What are the typical biopsy findings in Mpox (Monkeypox) and how is it managed?

Mpox Biopsy Findings

Mpox skin biopsies demonstrate characteristic histologic features including ballooning degeneration of basal keratinocytes, full-thickness epidermal necrosis with marked acanthosis, multinucleated syncytial keratinocytes, and a lichenoid-mixed inflammatory infiltrate with progressive exocytosis. 1

Histopathologic Features by Stage

Early Lesions

• Ballooning degeneration of basal keratinocytes with spongiosis in a mildly acanthotic epidermis 1
• Lichenoid-mixed inflammatory cell infiltrate beginning to form 1
• Inflammation of superficial and deep vascular plexes, eccrine units, and follicles 1

Advanced Lesions

• Full-thickness necrosis of markedly acanthotic epidermis containing few viable keratinocytes 1
• Progressive exocytosis accompanying keratinocyte necrosis 1
• Multinucleated syncytial keratinocytes as the hallmark viral cytopathic effect 1

Diagnostic Confirmation Methods

Immunohistochemistry

• Viral antigen detected within keratinocytes of the lesional epidermis 1
• Positive staining in follicular and eccrine epithelium 1
• Few dermal mononuclear cells may show viral antigen 1

Electron Microscopy

• Virions at various stages of assembly visible within keratinocyte cytoplasm 1
• Confirms orthopoxvirus morphology 1

Molecular Testing (Gold Standard)

• PCR testing of lesion specimens is the definitive diagnostic method and should be performed on all suspected cases 2, 3
• Molecular and genomic methods are far more reliable than serology-based tests, which lack specificity and cross-react with other orthopoxviruses 3

Tissue Distribution in Severe/Fatal Cases

Mucocutaneous Involvement

• Necrotizing and proliferative epithelial changes in all cases 4
• MPXV antigen and DNA detected in all tissue specimens examined 4

Systemic Dissemination (Immunocompromised Patients)

• Digestive tract lesions present in all deceased patients with autopsy evaluation 4
• Systemic tissue necrosis with thrombotic vasculopathy in lymphoid tissues, lung, or other solid organs in 50% of fatal cases 4
• Bronchopneumonia in 50% and acute lung injury in one-third of fatal cases 4

Differential Diagnosis

The histologic differential includes:

• Herpes simplex virus - can be differentiated histologically, immunohistochemically, and by electron microscopy 1
• Varicella - requires PCR for definitive differentiation 1
• Smallpox and other poxviruses - differentiated using PCR assay for the monkeypox extracellular-envelope virus protein gene 1

Management Approach

Biopsy Indications

• Biopsy should be performed when diagnosis cannot be established by clinical presentation alone or when PCR testing is not immediately available 1
• Obtain tissue from the periphery of lesions for optimal diagnostic yield 1

Treatment Strategy

• First-line therapy is supportive care focusing on skin care and symptom relief with analgesics 2
• Tecovirimat is available through expanded access programs for severe cases, particularly in immunocompromised patients with CD4 count <200 cells/μL 2, 5
• Medical debridement with collagenase for severe lesions 5
• Antibiotic treatment for bacterial superinfection 5

Critical Pitfalls

• Coinfections identified in 31% of biopsy cases and 67% of autopsy cases may complicate diagnosis and treatment 4
• Significant viral DNA in tissues necessitates enhanced biosafety measures in healthcare and autopsy settings 4
• Urological consultation required in only 7.4% of genital lesion cases; most can be managed conservatively without surgical intervention 5

Follow-up Considerations

• Mean follow-up of 20.3 days shows 23.5% of patients have significant penile skin changes, significantly associated with initial lesion size (P = .001) 5
• No surgical interventions required in reported series of 68 patients treated with tecovirimat 5