Skin, Deep fungal infection, PASD stain

Traumatic foot ulcer can be complicated by fungal infection. The biopsy shows skin with marked mixed inflammation including a granulomatous component and irregular reactive surface epidermal hyperplasia (pseudoepitheliomatous hyperplasia: acanthosis, hyperkeratosis with some surface crusting) with intraepidermal pustules. The epidermis is reactive with no dysplasia or malignancy. Numerous scattered large fungal spores are present showing thick walls and variable numbers of endospores; there is possible budding. The fungi are highlighted with PAS and GMS staining. Confirmatory fungal typing would require fungal culture. Gram and acid-fast bacillus stains were negative. Direct immunofluorescence was negative for IgG, IgA, IgM, and C3.

Differentials for the fungal infection include coccidioidomycosis and blastomycosis. Blastomyces dermatitidis lives in soil and is endemic to Mississippi, Ohio, Mid-Atlantic States, and parts of Ontario, Quebec, and Manitoba. Histologically, it is characterized by round, multinucleate, broad-based budding yeast with thick double refractive walls. It is most often contracted via inhalation of spores with chronic pneumonia being the most commons presentation. It manifests in skin as verrucous or ulcerative lesions or subcutaneous nodules. Diagnosis is via culture or histology. Serology is not useful. Most patients will require treatment with antifungals.

Coccidioidomycosis is caused by coccidioides spp. In the soil of southwestern United States desert regions, south-central Washington, and Central and South America. C. immitis is limited to California, while C. posadasii is found everywhere else, with no clinical difference. In tissue, it appears as spherules rather than spores, containing endospores with occasional atypical spherules resembling budding cells. Coccidioides spp is most commonly spread via inhalation; “valley fever” refers to an associated self-limited pneumonia. Cutaneous manifestations include erythema nodosum, acute generalized exanthema, Sweet’s syndrome, and, erythema multiforme. Primary cutaneous infection via skin inoculation is rare and has a much shorter incubation period. Antifungals may not be necessary, aside from severe cases or immunocompromised. Diagnosis is made based on cytology/biopsy, culture, and serology.

In this case, the patient endorsed trauma to the foot and denied systemic symptoms or travel to regions endemic to coccidioidomycosis. Chest x-ray was negative for pulmonary involvement; she likely acquired the infection through direct inoculation. There was a clinical suspicion of blastomycosis and she was treated as such with itraconazole; however no organism was found on the culture. In general, these fungi may be difficult to distinguish on histology alone; therefore, clinical information, serology, and fungal cultures may be required to aid diagnosis.

This slide shows PASD stain. See related content for H&E and GMS stains.

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