Dermatology MCQ - Viral Infections - HPyV9-associated hyperkeratotic skin lesions

A 62-year-old man, 5 years post-heart transplant on maintenance immunosuppression (tacrolimus, mycophenolate mofetil, prednisone), presents with multiple hyperkeratotic, verrucous plaques on his arms and legs. The lesions are slowly progressive and asymptomatic. Biopsy shows hyperkeratosis, papillomatosis, and acanthosis with enlarged keratinocytes exhibiting basophilic intranuclear inclusions. PCR testing of the lesion is positive for human polyomavirus 9 (HPyV9). Which of the following is the most accurate statement regarding this infection?

A) It is associated with a high risk of systemic dissemination and mortality
B) It commonly transforms into invasive squamous cell carcinoma
C) It is typically self-limited and regresses upon reduction of immunosuppression
D) It requires immediate treatment with intravenous cidofovir
E) It is exclusively linked to renal transplant recipients

Correct Answer: C) It is typically self-limited and regresses upon reduction of immunosuppression

Explanation

This presentation describes HPyV9-associated hyperkeratotic skin lesions in an organ transplant recipient (OTR), a rare manifestation of cutaneous polyomavirus infection.

Key Clinical Features of HPyV9-Associated Lesions:

• Population: Immunosuppressed OTRs (e.g., heart, kidney, liver), not limited to renal transplants.

• Appearance: Hyperkeratotic, verrucous, or papillomatous plaques that are slow-growing and often asymptomatic. They can mimic warts or seborrheic keratoses.

• Distribution: Typically on sun-exposed areas (arms, legs, face).

• Histopathology:

  • Hyperkeratosis, papillomatosis, acanthosis.

  • Enlarged keratinocytes with basophilic intranuclear inclusions (viral cytopathic effect).

• Viral Detection: HPyV9 DNA identified by PCR or in situ hybridization.

Natural History and Management:

• Benign and self-limited: Unlike oncogenic polyomaviruses (e.g., MCPyV in Merkel cell carcinoma), HPyV9 lesions are not associated with malignancy or systemic dissemination.

• Regression: Lesions often resolve spontaneously with reduction of immunosuppression (e.g., lower tacrolimus dose) or immune reconstitution.

• Treatment:

  • Observation is first-line due to benign nature.

  • Topical therapies (e.g., salicylic acid, imiquimod) or cryotherapy may be used for cosmetic reasons.

  • No need for systemic antivirals (e.g., cidofovir) unless widespread and symptomatic.

Why Not the Other Options?

• (A) High risk of systemic dissemination: HPyV9 is not associated with visceral involvement or mortality; it is confined to the skin.

• (B) Transformation into SCC: No evidence of malignant transformation. HPV, not HPyV9, is linked to SCC in OTRs.

• (D) Immediate IV cidofovir: Reserved for severe systemic polyomavirus infections (e.g., BK virus nephropathy), not indicated for benign cutaneous HPyV9 lesions.

• (E) Exclusively in renal transplant recipients: Reported in various OTRs (heart, liver, lung), not just renal.

Prognosis:
Excellent. Lesions are benign and often resolve with immune recovery. Regular skin exams are recommended for OTRs due to increased risk of other skin cancers (e.g., SCC).

Takeaway:
HPyV9 is an emerging cutaneous polyomavirus in OTRs causing benign hyperkeratotic lesions. It should be distinguished from other viral warts (HPV) and premalignant lesions via biopsy and PCR.