Diagnosis from Tissue: Histology and Identification

Abstract

The diagnosis and initiation of appropriate treatment against invasive fungal infections depend upon accurate identification of pathogens by pathologists and clinical microbiologists. Histopathology is often critical in providing diagnostic insight in patients with suspected fungal infections, and such findings are incorporated into the definitions of proven or probable disease caused by certain pathogens. Such examinations can offer provisional identifications of fungal organisms, which can help guide initial therapy while laboratory results are pending. Common etiologic agents of invasive mycoses may be recognized based on morphologic characteristics observed in tissue and biologic fluids, such as those obtained from bronchoalveolar lavage and bronchial washings. However, care should be taken in the interpretation of these findings, as there may be a false sense of the ability to correctly categorize fungal organisms to the genus or species level by morphologic features alone. Studies have demonstrated discordant results between histopathology and laboratory results due to overlapping morphologic features, morphologic mimics, and sampling errors. Thus, histopathology plays an integral role in providing a differential of potential fungal pathogens but must be combined with results from laboratory studies, including cultures, antigen tests, serology, and molecular assays, in order to improve accuracy in the identification of etiologic agents of fungal infections. Inaccurate identification of the infecting organism can lead to inappropriate antifungal therapy and possibly poor clinical outcomes.

A combined diagnostic approach for the investigation of lesions resembling aspergillosis in Caribbean sea fans (Gorgonia spp.)

“…11 Histological identification of fungi can be problematic due to overlapping morphological features and challenges in accurately assessing morphology in 2-dimensional tissue sections. 27 Structures convincingly resembling conidiophores were never seen within tissue sections to allow more specific histological identification of fungus-like organisms. Consistent with the histological findings, microbiological and molecular techniques identified several different fungi associated with these lesions.…”

“…Fungal cultures are considered the complementary gold standard tool for laboratory diagnosis, 11,27 but can be time consuming and technically challenging. As demonstrated by our study, a major challenge for marine mycology is the inability to easily culture the microbially diverse fungal populations, with plating methods favoring the isolation of faster growing generalist and osmotolerant genera, and many fungi not sporulating in culture, making visual identification challenging.…”

Dermatopathology and the Diagnosis of Fungal Infections

“…These moulds can disseminate via the bloodstream and can cause skin lesions ( 20 ). It is not possible to distinguish the species by microscopic appearance in tissue ( 19 , 31 ) ( Table 4 ). As there can be important differences in the treatment of infections caused by different species histology reports generally describe the type of fungal structures seen, for example, hyalohyphomycosis, rather than suggesting a causative organism ( 19 , 31 ).…”

Outbreaks of Fungal Infections in Hospitals: Epidemiology, Detection, and Management

“…Within tissue, hyphae may be: (i) hyaline septate, e.g., Aspergillus, Fusarium species; (ii) broad ribbon-like with rare septation which includes members of the order Mucorales; and (iii) pigmented or dematiceous, e.g., Cladophialophora, Exophiala, spp. [7]. However, the diagnostic accuracy of identification to genus or species level is less than 80% [8,9].…”

“…Either broad-range (or panfungal) assays for capturing "all fungi" or assays tailored to detect a specific genus/species may be used to directly detect fungal DNA in clinical specimens [2]. Panfungal PCR followed by DNA sequencing allows for the identification of the pathogen from a diverse range of clinical specimens, including formalin fixed paraffin embedded (FFPE) tissue, although the examination of the latter is only recommended where fungal forms are seen on histopathology [2,7,11]. One study reported results for blood, cerebrospinal fluid (CSF), and aspirates where the sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) were 100, 96, 100, and 86%, respectively.…”