Challenges and Pitfalls of Morphologic Identification of Fungal Infections in Histologic and Cytologic Specimens

Abstract

Despite the advantages of providing an early presumptive diagnosis, fungal classification by histopathology can be difficult and may lead to diagnostic error. To assess the accuracy of histologic diagnosis of fungal infections vs culture ("gold standard"), we performed a 10-year retrospective review at our institution. Of the 47 of 338 positive mold and yeast cultures with concurrent surgical pathology evaluation without known history of a fungal infection, 37 (79%) were correctly identified based on morphologic features in histologic and/or cytologic specimens. The 10 discrepant diagnoses (21%) included misidentification of septate and nonseptate hyphal organisms and yeast forms. Errors resulted from morphologic mimics, use of inappropriate terminology, and incomplete knowledge in mycology. The accuracy did not correlate with preceding antifungal therapy (P = .14) or use of special stains (P = .34) and was not operator-dependent. Among 8 discrepancies with clinical follow-up available, 2 potential adverse clinical consequences resulted. While histopathologic identification of fungi in tissue sections and cytologic preparations is prone to error, implementation of a standardized reporting format should improve diagnostic accuracy and prevent adverse outcomes.

E6/E7 proteins are potential markers for the screening and diagnosis of cervical pre‑cancerous lesions and cervical cancer in a Chinese population

“…Histology is recognized as the gold standard for diagnosing the pathological process of CC. CIN2 + is considered a precancerous lesion and, if left untreated, this may progress to cervical cancer; therefore, if a patient exhibits a CIN2 + lesion, this should be treated (17,29). However, it is unknown which kind of lesions will finally lead to infiltrative cancers.…”

Utility of PCR in Diagnosis of Invasive Fungal Infections: Real-Life Data from a Multicenter Study

“…Conversely, in 12 cases broad-range PCR failed to detect IFI, as cultures and the antigen tests performed displayed the existence of an underlying infection. The discrepancies observed between microscopy, culture, and PCR might have occurred for multiple reasons (30). Fungal contamination (30,31), loss of fungal viability (30,32), aggressive specimen processing (33), and examination of samples from two different areas (26) are some of the potential explanations.…”

“…The discrepancies observed between microscopy, culture, and PCR might have occurred for multiple reasons (30). Fungal contamination (30,31), loss of fungal viability (30,32), aggressive specimen processing (33), and examination of samples from two different areas (26) are some of the potential explanations. However, regardless of the reason for the lack of fungal growth or for a negative fungal PCR result, fungal elements in tissues causing pathology should be treated immediately (32).…”

Improving Molecular Detection of Fungal DNA in Formalin-Fixed Paraffin-Embedded Tissues: Comparison of Five Tissue DNA Extraction Methods Using Panfungal PCR

“…Histopathologic examination remains one of the major diagnostic tools in mycology because it permits rapid, presumptive identification of fungal infections. In recent years, however, there have been cases with discrepant histologic and culture results at final diagnosis; such discrepancies could lead to unnecessary pharmaceutical exposure and/or inappropriate treatment (17,24).Recent efforts to improve the sensitivity and specificity of diagnostic tests have focused on culture-independent methods, in particular, nucleic acid-based methods, such as PCR assays. PCR-based detection of fungal DNA sequences can be rapid, sensitive, and specific and can be applied to fresh and FFPE tissues (16).…”