Human pathology最新文献

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Nodal large B-cell lymphoma with intrasinusoidal growth: A clinicopathologic study of a distinctive pattern with diagnostic overlap with intravascular large B-cell lymphoma. 结性大b细胞淋巴瘤伴脉管内生长:一种诊断与血管内大b细胞淋巴瘤重叠的独特模式的临床病理研究。
IF 3 2区 医学
Human pathology Pub Date : 2026-10-01 DOI: 10.1016/j.humpath.2026.106274
Hyungjin Kim, Sei Na, Yoon Kyung Jeon, Jeong-Ok Lee, Sang-A Kim, Ji Yun Lee, Sejoon Lee, Hongseok Yun, Jin Ho Paik
{"title":"Nodal large B-cell lymphoma with intrasinusoidal growth: A clinicopathologic study of a distinctive pattern with diagnostic overlap with intravascular large B-cell lymphoma.","authors":"Hyungjin Kim, Sei Na, Yoon Kyung Jeon, Jeong-Ok Lee, Sang-A Kim, Ji Yun Lee, Sejoon Lee, Hongseok Yun, Jin Ho Paik","doi":"10.1016/j.humpath.2026.106274","DOIUrl":"10.1016/j.humpath.2026.106274","url":null,"abstract":"<p><p>Large B-cell lymphoma (LBCL) can show luminal growth in lymph nodes and extranodal sites, but nodal cases with intrasinusoidal growth may be difficult to distinguish from intravascular LBCL (IVLBCL). We retrospectively reviewed 19 LBCLs with luminal growth and classified them as nodal LBCL with intrasinusoidal growth (LBCL-IS; n = 5), extranodal LBCL with intravascular growth without hemophagocytic lymphohistiocytosis (HLH; n = 9), or extranodal LBCL with intravascular growth and HLH (n = 5). Compared with combined extranodal cases, nodal LBCL-IS was associated with older age (>75 years, 80.0% vs 14.3%; P = 0.017), fewer B symptoms (2/5 vs 12/13 evaluable cases; P = 0.044), absence of bone marrow involvement (0% vs 64.3%; P = 0.033), and lower serum lactate dehydrogenase levels (median, 327 vs 826 IU/L; P = 0.006). Limited-stage disease and low or low-intermediate International Prognostic Index scores occurred only in nodal LBCL-IS. Nodal cases largely shared a non-germinal center B-cell phenotype with extranodal cases, whereas Epstein-Barr virus positivity was confined to nodal LBCL-IS (2/5, 40.0%). Among extranodal cases, CD5 expression was associated with a higher complete response rate after initial chemotherapy (7/7 vs 1/5; P = 0.010). All five patients with nodal LBCL-IS achieved complete response after initial rituximab-based chemotherapy. Nodal LBCL-IS also showed longer progression-free and overall survival than HLH-associated extranodal LBCL (P = 0.021 and P = 0.049, respectively), although the small cohort size warrants cautious interpretation. These findings suggest that, despite its histologic resemblance to IVLBCL, nodal LBCL-IS represents a distinctive nodal growth pattern whose recognition may be clinically important.</p>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":" ","pages":"106274"},"PeriodicalIF":3.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149108765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Claudin 18.2 immunohistochemistry in gastroesophageal adenocarcinomas: A study of interobserver variability among gastrointestinal pathologists. 胃食管腺癌的Claudin 18.2免疫组织化学:一项胃肠病理学家间观察变异性的研究。
IF 3 2区 医学
Human pathology Pub Date : 2026-10-01 DOI: 10.1016/j.humpath.2026.106279
Albert Sy, Ahmad Alkashash, Michael G Drage, Miranda E Machacek, Angela R Shih, Stuti G Shroff, M Lisa Zhang, Jonathan N Glickman
{"title":"Claudin 18.2 immunohistochemistry in gastroesophageal adenocarcinomas: A study of interobserver variability among gastrointestinal pathologists.","authors":"Albert Sy, Ahmad Alkashash, Michael G Drage, Miranda E Machacek, Angela R Shih, Stuti G Shroff, M Lisa Zhang, Jonathan N Glickman","doi":"10.1016/j.humpath.2026.106279","DOIUrl":"https://doi.org/10.1016/j.humpath.2026.106279","url":null,"abstract":"<p><strong>Background: </strong>Gastroesophageal adenocarcinomas expressing claudin 18.2 (CLDN18) are candidates for targeted therapies such as zolbetuximab. Immunohistochemical staining for CLDN18 above a certain threshold is used to establish treatment eligibility. The purpose of this study was to evaluate the interobserver variability among pathologists in scoring CLDN18 immunostaining.</p><p><strong>Design: </strong>Six gastrointestinal pathologists evaluated CLDN18 staining on digitally scanned slides from a nonconsecutive cohort of 47 cases and a consecutive cohort of 48 cases of gastroesophageal adenocarcinoma. Each rater estimated the percentage of tumor cells showing 0, 1+, 2+, or 3+ membranous staining intensity (producing an overall H-score) and also noted whether they would score the carcinoma as positive according to the cutoff for zolbetuximab eligibility (≥75% of tumor cells with 2+ or 3+ staining). Factors potentially influencing scoring such as heterogeneity of staining and technical or sample factors were also noted. Interobserver agreement was assessed using kappa statistics (categorical scores) and intraclass correlation coefficients (ICCs) (continuous measures).</p><p><strong>Results: </strong>Interobserver agreement for overall H-scores was good, with an ICC of 0.85 and 0.91 in the two cohorts. There was substantial interobserver agreement (Fleiss kappa = 0.63 and 0.72 for the two cohorts) regarding eligibility for zolbetuximab therapy, For the nonconsecutive cohort, there was complete concordance among all raters in 32 cases in the nonconsecutive cohort (68%) (8 cases eligible, 24 cases ineligible). For estimated proportions of tumor cells showing 0, 1+, 2+, and 3+ CLDN18 staining, the ICCs were 0.84, 0.29, 0.41, and 0.70, respectively. Cases with heterogeneous staining also showed greater variability (kappa 0.49 vs. 0.71 for zolbetuximab eligibility).</p><p><strong>Conclusion: </strong>The study demonstrated substantial interobserver agreement among gastrointestinal pathologists in evaluating CLDN18 staining for the purposes of zolbetuximab eligibility. Assessment of weaker staining intensities was a source of greater variability. These findings highlight the need for standardized scoring of CLDN18 staining for the purposes of treatment planning, ideally with a consensus approach in difficult cases.</p>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":" ","pages":"106279"},"PeriodicalIF":3.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149108478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Prognostic value of the extramural perivenous infiltration in locally advanced gastric cancer: A retrospective clinical study. 局部进展期胃癌外周静脉浸润预后价值的回顾性临床研究。
IF 3 2区 医学
Human pathology Pub Date : 2026-09-25 DOI: 10.1016/j.humpath.2026.106271
Yuanyuan Zhang, Xinli Liu, Caizhen Feng, Huimin Zhao, Yinli Zhang, Xinyi Gou, Yingjiang Ye, Bo Han, Jin Cheng
{"title":"Prognostic value of the extramural perivenous infiltration in locally advanced gastric cancer: A retrospective clinical study.","authors":"Yuanyuan Zhang, Xinli Liu, Caizhen Feng, Huimin Zhao, Yinli Zhang, Xinyi Gou, Yingjiang Ye, Bo Han, Jin Cheng","doi":"10.1016/j.humpath.2026.106271","DOIUrl":"10.1016/j.humpath.2026.106271","url":null,"abstract":"<p><strong>Background: </strong>Gastric cancer (GC) remains a leading cause of cancer-related mortality worldwide. This study aims to investigate the prognostic value of extramural perivenous infiltration (EMPVI) and to establish a dynamic prediction model for locally advanced GC.</p><p><strong>Methods: </strong>We retrospectively analyzed 223 consecutive patients with locally advanced GC who underwent D2 gastrectomy followed by adjuvant chemotherapy between September 2014 and April 2019. D2-40 and elastic fiber staining were performed to distinguish EMPVI and extramural venous invasion (EMVI), with results compared to hematoxylin and eosin (H&E) staining using weighted kappa (κ) statistics. The Kaplan-Meier method with log-rank test was used to estimate the 5-year disease-free survival (DFS). The chi-square (χ<sup>2</sup>) test was applied to analyze the associations between clinicopathological characteristics and EMPVI or 5-year DFS. Variables significant in univariate analysis were entered into a multivariate Cox regression model. All tests were two-sided, and P < 0.05 was considered statistically significant.</p><p><strong>Results: </strong>EMPVI was more common than EMVI (54.7% vs. 18.4%). EMPVI positivity correlated with worse 5-year DFS (P = 0.000) and was significantly associated with tumor stage (T), lymph node metastasis, perineural invasion, and tumor deposits (P < 0.01). Univariate analysis identified EMPVI, tumor stage (T), lymph node metastasis, perineural invasion, tumor deposits, Lauren classification, and tumor differentiation as risk factors for 5-year DFS (P < 0.05). Multivariate Cox regression analysis confirmed EMPVI (P = 0.000), Lauren classification (P = 0.001), and tumor stage (T) (P = 0.018) as independent prognostic indicators for 5-year DFS.</p><p><strong>Conclusions: </strong>EMPVI serves as a novel and robust independent prognostic indicator in locally advanced GC.</p>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":" ","pages":"106271"},"PeriodicalIF":3.0,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149060505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
RAS/RAF/MAPK alterations in prostatic adenocarcinoma: A multi-institutional study. 前列腺癌中RAS/RAF/MAPK的改变:一项多机构研究
IF 3 2区 医学
Human pathology Pub Date : 2026-09-23 DOI: 10.1016/j.humpath.2026.106270
Garrett J Chan, Xiaolin Zhu, Jung Woo Kwon, Melissa Tjota, Dane R Wuori, Dimitrios Korentzelos, Maedeh Mohebnasab, Nancy Y Greenland, Bradley A Stohr, Jeffry P Simko, Chien-Kuang Cornelia Ding, Deepika Sirohi
{"title":"RAS/RAF/MAPK alterations in prostatic adenocarcinoma: A multi-institutional study.","authors":"Garrett J Chan, Xiaolin Zhu, Jung Woo Kwon, Melissa Tjota, Dane R Wuori, Dimitrios Korentzelos, Maedeh Mohebnasab, Nancy Y Greenland, Bradley A Stohr, Jeffry P Simko, Chien-Kuang Cornelia Ding, Deepika Sirohi","doi":"10.1016/j.humpath.2026.106270","DOIUrl":"10.1016/j.humpath.2026.106270","url":null,"abstract":"<p><p>RAS/RAF/MAPK pathway alterations are rare in prostatic adenocarcinoma (PCa) but are implicated in metastasis and progression. Previous studies suggest that these alterations are more common in rare and aggressive histologic PCa subtypes. We reviewed the clinical and morphologic features of PCa with these alterations at our 3 institutions. PCa cases with RAS/RAF/MAPK pathway alterations identified by next generation sequencing (NGS) were selected for our cohort. Clinical, morphologic, and molecular features were compiled. Additionally, PCa cases with these alterations were identified in the Cancer Genome Atlas (TCGA) for comparison. From our 3 institutions, 44 cases of PCa (4.3%) with RAS/RAF/MAPK alteration(s) were identified by NGS (20 metastatic and 24 primary samples). Primary samples included prostate biopsies, radical prostatectomies, and transurethral resections of the prostate. Alterations were found in BRAF (21 cases), HRAS (10), KRAS (5), and MAPK genes (9). Most cases were grade group 5 (23/35, 66%). Aggressive histologic features were seen in 69% of cases (24/35). De-novo or subsequent metastatic disease developed in 84% of cases (37/44). Review of the TCGA dataset showed a similar proportion of RAS/RAF/MAPK-altered cases, and a subset had aggressive histologic patterns. Our data reinforces that mutations in the RAS/RAF/MAPK pathway in PCa are uncommon, but a majority of our cases showed high Gleason grade, metastases, and castration resistance, with a subset showing aggressive histologic features. Activating BRAF fusions were identified. As a significant number of cases did not show co-occurring alterations in driver genes, RAS/RAF/MAPK alterations may be driving tumorigenesis in a subset of PCa cases.</p>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":" ","pages":"106270"},"PeriodicalIF":3.0,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149030464","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Clinical utilization of CYP17A1 and CYP11B2 in evaluating cortisol- and aldosterone-producing adrenal nodules. CYP17A1和CYP11B2在评估皮质醇和醛固酮生成肾上腺结节中的临床应用。
IF 3 2区 医学
Human pathology Pub Date : 2026-09-22 DOI: 10.1016/j.humpath.2026.106272
Pooneh Jabbaripour Sarmadian, Ezra G Baraban, Tamara L Lotan, Pedram Argani, Alexander S Baras, Ciera Mangone, Lilah Morris-Wiseman, Stanley M Chen Cardenas, Amir H Hamrahian, Andres Matoso, Huili Li
{"title":"Clinical utilization of CYP17A1 and CYP11B2 in evaluating cortisol- and aldosterone-producing adrenal nodules.","authors":"Pooneh Jabbaripour Sarmadian, Ezra G Baraban, Tamara L Lotan, Pedram Argani, Alexander S Baras, Ciera Mangone, Lilah Morris-Wiseman, Stanley M Chen Cardenas, Amir H Hamrahian, Andres Matoso, Huili Li","doi":"10.1016/j.humpath.2026.106272","DOIUrl":"10.1016/j.humpath.2026.106272","url":null,"abstract":"<p><p>Mild autonomous cortisol secretion (MACS) has been increasingly recognized as a risk factor for cardiometabolic comorbidities and increased mortality. While CYP11B2 immunohistochemistry (IHC) based HISTALDO classification is well established for evaluating primary aldosteronism (PA), the clinical utility of CYP17A1 IHC in assessing cortisol- and aldosterone-producing adrenal nodules remains underexplored. We investigated the clinical utility of CYP17A1 IHC, in combination with mHISTALDO patterns, to distinguish cortisol-producing adrenal lesions across a spectrum of adrenal pathologies, focusing on patients with MACS only, PA only, and PA + MACS. As expected, normal adrenal cortex demonstrated diffuse, strong (3+) CYP17A1 expression in the zona fasciculata and zona reticularis, whereas markedly reduced CYP17A1 was seen in secondary adrenal atrophy. Non-functional adenomas showed patchy, weak CYP17A1 expression, while functioning adrenocortical carcinomas demonstrated marked intratumoral heterogeneity with loss of zonation. MACS adenomas showed diffuse (≥90%) CYP17A1 labeling, predominantly of strong intensity, though not exceeding that of the background cortex. Non-classical mHISTALDO patterns were identified in all PA + MACS patients, in which the adenomas were CYP17A1-positive and CYP11B2-negative. No overlapping labeling of CYP17A1 and CYP11B2 was observed in MACS and PA + MACS. In contrast, classical mHISTALDO patterns were present in all PA-only patients, with variable colocalization of CYP17A1 positivity in all CYP11B2-positive adenomas, without autonomous cortisol secretion. The colocalization ranged from small focal to diffuse, with weak to strong CYP17A1 intensity. The lack of hypercortisolism in PA-only patients argued against the cortisol-producing action of CYP17A1 in classical mHISTALDO. In summary, diffuse CYP17A1 expression was associated with adrenal nodules in MACS and in PA + MACS with non-classical patterns, and may provide supportive histologic evidence for lesions associated with cortisol co-secretion. In patients with classical patterns, CYP17A1 positivity in CYP11B2-positive adenomas may be misleading and should not be interpreted as evidence of cortisol overproduction. The combined use of CYP17A1 IHC and the mHISTALDO classification in PA patients may provide a diagnostic adjunct for identifying lesions with potential hormone co-secretion; however, clinical and biochemical correlation is essential in determining functional impact. In patients with PA, a non-classical mHISTALDO pattern and a CYP17A1-positive, CYP11B2-negative nodule may warrant additional evaluation for cortisol co-secretion and consideration of postoperative adrenal insufficiency. Our findings are preliminary, hypothesis-generating, and require validation in larger, independent cohorts.</p>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":" ","pages":"106272"},"PeriodicalIF":3.0,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149024705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Characterization of histologic spectrum and T-cell clonality in immune effector cell-associated enteritis. 免疫效应细胞相关性肠炎的组织学谱和t细胞克隆特征。
IF 3 2区 医学
Human pathology Pub Date : 2026-09-19 DOI: 10.1016/j.humpath.2026.106267
Chirag Patel, Jinjun Cheng, Jiehao Zhou, Marcela Salomao, Ruchi Patel, Kelsey McHugh, Natasha Lewis, Maxwell Smith, Xiaoyan Liao
{"title":"Characterization of histologic spectrum and T-cell clonality in immune effector cell-associated enteritis.","authors":"Chirag Patel, Jinjun Cheng, Jiehao Zhou, Marcela Salomao, Ruchi Patel, Kelsey McHugh, Natasha Lewis, Maxwell Smith, Xiaoyan Liao","doi":"10.1016/j.humpath.2026.106267","DOIUrl":"10.1016/j.humpath.2026.106267","url":null,"abstract":"<p><p>Immune effector cell (IEC) therapies using chimeric antigen receptor T cells (CAR-T) targeting B-cell maturation antigen or CD19 are FDA-approved treatments for refractory B -cell lymphoma, B-lymphoblastic leukemia, and multiple myeloma. Increasing evidence has suggested that these therapies can induce gastrointestinal injury, but the clinicopathologic spectrum and its association with clonal T-cell proliferation remain poorly defined. We retrospectively analyzed 42 GI biopsy specimens from 11 CAR-T-treated patients (8 with multiple myeloma, 2 diffuse large B-cell lymphoma, 1 acute B-lymphoblastic leukemia), comprising 4 women and 7 men (median age 68 years), with diarrhea as the predominant symptom (94%), arising at a median 4.9 months post CAR-T. Histologic evaluation, particularly of the duodenum, revealed a distinctive four-component composite histologic signature, termed a \"CVID-peptic-celiac-autoimmune enteropathy-like\" enteritis, characterized by plasma cell paucity (CVID-like), gastric foveolar metaplasia and Brunner gland hyperplasia (peptic duodenitis-like), intraepithelial lymphocytosis (celiac-like), and goblet cell loss with villous blunting and increased crypt epithelial apoptosis (autoimmune enteropathy-like), accompanied with atypical lamina propria lymphoid infiltrates. Those changes were most prominent in the duodenum and jejunum, less so in the ileum, and were generally mild to absent in the stomach, colon, and esophagus. Integration of histology with T-cell clonality analysis stratified the cases into two groups: the not tested/likely non-clonal group (n = 6) showed limited histologic features with isolated CVID-, peptic-, and/or autoimmune enteropathy-like changes, milder, transient symptoms, and favorable outcomes. The clonal group (n = 5) demonstrated more severe enteritis with a full composite CVID-peptic-celiac-autoimmune enteropathy-like enteritis, persistent symptoms, repeat biopsies, and higher mortality (40%). Our findings suggest a spectrum of histopathologic features of IEC-associated enteritis, characterized by a composite histologic signature that may progress to atypical lymphocytosis, often in association with clonal T-cell expansion. Recognition of this histologic pattern and incorporation of clonality testing may aid in diagnosis, risk stratification, and prognostication.</p>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":" ","pages":"106267"},"PeriodicalIF":3.0,"publicationDate":"2026-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149008459","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Germline cancer predisposition gene mutations and upgrade rate to breast cancer among patients with pleomorphic and florid lobular carcinoma in situ. 多形性和花型小叶原位癌患者的种系癌易感基因突变和乳腺癌升级率。
IF 3 2区 医学
Human pathology Pub Date : 2026-09-18 DOI: 10.1016/j.humpath.2026.106262
Komal Ijaz, Banu Arun, Diane M Weber, Therese Bartholomew Bevers, Min Yi, Kelly K Hunt, Lavinia P Middleton
{"title":"Germline cancer predisposition gene mutations and upgrade rate to breast cancer among patients with pleomorphic and florid lobular carcinoma in situ.","authors":"Komal Ijaz, Banu Arun, Diane M Weber, Therese Bartholomew Bevers, Min Yi, Kelly K Hunt, Lavinia P Middleton","doi":"10.1016/j.humpath.2026.106262","DOIUrl":"10.1016/j.humpath.2026.106262","url":null,"abstract":"<p><strong>Background: </strong>Pleomorphic lobular carcinoma in situ (PLCIS) and florid lobular carcinoma in situ (FLCIS) are uncommon entities with variable rates of upgrades. Germline pathogenic variant cancer predisposition genes (PVs) are associated with increased breast cancer risk and influences management recommendations.</p><p><strong>Design: </strong>Patients diagnosed with PLCIS and FLCIS over a 24-year period were identified. Clinical, radiologic, pathologic, treatment, and genetic testing was extracted from the electronic health record. The immediate rate of upgrade to invasive breast cancer and subsequent recurrence rates were calculated.</p><p><strong>Results: </strong>Forty-six patients with PLCIS and FLCIS as the most significant lesion on biopsy were identified. Of those with genetic testing, the majority had no germline PV (82.6%). Of those with PV, germline mutations in CHEK2 (4.3%), CDH1 (2.2%), BRCA2(2.2%), and VHL (2.2%) were identified. Forty-six patients underwent surgery to include wide local excision in (84.7%) and mastectomy in (15.2%). Twenty-four percent of patients with PLCIS (n = 11) had an upgrade to invasive carcinoma on excision, of which five had PV (36%). Upgrades to cancer were more common in patients with PV (p = 0.0198). Six patients (13%), developed ipsilateral breast cancer recurrences, of which 3 (50%) had known PV with a median time to recurrence of 83.8 months.</p><p><strong>Conclusion: </strong>In patients with PLCIS and PV, the presence of PV may represent an additive risk factor for the presence of invasive carcinoma on excision and ipsilateral breast cancer recurrence. Knowledge of the oncogenic drivers of tumors in these patients may help to improve risk assessment, surveillance and treatment recommendations.</p>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":" ","pages":"106262"},"PeriodicalIF":3.0,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149001666","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Reagent-free multiple histological staining via generative AI for rapid pathology diagnosis. 基于生成式AI的无试剂多重组织学染色快速病理诊断。
IF 3 2区 医学
Human pathology Pub Date : 2026-09-17 DOI: 10.1016/j.humpath.2026.106269
Lulin Shi, Bingxin Huang, Zoe Y M Hung, Ronald C K Chan, Terence T W Wong
{"title":"Reagent-free multiple histological staining via generative AI for rapid pathology diagnosis.","authors":"Lulin Shi, Bingxin Huang, Zoe Y M Hung, Ronald C K Chan, Terence T W Wong","doi":"10.1016/j.humpath.2026.106269","DOIUrl":"10.1016/j.humpath.2026.106269","url":null,"abstract":"<p><strong>Background: </strong>Histological special stains (e.g., Masson's trichrome, Elastin van Gieson, periodic acid-Schiff) are typically utilized as a supplementary method to highlight specific tissue structures that may not be visible in the hematoxylin and eosin (H&E) stain. However, conventional pathology work flow suffers from long turn-around waiting times and the use of a large amount of laboratory materials.</p><p><strong>Method: </strong>In this paper, we employ a parameter-efficient fine-tuning method to adapt a general-purpose vision model into a task-specific model, which enables the automatic and simultaneous synthesis of multiple histological stains. By adapting the InstructPix2Pix using Low-Rank Adaptation (LoRA) with a high rank (r = 512), we enable the automatic and simultaneous synthesis of multiple histological stains from label-free autofluorescence (AF) images. Our approach leverages AF images as structural anchors to ensure topological consistency, while text prompts serve as precise semantic controllers for stain selection. Crucially, we introduce the Fréchet Inception Distance using Pathology Language-Image Pre-training embeddings (FID-PLIP) to evaluate generation quality, overcoming the limitations of traditional pixel-wise metrics in capturing diagnostically relevant features.</p><p><strong>Results: </strong>Experiments demonstrate that our method achieves high structural fidelity and diagnostic consistency, with Pearson correlation coefficients of 0.83 for Masson's Trichrome and 0.92 for Elastin van Gieson against ground truth stains.</p><p><strong>Conclusion: </strong>This reagent-free, time-efficient framework offers a robust alternative for clinical pathological examination, significantly accelerating diagnosis workflows.</p>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":" ","pages":"106269"},"PeriodicalIF":3.0,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148989798","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
T-pit is a novel, sensitive biomarker for conventional chordoma. T-Pit是一种新的、敏感的常规脊索瘤生物标志物。
IF 3 2区 医学
Human pathology Pub Date : 2026-09-17 DOI: 10.1016/j.humpath.2026.106268
Jiamin Chen, Lei Sun, Peiliang Li, Yuyang Dai, Xinghuan Ding, Liang Zhang, Enshan Feng, Xingang Zhou
{"title":"T-pit is a novel, sensitive biomarker for conventional chordoma.","authors":"Jiamin Chen, Lei Sun, Peiliang Li, Yuyang Dai, Xinghuan Ding, Liang Zhang, Enshan Feng, Xingang Zhou","doi":"10.1016/j.humpath.2026.106268","DOIUrl":"10.1016/j.humpath.2026.106268","url":null,"abstract":"<p><p>T-PIT is a reliable and sensitive marker for the diagnosis of corticotroph tumors, particularly in histologically atypical cases. During routine clinical work, we incidentally observed positive T-PIT expression in chordoma. To further clarify the diagnostic utility of T-PIT, we evaluated its immunohistochemical expression alongside that of brachyury in a series of tumors, including chordoma (n = 23), corticotroph tumors (n = 29), hemangioblastoma (n = 10), chordoid meningiomas (n = 2), chordoid glioma (n = 3), low-grade chondrosarcoma (n = 4), small cell carcinoma (n = 4), germinoma (n = 5) and low-grade glioma (n = 38). Notably, all chordoma cases (100%)-comprising 18 primary and 5 recurrent tumors-exhibited concurrent positivity for both T-PIT and brachyury. All cases of corticotroph tumors expressed T-PIT protein but were negative for brachyury protein. Sixty percent of germinoma cases expressed T-PIT, and 100% expressed brachyury. However, T-PIT and brachyury were not expressed in any cases of hemangioblastomas, chordoid meningiomas, chordoid glioma, low-grade chondrosarcoma, small cell carcinoma, or low-grade glioma. Our study indicated that T-PIT expression, as well as brachyury expression, is commonly observed in chordoma. Although corticotroph adenomas (PitNET) do not resemble the histology of chordomas, using T-PIT positivity alone as a diagnostic marker for these tumors may lead to misdiagnosis.Our findings also provide new insights into the role of T-PIT in notochord development and chordoma formation.</p>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":" ","pages":"106268"},"PeriodicalIF":3.0,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148989796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Enteric glial cell remodeling at diagnosis is associated with reduced mucosal inflammation at follow-up in pediatric ulcerative colitis. 诊断时肠胶质细胞重塑与儿童溃疡性结肠炎随访时粘膜炎症减少相关。
IF 3 2区 医学
Human pathology Pub Date : 2026-09-14 DOI: 10.1016/j.humpath.2026.106265
Harry J Rosenberg, Dongfang Yang, Riti S Bhalla, Phinnara Has, Michael I Herzlinger, Jason M Shapiro, Murray B Resnick
{"title":"Enteric glial cell remodeling at diagnosis is associated with reduced mucosal inflammation at follow-up in pediatric ulcerative colitis.","authors":"Harry J Rosenberg, Dongfang Yang, Riti S Bhalla, Phinnara Has, Michael I Herzlinger, Jason M Shapiro, Murray B Resnick","doi":"10.1016/j.humpath.2026.106265","DOIUrl":"10.1016/j.humpath.2026.106265","url":null,"abstract":"<p><p>Enteric glial cells (EGCs) comprise a key component of the enteric nervous system (ENS), and there is currently no standardized approach to characterizing EGCs in human gastrointestinal (GI) disease. Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is a group of chronic GI disorders in which predicting responsiveness to treatment is an ongoing challenge. We use glial-specific immunohistochemistry (IHC) for SOX10 to assess EGC patterns in IBD colon and whether these patterns correspond to early histologic outcomes in pediatric patients. Approximately half (22 of 47) of pediatric UC patients in our cohort demonstrate ectopically located non-basal glial aggregates (NBGAs) in colonic mucosa. Pediatric UC patients with NBGAs are more likely to exhibit improved mucosal pathology (OR 8.00, p = 0.0048) at approximately 1-year follow-up compared to UC patients without NBGAs. Patients with NBGAs show reduced Geboes Score and Nancy Histological Index values at follow-up compared to diagnosis (p = 0.011, p = 0.0071, respectively), while patients without NBGAs do not show reduced scores. UC patients with NBGAs are more likely to demonstrate reduced fecal calprotectin at follow-up compared to patients without NBGAs (OR 12.2, p = 0.01). These findings stratify pediatric UC patients based on EGC profiles and initial clinical course, and they may help guide therapeutic decisions early in disease. The study is the first to implement a routine approach to documenting EGCs in GI mucosal pathology.</p>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":" ","pages":"106265"},"PeriodicalIF":3.0,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148968214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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