Osteofibrous dysplasia (OFD) and adamantinoma are rare primary bone tumors. The present study is a clinico-pathological analysis of OFDs and adamantinomas, highlighting the value of distinguishing these tumors from their mimics and evaluating their proximity. OFDs, adamantinomas, fibrous dysplasias (FDs), and intraosseous synovial sarcomas (SS) of the tibia and fibula, diagnosed from 2012 to 2024 (12 years) were retrieved. Fifty-eight tumors were reviewed, and finally, 19 OFDs and 28 adamantinomas were analyzed. After a review, the diagnosis was modified in 12/58 (20.7%) tumors; with 4 OFDs revised to FDs; 2 FDs to OFDs; 2 intra-osseous SSs to classic adamantinomas; 3 OFD-like adamantinomas to classic adamantinomas, and a single de-differentiated adamantinoma to classic adamantinoma. The median age for OFD (10 years) was lower than that of adamantinoma (25 years). The radiological impression concurred with the histopathological diagnosis in 40% of OFDs and 60% of adamantinomas. Among 28 adamantinomas, there was a single OFD-like adamantinoma, 25 classic adamantinomas, and 2 dedifferentiated adamantinomas. Pan keratin (AE1/AE3) was positive in 18/19 (94.7%) OFDs and 19/20 (95%) adamantinomas. P40 (5/5, 100%) and p63 (6/8, 75%) were useful in the diagnosis of adamantinoma. Most adamantinomas were treated with surgery. None of the OFDs progressed to an adamantinoma during a median follow-up of 51.15 months(range = 4.36 to 97.94 months). Five out of 28 (17.9%) patients with an adamantinoma developed recurrences and 5 (17.9) developed metastases. The most commonly associated patterns with recurrences and metastasis in a classic adamantinoma were spindle and basaloid. The present study constitutes the first and the largest series of OFDs and adamantinomas from our subcontinent. OFD, OFD-like adamantinoma and adamantinoma may display overlapping clinico-radio-pathological profiles, and as such are potentially associated with diagnostic errors. Although there is a morphological continuum between OFD and adamantinoma, we did not observe a disease progression during the limited follow-up. It is crucial to distinguish an OFD and an adamantinoma from their various mimics, given treatment-associated implications. A long-term follow-up is suggested, as recurrences and metastases can occur late during the disease course.
The middle ear is an anatomic region that many pathologists may not feel comfortable reviewing. A variety of neoplastic and non-neoplastic lesions may occur in this anatomically complex space, but specimens are uncommon so the full spectrum of alterations remains obscure. This study was prompted by anecdotally encountered cases of unexpected S100 and PAX8 expression in middle ear specimens which led to diagnostic confusion. Twelve cases of otitis media were studied. In each case there was no clinical or radiological suspicion for neoplasia. Immunohistochemistry for S100 and PAX8 were performed on each case, with SOX10 and CD1a also done on a subset. Varying degrees of S100 immunoexpression was seen in the middle ear stroma of 12 cases, while the same cells were negative for SOX10 (0 of 11) and CD1a (0 of 3) in all cases tested. PAX8 was positive in the cuboidal middle ear epithelium in 11 of 11 tested cases. Expression was seen both in the lining surface components as well as in areas of glandular metaplasia. S100 is unexpectedly positive in middle ear stroma, a finding which can lead to diagnostic confusion, particularly for nerve sheath tumors. PAX8, on the other hand, is unexpectedly positive in middle ear epithelium, a pitfall for diagnosing various neoplasms, especially endolymphatic sac tumor of the inner ear. Awareness of these immunoexpression patterns will help avoid misdiagnoses. In particularly difficult cases, additional immunohistochemistry and clinical/radiographic correlation can clarify the diagnosis.
The integration of artificial intelligence (AI) into pathology practice is anticipated to drive substantial advancements. Numerous AI-based applications have been reported but the extent of their current clinical applicability remains uncertain. An evidence-informed clinical readiness review was conducted using the assistance of ChatGPT 5.1 Plus Thinking (OpenAI, San Francisco, CA). The initial summary provided by the large language model (LLM) was supplemented with additional data collected through further questioning and "conversation" between the authors and the LLM. The results were verified for accuracy and summarized by topic. The LLM provided useful outlines but extensive and time-consuming additional searches by the authors were needed to collect clinically relevant best evidence. Deep learning models (DLMs) for assistive diagnosis of prostate and breast cancer are being implemented in selected laboratories. DLMs for Pap smear assessment, metastasis detection, molecular inference, and other tasks have achieved promising results in curated settings but need further clinical validation. A variety of chatbots have been developed that show promise to enhance communications with patients and improve laboratory logistics. To date DLMs have shown great potential to improve the integration of clinico-pathologic data and can improve the diagnosis of selected entities. DLMs that can diagnose a more substantial number of pathological entities and provide better standardization of results reporting, prospective multicenter validation, and more detailed cost benefit analysis of AI-based models are needed prior to widespread adoption into the daily clinical practice of pathology.
Primary biliary cholangitis (PBC) is a chronic autoimmune cholestatic liver disease characterised by immune-mediated injury of small intrahepatic bile ducts, ultimately leading to progressive fibrosis, cirrhosis, and liver-related complications. Although diagnosis is typically established through cholestatic biochemical abnormalities and positivity of anti-mitochondrial antibodies, liver biopsy remains an important diagnostic tool in selected clinical settings, including atypical presentations, suspected overlap syndromes, and assessment of post-transplant liver dysfunction. Traditionally, the histopathology of PBC has been defined by chronic non-suppurative destructive cholangitis, progressive ductopenia, and biliary fibrosis. However, PBC encompasses a broader histopathological spectrum than traditionally recognised. In addition to classical lesions, contemporary liver biopsies may demonstrate distinct phenotypic patterns, including non-destructive ductopenia, inflammatory overlap-like changes, porto-sinusoidal vascular disease-associated lesions, and therapy-modified morphology. Recognition of these manifestations is important for accurate diagnosis, prognostic assessment, and avoidance of common diagnostic pitfalls. This review summarises the expanding histopathological spectrum of PBC in native and transplanted livers, with emphasis on emerging morphological phenotypes, treatment-related changes, recurrent disease after liver transplantation, and contemporary differential diagnostic challenges.
Myoepithelioma-like tumor of the vulvar region (MELTVR) is a rare SMARCB1-deficient mesenchymal neoplasm of adult women that can mimic malignant vulvar sarcomas, particularly epithelioid sarcoma. Although loss of SMARCB1/INI1 expression is a defining feature, the comprehensive genomic landscape of MELTVR remains poorly characterized. We report two cases of MELTVR and performed integrated histopathologic, immunophenotypic, and molecular analyses, including whole-exome sequencing (WES) with copy number assessment and targeted RNA-based fusion testing using the Archer FusionPlex Sarcoma panel. Histologically, both tumors consisted of relatively uniform epithelioid to short spindle cells in solid nests and cords within focal myxoid stroma, with complete loss of INI1 and positivity for smooth muscle markers and focal ER/EMA expression. Genomic profiling demonstrated a quiet molecular background in both cases, with low tumor mutation burden (0.45 and 1.03 mut/Mb) and no pathogenic SNVs/indels in major cancer-associated genes. One case showed a focal homozygous deletion of the SMARCB1 locus at 22q11.2, whereas the other case exhibited INI1 loss without detectable SMARCB1 mutation or copy number loss, suggesting heterogeneous mechanisms of inactivation. CDKN2A copy number remained neutral in both tumors. No canonical sarcoma-associated gene rearrangements, including EWSR1, FUS, PLAG1, or NR4A3, were identified. Together with a review of previously reported cases, these findings support MELTVR as an SMARCB1-inactivated neoplasm with low genomic complexity and highlight the diagnostic value of NGS-based profiling in excluding malignant mimics and preventing overtreatment.
Appendiceal tumors are uncommon, and their coexistence as collision tumors is exceedingly rare, with fewer than 20 cases reported to date. The objective is to report a multi-center case series and literature review of appendiceal collision tumors, providing a comprehensive summary of clinicopathological features and outcomes. Electronic records from five tertiary centers (2016-2024) were searched. Cases with appendiceal collision tumors composed of a neuroendocrine tumor (NET) and a second component of low- or high-grade appendiceal mucinous neoplasm (LAMN/HAMN) or adenocarcinoma were included. Additional cases with the same diagnostic combinations were identified through a PubMed literature search since 2000. Clinical, pathologic, and survival data were collected and analyzed. Thirty-three cases were identified, including 17 multi-institutional and 16 literature-derived cases, with an estimated incidence of 0.11% among appendectomies. Most tumors consisted of localized NET and LAMN. Gastrointestinal (GI) symptoms were present in 62.5-65.6% of cases, and tumors were identified by imaging in 53.1-75.0%. Outcome tracks the higher-stage and grade component. Patients with localized tumors had excellent outcomes (2-year progression-free survival [PFS] and overall survival [OS]: 100%). In contrast, cases with metastatic LAMN/HAMN had 2-year PFS 66.7% and OS 100%, while those with metastatic adenocarcinoma had 2-year PFS 0% and OS 66.7%. This study represents the largest series and literature review of appendiceal collision tumors to date. These rare tumors most often consist of localized NET and LAMN, typically present with GI symptoms, are often detected by imaging. The prognosis is dictated by the component of higher stage and grade.
To analyze the clinicopathological features of low-grade oncocytic tumor of the kidney (LOT) and to explore its cellular origin, immunohistochemical, and molecular characteristics. A retrospective analysis was conducted on the clinicopathological features and immunophenotypes of 7 cases of LOT diagnosed at two institutions from 2022 to 2025. The immunohistochemical expression of L1 cell adhesion molecule (L1CAM) was supplemented in LOT and control groups. High-throughput DNA targeted sequencing was applied to analyze the molecular genetic characteristics, and relevant literature was reviewed. Among the 7 patients, there were 2 males and 5 females, aged 52 to 74 years (median age 61 years). Tumor diameter ranged from 1.0 to 7.0 cm (mean diameter 3.9 cm). Grossly, the tumors were well-circumscribed, solid, and gray-brown. Microscopically, they exhibited a solid nested growth pattern with focal tubular structures. Edematous areas were observed in the stroma. Tumor cells had uniform round to oval nuclei and eosinophilic cytoplasm with perinuclear halos. Occasional binucleated cells were noted. Immunohistochemical staining showed that all cases were diffusely positive for CK7 and L1CAM, negative for CD117, and positive for PAX8, SDHB, and FH. Other markers including Vimentin, CD117, CD10, CAIX, P504S, TFE3, TFEB, and ALK (D5F3) were negative. High-throughput sequencing detected MTOR gene mutations in 6 cases, while non-mTOR pathway-related molecular alterations, including BRAF, LRP1B, and XRCC1, were identified in one case. Up to the last follow-up (median follow-up time 11 months), all patients were alive without disease progression. This study suggests that LOT may originate from principal cells of the collecting duct and distal renal tubule. Morphologically, it is characterized by a nested growth pattern with stromal edema, and immunohistochemically, it shows positivity for CK7 and negativity for CD117. The consistent positive expression of L1CAM in this study serves as a useful complementary marker for the differential diagnosis of LOT from other morphologically similar eosinophilic renal tumors. Regarding molecular genetics, this study not only explored the characteristics of mTOR pathway gene mutations in LOT but also identified one case with non-mTOR pathway-related molecular alterations, providing new supplementary information for the molecular landscape of LOT. Considering the cellular origin and indolent biological behavior of LOT, these findings contribute to further refinement of the classification system and nomenclature for this type of tumor. Additionally, this study provides important case data supporting LOT in the Chinese population.
Neuroendocrine tumors (NETs) of the gynecologic tract are diagnostically challenging because of their heterogeneity. Delta-like ligand 3 (DLL3), an inhibitory Notch receptor ligand, is frequently overexpressed in NETs and has emerged as a potential diagnostic and therapeutic target. This study evaluated DLL3 expression in 76 paraffin-embedded tissue samples from 74 patients, including cervical and ovarian small cell carcinomas/NETs, cervical large cell carcinoma/NET, metastatic NETs, dedifferentiated/undifferentiated carcinomas, carcinosarcomas, and high-grade serous carcinomas. DLL3 positivity was defined by cytoplasmic staining and assessed by staining intensity (0-3+) and percentage of positive tumor cells. DLL3 expression was detected in 83% of cervical small cell carcinomas/NETs, 67% of ovarian small cell carcinomas/NETs, and 100% of cervical large-cell carcinoma/NETs, all showing strong (3+) staining and seen in 5% to 100% of the tumor cells. Metastatic NETs demonstrated lower expression (14%, 3+), which was seen in 90% of the tumor cells. Among dedifferentiated/undifferentiated carcinomas, 60% showed DLL3 positivity in scattered undifferentiated foci with staining intensities ranging from 1+ to 3+. DLL3 expression was also identified in 62% of carcinosarcomas within scattered foci of sarcomatous areas, with 2+ to 3+ intensity. In contrast, high-grade serous carcinomas lacked DLL3 expression. These findings demonstrate frequent DLL3 expression in gynecologic NETs and selected dedifferentiated malignancies, supporting DLL3 as a promising diagnostic marker and potential therapeutic target in gynecologic cancers.
Aortic diseases contribute substantially to morbidity and mortality through inflammatory and degenerative mechanisms, yet existing classification schemes for inflammatory aortic pathology have limitations in the surgical pathology setting. This study aimed to characterize inflammatory diseases of the aorta using a standardized consensus-based reporting system. A retrospective cross-sectional review of archival aortic surgical pathology cases from 2009 to 2016 was performed, with histologic evaluation using elastic and trichrome stains and classification according to the Society for Cardiovascular Pathology-Association for European Cardiovascular Pathology consensus statement. Among 170 cases (mean age 61.9 years; 72% male), atherosclerosis predominated (86.5%), followed by aortitis/periaortitis (12.9%) and atherosclerosis with excessive inflammation (2.4%). Severe atherosclerosis accounted for 65.3% of cases, with frequent calcification and plaque disruption. Lymphoplasmacytic inflammation was the most common pattern of aortitis/periaortitis. Application of the consensus grading system enables standardized and reproducible characterization of inflammatory aortic diseases and supports its routine use in surgical pathology practice.
IgG4-related disease (IgG4-RD) diagnosis remains challenging due to subjective histopathological interpretation. This study aimed to develop and internally evaluate a quantitative pathological scoring system to improve diagnostic accuracy. We retrospectively reviewed 96 patients with marked lymphoplasmacytic infiltration diagnosed between 2012 and 2024, classified as IgG4-RD (n = 47) or non-IgG4-RD (n = 49) according to the 2019 ACR/EULAR criteria. Eight histopathological parameters were quantified, including IgG4+/CD138+ ratio, IgG4+ plasma cell count/high-power field, storiform fibrosis, obliterative venulitis, perineural inflammation, tertiary lymphoid structures, nerve bundles, and eosinophilic infiltration. Mann-Whitney U test, ROC curve analyses, subgroup analyses, and calibration curve were performed. A weighted scoring system was constructed based on parameter diagnostic performance. Significant intergroup differences were observed in all parameters except lymphoplasmacytic infiltration (all P < 0.05). The 12-point scoring system (≥5.5-point threshold) demonstrated excellent diagnostic accuracy (AUC 0.996, 95% CI: 0.988-1.000), with 95.74% sensitivity and 100.00% specificity. A simplified four-parameter version achieved an AUC of 0.994 (0.986-1.000), sensitivity 93.62%, and specificity 100.00%. This novel histopathology-based scoring system provides a standardized, reproducible tool for IgG4-RD diagnosis, enhancing objectivity and consistency in pathological assessment, and serves as a valuable complement to existing diagnostic frameworks for routine clinical practice.
Xanthogranulomatous cholecystitis (XGC) is an uncommon histologic variant of chronic cholecystitis characterized by marked fibrosis with infiltration of macrophages and foamy histiocytes. Lymphoplasmacytic cholecystitis (LPC), another variant, has historically been considered specific to primary sclerosing cholangitis (PSC) and is associated with autoimmune pancreatitis. IgG4-related cholecystitis (IgG4-RC) represents gallbladder involvement in IgG4-related disease (IgG4-RD), in which autoimmune pancreatitis is the most common manifestation. Approximately 25-32% of patients with autoimmune pancreatitis demonstrate concomitant IgG4-related cholecystitis. This study aimed to evaluate the clinicopathological and immunohistochemical relationships among XGC, LPC, and IgG4-RC. Eight hundred cases of conventional chronic cholecystitis were retrospectively reviewed. Cases of XGC, LPC, and IgG4-RC were identified using established histologic criteria, including dense lymphoplasmacytic inflammation, storiform fibrosis, obliterative phlebitis, and quantification of IgG- and IgG4-positive plasma cells. Twenty-six cases of LPC and fifty-nine cases of XGC were identified. All LPC cases demonstrated fewer than 50 IgG- and IgG4-positive plasma cells per high-power field (HPF), with an IgG4/IgG ratio below 40%. In contrast, 11.3% (5/44) of evaluable XGC cases showed more than 50 IgG4-positive plasma cells per HPF and an IgG4/IgG ratio exceeding 40%. Among these five cases, three additionally exhibited all three characteristic histopathologic features of IgG4-RD: dense lymphoplasmacytic inflammation, storiform fibrosis, and obliterative phlebitis. LPC appears to represent a distinct variant of chronic cholecystitis and does not share histologic or immunologic features with IgG4-related cholecystitis, aside from increased plasma cells. XGC, however, may share certain clinicoradiologic and histologic features with IgG4-RC. These overlapping features alone are insufficient to establish a diagnosis of IgG4-RD and may reflect coincidental findings, particularly in patients with multiorgan IgG4-related disease involvement.
Epstein-Barr virus-positive (EBV+) classic Hodgkin lymphoma (cHL) may mimic EBV+ diffuse large B-cell lymphoma, not otherwise specified (DLBCL, NOS), creating a clinically relevant diagnostic pitfall. We retrospectively reviewed 62 immunocompetent patients with EBV+ large B-cell neoplasms and classified cases into five reproducible pattern-based groups: monomorphic EBV+ DLBCL, polymorphic/immune-environment rich EBV+ DLBCL (polyDLBCL), EBV+ cHL with retained B-cell marker expression, canonical EBV+ cHL, and rare EBV+ mediastinal gray-zone lymphoma. The principal diagnostic challenge was the distinction between polyDLBCL and EBV+ cHL, both of which may contain Hodgkin/Reed-Sternberg-like cells in inflammatory backgrounds. OCT2 was the most informative B-cell marker, but partial OCT2 retention in EBV+ cHL should not alone prompt reclassification as DLBCL. CD20 and CD79a showed substantial overlap, whereas CD15 and IMP3 lacked sufficient specificity. GATA3 expression supported canonical EBV+ cHL, but negativity did not exclude cHL, particularly when the B-cell program was retained. EBER-positive cell-size distribution and EBV latency type (98% were type II) were of limited discriminatory value. Tumor-cell PD-L1 expression was highest in canonical cHL and lower in cHL with B-cell marker retention and monomorphic DLBCL. Clinically, younger patients more often had nodal cHL and favorable outcomes, whereas older patients showed more monomorphic histology, more advanced disease and poorer prognosis. Adverse outcome correlated most strongly with age and EBV lytic reactivation. These findings support an immune-environment-rich EBV-positive large B-cell lymphoma continuum in which strict separation of EBV+ cHL from polymorphic EBV+ DLBCL may not fully reflect the underlying biology.
Cystic lesions of the kidney represent a heterogeneous group of conditions ranging from non-neoplastic processes to benign and malignant neoplasms. With the widespread use of cross-sectional imaging, these lesions are detected with increasing frequency, often incidentally during radiologic evaluation. The Bosniak classification system remains the primary radiologic framework for estimating malignancy risk and guiding management decisions for cystic renal masses. However, imaging findings alone are frequently insufficient for definitive diagnosis, and accurate classification often requires integration with gross and histopathologic evaluation. In this review, we provide an integrated overview of cystic renal lesions with emphasis on their clinical, radiologic, gross, histopathologic, and immunohistochemical characteristics. The spectrum includes non-neoplastic entities to benign and malignant neoplasms. In addition, tumors that are typically solid but may demonstrate prominent cystic change are discussed, highlighting the importance of including these entities in the differential diagnosis when evaluating complex cystic renal masses. Understanding the morphologic spectrum and recognizing key diagnostic features are essential for distinguishing benign cysts from cystic neoplasms and for avoiding both underdiagnosis and overtreatment. Radiologic-pathologic correlation and a structured diagnostic approach are critical for accurate classification and optimal patient management. Continued refinement of imaging criteria and improved multidisciplinary collaboration will further enhance the diagnostic evaluation and clinical management of cystic renal lesions.
Vascular anomalies encompass a heterogeneous spectrum of tumors and malformations where accurate classification is essential for appropriate clinical management. The International Society for the Study of Vascular Anomalies (ISSVA) 2025 classification represents the contemporary global standard for vascular lesions however; antiquated and biologically imprecise terminology continues to pervade in routine diagnostic practice. In this retrospective study, 164 biopsy-proven vascular anomalies diagnosed between January 2018, and December 2023 were reviewed and reclassified according to ISSVA 2025 criteria based on morphology, special stains, and immunohistochemistry where indicated. Reclassification was required in 96 cases (58.53%), confirming substantial discordance between prevailing terminology and current standards. Vascular malformations were the predominant lesions (67.7%) and required reclassification in majority of cases (88.5%) with venous malformations being the most frequent category that were reassigned. The term 'cavernous hemangioma' emerged as the single most frequent source of diagnostic error (n = 28), contributing to 50% reclassification to venous malformation. Vascular tumors comprised 51 cases (31.1%), of which 9 (17.6%) were reclassified to various other entities. Five cases were reassigned to intramuscular fast-flow vascular anomaly which is a newly delineated entity in the ISSVA 2025 classification. GLUT-1 immunohistochemistry was performed in six cases where distinction between infantile and congenital hemangioma subtypes was required based on histomorphology. The challenges observed were the continued use of outdated terminology, limited availability of imaging studies to aid in classifying fast and slow-flow lesions, and lack of molecular diagnostic platforms posing significant barriers to the systematic adoption of ISSVA 2025 in resource-limited settings.
Head and neck squamous cell carcinoma (SCC) has many subtypes, including basaloid (BSCC) and adenosquamous carcinoma (ASC). We describe a surface-derived carcinoma with features of both BSCC and ASC, along with frequent myoepithelial differentiation. Five cases were retrieved, slides were reviewed and results tabulated. DNA- and RNA-sequencing were performed in 4 and 5 cases, respectively. Patients were 4 men and 1 woman, from 55 to 78 years (mean, 68.6). Sites of origin were 2 hypopharynx, 2 oral cavity and 1 oropharynx. All cases demonstrated basaloid morphology and duct formation. Squamous dysplasia was in the overlying epithelium in 4 of 5. The tumors showed marked pleomorphism, mitotic activity, and necrosis. By immunohistochemistry, the tumors demonstrated non-diffuse p40/p63 expression sparing ducts. SOX10 and S100 were positive to varying extents in all, while SMA/SMMS was positive in 4 of 5. MYB IHC/RNA ISH were positive in all cases. Neuroendocrine markers were negative. Sequencing demonstrated SCC-like genetics with TP53 mutations (4 of 4), 11q13 amplification (3 of 4), and structural variants of unknown significance in 2 of 5 (Case 4 GLI3::ZNF804B, Case 5 ZNF521::AC090403.1 and CYLD::FSTL1). We demonstrate SCCs with basaloid features, non-diffuse p40/p63, as well as ductal and often myoepithelial differentiation. Despite features which traditionally point to a salivary-type carcinoma, especially high-grade AdCC, they exhibited squamous dysplasia/conventional SCC, SCC-like mutational profiles, and absence of MYB/MYBL1/NFIB fusions, strongly supporting squamous derivation. We propose the term basaloid ASC mimicking AdCC (BAC MAC). Recognition of this new SCC variant is important to avoid misdiagnosis and mismanagement.
Cytologic sampling is widely practiced for diagnosis of advanced lung cancer. In the present era of targeted therapy, distinguishing adenocarcinoma (ADC) from squamous cell carcinoma (SCC) is pivotal for tailoring the tissue for molecular testing. Studies on application of immunocytochemistry (ICC) on direct smears remain limited in literature. This study was aimed to assess the utility of TTF -1 and p40 antibodies on direct cytologic smears to distinguish ADC from SCC. Lung cytologic samples from 2016 to 2022, that were morphologically non-small cell carcinoma (NSCLC) were subjected to ICC using TTF-1 and p40 antibodies which were applied directly on destained 95% ethanol-fixed Papanicolaou- stained smears. Based on the expression, the results were compared with the cytomorphological and histopathological diagnosis. Of the 44 cases of adenocarcinoma that were positive for TTF-1 by immunocytochemistry, 43 were positive by immunohistochemistry (IHC) in paraffin-embedded biopsy, with a sensitivity of 97.2% and positive predictive value (PPV) of 100%. All cases of SCC were positive for p40 both by ICC and IHC; sensitivity and PPV were 100% each. The agreement between ICC and IHC for both the markers were significant with a Kappa = 1.0. A two-marker panel consisting of TTF-1 and p40 antibodies on direct smears serves as a valuable tool in distinguishing ADC from SCC, thus overcoming the morphologic pitfalls of cytomorphology. Cytologic smears can be conveniently used for ICC, thus negating the need for immunohistochemistry and serving as a measure to conserve tissue for molecular testing.
Amiodarone-induced liver injury (AILI) is a known risk of amiodarone therapy, with presentations ranging from asymptomatic aminotransferase elevations to severe or fatal hepatitis and cirrhosis. Due to limited understanding of its histopathologic features, we conducted a retrospective cross-sectional re-analysis of liver biopsy samples from patients on amiodarone from two centers. Of the 48 liver biopsy samples, 42 (87%) exhibited histologic evidence of AILI. All patients showed minimal or mild macrovesicular steatosis. Ballooned hepatocytes were observed in 36 cases (86%), with 25 (69%) displaying a periportal distribution, 8 (22%) centrilobular, and 3 (8%) panacinar in distribution. Mallory-Denk bodies were found in 36 samples (76%)-18 (50%) were numerous and 18 (50%) multiple. Cholestasis was present in 10 patients, 7 (70%) of whom died. In contrast, 10 (31%) of the 32 patients without cholestasis died. This represents a significantly increased mortality risk for patients with AILI and cholestasis (p = 0.03). While AILI shares features with the more generally known metabolic dysfunction-associated steatotic liver disease, our findings indicate that a prominence of periportal distribution of ballooned hepatocytes and Mallory-Denk bodies despite a minimum of macrovesicular steatosis are characteristic of AILI. Furthermore, cholestasis in biopsy samples may suggest a poorer prognosis in patients on amiodarone.
Primary central nervous system (CNS) sarcomas are rare, heterogeneous mesenchymal neoplasms that account for less than 1% of CNS tumours and pose significant diagnostic challenges due to their morphological diversity and overlap with other CNS neoplasms. This retrospective study analysed 65 cases of primary CNS sarcomas diagnosed over a 12-year period (2014-2025) at a tertiary care centre. Clinical, demographic, and radiological details were retrieved from institutional records, and all cases were reviewed using an integrated diagnostic approach incorporating histopathology, immunohistochemistry, and molecular studies, including fluorescence in situ hybridization and reverse transcriptase polymerase chain reaction, and classified according to the 2021 World Health Organization Classification of Tumours of the Central Nervous System. The cohort showed a male predominance (male:female = 1.3:1), with a mean age of 28.6 years (median: 22 years), and predominantly affected children and young adults. Tumours most frequently involved the spinal and paraspinal regions (60%, n = 39). Ewing sarcoma was the most common subtype (58.5%), followed by solitary fibrous tumour (10.8%) and malignant peripheral nerve sheath tumour (7.7%), while rhabdomyosarcoma, alveolar soft part sarcoma, angiosarcoma, and other rare sarcomas were encountered less frequently. Accurate diagnosis required careful correlation of clinical and radiological findings with morphology, immunophenotype, and molecular alterations. Primary CNS sarcomas comprise a diverse group of tumours with distinct pathological and molecular features, and precise classification requires integrating demographic, radiological, histopathological, immunohistochemical, and molecular findings for optimal diagnosis and patient management.
Bland thyroid follicles are occasionally identified within cervical lymph nodes, raising the differential diagnosis of benign thyroid inclusions versus metastatic papillary thyroid carcinoma. Proposed criteria for benign thyroid inclusions include lack of cytologic atypia, subcapsular or central nodal location, and involvement of only one or two lymph nodes. We observed several cases of fibrosing variant Hashimoto thyroiditis with multifocal thyroid tissue in cervical lymph nodes despite the absence of identifiable primary carcinoma. The pathology archives from 2014 to 2024 were searched for cases of fibrosing variant Hashimoto thyroiditis. Cases were reviewed for occult papillary thyroid carcinoma and thyroid tissue within sampled lymph nodes. IgG4 staining results were recorded. HBME-1, BRAF V600E, and NRAS Q61R immunostains were performed on nodal thyroid tissue. Thirty-six patients were identified (28 females, 8 males; median age 54 years, range 26-83). Increased IgG4-positive plasma cells were present in 29 cases. Lymph nodes were sampled in 23 patients, and thyroid tissue was identified in 8. No primary papillary thyroid carcinoma was identified in 6 of these 8 patients, including 4 in whom the entire thyroid gland was submitted for microscopic examination. HBME-1, BRAF V600E, and NRAS Q61R were negative in all nodal thyroid tissue. Our findings suggest that multifocal thyroid tissue within cervical lymph nodes is relatively common in fibrosing variant Hashimoto thyroiditis. The absence of primary carcinoma in most cases, together with bland cytology and negative immunohistochemical findings, supports the possibility that these represent benign thyroid inclusions that fall outside traditionally accepted diagnostic criteria.
Angiectatic sinonasal polyps (ANPs) are a rare but clinically significant entity in sinonasal pathology, often resembling neoplasms and complicating diagnostic accuracy. Due to their potential for serious complications, ANPs warrant closer investigation. This study aims to explore the clinicopathological characteristics of ANPs, emphasizing their diagnostic challenges and identifying key features for accurate identification. Among 189 inflammatory sinonasal polyps evaluated over 8 years, 20 cases (10.6%) were ANPs, predominantly affecting males (70%) and patients older than 30 years (65%). The left maxillary sinus was most involved (75%). Nasal obstruction (100%), rhinorrhea (90%), bleeding on touch (80%), and rapid growth (70%) were frequent. Radiology showed expansile lesions with bone remodeling (100%) and erosion (30%). Histopathology revealed vascular proliferation (100%), stromal edema and chronic inflammation (95%), atypical fibroblasts (80%), and infarction and squamous metaplasia (50%). All were treated by surgical excision; despite intraoperative bleeding (55%), no recurrences were observed during 6-month follow-up, indicating excellent prognosis. ANPs are a diagnostic challenge within the broader category of SNPs, often presenting with features that mimic malignancy. However, they exhibit a distinctive histopathological profile, characterized by vascular proliferation and eosinophilic matrix deposition, which can aid in their diagnosis and guide treatment strategies.