histopathology and Immunophenotype:

• Biopsy: Shows a band-like lymphoid infiltrate in the upper dermis with atypical lymphocytes with cerebriform nuclei epidermotropism (lymphocytes migrating into the epidermis).

• Immunohistochemistry: Tumor cells are CD3+ (T-cell marker) and CD4+, and usually CD30- in early stages. Loss of CD7 is common.

Role of Human Polyomavirus 6 (HPyV6):

• Emerging Association: HPyV6 DNA has been detected in a subset of MF lesions, though its pathogenic role is not yet definitive. It may act as a cofactor in lymphomagenesis in immunocompromised hosts.

• Contrast with Other Polyomaviruses:

  • MCPyV is clearly causal in Merkel cell carcinoma (neuroendocrine tumor).

  • TSPyV causes trichodysplasia spinulosa (folliculocentric papules).

• HPyV6 is not typically associated with non-lymphoid skin tumors.

Why Not the Other Options?

• (B) Primary cutaneous CD30+ lymphoproliferative disorder: Includes lymphomatoid papulosis or anaplastic large cell lymphoma. Lesions are often nodular and ulcerated, and cells are CD30+.

• (C) Merkel cell carcinoma: A neuroendocrine tumor positive for CK20 (dot-like pattern) and associated with MCPyV, not HPyV6.

• (D) Viral-associated trichodysplasia: Caused by TSPyV, presenting with spiny follicular papules on the face, not flat violaceous plaques.

• (E) De novo cutaneous T-cell lymphoma: MF is a specific, well-defined entity; the history and findings are classic for MF.

Management:

• Staging: Evaluate for extracutaneous involvement (lymph nodes, blood, viscera).

• Skin-directed therapy: Topical corticosteroids, nitrogen mustard, or phototherapy for early disease.

• Systemic therapy: Retinoids, interferon, or chemotherapy for advanced disease.

Prognosis:
Indolent in early stages (patches/plaques) but may progress to tumors or Sézary syndrome (leukemic variant) in advanced cases.

Note: The association between HPyV6 and mycosis fungoides is still under investigation, but this case highlights the potential role of viral pathogens in lymphomagenesis in immunocompromised hosts.