Pancreatic ductal adenocarcinoma (PDAC) is characterized by a dense desmoplastic and immunosuppressive tumor microenvironment that limits immune surveillance and therapeutic delivery. Emerging evidence indicates that PDAC harbors low-biomass but biologically relevant intratumoral microbial communities. This review synthesizes current evidence on the existence, spatial localization, functional relevance, and translational implications of the intratumoral microbiome in PDAC. A narrative literature review was conducted using PubMed/MEDLINE, Scopus, Web of Science, and Google Scholar to identify English-language studies on the PDAC intratumoral microbiome, tumor-resident bacteria and fungi, tumor microenvironment interactions, spatial and single-cell analyses, contamination control, and therapeutic response. Tumor-resident bacterial and fungal communities in PDAC may influence immune reprogramming, fibro-inflammatory signaling, metabolic stress responses, postoperative survival, and therapy response. These microbes interact with myeloid cells, dendritic cells, T cells, cancer-associated fibroblasts, stromal architecture, and hypoxic niches. Spatial and single-cell studies suggest that microbial signals align with distinct tumor niches, supporting localized microbe–host crosstalk. The intratumoral microbiome is emerging as a non-genetic regulator of PDAC biology. Integrated microbial, immune, stromal, and metabolic profiling may support future precision-oncology strategies. Not applicable.
Head and neck squamous cell carcinoma (HNSCC) is a major global health concern with high morbidity and mortality. Programmed death ligand-1 (PD-L1), an immune checkpoint protein, plays a key role in tumor immune evasion and has emerged as an important biomarker for immunotherapy. Human papillomavirus (HPV)-associated HNSCC represents a distinct subset with different biological behavior and prognosis. To evaluate PD-L1 expression in HNSCC and determine its correlation with HPV status and clinicopathological parameters. This hospital-based cross-sectional study included 100 histopathologically confirmed cases of HNSCC. PD-L1 expression was assessed by immunohistochemistry and scored using the Combined Positive Score (CPS). HPV status was evaluated using cobas HPV DNA testing and RNA in situ hybridization for E6/E7 mRNA. Statistical analysis was performed using the Chi-square test, with p < 0.05 considered significant. PD-L1 expression was observed in a substantial proportion of HNSCC cases. HPV DNA-positive tumors showed a higher frequency of PD-L1 expression compared to HPV DNA-negative tumors (73.8
Infection-associated bone marrow fibrosis is an uncommon and under-recognized manifestation of severe systemic infection and may pose a significant diagnostic challenge when accompanied by cytopenias and hyperinflammatory features. We report the case of a 31-year-old male who presented with persistent high-grade fever, hepatosplenomegaly, pancytopenia, hyperferritinemia, and raised inflammatory markers, raising clinical suspicion for hemophagocyticlymphohistiocytosis. Bone marrow examination revealed a hypocellular marrow with marked suppression of trilineage hematopoiesis and extensive intertrabecular fibrosis (MF-3 reticulin fibrosis according to the European Consensus grading system). Notably, overt intramedullary bacterial colonies were identified within the marrow spaces, while no hemophagocytosis, granulomas, or evidence of hematolymphoid malignancy was seen. Microbiological evaluation confirmed multidrug-resistant Gram-negative sepsis due to Acinetobacter calcoaceticus–baumannii complex and Pseudomonas aeruginosa. This case highlights a rare but important diagnostic pitfall in which overwhelming bacterial infection results in severe secondary bone marrow fibrosis and mimics hemophagocytic syndromes. Recognition of this entity is critical, as timely bone marrow evaluation can redirect diagnosis and management in patients with sepsis and unexplained cytopenias.
Multiple primary malignancies (MPMs) are defined as two or more histologically distinct primary neoplasms occurring in the same individual, either simultaneously or sequentially. Synchronous presentation of two unrelated malignancies is uncommon and poses important diagnostic and therapeutic challenges. Extramedullary plasmacytoma (EMP) accounts for less than 5
Gonadoblastoma is a rare in situ germ cell tumor composed of primitive germ cells admixed with sex cord–stromal elements, typically arising in dysgenetic gonads containing Y chromosome material. It is most commonly associated with disorders of sex development, particularly complete gonadal dysgenesis (Swyer syndrome). We report an interesting case of 26-year-old phenotypic female who presented with primary amenorrhea and was found to have a 46,XY karyotype with bilateral dysgenetic gonads. CECT and MRI evaluation revealed a hypoplastic uterus with non-visualization of bilateral ovaries. Histopathological examination following a prophylactic bilateral gonadectomy demonstrated characteristic nests of germ cells and sex cord stromal elements with focal calcification and PAS-positive basement membrane material. Immunohistochemistry showed strong nuclear positivity for OCT3/4 in the germ cell component and cytoplasmic positivity for inhibin in the sex cord component, confirming the diagnosis of Gonadoblastoma. This case highlights the importance of considering gonadal dysgenesis in patients presenting with primary amenorrhea and emphasizes the need for karyotype analysis in such cases. The identification of Y chromosome material warrants prophylactic bilateral gonadectomy because of the significant risk of Gonadoblastoma and invasive malignant germ cell tumors. Early surgical intervention with meticulous HPE after extensive sampling is mandatory for an accurate diagnosis which plays a crucial role in enhancing long term disease free survival and preventing adverse outcomes.
Congenital round cell soft tissue sarcoma with metastasis to the placenta is rarely described. We report a case of a large soft tissue sarcoma of the left neck from a female fetus delivered at 36 weeks and 3 days with metastasis to the stem villous vessels of the placenta. The tumor showed mixed features of Ewing sarcoma/primitive neuroectodermal tumor (PNET) and infantile fibrosarcoma with ETV6 :: NTRK3 fusion gene transcript. The clinical significance and diagnostic pitfalls are discussed.
Gut dysbiosis, defined as an imbalance in the gut microbiota’s composition and function, plays a key role in the development of cancer. It alters microbial diversity, disrupts immune function, weakens the gut barrier, and promotes long-term inflammation, contributing to tumour onset and progression. Contributing factors include diet, stress, disrupted sleep, inactivity, antibiotics, environmental exposures, and changes in host genetics or epigenetics. These factors reduce the production of protective microbial byproducts like short-chain fatty acids (SCFAs) and increase the formation of harmful compounds such as nitrosamines and secondary bile acids. Certain bacteria like Fusobacterium nucleatum, Helicobacter pylori, Escherichia coli (pks+), Bacteroides fragilis, and Streptococcus gallolyticus have been linked to cancer through their ability to cause inflammation, damage DNA, or interfere with immune detection. Based on this understanding, approaches such as probiotics, prebiotics, changes in diet, faecal microbiota transplantation (FMT), and targeted microbial treatments are being explored to restore microbial balance and reduce cancer risk. These findings highlight the microbiome’s role in the carcinogenetic pathway.
Gastric carcinoma remains a major global health burden with poor prognosis due to its biological heterogeneity and lack of reliable prognostic biomarkers. Octamer-binding transcription factor4 (OCT4), a stem cell–associated transcription factor, along with Ki67 and E-cadherin, has been implicated in tumour proliferation, invasiveness and progression. However, data on their combined expression in gastric carcinoma from eastern India are limited. To evaluate the immunohistochemical expression of OCT4 in gastric carcinoma and assess its association with tumour proliferation (Ki67), tumour invasiveness (E-cadherin) and clinicopathological parameters in a tertiary care centre in Odisha. This hospital-based prospective study included 94 histologically confirmed gastric adenocarcinoma cases over a period of two years. Immunohistochemistry for OCT4, Ki67 and E-cadherin was performed on all the resected samples of total of 94 cases. OCT4 expression was assessed using immunoreactivity score, with clinicopathological variables were analysed in all the cases using appropriate statistical tests and correlation analysis. The mean age was 57.4 years with male predominance. Tubular type adenocarcinoma was the most common subtype, followed by poorly cohesive type. Poorly cohesive type showed high OCT4 expression (96.7
Spindle cell/sclerosing rhabdomyosarcoma is a rare and aggressive subtype of rhabdomyosarcoma, and uncommon in the sphenoid sinus. We report a case of a 17-year-old male presented with bilateral facial swelling, headache, and visual blurring. Imaging showed an ill-defined, heterogeneously enhancing skull base mass involving the sphenoid sinus with intracranial and orbital extension, radiologically mimicking as esthesioneuroblastoma. Endoscopic endonasal debulking biopsy was suggestive of a spindle cell/sclerosing rhabdomyosarcoma on histopathological examination. Immunohistochemistry showed diffuse desmin and nuclear MyoD1 expression, and next-generation sequencing identified a MYOD1 p.Leu122Arg mutation, rendered the definitive diagnosis. The tumor was classified as FNCLCC grade G3, AJCC Stage III (T2b N0 M0), Intergroup Rhabdomyosarcoma Study Group (IRSG) Clinical Group III. Given the unresectable nature of the lesion, multimodal therapy including vincristine, actinomycin D (dactinomycin), and cyclophosphamide chemotherapy and proton beam radiotherapy was planned. Histology, immunohistochemistry, and molecular analysis are the cornerstones of the diagnostic planning process of this rare type of neoplasm. This case highlights the diagnostic challenges, aggressive behaviour, critical role of molecular testing and management protocols in Spindle cell/sclerosing rhabdomyosarcoma arising at an unusual skull base location.
Standardization of the pre-analytical phase, including prompt specimen sectioning and appropriate fixation, is essential for preserving tissue morphology and protein integrity. However, these practices are not consistently implemented in many pathology laboratories, particularly in resource-limited settings. This study aimed to compare histopathological features and predictive biomarkers in invasive breast carcinomas processed under optimal conditions versus routine conditions. A total of 49 surgical fresh specimens of breast cancer were grossly examined and bisected. A representative tumor fragment from each specimen (1.0 × 1.0 × 0.2 cm) was immediately fixed in 10
Digital pathology and artificial intelligence (AI) are fundamentally transforming neuropathological diagnosis by enabling high-throughput, reproducible, and quantitative analysis of complex neural tissue specimens. This comprehensive review examines the current state of AI applications in neuropathological diagnosis, including tumor classification, neurodegenerative disease assessment, and inflammatory condition evaluation, with a focus on recent advancements and methodological limitations. A systematic literature search was conducted for studies published between January 2015 and December 2025. Following PRISMA 2020 guidelines, 58 studies were included. AI systems, particularly deep learning models applied to whole-slide images, demonstrated high diagnostic accuracy for brain tumor classification, moderate accuracy for neurodegenerative disease grading, and emerging utility in demyelinating disease assessment. However, significant heterogeneity exists in the methodologies of the included studies. While AI models show promise in automating routine tasks and integrating morphological with molecular data, their performance varies considerably across different neuropathological subfields due to differences in dataset sizes, annotation quality, and the inherent complexity of the diseases. Digital pathology combined with AI represents a substantial advancement in neuropathological diagnosis. While current evidence supports the potential of AI systems to achieve high diagnostic accuracy, particularly in neuro-oncology, widespread clinical implementation remains constrained by challenges related to standardization, prospective multi-center validation, and the interpretability of deep learning models.
Pelvic inflammatory disease (PID) is an infection-induced inflammation of the upper female genital tract, which may involve the endometrium, fallopian tubes, ovaries, or pelvic peritoneum. Although Neisseria gonorrhoeae and Chlamydia trachomatis are well-established etiologic agents, anaerobic bacteria are increasingly recognized as significant contributors, particularly following intrauterine device (IUD) placement. Although best known as part of the oropharyngeal flora, Fusobacterium necrophorum also colonizes the gastrointestinal and female urogenital tracts and is a rare cause of PID. Its pathogenic potential outside the head and neck region is seldom reported, and fatal cases are exceptionally uncommon. In this case, a 46-year-old woman was found deceased at home approximately one month after IUD insertion. Postmortem examination revealed diffuse fibrinopurulent peritonitis, acute salpingitis, and a right ovarian cyst with surrounding inflammation. Cultures of peritoneal fluid and spleen were positive for F. necrophorum, confirming bacteremia. The cause of death was determined to be PID due to F. necrophorum infection. The IUD placement was considered a plausible contributing factor in the ascending infection. This case represents an exceedingly rare instance of fatal pelvic inflammatory disease caused by F. necrophorum. It highlights the importance of comprehensive microbiological investigations, integration of histopathological findings, and maintaining a broad differential diagnosis in forensic autopsy cases presenting with severe pelvic sepsis.
Cytology plays a critical role in cancer screening and diagnostics. However, developing robust deep learning models for cytology remains challenging because of the high morphological variability of individual cells, differences in staining and sample preparation, and the limited availability of large and annotated datasets. While recent histology foundation models have shown remarkable generalization across tissue types, their direct application to cytology tasks remains unexplored, as cytological slides emphasize cellular morphology rather than tissue architecture. We investigate the effectiveness of applying histology foundation models for cytological classification using a weakly supervised Multiple Instance Learning (MIL) approach. We evaluate several pre-trained histological models as feature extractors, alongside two MIL algorithms, and explore different classification strategies. Our results demonstrate that leveraging histology foundation models yields superior performance compared to ImageNet-based extraction or training from scratch, particularly on small datasets. We further develop a cytology-specific feature extractor based on DINOv3, which outperforms larger models with higher parameter counts. Our findings support the feasibility of cytology-adapted foundation models for whole-slide analysis and highlight their potential within weakly supervised learning frameworks under limited annotation settings.
Eosinophilic cystitis (EC) is an uncommon inflammatory disorder that was initially identified by Brown Palubinskas in 1960. Histopathological diagnosis is characterized by inflammation throughout the bladder wall, accompanied by eosinophilia. Patients typically exhibit a range of urological symptoms, including increased frequency of urination, burning micturition, visible or microscopic haematuria, suprapubic pain and urinary retention. In this unusual case, a young female with clinical and radiological signs indicative of bladder carcinoma was ultimately diagnosed with eosinophilic cystitis following a bladder biopsy. The patient was managed conservatively with antibiotics, antihistamines and corticosteroids.
The classification of breast cancer has undergone a paradigm shift with the identification of HER2-low and HER2-ultra-low subtypes, representing a continuum of HER2 protein expression. These categories challenge the traditional binary system of HER2-positive and HER2-negative cancers, offering new insights into tumor biology and therapeutic opportunities. This review was done to look into the emerging concepts of HER2-low and ultra-low breast cancers, their molecular characteristics, diagnostic challenges, and evolving therapeutic landscape. A comprehensive review of recent literature was conducted, focusing on definitions, diagnostic criteria, and clinical implications of HER2-low (immunohistochemistry (IHC) 1 + or 2+, FISH-negative) and HER2-ultra-low (IHC 0 with faint staining) breast cancers. Emphasis was placed on assay standardisation, emerging diagnostic modalities, and ongoing clinical trials evaluating targeted therapies. HER2-low and ultra-low tumors demonstrate distinct molecular signatures and clinical behaviours compared with both HER2-positive and completely HER2-negative counterparts. Conventional immunohistochemistry often fails to accurately distinguish these subgroups due to limited sensitivity. Novel, standardised, and more sensitive assays are essential to reliably identify these categories. Several ongoing trials are exploring the efficacy of novel anti-HER2 agents and antibody-drug conjugates in these subtypes, indicating promising therapeutic potential. Recognition of HER2-low and HER2-ultra-low breast cancers marks a critical evolution in breast cancer pathology and precision oncology. Improved diagnostic tools and targeted therapies may enable more personalised treatment approaches, refining prognostic assessment and improving patient outcomes.
Follicular variant of papillary thyroid carcinoma (FV-PTC) is a distinct subtype of thyroid cancer with intermediate clinical behavior between classical papillary and follicular carcinomas. While generally associated with favorable prognosis, FV-PTC can rarely present with distant metastases, including to the skull and scalp, posing diagnostic and therapeutic challenges. We report a 51-year-old woman initially diagnosed with primary hypothyroidism and a thyroid goitre, later confirmed as FV-PTC after total thyroidectomy. Three years postoperatively, she developed a painless scalp lump. Magentic resonance imaging (MRI) revealed a large heterogeneously enhancing mass involving bilateral frontal skull bones with bone erosion and extension into scalp tissues, compressing adjacent brain structures without parenchymal invasion. Surgical excision of the scalp mass confirmed metastatic follicular thyroid carcinoma. The patient was managed with levothyroxine replacement and calcium supplementation after receiving radioiodine ablation therapy. This case highlights the importance of recognizing late solitary skull and scalp metastases in FV-PTC, which can lead to bone erosion and potential involvement of the brain parenchyma. The complementary use of MRI and computed tomography (CT) is vital for thorough assessment of both soft tissue and bony invasion. Given the risk of intracranial extension, management often requires a neurosurgical approach combined with reconstructive surgery to achieve effective tumor resection and restore structural integrity. Long-term surveillance and multidisciplinary treatment strategies remain essential to optimize outcomes in these complex and atypical metastatic presentations.
Renal involvement is a frequent and often severe manifestation of systemic diseases, including autoimmune, metabolic, vascular, and hematologic conditions. The kidney’s unique vascular and structural features render it particularly vulnerable to systemic insults. Renal pathology not only reflects the nature of the underlying disorder but also plays a pivotal role in diagnosis, risk stratification, and therapeutic planning. This narrative review provides a comprehensive overview of the major histopathological patterns encountered in systemic diseases affecting the kidney, highlighting the diagnostic utility of renal biopsy and ancillary studies, and addressing current diagnostic challenges. We examined the renal pathological hallmarks of key systemic diseases, including lupus nephritis, ANCA-associated vasculitis, diabetic nephropathy, amyloidosis, and hypertensive nephrosclerosis. Diagnostic tools such as light microscopy, immunofluorescence, electron microscopy, and immunohistochemistry were reviewed in the context of their application to biopsy interpretation. While each disease exhibits characteristic morphologic features, overlapping patterns and nonspecific findings frequently complicate interpretation. Challenges such as masked immune deposits, limited sampling, and coexisting pathologies may lead to misclassification. Accurate diagnosis requires correlation with clinical, serologic, and imaging findings in a multidisciplinary context. Renal biopsy remains the gold standard for evaluating systemic diseases with renal involvement. Integrating traditional histopathology with emerging technologies—such as digital image analysis, molecular typing, and AI-based pattern recognition—holds promise for improved classification, prognostication, and personalized patient care.
Early myocardial calcification is an uncommon histopathological finding and is usually associated with chronic myocardial injury. Rapid intramyocyte microcalcification following global ischemia is rarely described. A 42-year-old previously healthy male suffered an out-of-hospital cardiac arrest while cycling. Following prolonged cardiopulmonary resuscitation and return of spontaneous circulation, he was admitted to ITU before being confirmed to have Hypoxic Ischemic Encephalopathy not compatible with life. Despite intensive supportive management for multiorgan failure patient was pronounced dead within 48 h of admission. There was no family history of heart disease or sudden cardiac death. The comprehensive forensic autopsy examination revealed no significant traumatic injuries that could account for death. Specialized cardiac examination showed subendocardial haemorrhagic infarction over the left ventricle. Histological examination demonstrated extensive focal intramyocyte microcalcification affecting sub endocardium of both ventricles in the areas of infarction with absence of fibrosis or inflammation. This case highlights rapid dystrophic intramyocyte microcalcification as a rare histological manifestation of severe global myocardial ischemia following cardiac arrest and resuscitation. Autopsy pathologists should be aware that subendocardial infarction with or without intramyocyte microcalcification and HIE occur secondary to cardiac arrest in those admitted to ITU and it is essential to investigate the cause of the primary cardiac arrest.
