Primary Cutaneous Blastomycosis of the Nose After Arboreal Inoculation: Molecular Diagnosis by Fungal PCR and Next-Generation Sequencing

BACKGROUND: Blastomycosis, caused by Blastomyces dermatitidis and the closely related Blastomyces gilchristii, is a systemic mycosis endemic to the Great Lakes region and the Mississippi and Ohio River valleys. Primary cutaneous blastomycosis from direct inoculation-without pulmonary or systemic involvement-is rare, with fewer than 50 cases reported in the literature. Diagnosis is particularly challenging when histochemical stains are negative and the tissue reaction pattern mimics squamous cell carcinoma. CASE PRESENTATION: A 39-year-old immunocompetent African American man presented with a progressive verrucous nasal mass after facial trauma sustained from a tree branch. Skin biopsy revealed prominent pseudoepitheliomatous hyperplasia with epidermal breakdown and granulomatous inflammation. The degree of epithelial hyperplasia with surface disruption raised initial concern for well-differentiated squamous cell carcinoma. Both Periodic Acid-Schiff (PAS) and Grocott-Gomori methenamine silver stains were initially reported as negative for fungal organisms. RESULTS: Fungal polymerase chain reaction with reflex next-generation sequencing performed on formalin-fixed paraffin-embedded tissue identified Blastomyces dermatitidis/gilchristii DNA, establishing a definitive diagnosis. Directed by this molecular result, retrospective review of the PAS stain identified a single yeast form morphologically consistent with Blastomyces, confirming that the initial organism burden was at the threshold of histochemical detection. Chest imaging and immunologic evaluation excluded pulmonary and systemic disease, supporting primary cutaneous inoculation blastomycosis. Treatment with itraconazole 200 mg twice daily resulted in significant reduction of the nasal lesion at 4-month follow-up. CONCLUSION: This case illustrates 3 diagnostic pitfalls in cutaneous blastomycosis. First, prominent pseudoepitheliomatous hyperplasia with epidermal breakdown can closely mimic well-differentiated squamous cell carcinoma, a well-recognized but underappreciated histologic confounder. Second, PAS and Grocott-Gomori methenamine silver stains may be falsely negative when organism burden is extremely low, as demonstrated by the identification of only a single yeast form on directed retrospective review. Third, fungal polymerase chain reaction with next-generation sequencing reflex from formalin-fixed paraffin-embedded tissue is a critical diagnostic tool when conventional histochemical methods and morphologic assessment are inconclusive. Primary cutaneous lastomycosis should remain in the differential diagnosis of verrucous facial lesions after penetrating trauma, even in immunocompetent patients.