Practical diagnostic approach to the presence of hyphae in neuropathology specimens with three illustrative cases

Abstract

Objectives: Early and accurate diagnosis remains crucial in the therapeutic management of invasive central nervous system fungal infections. Different molds have intrinsic resistance to antifungal agents; thus, morphologic differentiation is helpful to clinicians. Methods: Using three examples, we present a guide on how to approach neuropathology specimens where hyphae are identified on initial histologic examination. Results: Hyphae can be classified into three basic groups: hyaline pauciseptated, hyaline septated, and pigmented or dematiaceous. The hyaline pauciseptated group includes the order of the Mucorales (previously Zygomyces) and is frequent in patients with decompensated diabetes and severe neutropenia. Aspergillus species constitutes the most frequently isolated mold in the hyaline septated group. However, other invasive hyaline septated molds include Fusarium species, which is frequently resistant to multiple antifungals, and Candida species Last, dematiaceous molds, although infrequent, can be found in neuropathology specimens, as happened during the outbreak of Exserohilum associated with manufacturing practices in a compound pharmacy. Conclusions: Categorizing hyphae into the three groups described allows pathologists to provide information that is useful for infectious disease treatment with an inclusive differential diagnosis of diverse fungal genera that share the same morphological features.