Annals of Diagnostic Pathology最新文献

{"title":"Clinicopathological analysis of osteofibrous dysplasia and adamantinoma: A single institution experience","authors":"Radhika Jayan ,&nbsp;Bharat Rekhi ,&nbsp;Mukta Ramadwar ,&nbsp;Poonam Panjwani","doi":"10.1016/j.anndiagpath.2026.152618","DOIUrl":"10.1016/j.anndiagpath.2026.152618","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":50768,"journal":{"name":"Annals of Diagnostic Pathology","volume":"82 ","pages":"Article 152618"},"PeriodicalIF":1.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146138129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of the diagnostic utility of an immunohistochemical panel (MYB, MYBL1, β-catenin, and LEF1) in basaloid tumors of the salivary glands","authors":"Wenmin Yang ,&nbsp;Chaoshan Wang ,&nbsp;Dan Zhang ,&nbsp;Lei Zhang ,&nbsp;Ling Nie","doi":"10.1016/j.anndiagpath.2026.152616","DOIUrl":"10.1016/j.anndiagpath.2026.152616","url":null,"abstract":"<div><div>Salivary gland tumors, including adenoid cystic carcinoma (ACC), pleomorphic adenoma (PA), basal cell adenoma (BCA), and basal cell adenocarcinoma (BCAC), share histologic features, making differential diagnosis difficult. However, these tumors differ in biological behavior, treatment strategy, and prognosis, so accurate pathological diagnosis is of great significance. In this study, we used a panel of immunohistochemical antibodies (MYB, MYBL1, β-catenin, and LEF1) to distinguish the abovementioned salivary basaloid tumors. For ACC, 80% (16/20) of cases were MYB-positive, and β-catenin was essentially negative. The BCAs and BCACs were characterized by frequent nuclear β-catenin and LEF1 expression, with positive rates 55% (16/29) and 76% (22/29), respectively. PAs were almost negative for the makers, except for a few cases with LEF1 (3/20) and MYB (1/20) positivity. MYB demonstrated a sensitivity of 80% and a specificity of 94% for ACCs. MYBL1 was negative in all included tumors. LEF1 exhibited a sensitivity of 76% and a specificity of 90% for BCAs and BCACs. β-catenin showed a low sensitivity (55%) but a high specificity (100%) for these tumors. Combined use of LEF1 and β-catenin improved sensitivity (90%) but resulted in a medium specificity (93%). In conclusion, the proposed immunohistochemical panel can improve diagnostic accuracy in basaloid tumors of the salivary glands.</div></div>","PeriodicalId":50768,"journal":{"name":"Annals of Diagnostic Pathology","volume":"82 ","pages":"Article 152616"},"PeriodicalIF":1.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146024375","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative accuracy of telecytology and in-person rapid on-site evaluation by specimen source: A multi-campus analysis","authors":"Agnes I. Udoh,&nbsp;Taylor Strange,&nbsp;Cecilia G. Clement","doi":"10.1016/j.anndiagpath.2026.152605","DOIUrl":"10.1016/j.anndiagpath.2026.152605","url":null,"abstract":"<div><div>Rapid on-site evaluation (ROSE) of fine-needle aspiration (FNA) specimens improves specimen adequacy, diagnostic accuracy, and patient management. Telecytology (TC) has emerged as a potential alternative to in-person ROSE, particularly in multi-campus healthcare systems where cytopathologist coverage is limited; however, its comparative accuracy across different specimen sources remains uncertain. In this retrospective study, all FNAs with ROSE preliminary diagnoses performed across three campuses in our health system from 2022 to 2023 were reviewed. ROSE interpretations rendered via in-person evaluation or TC were compared with final diagnoses. Major discrepancies were defined as benign-to-malignant or malignant-to-benign discordance. Diagnostic accuracy was analyzed by specimen source, and chi-square tests were used to assess statistical significance. Of 2836 FNAs performed, 1697 underwent ROSE, including 1459 in-person and 238 TC cases. Major discrepancies occurred in 3% of in-person ROSE cases and 5% of TC cases, with no statistically significant difference (<em>p</em> = 0.2429). TC demonstrated numerically higher concordance than in-person ROSE for several visceral sites, including liver, kidney/adrenal, pancreatobiliary, and upper gastrointestinal FNAs, though none reached statistical significance. In contrast, in-person ROSE showed significantly higher accuracy for lymph node, head and neck, and bone/soft tissue FNAs. Overall, TC demonstrated accuracy comparable to in-person ROSE, with performance varying by specimen source. These findings support the feasibility of TC while underscoring the importance of specimen-specific evaluation, ongoing quality assurance, and prospective validation in multi-campus cytopathology practices.</div></div>","PeriodicalId":50768,"journal":{"name":"Annals of Diagnostic Pathology","volume":"82 ","pages":"Article 152605"},"PeriodicalIF":1.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146078909","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Histology of amiodarone-induced liver injury revisited: A retrospective morphologic analysis","authors":"Beena U. Ahsan ,&nbsp;Maria Westerhoff ,&nbsp;Lindsey Yassan ,&nbsp;Rong Xia ,&nbsp;John Hart","doi":"10.1016/j.anndiagpath.2026.152623","DOIUrl":"10.1016/j.anndiagpath.2026.152623","url":null,"abstract":"<div><div>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 (<em>p</em> = 0.03).</div><div>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.</div></div>","PeriodicalId":50768,"journal":{"name":"Annals of Diagnostic Pathology","volume":"82 ","pages":"Article 152623"},"PeriodicalIF":1.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146167613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"H3-3A gene mutation analysis in giant cell tumor of bone and its histologic mimics: A single institutional study from India","authors":"Shantveer G. Uppin ,&nbsp;Monalisa Hui ,&nbsp;Derin Mary Thomas ,&nbsp;Megha S. Uppin ,&nbsp;Vinay Nalla ,&nbsp;K. Nageshwara Rao ,&nbsp;Rajeev Reddy ,&nbsp;Himakanth Lingala","doi":"10.1016/j.anndiagpath.2026.152606","DOIUrl":"10.1016/j.anndiagpath.2026.152606","url":null,"abstract":"<div><div>Though the diagnostic utility of H3.3G34W immunohistochemistry (IHC) for giant cell tumor of bone (GCTB) is well established, it is limited by a proportion of cases with variant <em>H3-3A</em> mutations [<em>H3-3A</em>: c.104G&gt;T p. Gly35Val (G34V), <em>H3-3A</em>: c.103G&gt;A p. Gly35Arg (G34R), <em>H3-3A</em>: c.103_104delinsCT p. Gly35Leu (G34L)], wild-type genotype and <em>H3-3A</em>:c.103G&gt;T p. Gly35Trp (G34W) mutation identified by sequencing but not by IHC. In this study, the <em>H3-3A</em> gene mutation by Sanger sequencing was analyzed in a large cohort of GCTB and its histological mimics. Sequencing of the H3-3A gene was performed to detect mutations in 148 GCTBs and 57 histologic mimics. The other osteoclast giant cell containing lesions histologically mimicking GCTB included were chondroblastoma (22), aneurysmal bone cyst (11), chondromyxoid fibroma (6), telangiectatic osteosarcoma (6), brown tumor of hyperparathyroidism (4), clear cell chondrosarcoma (3), osteoid osteoma (2), osteoblastoma (2) and giant cell reparative granuloma (1). Of the 148 GCTBs tested, 129 showed <em>H3-3A</em> gene mutations by Sanger sequencing and remaining 19 were wild type. The different <em>H3-3A</em> mutations detected included 126 <em>H3-3A</em>:c.103G&gt;T p. Gly35Trp (G34W), one each of <em>H3-3A</em>: c.103G&gt;A p. Gly35Arg (G34R), <em>H3-3A</em>: c.104G&gt;T p. Gly35Val (G34V) and <em>H3-3A</em>: c.103_104delinsCT p. Gly35Leu (G34L). The results of <em>H3-3A</em> gene sequencing were in concordance with the immunohistochemical expression for H3.3G34W/R/V in 129 tumors. All the 57 osteoclast giant cell-containing lesions, other than GCTB, except one (1) case of chondroblastoma, did not show any mutations in the <em>H3-3A</em> gene. The latter case showed <em>H3-3A</em>: c.110A&gt;T p. Lys37Met (K36M) mutation. The <em>H3-3A</em> gene sequencing assay demonstrated a sensitivity of 87.16% and an absolute specificity of 100% among the cases analyzed in the study. Determination of the <em>H3-3A</em> gene mutation by sequencing is a highly sensitive and absolutely specific diagnostic tool for the diagnosis of GCTB and differentiation from its histologic mimics.</div></div>","PeriodicalId":50768,"journal":{"name":"Annals of Diagnostic Pathology","volume":"82 ","pages":"Article 152606"},"PeriodicalIF":1.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145981708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polyarteritis nodosa with isolated organ involvement requiring resection in the genitourinary system","authors":"Busra Yaprak Bayrak ,&nbsp;Selva Kabul ,&nbsp;Suheda Zeynep Seday ,&nbsp;Sule Ozsoy ,&nbsp;Hazal Taş Solak ,&nbsp;Kutsal Yorukoglu ,&nbsp;Kemal Kosemehmetoglu ,&nbsp;Mahmut Akgul","doi":"10.1016/j.anndiagpath.2026.152615","DOIUrl":"10.1016/j.anndiagpath.2026.152615","url":null,"abstract":"<div><div>Polyarteritis nodosa (PAN) is a necrotizing vasculitis of medium-sized arteries that is classically described as a multisystem disease. However, PAN may rarely present with isolated organ involvement, occasionally leading to irreversible organ loss before a definitive diagnosis is established. Data on such presentations remain limited and are largely confined to isolated case reports. We retrospectively evaluated eight patients diagnosed with PAN from multiple centers, focusing on clinical presentation, imaging findings, serological results, histopathological features, treatment approaches, and outcomes. The cohort included six women and two men, with ages ranging from 25 to 76 years. Clinical presentation was highly heterogeneous and frequently dominated by life-threatening genitourinary events, including massive renal hemorrhage, retroperitoneal hematoma, renovascular disease with aneurysm formation and infarction, and acute testicular pain and swelling. Five of the eight patients were classified as having isolated, single-organ PAN, predominantly involving the kidney and, less frequently, the testis. In these patients, organ loss was often the event that led to definitive diagnosis. Imaging findings supported vascular patterns consistent with PAN, including hematoma, arterial stenosis, aneurysmal changes, and ischemic sequelae. Serological evaluation was largely nondiagnostic, with predominant ANCA negativity. Histopathological examination consistently demonstrated necrotizing arteritis of medium-sized arteries with fibrinoid necrosis, thrombosis, and transmural inflammation, without glomerular or granulomatous involvement. Multisystem disease was identified in three patients, including one fatal presentation diagnosed at autopsy. This multicenter case series highlights isolated-organ PAN as a rare but clinically significant presentation, frequently recognized only after catastrophic vascular complications result in resection. Our findings emphasize the pivotal role of surgical pathology and clinicopathological correlation in establishing the diagnosis and underscore the need to consider PAN in unexplained renal or testicular vascular catastrophes, even in the absence of classic systemic features.</div></div>","PeriodicalId":50768,"journal":{"name":"Annals of Diagnostic Pathology","volume":"82 ","pages":"Article 152615"},"PeriodicalIF":1.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146024377","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diagnostic and prognostic inferences of Tricho-rhino-phalangeal Syndrome 1 (TRPS1) protein immunohistochemical expression in primary epithelial ovarian cancers","authors":"Rokia Masoud ,&nbsp;Amal Abd El hafez ,&nbsp;Eman E. Saad ,&nbsp;Amr Hossam ,&nbsp;Amany Hassan","doi":"10.1016/j.anndiagpath.2026.152608","DOIUrl":"10.1016/j.anndiagpath.2026.152608","url":null,"abstract":"<div><div>Tricho-rhino-phalangeal Syndrome 1 (TRPS1) protein is a transcription factor that is altered in multiple cancers. Its role in epithelial ovarian cancers (EOCs) is still unexplored. This cross-sectional study investigates the immunohistochemical (IHC) expression of TRPS1 in EOCs exploring its diagnostic, prognostic and therapeutic inferences in a total of 127 EOC patients diagnosed at Oncology Center, Mansoura University. Tissue microarray sections were stained with anti-TRPS1. Based on quantitative scoring, TRPS1 was expressed in 74% of EOCs: 26% low-positive and 48% high-positive expression. TRPS1 was expressed in endometrioid, clear cell, high-grade serous, mucinous, and low-grade serous carcinomas (92.9, 78.6, 73.8, 71.4, and 50%, respectively), with a high-positive expression in endometrioid (71.5%), followed by mucinous (57.1%), then high-grade serous (50%) carcinomas. There were no statistically significant associations with most of the analyzed variables or survival outcomes, though the TRPS1-positive group had slightly better overall and disease-free survival early on, but this advantage diminished over time. In conclusion, TRPS1 is substantially expressed in EOCs and across different histological subtypes. It may be used in diagnosis of EOC; however, it is not a reliable prognostic marker. Alongside breast carcinoma, EOC should be considered in differential diagnosis it TRPS1 -positive metastatic lesions of unknown primary.</div></div>","PeriodicalId":50768,"journal":{"name":"Annals of Diagnostic Pathology","volume":"82 ","pages":"Article 152608"},"PeriodicalIF":1.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145967713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Macroscopic and microscopic features indicating serosal invasion of colonic adenocarcinoma","authors":"Chalisa Wongcharoen ,&nbsp;Saowalak Hunnangkul ,&nbsp;Ananya Pongpaibul ,&nbsp;Napat Angkathunyakul","doi":"10.1016/j.anndiagpath.2026.152619","DOIUrl":"10.1016/j.anndiagpath.2026.152619","url":null,"abstract":"<div><h3>Objectives</h3><div>Colonic adenocarcinoma poses a significant global health burden. Accurate detection of serosal invasion (pT4) is crucial for prognosis, yet inconsistent grossing protocols create diagnostic challenges. We aimed to evaluate macroscopic predictors of serosal invasion, determine the minimum tumor blocks required for accurate staging, and assess pT4 frequency at Siriraj Hospital.</div></div><div><h3>Materials and methods</h3><div>We performed a retrospective review of a cohort comprising 218 patients diagnosed with colonic adenocarcinoma. The assessment was conducted by gastrointestinal pathologists and a trainee, integrating clinical records and macroscopic characteristics. Macroscopic features were categorized, including serosal surface appearance (smooth, irregular, bulging, perforated, adherent), tumor circumferential involvement, and depth of invasion on the cut surface (confined to muscularis propria, into pericolic tissue, or through serosa), correlated with histopathological evaluation according to the AJCC Cancer Staging Manual, 8th edition. Statistical analyses were executed to identify independent predictors of pT4a staging.</div></div><div><h3>Results</h3><div>The pT4 prevalence was 20.2% (pT4a: 14.7%, pT4b: 5.5%). Multivariate analysis confirmed irregular serosa as a strong predictor (aOR: 7.03, 95% CI: 1.99–24.71). Notably, macroscopic observation of tumor penetration through the serosa on the cut surface exhibited the highest predictive value (aOR: 48.76, 95% CI: 9.43–252.15). Data indicated that submitting at least two blocks from the tumor-serosa interface ensured reliable staging.</div></div><div><h3>Conclusions</h3><div>Our pT4 rates align with international benchmarks. Irregular serosa and macroscopic serosal penetration are robust pT4a predictors. We recommend meticulous gross examination and submitting a minimum of two blocks from the deepest invasion point to optimize staging accuracy.</div></div>","PeriodicalId":50768,"journal":{"name":"Annals of Diagnostic Pathology","volume":"82 ","pages":"Article 152619"},"PeriodicalIF":1.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146127033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LEF1 and IL13RA2 in testicular sex cord–stromal tumors: LEF1 as a potential diagnostic marker for Sertoli cell tumors","authors":"Mario Della Mura ,&nbsp;Joana Sorino ,&nbsp;Gerardo Cazzato ,&nbsp;Alessandro Rizzo ,&nbsp;Carlo Gentile ,&nbsp;Giovanni Musci ,&nbsp;Rosanna Nenna ,&nbsp;Alessandro D'Amuri ,&nbsp;Annamaria Lavecchia ,&nbsp;Roberta Lucianò ,&nbsp;Giuseppe Ingravallo","doi":"10.1016/j.anndiagpath.2026.152622","DOIUrl":"10.1016/j.anndiagpath.2026.152622","url":null,"abstract":"<div><div>Testicular sex cord–stromal tumors (TSCSTs) are rare and heterogeneous neoplasms, most commonly represented by Leydig cell tumors (LCTs) and Sertoli cell tumors (SCTs). While SCTs are characterized by activation of the Wnt/β-catenin pathway, immunohistochemical detection of β-catenin is often limited by variable staining patterns and interpretative challenges. Lymphoid enhancer factor 1 (LEF1), a nuclear transcription factor cooperating with β-catenin, may represent a more reliable surrogate marker. In parallel, the expression of the cancer/testis antigen IL13Rα2 in TSCSTs has not been previously investigated. To the aim, we retrospectively analyzed 17 TSCSTs (12 LCTs and 5 SCTs) diagnosed between 2020 and 2025 at four Italian institutions. All cases were reviewed according to current WHO and GUPS/ISUP TESST criteria. Immunohistochemistry for β-catenin, LEF1, and IL13Rα2 was performed, assessing staining pattern and extent. Non-neoplastic testicular tissue and selected mimickers were included as controls. All SCTs showed strong and diffuse nuclear LEF1 expression (5/5, 100%), associated with nuclear and cytoplasmic β-catenin staining. In contrast, there was no significant LEF1 expression in all LCTs, control cases, and non-neoplastic testicular parenchyma. Focal IL13Rα2 expression was observed in a subset of LCTs (4/12, 33.3%), whereas all SCTs were negative. Therefore, in the differential diagnosis between SCT and LCT, our results suggest LEF1 is a highly sensitive and specific immunohistochemical marker and may represent a robust alternative to β-catenin, offering clearer nuclear staining and easier interpretation. The detection of IL13Rα2 in a subset of LCTs is a novel finding and suggests potential biological and therapeutic relevance, warranting further investigation in larger and clinically aggressive cohorts.</div></div>","PeriodicalId":50768,"journal":{"name":"Annals of Diagnostic Pathology","volume":"82 ","pages":"Article 152622"},"PeriodicalIF":1.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146167644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive next generation sequencing of middle ear neuroendocrine tumors","authors":"Justin A. Bishop ,&nbsp;Jing Xu ,&nbsp;Lester D.R. Thompson","doi":"10.1016/j.anndiagpath.2026.152620","DOIUrl":"10.1016/j.anndiagpath.2026.152620","url":null,"abstract":"<div><div>Middle ear neuroendocrine tumor (MeNET) is a distinctive, uncommon neoplasm of the ear. Previously regarded as “middle ear adenoma” among other names, it was found to be consistently positive for neuroendocrine markers, with differentiation analogous to normal intestinal L cells, and has therefore been classified similarly to other neuroendocrine tumors throughout the body. Nevertheless, MeNETs have an unusual two-cell population and therefore may be unique among NETs. We sought to characterize a group of MeNETs by next-generation sequencing (NGS).</div><div>Six MeNETs from the authors' archives were retrieved, with histologic and immunohistochemical results tabulated. Targeted DNA and RNA NGS were attempted on all cases. Clinical follow-up was obtained.</div><div>The MeNETs arose in the middle ears of five men and one woman, ranging from 31 to 57 years (median, 47.5 years). Four cases were grade 1 and two cases grade 2 (one based on necrosis and one based on an elevated Ki67 index). DNA NGS was successful in five of six cases, with probable pathogenic variants including: <em>ATRX</em> mutations in two cases, chromosome 22 deletion, and <em>DNMT3A</em>, <em>STAG2</em>, <em>RB1</em>, <em>HRAS</em>, <em>NF1</em>, and <em>SF3B1</em> mutations in one case each. In general, the variants were found at low allele frequencies. RNA NGS was successful in all cases, with one case harboring a fusion of unknown significance (<em>R3HDM2</em>::<em>EP400</em>). Follow up available in all cases, with five patients without disease (mean, 74 months; median, 17 months), with one patient (one of the grade 2 tumors) experiencing widespread distant metastases and dying 96 months after diagnosis.</div><div>Despite the consistent appearance of MeNET, they are heterogeneous at the molecular level, with low mutational burdens but lacking consistent, recurrent alterations. This is similar to well-differentiated NETs of other organs, in particular the small intestine and lung. Overall, our findings support the grouped classification of MeNET within the larger NET scheme.</div></div>","PeriodicalId":50768,"journal":{"name":"Annals of Diagnostic Pathology","volume":"82 ","pages":"Article 152620"},"PeriodicalIF":1.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146133608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}