Diagnostic Histopathology最新文献

{"title":"Fluorescence in situ hybridization (FISH) as a diagnostic tool in infectious diseases: translational insights for diagnostic histopathology","authors":"Judith Kikhney,&nbsp;Kurosh Sarbandi,&nbsp;Dinah von Schöning,&nbsp;Annette Moter","doi":"10.1016/j.mpdhp.2026.06.011","DOIUrl":"10.1016/j.mpdhp.2026.06.011","url":null,"abstract":"<div><div>In the diagnostic histopathology of infectious diseases, histological examination may, in addition to demonstrating inflammation - reveal structures in clinical specimen that are morphologically compatible with microorganisms. However, it is often difficult to ascertain whether those structures indeed represent bacteria or fungal pathogens and to determine their exact identity. In addition, findings from histopathology and medical microbiology are not always congruent, since different areas of a specimen are typically investigated by the respective disciplines. Here, we present FISHseq – the combination of Fluorescence <em>in situ</em> hybridization in combination with PCR and sequencing – as a tool to bridge the gap between histopathology, microbiology and molecular pathogen detection. FISHseq visualizes and identifies microorganisms <em>in situ</em>, even on the identical sample slide to be used for histopathology. Moreover, FISH reveals the living mode of the microorganisms, i.e. if they grow in hard-to-detect and hard-to-treat biofilms. This review describes how the method has been translated from a research technique in environmental microbiology into an accredited, quality-controlled diagnostic tool in medical microbiology and highlights recent developments. In the future, FISHseq may galvanize traditionally separate disciplines such as histopathology and microbiology by enabling integrated interpretation of tissue specimens and advancing tissue-based diagnostics of infectious diseases.</div></div>","PeriodicalId":39961,"journal":{"name":"Diagnostic Histopathology","volume":"32 9","pages":"Pages 509-519"},"PeriodicalIF":0.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148949405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Best practices and pitfalls in the histological assessment of invasive fungal sinusitis","authors":"Kevin Clare,&nbsp;Soo Yeon Sohn,&nbsp;Melissa Gitman,&nbsp;Michael Nowak,&nbsp;Brandon Veremis,&nbsp;Elisabet Pujadas","doi":"10.1016/j.mpdhp.2026.07.001","DOIUrl":"10.1016/j.mpdhp.2026.07.001","url":null,"abstract":"<div><div>Acute invasive fungal sinusitis (AIFS) is a rapidly progressive fungal infection commonly affecting immunocompromised individuals and patients with poorly controlled diabetes mellitus. Clinical presentation is often nonspecific, including fever, facial pain, nasal congestion, or purulent discharge, which may delay diagnosis. Prompt recognition is essential, as delayed treatment is associated with substantial morbidity and mortality. Definitive diagnosis of AIFS relies on histologic demonstration of fungal hyphae with associated tissue invasion and damage. Intraoperative frozen section consultation plays a critical role in guiding urgent surgical and medical management but can be challenging due to frozen section artifact and limitations, as well as morphologic mimics. We explore representative clinical and histopathologic vignettes spanning from AIFS to non-invasive and chronic fungal infections and illustrate common pitfalls that may lead to diagnostic uncertainty and error. Given the potential consequences of both false-negative and false-positive diagnoses (including delayed therapy or inappropriately extensive surgical debridement) standardized specimen handling, careful histologic evaluation, and clear communication with multidisciplinary teams are essential. This review provides a practical histopathologic framework to support accurate diagnosis and effective intraoperative consultation.</div></div>","PeriodicalId":39961,"journal":{"name":"Diagnostic Histopathology","volume":"32 9","pages":"Pages 533-540"},"PeriodicalIF":0.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148949406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unlocking pathogens from preserved tissues: challenges and limitations of microbial retrieval from formalin-fixed paraffin-embedded (FFPE) samples in clinical diagnostics","authors":"Andrea Avendano-Viloria,&nbsp;Alberto E. Paniz-Mondolfi,&nbsp;Rachel Brody,&nbsp;Carlos Cordon-Cardo,&nbsp;Melissa Ait Said","doi":"10.1016/j.mpdhp.2026.06.012","DOIUrl":"10.1016/j.mpdhp.2026.06.012","url":null,"abstract":"<div><div>Formalin-fixed paraffin-embedded (FFPE) tissues are central to diagnostic pathology and frequently constitute the only remaining substrate when infection is recognized retrospectively, cultures are negative, or fresh tissue is unavailable. For pathologists, FFPE blocks allow molecular confirmation of infection directly from the lesion, adding useful information to routine microscopy and special stains. This helps guiding treatment choices and further diagnostic outcomes. This review exclusively addresses pathogenic microorganisms and does not consider commensal microbiota or dysbiosis, given the distinct analytical and methodological challenges inherent to pathogen detection within the host endogenous microbiome. It focuses on nucleic acid–based molecular detection, targeted and unbiased sequencing approaches, and does not address protein-based methods. We summarize the challenges imposed by fixation chemistry (e.g., cross-linking, depurination, base damage) and FFPE block handling, which fragment nucleic acids, inhibit polymerases, and increase sequence artifacts narrowing the range of amplifiable targets and reducing coverage in amplification-dependent assays such as conventional/long-range PCR, qPCR, and PCR steps in NGS. Targeted approaches including species-specific PCR/Sanger and amplicon-based NGS provide sensitivity for prespecified organisms, whereas metagenomic NGS (mNGS) detects unexpected or polymicrobial infections but is susceptible to low biomass, excess host DNA, and environmental or reagent contamination. This review outlines a practical, end-to-end framework for pathologists conducting metagenomic analysis from FFPE tissues, spanning pre-analytic, analytic, and post-analytic phases. The workflow emphasizes complete deparaffinization, optimized proteinase K digestion with heat- or chemically assisted decrosslinking, judicious amplicon design and polymerase selection, and enzymatic repair to improve template quality. Effective implementation requires close, bidirectional collaboration among clinicians, pathologists, microbiologists, and bioinformaticians to translate archival FFPE findings into clinically actionable pathogen diagnostics.</div></div>","PeriodicalId":39961,"journal":{"name":"Diagnostic Histopathology","volume":"32 9","pages":"Pages 520-532"},"PeriodicalIF":0.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148949407","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recognizing parasitic helminths in tissue: histopathological insights into fascioliasis and echinococcosis","authors":"Sumeyra Kartal,&nbsp;Hatice Ozer,&nbsp;Hatice Reyhan Egilmez","doi":"10.1016/j.mpdhp.2026.06.016","DOIUrl":"10.1016/j.mpdhp.2026.06.016","url":null,"abstract":"<div><div>Fascioliasis and echinococcosis are both parasitic diseases that present a significant threat to public health worldwide. These helminthic diseases are classified as neglected by the World Health Organization (WHO). Due to increased travel and migration, diagnostic challenges can be presented for physicians especially in areas where they are not endemic. While diagnoses are made using imaging and microbiological, serological and molecular methods, the lack of diagnostic algorithms can complicate matters. Both diseases can occur ectopically outside the liver, where they are most commonly found, and sometimes both can be confused with tumors in terms of clinical features, and alveolar echinococcosis can even metastasize. Although <em>Fasciola</em> spp. rarely seen directly in histopathologic specimens, they can be distinguished from other liver flukes by their morphology, such as spinous tegument, highly branched ceca, and their relatively bigger size, leading to diagnosis. The multilayered structure of the metacestode of <em>Echinococcus</em> spp. and/or the presence of protoscoleces/hooklets are also important in differential diagnosis. When both diseases are histopathologically evident, familiarity with their findings helps prevent a prolonged diagnostic process. This article aims to give insights on histopathology of these parasites and their host reactions for training and practicing pathologists.</div></div>","PeriodicalId":39961,"journal":{"name":"Diagnostic Histopathology","volume":"32 9","pages":"Pages 582-594"},"PeriodicalIF":0.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148961541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"State-of-the-art approaches for infectious disease diagnostics: single-cell, spatial and next-generation sequencing enhanced by artificial intelligence","authors":"Derek S. Angulo-Valdez,&nbsp;Maria Eugenia Garcia-Thomas,&nbsp;Maria V. Guijarro,&nbsp;Glyn D. Palmer,&nbsp;Alberto E. Paniz Mondolfi,&nbsp;Carlos Cordon-Cardo,&nbsp;Leandro Balzano-Nogueira","doi":"10.1016/j.mpdhp.2026.06.013","DOIUrl":"10.1016/j.mpdhp.2026.06.013","url":null,"abstract":"<div><div>Infectious diseases remain a major global cause of morbidity and mortality, yet timely and definitive diagnosis is often delayed by overlapping clinical presentations, pathogen diversity, and host-dependent variability in disease progression. Although conventional diagnostics (culture, serology, targeted polymerase chain reaction) have transformed clinical microbiology, they are limited by predefined targets, restricted multiplexing capacity, and reduced sensitivity in complex or pre-treated cases. These limitations have accelerated the development of high-resolution molecular approaches. Single-cell transcriptomics enables the identification of infection-specific immune states and cell-type transcriptional profiles linked to disease severity. Co-transcriptomics capture host and pathogen gene expression within individual cells, revealing co-regulatory programs. Spatial transcriptomics adds tissue context by mapping inflammatory niches and infection microenvironments. Meanwhile, shotgun-metagenomics and long-read sequencing support pathogen-agnostic detection and antimicrobial resistance profiling. Artificial intelligence-driven analytical frameworks integrate these multimodal datasets into clinically interpretable signatures. Collectively, these technologies are redefining infectious disease diagnostics by shifting from isolated pathogen identification to comprehensive molecular phenotyping, paving the way for more precise prognosis and personalized therapeutic strategies. This review aims to summarize current advances in these emerging technologies, discuss their strengths and limitations, and evaluate their translational potential for clinical implementation in infectious disease diagnostics.</div></div>","PeriodicalId":39961,"journal":{"name":"Diagnostic Histopathology","volume":"32 9","pages":"Pages 541-555"},"PeriodicalIF":0.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148949408","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chronic granulomatous bacterial infections – actinomycosis, nocardiosis and botryomycosis: a histopathological approach for diagnostics","authors":"Andrés Tirado-Sánchez,&nbsp;Luis Miguel Moreno,&nbsp;Jesús Alberto Cárdenas-de la Garza,&nbsp;Alexandro Bonifaz","doi":"10.1016/j.mpdhp.2026.06.015","DOIUrl":"10.1016/j.mpdhp.2026.06.015","url":null,"abstract":"<div><div>Chronic filamentous and non-filamentous bacterial granulomatous diseases, including actinomycosis, nocardiosis, and botryomycosis, are uncommon and rarely fatal diseases. Diagnosis is supported by microbiological and molecular evaluation; however, histological diagnosis enables precise conclusions to be reached, thereby facilitating the initiation of appropriate and timely treatment. A common tissue reaction seen in the three clinical entities under review is the Splendore-Hoeppli phenomenon. This reaction is characterized by the presence of radiant, eosinophilic material in the form of an asteroid or mace around infectious and non-infectious agents. The objective of this article is to offer a comprehensive yet concise approach to the histo-morphological evaluation of chronic filamentous and non-filamentous bacterial granulomatous diseases.</div></div>","PeriodicalId":39961,"journal":{"name":"Diagnostic Histopathology","volume":"32 9","pages":"Pages 573-581"},"PeriodicalIF":0.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148949403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HTLV-1 and adult T-cell leukemia/lymphoma: a review of epidemiologic trends, pathogenesis and diagnostic practices","authors":"Luis C. Ascanio,&nbsp;Andrea Coetzee,&nbsp;Devin Nelson,&nbsp;Hani El Achkar,&nbsp;Matthew Shapiro,&nbsp;Christian Salib,&nbsp;Davis Gajzer,&nbsp;Dalia Abdel Azim,&nbsp;Alina Dulau-Florea,&nbsp;Bruce Petersen,&nbsp;Amy Duffield,&nbsp;Shafinaz Hussein","doi":"10.1016/j.mpdhp.2026.06.001","DOIUrl":"10.1016/j.mpdhp.2026.06.001","url":null,"abstract":"<div><div>Human T-lymphotropic viruses (HTLV) are a group of complex RNA retroviruses, comprising four subtypes, with distinct geographical distribution and disease associations. HTLV subtype 1 (HTLV-1), the most prevalent, is the only subtype capable of oncogenesis and is responsible for adult T-cell leukemia/lymphoma (ATLL), an aggressive mature T-cell lymphoma. Focal endemicity and low prevalence in many regions contribute to the under recognition of HLTV-1 infection and ATLL. Increasing global migration and evidence of rising cases of ATLL in non-endemic areas warrants the consideration of this entity in the differential diagnosis of T-cell lymphomas. ATLL develops in a small subset of individuals after decades of latent HTLV-1 infection. Lymphomagenesis involves clonal expansion of infected T cells, immune evasion, and accumulation of host genetic and epigenetic alterations. The diagnosis of ATLL can be challenging, and integration of serologic, molecular, histopathologic, and clinical data is critical for definitive identification of this neoplasm. Advancements in diagnostic tools, such as immunohistochemical stains, serologic assays and molecular tests, have improved diagnostic accuracy. This review will focus on the epidemiological features of these unique retroviruses and the diagnostic strategies and tools available for diagnosis of HTLV-1 infection and ATLL.</div></div>","PeriodicalId":39961,"journal":{"name":"Diagnostic Histopathology","volume":"32 8","pages":"Pages 403-414"},"PeriodicalIF":0.0,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148661203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rare and uncommon gastrointestinal infections in diagnostic pathology: a mini review","authors":"Sarah Ruane,&nbsp;Dane Pointing","doi":"10.1016/j.mpdhp.2026.06.007","DOIUrl":"10.1016/j.mpdhp.2026.06.007","url":null,"abstract":"<div><div>Gastrointestinal (GI) infections are a major cause of morbidity and mortality worldwide, particularly in patients who are immunosuppressed. GI infections can be asymptomatic, but commonly present with diarrhoea, abdominal pain and weight loss. In severe and disseminated cases, patients can also present with atypical symptoms ranging from confusion to cardiovascular shock. Traditionally GI infections have been diagnosed primarily with serological and stool examination, but increasingly endoscopic investigation and biopsy utilisation has meant histopathologists are also an integral diagnostic aid. However, diagnosis is often challenging for pathologists for a variety of both clinical and pathological reasons. Nevertheless, being able to identify these organisms is essential, as misdiagnosis can have devastating consequences for patients, including but not limited to patients being mislabelled and therefore mistreated as inflammatory bowel disease. We present seven cases of uncommon GI infections diagnosed at our institution, including viral, protozoan and helminth infective organisms. Our aim is to impart the important clinical, endoscopic, morphological and immunohistochemical findings that can act as helpful aids to histopathologists, so that they can identify these ‘needles’ in amongst their biopsy haystacks!</div></div>","PeriodicalId":39961,"journal":{"name":"Diagnostic Histopathology","volume":"32 8","pages":"Pages 497-504"},"PeriodicalIF":0.0,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148661289","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuropathology of SARS-CoV-2 infection","authors":"Satomi Hiya,&nbsp;Carolina Maldonado-Díaz,&nbsp;Cheyanne Slocum,&nbsp;Jamie M Walker,&nbsp;Timothy E Richardson,&nbsp;Melissa Umphlett","doi":"10.1016/j.mpdhp.2026.06.005","DOIUrl":"10.1016/j.mpdhp.2026.06.005","url":null,"abstract":"<div><div>The coronavirus disease 2019 (COVID-19) has generated an unprecedented body of neuropathological and neuroimmunological literature. Initial concerns regarding direct viral neuroinvasion have gradually evolved into a more complex model in which systemic inflammation, endothelial dysfunction, microthrombosis, and immune dysregulation collectively shape histopathology. Although studies of muscle and peripheral nerve involvement are fewer compared to those of the central nervous system (CNS), in-depth clinicopathological observations have provided important mechanistic insights into COVID-19–associated neuropathology. In the CNS, acute findings are largely dominated by hypoxic ischemic injury, with coagulopathy contributing to both infarction and hemorrhagic changes. Subacute to chronic phases are characterized by microglial activation and perivascular inflammatory infiltrates, supported by molecular evidence of persistent immune dysregulation. Emerging data demonstrate molecular overlap with certain age-related neurodegenerative pathways, stimulating investigation into potential links between long COVID cognitive impairment (“brain fog”) and post-infectious immune imbalance. In the neuromuscular system, critical illness myopathy and polyneuropathy (CIM/CIP) represents an essential disease framework, with heterogeneous histological features; rhabdomyolysis, disuse myopathy, thick filament myopathy, acute myopathy with scattered/diffuse necrosis. Superimposed systemic inflammation further drives inflammatory myopathy in both acute and post-infectious settings. Long COVID research has been facilitated by the relative accessibility of skeletal muscle biopsy, revealing persistent mitochondrial abnormalities and upregulation of tissue remodeling pathways. Although histopathology captures only a single temporal snapshot of a dynamic systemic disease process, careful integration of morphology with clinical and molecular data enables meaningful mechanistic interpretation. The neuropathological experience of COVID-19 provides critical lessons for clinical practice and strengthens preparedness for future infectious crises.</div></div>","PeriodicalId":39961,"journal":{"name":"Diagnostic Histopathology","volume":"32 8","pages":"Pages 461-474"},"PeriodicalIF":0.0,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148661292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Practical surgical pathology of common pulmonary infections","authors":"Emily Wendel,&nbsp;Mary Beth Beasley","doi":"10.1016/j.mpdhp.2026.06.003","DOIUrl":"10.1016/j.mpdhp.2026.06.003","url":null,"abstract":"<div><div>The lungs may be involved, either primarily or secondarily, by virtually any type of infection (bacterial, mycobacterial, fungal, viral, or parasitic). The type of infection present is often dependent on the immune status of the patient as well as the endemic organisms in a given geographic region. Pulmonary infections, particularly common bacterial pneumonias, are frequently diagnosed clinically based on a combination of clinical presentation and radiographic findings and culture results. Molecular techniques and mass spectrometry may enhance identification of organisms. Serologic testing and techniques such as direct fluorescent antibody testing may also be employed. From a surgical pathology standpoint, infections are most commonly encountered in biopsies or resections for pulmonary nodules or non-resolving infiltrates. Such specimens often exhibit granulomatous inflammation but other inflammatory patterns may be encountered depending on the organism or immune status of the patient. The aim of this article is to review the most common pulmonary infections and their histologic findings encountered in the setting of surgical pathology, with focus on mycobacterial infections and fungi, testing strategies, and review of differential diagnoses.</div></div>","PeriodicalId":39961,"journal":{"name":"Diagnostic Histopathology","volume":"32 8","pages":"Pages 438-449"},"PeriodicalIF":0.0,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148661293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}