Histopathologic Analysis of Fungi

Here's a short diagram of some of the common dimorphic fungi in host tissue. In this image, we see Coccidioides immitis, Sporothrix schenckii, and Paracoccidioides brasiliensis. Of these, Coccidioides is the only non-thermally dimorphic fungus (i.e.: the dimorphism is not due to the change in temperature--see former #micromeded post on fungal dimorphism) and Sporothrix is the only dimorphic fungus to typically infect only the skin and soft tissue. Paracoccidioides is similar to the other dimorphic fungi (Blastomyces, Histoplasma) in that it is thermally dimorphic and causes systemic disease.

This image is meant to be a quick and dirty comparison between Aspergillus sp. in tissue and Mucormycetes in tissue. Aspergilloses and Mucomycoses can be difficult to distinguish, but in this figure, I go through some of the main differences evident on histology--for an exact diagnosis, it is important to differ to microbiological examination (phenotypic analysis with lactophenol blue, DNA, or maybe even MALDI-TOF).

When you come across a caseating granuloma (an inflammatory reaction with lymphocytes, epithelioid histiocytes, multinucleated giant cells, AND necrosis), performing a Grocott's methenamine silver (GMS) stain (for fungi) and a Ziehl-Neelsen stain (for acid-fast bacteria--Mycobacteria and Nocardia) can help determine the etiology of the granulomatous reaction. If both the ZN and GMS stains are negative, more testing is required to determine the etiology. For a great review of the possible etiologies of granulomatous disease check out this article and this article (the latter suggested by Dr. Sanjay Mukhopadhyay via Twitter).