{"title":"Expression of INSM1 in salivary carcinoma showing thymus-like elements (CASTLE).","authors":"Eiichi Sasaki, Katsuhiro Masago","doi":"10.1016/j.anndiagpath.2025.152535","DOIUrl":"10.1016/j.anndiagpath.2025.152535","url":null,"abstract":"","PeriodicalId":50768,"journal":{"name":"Annals of Diagnostic Pathology","volume":"79 ","pages":"152535"},"PeriodicalIF":1.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144800870","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":"In reply: SOX10 and TRPS1 in triple-negative breast cancer: Promise, pitfalls, and the need for broader validation","authors":"Shaimaa Abdelraouf Elgohary","doi":"10.1016/j.anndiagpath.2025.152558","DOIUrl":"10.1016/j.anndiagpath.2025.152558","url":null,"abstract":"","PeriodicalId":50768,"journal":{"name":"Annals of Diagnostic Pathology","volume":"80 ","pages":"Article 152558"},"PeriodicalIF":1.4,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145003687","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}
Yutong Fu, Shixuan Du, Saisai Nie, Qiqi Shao, Wenli Guo, Yuehong Li , Lei Lou
{"title":"Diagnostic value of SSTR2A, ATRX, and clusterin immunohistochemical expression in high-grade gastroenteropancreatic neuroendocrine neoplasms","authors":"Yutong Fu, Shixuan Du, Saisai Nie, Qiqi Shao, Wenli Guo, Yuehong Li , Lei Lou","doi":"10.1016/j.anndiagpath.2025.152560","DOIUrl":"10.1016/j.anndiagpath.2025.152560","url":null,"abstract":"<div><div>High-grade gastroenteropancreatic neuroendocrine neoplasms (NENs) are a heterogeneous group of rare tumors, classified into well-differentiated neuroendocrine tumors grade 3 (G3 NETs) and poorly differentiated neuroendocrine carcinomas (NECs). Distinguishing G3 NETs from NECs is challenging. We aimed to summarize the clinicopathologic characteristics of G3 NETs; examine the expression of somatostatin receptor 2A (SSTR2A), clusterin, and ATRX in G3 NETs and NECs; and explore the diagnostic and prognostic value of combining these markers for the differential diagnosis of G3 NETs. Data on 87 patients with high-grade NENs (G3 NETs: 18, NECs: 69) were retrospectively collected and classified according to the 5th edition of the WHO Classification of Digestive System Tumors. Immunohistochemistry was performed for SSTR2A, ATRX, and clusterin. Relationships between protein expression and clinicopathological features were analyzed. The diagnostic significance of combining these markers was assessed using receiver operating characteristic curves. SSTR2A protein expression, loss of ATRX expression, and positivity rate for clusterin were significantly higher in G3 NETs than in NECs [77.8 % (14/18) vs. 42.0 % (29/69), 61.1 % (11/18) vs. 33.3 % (23/69), and 77.8 % (14/18) vs. 30.4 % (21/69), respectively]. ATRX expression loss was significantly more common in large-cell than small-cell NECs. In differentiating G3 NETs from NECs, the area under the curve of the combined diagnosis using SSTR2A, clusterin, and ATRX was significantly higher than the individual values (0.833 vs. 0.679, 0.737, and 0.639, respectively). Combining SSTR2A, clusterin, and ATRX improves diagnostic accuracy. Our immunohistochemical assessment provides diagnostic insights for distinguishing G3 NETs from NECs.</div></div>","PeriodicalId":50768,"journal":{"name":"Annals of Diagnostic Pathology","volume":"80 ","pages":"Article 152560"},"PeriodicalIF":1.4,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145026307","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}
Xin Wang , Eundong Park , Nusret Bekir Subasi , Andrea Lightle , Hwajeong Lee
{"title":"Diagnostic utility of PSMA immunohistochemistry in colorectal mass biopsy","authors":"Xin Wang , Eundong Park , Nusret Bekir Subasi , Andrea Lightle , Hwajeong Lee","doi":"10.1016/j.anndiagpath.2025.152557","DOIUrl":"10.1016/j.anndiagpath.2025.152557","url":null,"abstract":"<div><div>Rendering a diagnosis of invasion can be challenging in a small biopsy of a large colorectal mass-forming lesion. However, this diagnosis can have major implications in the management of patients with rectal cancer. Prostate-specific membrane antigen (PSMA) is associated with tumor neoangiogenesis. We compared PSMA expression in biopsies of invasive colorectal cancer (CRC) and in resected adenomas. 65 biopsies from invasive CRC, 48 surgically resected large adenomas and 5 CRC biopsies with sampling error (precursor adenoma was sampled without invasion) were retrieved. PSMA and CD34 immunohistochemistry were performed and the ratio of PSMA+ neovasculature to CD34+ vasculature within the tumors was compared between CRC biopsies and adenomas. In the CRC cohort, clinicopathological characteristics including desmoplasia, the amount of benign/nondysplastic tissue and tumor grade were evaluated for correlation with endothelial PSMA expression. PSMA/CD34 ratio was significantly lower in adenomas (2.8 %) and in CRC biopsies with sampling error (2.5 %) than in CRC biopsies (19.1 %). Using a 5 % cut-off, the sensitivity, specificity, positive, and negative predictive values for accurate diagnosis of CRC were 78.5 %, 83.3 %, 86.4 % and 74.1 %, respectively. A lower PSMA/CD34 ratio was associated with a higher percentage of benign tissue in the biopsy, but no other association was found between PSMA/CD34 ratio and other clinicopathologic parameters. PSMA expression is significantly higher in CRC biopsies than in precursor lesions and adenomas irrespective of the presence of desmoplasia. Our observation indicates that PSMA can serve as an adjunctive tool to confirm invasion in challenging biopsies with inconspicuous desmoplasia.</div></div>","PeriodicalId":50768,"journal":{"name":"Annals of Diagnostic Pathology","volume":"80 ","pages":"Article 152557"},"PeriodicalIF":1.4,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144921526","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}
Yu Pan , Xiaona Zuo , Xiaolong Sui , Lei Jiang , Jiaosheng Xu , Zifen Gao , Guohua Yu
{"title":"Diagnostic challenges and considerations in CD30-negative classical Hodgkin lymphoma from biopsy specimens","authors":"Yu Pan , Xiaona Zuo , Xiaolong Sui , Lei Jiang , Jiaosheng Xu , Zifen Gao , Guohua Yu","doi":"10.1016/j.anndiagpath.2025.152556","DOIUrl":"10.1016/j.anndiagpath.2025.152556","url":null,"abstract":"<div><div>This study aimed to investigate the clinicopathological features and diagnostic strategies of CD30-negative classic Hodgkin lymphoma (cHL) based on core needle biopsy specimens. Six cases diagnosed at Yantai Yuhuangding Hospital and Beijing Gaobo Boren Hospital were retrospectively analyzed. The diagnosis was established through integrated evaluation of histomorphology and immunohistochemical (IHC) profiling. All cases underwent repeated CD30 immunostaining using multiple antibody clones and platforms to confirm true CD30 negativity. The cohort comprised five males and one female (male-to-female ratio 5:1), with a median age of 17.5 years (range: 6–86 years). Histological subtypes included four cases of mixed cellularity and two of nodular sclerosis, all demonstrating characteristic morphological features of cHL. CD30 expression was entirely absent in five cases and weakly positive in scattered tumor cells in one case. To ensure diagnostic accuracy, repeat biopsies were performed in four patients. IHC analysis revealed consistent expression of PAX5, C-MYC, ATF3, and p53 in all six cases, with variable positivity for CD20 (3/6), LCA (1/6), MUM1 (4/6), OCT2 (4/6), and BOB.1 (1/6). Epstein-Barr virus–encoded RNA (EBER) was positive in five cases (83.3 %), with none of the cases undergoing flow cytometry (FCM). Five patients received ABVD chemotherapy; four achieved complete remission, one died, and one was lost to follow-up. IDiagnosis was established based on histomorphological identification of Reed–Sternberg–like cells within a characteristic inflammatory background, in conjunction with an extended immunophenotypic panel. CD30 immunostaining was repeated using different clones and platforms to exclude technical artifacts. In cases with persistent CD30 negativity, complete excision was performed when feasible, and diagnosis was confirmed only if R-S–like cells concurrently exhibited: (1) variable or weak CD20 and LCA expression, never both strongly positive; (2) weak or absent PAX5 and MUM1; (3) discordant BOB.1 and OCT2 expression; and (4) positive c-MYC, p53, and ATF3 nuclear staining. Cases failing to meet all criteria were excluded. In conclusion, CD30-negative cHL diagnosed on limited biopsy material tends to affect younger male patients and retains typical morphological and immunophenotypic hallmarks of cHL. A thorough diagnostic approach incorporating multi-clone CD30 IHC and repeat sampling when necessary is crucial to avoid misdiagnosis in these diagnostically ambiguous cases.</div></div>","PeriodicalId":50768,"journal":{"name":"Annals of Diagnostic Pathology","volume":"80 ","pages":"Article 152556"},"PeriodicalIF":1.4,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144932049","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}
Serena Salzano , Giada Maria Vecchio , Manuel Mazzucchelli , Marco Furci , Claudio Trovato , Gaetano Magro , Giuseppe Broggi
{"title":"p63 immunohistochemical expression in tumor cells of high-grade invasive breast carcinomas on core biopsy: a potential diagnostic pitfall","authors":"Serena Salzano , Giada Maria Vecchio , Manuel Mazzucchelli , Marco Furci , Claudio Trovato , Gaetano Magro , Giuseppe Broggi","doi":"10.1016/j.anndiagpath.2025.152554","DOIUrl":"10.1016/j.anndiagpath.2025.152554","url":null,"abstract":"<div><div>In breast pathology, p63 is a highly specific myoepithelial marker, crucial for distinguishing in situ from invasive lesions. Its expression is characteristically absent in the neoplastic cells of invasive carcinoma. However, in our diagnostic experience focal p63 expression in neoplastic cells of some high-grade breast tumors has been observed. This study aimed to describe the expression pattern of p63 in high-grade versus low and intermediate-grade invasive breast carcinomas. We performed a retrospective immunohistochemical analysis for p63 on a cohort of 60 breast core biopsies. The cases included 20 Grade 3 (G3), 20 Grade 2 (G2) and 20 Grade 1 (G1) invasive breast carcinomas, graded according the Nottingham grading system. Nuclear p63 expression in neoplastic cells was assessed and described. Positive p63 staining in neoplastic cells was identified in 16 out of 20 (80 %) high-grade invasive carcinomas. The staining pattern was typically focal and moderate in intensity. Conversely, all but one case of invasive breast carcinoma G2 showed absolute negativity for p63. All cases of low-grade invasive carcinoma also showed clear negativity for p63. A clear association between p63 expression in neoplastic cells and G3 grading was observed.</div><div>Our findings suggest that p63 expression can be a feature of high-grade invasive breast carcinoma. Although this findings represents a potential diagnostic pitfall, especially on small core biopsy samples, the awareness of this possibility can also allow p63 to serve as a helpful ancillary clue for identifying high-grade disease.</div></div>","PeriodicalId":50768,"journal":{"name":"Annals of Diagnostic Pathology","volume":"80 ","pages":"Article 152554"},"PeriodicalIF":1.4,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144932047","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":"“Letter to the editor: MTAP and p16 as immunohistochemical surrogates of CDKN2A/B homozygous deletion in central nervous system tumors: A multicentre Italian experience.”","authors":"Sanhia Maheshwari","doi":"10.1016/j.anndiagpath.2025.152555","DOIUrl":"10.1016/j.anndiagpath.2025.152555","url":null,"abstract":"","PeriodicalId":50768,"journal":{"name":"Annals of Diagnostic Pathology","volume":"80 ","pages":"Article 152555"},"PeriodicalIF":1.4,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144921527","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}
Lina Han, Van Tuong Nguyen, Ruifang Zheng, Franklin Fuda, Miguel D. Cantu, Prasad Koduru, Jesse M. Jaso, Olga K. Weinberg, Sharon Germans, Mingyi Chen, Jing Xu, Weina Chen
{"title":"B/T mixed phenotype acute leukemia revealing immunophenotypic lineage-genotype associations and frequent myelodysplasia-related cytogenetic/gene abnormalities: implication for diagnosis and treatment","authors":"Lina Han, Van Tuong Nguyen, Ruifang Zheng, Franklin Fuda, Miguel D. Cantu, Prasad Koduru, Jesse M. Jaso, Olga K. Weinberg, Sharon Germans, Mingyi Chen, Jing Xu, Weina Chen","doi":"10.1016/j.anndiagpath.2025.152540","DOIUrl":"10.1016/j.anndiagpath.2025.152540","url":null,"abstract":"<div><div>B/T mixed-phenotype acute leukemia (MPAL) is a rare subtype of leukemia with diagnostic and therapeutic challenges due to its rarity, genomic diversity, and evolving diagnostic criteria. We report six cases of B/T MPAL with clinicopathological and genomic characterization. Most cases (5/6) demonstrated immunophenotypic/lineage-genotype-associations, i.e., T-lineage predominant B/T MPAL with T-lymphoblastic leukemia (T-ALL) genotype whereas B/T-lineage codominant B/T MPAL with combined T-ALL/B-ALL genotype. Furthermore, most patients (5/6) carried myelodysplasia-related (MR) cytogenetic-gene-alterations [MR-CG-Gene, as defined in acute myeloid leukemia (AML)-MR (AML-MR)], harboring ALL-genotype, and responded well to ALL-based induction regimens. These findings indicate that B/T MPAL with MR-CG-Gene is more appropriately diagnosed as MPAL rather than AML-MR. Our study is the first to demonstrate immunophenotypic lineage-genotype associations and frequent MR-CG-Gene in B/T MPAL and advocate more studies to refine diagnostic criteria.</div></div>","PeriodicalId":50768,"journal":{"name":"Annals of Diagnostic Pathology","volume":"80 ","pages":"Article 152540"},"PeriodicalIF":1.4,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144906888","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 SOX6 immunohistochemical expression as a diagnostic marker in the distinction of epithelioid mesothelioma from lung carcinomas","authors":"Fatma Samy Hafez , Safaa Mahmoud Mohamed Abdelkhalek , Shaimaa Abdelraouf Elgohary","doi":"10.1016/j.anndiagpath.2025.152553","DOIUrl":"10.1016/j.anndiagpath.2025.152553","url":null,"abstract":"<div><div>Epithelioid mesothelioma (EM) is a pleural malignancy whose many histopathologic patterns may overlap considerably with those of lung adenocarcinoma (LAC) or poorly differentiated squamous cell carcinoma (SCC). This study aimed to evaluate the diagnostic role of SOX6 immunohistochemical expression in EM, study its differential expression in EM, LAC, and SCC, and evaluate the utility of various combinations of SOX6 with established EM markers calretinin and D2–40. The study included 39 EM, 21 LAC, and 11 SCC cases. SOX6 expression was detected in 71.8 % of EM cases. Conversely, all SCC cases were SOX6-negative, and only two LAC cases were SOX6-positive (<em>P</em> < 0.001). The sensitivity and specificity of SOX6 in identifying EM was 71.8 % and 93.8 %, respectively. Calretinin and D2–40 expression was detected in 100 % and 97.4 % cases of EM, respectively. The diagnostic sensitivity of SOX6 for EM in combination with D2–40 and/or calretinin was higher than SOX6 as a solitary marker. Notably, the sensitivity of calretinin and/or SOX6 positive expression was 100 % higher than that of SOX6 combination with D2–40. Although the sensitivity of SOX6 is lower than that of other established markers for EM, it may be a fairly specific marker for the diagnosis of EM. Therefore, the inclusion of SOX6 into an immunohistochemical panel may have diagnostic utility in distinguishing between EM and lung carcinomas. However, more research is needed on a wider array of tumor types from various organs to truly understand its global specificity.</div></div>","PeriodicalId":50768,"journal":{"name":"Annals of Diagnostic Pathology","volume":"80 ","pages":"Article 152553"},"PeriodicalIF":1.4,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144988605","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":"Radiological-pathological correlation in encapsulated papillary carcinoma of the breast","authors":"Ying Zhang , Ya Gao , Jinrong Wei , Zhifen Dong","doi":"10.1016/j.anndiagpath.2025.152552","DOIUrl":"10.1016/j.anndiagpath.2025.152552","url":null,"abstract":"<div><div>The study aims to investigate the radiological-pathological correlation in encapsulated papillary carcinoma (EPC) of the breast. We recruited patients with breast EPC between April 2016 and March 2025, and divided them into 3 histologic subtypes: pure EPC, EPC with ductal carcinoma in situ (DCIS), and EPC with invasive carcinoma (IC). Clinical, pathological, mammographic and ultrasonographic manifestations of the three histologic subtypes were analyzed. A total of 48 female patients with EPC were enrolled, with an average onset age of 62.2 ± 12.7 years. Histopathological analysis revealed 25 (52.1 %) pure EPC, 10 (20.8 %) EPC with DCIS, and 13 (27.1 %) EPC with IC. Immunohistochemistry indicated Luminal A predominated in pure EPC and EPC with IC, while Luminal B was more common in EPC with DCIS. The majority of mammography images showed high density or equal density masses with regular shape, and there were no significant differences in the size, morphology, margin, or internal calcification of tumors among the three histologic subtypes (<em>P</em> > 0.05). The majority of ultrasonography images of EPCs showed cystic and solid echogenicity masses with regular morphology and rich blood flow signals. There were no significant differences in the size, echo type, margin, posterior echo enhancement, or blood flow of tumors among the three histologic subtypes of EPC (<em>P</em> > 0.05), but the EPC with IC had a higher proportion of irregular morphology compared with pure EPC (<em>P</em> < 0.05). Therefore, mammography or ultrasonography alone is insufficient to distinguish the histologic subtypes of EPC, but irregular shape on ultrasonography should raise suspicion for non-pure EPC subtypes.</div></div>","PeriodicalId":50768,"journal":{"name":"Annals of Diagnostic Pathology","volume":"80 ","pages":"Article 152552"},"PeriodicalIF":1.4,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144888659","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}