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Cryptococcus neoformans/gattii and Histoplasma capsulatum var. capsulatum infections on tissue sections: Diagnostic pitfalls and relevance of an integrated histomolecular diagnosis

Summary

This research addresses the challenge of identifying two common fungal infections (cryptococcosis and histoplasmosis) when examining tissue samples under a microscope. The study found that these infections often look similar and can be confusing for pathologists. The researchers discovered that looking for specific fungal features, particularly ‘dented-looking’ yeasts, can help differentiate cryptococcosis from histoplasmosis. When standard laboratory tests on fresh tissue aren’t available, using molecular testing (genetic analysis) on preserved tissue samples can successfully identify the fungus in about 75% of cases.

Background

Cryptococcus neoformans/gattii and Histoplasma capsulatum var. capsulatum infections may present atypical histopathological features that complicate diagnosis on tissue sections. Both fungi can present similar pseudotumor appearances clinically and radiologically. Standard mycological identification using culture is not possible on formalin-fixed paraffin-embedded tissue samples.

Objective

To estimate the frequency of atypical histopathological features in C. neoformans/gattii and H. capsulatum var. capsulatum infections and assess the usefulness of these features in differentiating both mycoses. To evaluate the relevance of integrated histomolecular diagnosis on formalin-fixed tissue when mycological identification is unavailable on fresh tissue.

Results

Expert pathologist review modified initial diagnosis in 25.9% of tissue samples. Dented-looking yeasts were significantly associated with C. neoformans/gattii (68.75%) versus H. capsulatum var. capsulatum (0%, P=.002). For 12 patients without initial mycological identification, integrated histomolecular diagnosis identified fungi in 75% of cases. Targeted MPS showed higher sensitivity than Sanger sequencing for cryptococcosis (P=.041).

Conclusion

Atypical histopathological features frequently occur in both mycoses, making morphological diagnosis challenging. Integrated histomolecular diagnosis on formalin-fixed tissue using PCR and sequencing is essential for accurate fungal identification when fresh tissue samples are unavailable, improving diagnostic accuracy and patient care.
  • Published in:Medical Mycology,
  • Study Type:Retrospective Observational Study,
  • Source: PMID: 39732625, DOI: 10.1093/mmy/myae126
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