Opinion - (2025) Volume 16, Issue 5
Received: 01-Sep-2025, Manuscript No. jch-26-178787;
Editor assigned: 03-Sep-2025, Pre QC No. P-178787;
Reviewed: 07-Sep-2025, QC No. Q-178787;
Revised: 22-Sep-2025, Manuscript No. R-178787;
Published:
29-Sep-2025
, DOI: 10.37421/2157-7099.2025.16.817
Citation: Schneider, Elisabeth. ”Cytology: Diagnosing Viral and Fungal Infections.” J Cytol Histol 16 (2025):817.
Copyright: © 2025 Schneider E. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution and reproduction in any medium, provided the original author and source are credited.
Cytological examination plays a pivotal role in the initial detection and characterization of various infectious agents, offering a direct window into cellular pathology. The ability to identify distinct morphological changes within cells or the presence of microbial elements provides crucial diagnostic clues. This review aims to synthesize current knowledge on the cytological hallmarks of viral and fungal infections, emphasizing their diagnostic utility and the specific features that aid in differentiation. Understanding these microscopic findings is fundamental for timely and accurate diagnoses in diverse clinical scenarios, directly impacting patient management strategies. The distinct cytological features of viral infections include intracellular inclusions, syncytia formation, and characteristic cellular swelling or lysis, all indicative of viral replication and cellular damage. These changes can be observed in various sample types, from exfoliated cells to tissue biopsies, providing a broad applicability for cytological diagnosis. [1] Fine-needle aspiration (FNA) cytology has emerged as a valuable tool for the detection and characterization of fungal infections across a spectrum of anatomical locations. This minimally invasive technique allows for direct sampling of lesions, enabling rapid cytological assessment. The characteristic cytomorphology of common fungal pathogens, such as Candida, Aspergillus, Cryptococcus, and Pneumocystis jirovecii, can be readily identified in FNA specimens, facilitating early diagnosis and guiding therapeutic interventions. [2] The cytological manifestations of herpes simplex virus (HSV) and varicella-zoster virus (VZV) infections are well-defined and critical for accurate diagnosis, particularly in samples from the cervix and oral cavity. Characteristic cytopathic effects, including the formation of multinucleated giant cells, the presence of intranuclear inclusions (often referred to as Cowdry type A), and acantholysis, are hallmark features. Techniques like Papanicolaou (Pap) smears and Tzanck smears are instrumental in the rapid identification of these viral cytopathic effects, paving the way for prompt antiviral treatment and effective infection control measures. [3] Invasive fungal infections, especially in immunocompromised patients, present a significant diagnostic challenge. Cytological examination offers an early detection mechanism by revealing the characteristic morphology of angioinvasive fungi such as Aspergillus and Zygomycetes. Their distinctive hyphal structures and patterns of tissue invasion can be identified, underscoring the importance of cytology in initiating timely therapeutic strategies, often in conjunction with microbiological and histopathological data. [4] Human papillomavirus (HPV) infection, a common viral pathogen, exhibits characteristic cytological changes in cervical Papanicolaou smears. The presence of koilocytosis, defined by perinuclear clearing and nuclear atypia, is a pathognomonic sign of HPV-induced cellular alterations. The integration of HPV cytology with advanced molecular testing strategies further enhances the accuracy and effectiveness of cervical cancer screening and subsequent management protocols. [5] Pneumocystis pneumonia (PCP) is a serious opportunistic infection that requires prompt diagnosis, particularly in immunocompromised individuals. Cytological examination of bronchoalveolar lavage (BAL) fluid is highly effective in identifying the characteristic morphology of Pneumocystis jirovecii cysts and trophic forms. The use of special stains, such as Gomori methenamine silver (GMS) or toluidine blue, significantly enhances the visualization and detection of these organisms, contributing to the sensitivity and specificity of cytological diagnosis in at-risk patients. [6] Cytomegalovirus (CMV) infection is another significant concern in immunocompromised populations, and its cytological identification is crucial for early management. The presence of characteristic 'owl's eye' inclusions, observed in both the nucleus and cytoplasm of infected cells, is a key diagnostic feature. Cytological screening in transplant recipients and other vulnerable individuals is essential for the timely detection and effective management of CMV disease, preventing potentially severe complications. [7] Liquid-based cytology (LBC) has demonstrated its utility in the detection of viral respiratory infections, including influenza and respiratory syncytial virus (RSV). LBC offers advantages over conventional methods, primarily through improved specimen preservation and its compatibility with downstream molecular testing. This technique facilitates the identification of viral cytopathic effects and aids in the efficient diagnosis of these common respiratory pathogens. [8] Oral candidiasis, a common fungal infection, requires careful cytological evaluation to distinguish between simple colonization and invasive disease. Cytological examination of oral lesions allows for the identification of yeast cells, pseudohyphae, and chlamydospores, which are indicative of Candida species. However, a definitive diagnosis often necessitates correlation with clinical signs and patient risk factors to guide appropriate treatment decisions. [9] Fungal meningitis, particularly cryptococcal meningitis, can be diagnosed effectively through cytological examination of cerebrospinal fluid (CSF). The characteristic encapsulated yeast forms of Cryptococcus neoformans are readily visualized in CSF samples, especially with India ink preparations or specific stains. Cytological diagnosis plays a critical role in enabling prompt initiation of antifungal therapy, which is paramount for improving patient outcomes in cases of fungal meningitis. [10]
The diagnostic landscape of infectious diseases has been significantly augmented by advances in cytological techniques, allowing for the identification of specific microbial agents and their impact on host cells. Viral infections often present with unique cytopathic effects, such as the formation of viral inclusions, syncytia, and cellular lysis, which are readily observable under microscopic examination. These findings, detailed in the 'Cytological Features of Viral and Fungal Infections: A Diagnostic Guide' [1], provide a foundational understanding for differentiating between various viral etiologies and guiding subsequent diagnostic workups. [1] In the realm of fungal infections, fine-needle aspiration (FNA) cytology has proven to be an indispensable tool. It facilitates the direct sampling of infected tissues, allowing for the characteristic morphology of common fungal pathogens like Candida, Aspergillus, Cryptococcus, and Pneumocystis jirovecii to be identified. The study by Lee et al. [2] highlights the importance of correlating these cytological findings with clinical history and employing ancillary techniques, such as special stains, to achieve definitive diagnoses and guide patient management for fungal infections. [2] The detection of herpes simplex virus (HSV) and varicella-zoster virus (VZV) infections relies heavily on recognizing specific cytopathic effects in exfoliated or aspirated cells. As described by Chen et al. [3], the presence of multinucleated giant cells, intranuclear inclusions (Cowdry type A), and acantholysis in cervical and oral cytology samples are critical indicators. The rapid diagnostic capabilities offered by Papanicolaou (Pap) smears and Tzanck smears are crucial for initiating timely antiviral therapy and implementing infection control measures. [3] Invasive fungal infections, particularly those occurring in immunocompromised individuals, necessitate early and accurate diagnosis. The work by Wong et al. [4] emphasizes the role of cytology in identifying the characteristic hyphal structures and tissue invasion patterns of angioinvasive fungi like Aspergillus and Zygomycetes. Cytological assessment can provide crucial information for guiding therapeutic decisions, often serving as a complement to microbiological and histopathological investigations. [4] Human papillomavirus (HPV) infection, a significant cause of cervical abnormalities, is typically identified through characteristic cytological changes in Papanicolaou smears. The presence of koilocytosis, a cellular alteration marked by perinuclear clearing and nuclear atypia, serves as a hallmark of HPV infection. Martinez et al. [5] discuss the integration of HPV cytology with molecular testing to enhance the effectiveness of cervical cancer screening and management strategies. [5] Diagnosing Pneumocystis pneumonia (PCP) in immunocompromised patients often involves the cytological examination of bronchoalveolar lavage (BAL) fluid. Walker et al. [6] detail the characteristic morphology of Pneumocystis jirovecii cysts and trophic forms, which are effectively visualized using special stains like Gomori methenamine silver (GMS) or toluidine blue. This cytological approach offers high sensitivity and specificity for diagnosing PCP in at-risk populations. [6] Cytomegalovirus (CMV) infection, a common opportunistic pathogen, is identifiable through characteristic cellular inclusions. Taylor et al. [7] describe the distinct 'owl's eye' appearance of nuclear and cytoplasmic inclusions indicative of CMV. Cytological screening in transplant recipients and other immunocompromised individuals is vital for the early detection and management of CMV disease, mitigating potential complications. [7] Liquid-based cytology (LBC) represents a modern advancement in the cytological detection of viral infections, particularly respiratory viruses like influenza and RSV. Thomas et al. [8] highlight the advantages of LBC, including enhanced specimen preservation and suitability for downstream molecular analysis, compared to conventional methods for identifying viral cytopathic effects. [8] Oral candidiasis requires careful cytological evaluation to differentiate between superficial colonization and invasive infection. Harris et al. [9] describe the morphology of Candida species, including yeast cells, pseudohyphae, and chlamydospores, in oral lesions. The interpretation of these findings must be integrated with clinical context and patient risk factors for accurate diagnosis and appropriate treatment. [9] The diagnosis of fungal meningitis, with a particular focus on Cryptococcal meningitis, can be aided by cytological examination of cerebrospinal fluid (CSF). Martin et al. [10] discuss the characteristic encapsulated yeast forms of Cryptococcus neoformans visualized in CSF samples. Cytology plays a crucial role in the prompt diagnosis of fungal meningitis, enabling the timely initiation of antifungal therapy and influencing patient outcomes. [10]
This compilation of research focuses on the critical role of cytology in diagnosing viral and fungal infections. It outlines the distinct morphological features that help differentiate between these pathogens at the cellular level, including viral inclusions, syncytia, and cellular changes for viral infections, and yeasts, hyphae, and spores for fungal infections. Specific viral infections like those caused by HSV, VZV, HPV, and CMV are discussed with their characteristic cytopathic effects. Similarly, fungal infections such as invasive candidiasis, PCP, and fungal meningitis are detailed, emphasizing diagnostic techniques like FNA and examination of various body fluids. The advancements in methods like liquid-based cytology are also highlighted for their improved diagnostic capabilities. Accurate cytological interpretation, often combined with clinical information and special stains, is crucial for timely diagnosis and effective patient management.
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