Human pathology最新文献

{"title":"Inside front cover - Masthead","authors":"","doi":"10.1016/S0046-8177(24)00133-3","DOIUrl":"10.1016/S0046-8177(24)00133-3","url":null,"abstract":"","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"150 ","pages":"Page IFC"},"PeriodicalIF":2.7,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141953576","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}

{"title":"Information for Authors","authors":"","doi":"10.1016/S0046-8177(24)00136-9","DOIUrl":"10.1016/S0046-8177(24)00136-9","url":null,"abstract":"","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"150 ","pages":"Page iv"},"PeriodicalIF":2.7,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141953579","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}

{"title":"Beneath HMGA2 alterations in pleomorphic adenomas: Pathological, immunohistochemical, and molecular insights","authors":"Ziyad Alsugair ,&nbsp;Charles Lépine ,&nbsp;Françoise Descotes ,&nbsp;Marie-Delphine Lanic ,&nbsp;Daniel Pissaloux ,&nbsp;Franck Tirode ,&nbsp;Jonathan Lopez ,&nbsp;Philippe Céruse ,&nbsp;Pierre Philouze ,&nbsp;Maxime Fieux ,&nbsp;Michel Wassef ,&nbsp;Anne-Catherine Baglin ,&nbsp;Onea Mihaela ,&nbsp;Claire Castain ,&nbsp;Anne Sudaka ,&nbsp;Emmanuelle Uro-Coste ,&nbsp;Anne Champagnac ,&nbsp;Valérie Costes-Martineau ,&nbsp;Marick Laé ,&nbsp;Nazim Benzerdjeb ,&nbsp;S. Wong","doi":"10.1016/j.humpath.2024.105633","DOIUrl":"10.1016/j.humpath.2024.105633","url":null,"abstract":"<div><h3>Aims</h3><p>Most salivary gland neoplasms are distinguished by specific recurrent gene fusions. Recently, a subset of pleomorphic adenomas (PAs) originated from the parotid gland harboring the <em>HMGA2</em>:<em>WIF1</em> fusion was described with a canalicular adenoma-like morphology and a greater propensity for recurrence and carcinomatous transformation.</p></div><div><h3>Methods and results</h3><p>This study delineates the clinicopathological attributes of 54 cases of PAs exhibiting <em>HMGA2</em> alterations, predominantly characterized by the <em>HMGA2</em>:<em>WIF1</em> fusion, alongside a comparative analysis of their morphological and immunohistochemical profiles. The cohort consisted of 23 females and 31 males (n = 54), mean age was 56.7 (25–84), tumors predominantly originated from the parotid gland (94.4%, 51/54), with 3 cases from seromucous glands (5.6%). Mean tumor size was 2.6 cm (0.8–7.5). No clinical difference (demographic, follow-up) was observed among histological subsets (conventional, hybrid, and pure). Complete excision was performed in all cases, with follow-up data available for 41% (22/54) of patients, showing 13.6% of recurrence (3/22) between 5 and 8 months. Various histological growth patterns were identified, with the pure hypercellular monomorphic subset being the most prevalent. The <em>HMGA2</em>:<em>WIF1</em> gene was identified in all subsets without any particular predominance. Novel gene partners of <em>HMGA2</em> were identified, comprising <em>NRXN1</em>, <em>INPP4B</em>, <em>MSRB3</em>, <em>PHLDA1</em>, and FLJ41278.</p></div><div><h3>Conclusions</h3><p>The present study reports that the <em>HMGA2</em>:<em>WIF1</em> gene fusion was present in all subsets of PAs without significant predominance. However, further investigations are warranted to explore the relationship between histological subsets of PAs and the molecular alterations underlying them.</p></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"152 ","pages":"Article 105633"},"PeriodicalIF":2.7,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0046817724001424/pdfft?md5=ccb1fc1a00cbacd5092e8291a6db1e61&pid=1-s2.0-S0046817724001424-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141874675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Improving histotyping precision: The impact of immunohistochemical algorithms on epithelial ovarian cancer classification","authors":"Hein S. Zelisse ,&nbsp;Frederike Dijk ,&nbsp;Mignon D.J.M. van Gent ,&nbsp;Gerrit K.J. Hooijer ,&nbsp;Constantijne H. Mom ,&nbsp;Marc J. van de Vijver ,&nbsp;Malou L.H. Snijders","doi":"10.1016/j.humpath.2024.105631","DOIUrl":"10.1016/j.humpath.2024.105631","url":null,"abstract":"<div><p>To improve the precision of epithelial ovarian cancer histotyping, Köbel et al. (2016) developed immunohistochemical decision-tree algorithms. These included a six- and four-split algorithm, and separate six-split algorithms for early- and advanced stage disease. In this study, we evaluated the efficacy of these algorithms. A gynecological pathologist determined the hematoxylin and eosin (H&amp;E)-based histotypes of 230 patients. Subsequently, the final histotypes were established by re-evaluating the H&amp;E-stained sections and immunohistochemistry outcomes. For histotype prediction using the algorithms, the immunohistochemical markers Napsin A, p16, p53, progesterone receptor (PR), trefoil factor 3 (TFF3), and Wilms’ tumor 1 (WT1) were scored. The algorithmic predictions were compared with the final histotypes to assess their precision, for which the early- and advanced stage algorithms were assessed together as six-split-stages algorithm. The six-split algorithm demonstrated 96.1% precision, whereas the six-split-stages and four-split algorithms showed 93.5% precision. Of the 230 cases, 16 (7%) showed discordant original and final diagnoses; the algorithms concurred with the final diagnosis in 14/16 cases (87.5%). In 12.4%–13.3% of cases, the H&amp;E-based histotype changed based on the algorithmic outcome. The six-split stages algorithm had a lower sensitivity for low-grade serous carcinoma (80% versus 100%), while the four-split stages algorithm showed reduced sensitivity for endometrioid carcinoma (78% versus 92.7–97.6%). Considering the higher sensitivity of the six-split algorithm for endometrioid and low-grade serous carcinoma compared with the four-split and six-split-stages algorithms, respectively, we recommend the adoption of the six-split algorithm for histotyping epithelial ovarian cancer in clinical practice.</p></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"151 ","pages":"Article 105631"},"PeriodicalIF":2.7,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0046817724001400/pdfft?md5=b87eac33d8406884627fd1aac7a57ac9&pid=1-s2.0-S0046817724001400-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141859619","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TRPS1 expression in MPNST is correlated with PRC2 inactivation and loss of H3K27me3","authors":"Rossana Lazcano ,&nbsp;Davis R. Ingram ,&nbsp;Gauri Panse ,&nbsp;Alexander J. Lazar ,&nbsp;Wei-Lien Wang ,&nbsp;Jeffrey M. Cloutier","doi":"10.1016/j.humpath.2024.105632","DOIUrl":"10.1016/j.humpath.2024.105632","url":null,"abstract":"<div><p>Initially described as a highly specific immunohistochemical marker for carcinomas of mammary origin, trichorhinophalangeal syndrome type 1 (TRPS1) has subsequently been detected in a variety of other non-mammary tumors. In this study, we examined the immunohistochemical expression of TRPS1 in 114 peripheral nerve sheath tumors, including 43 malignant peripheral nerve sheath tumors (MPNSTs), 58 schwannomas, including 9 cellular neurofibromas, and 13 neurofibromas, including 1 atypical neurofibroma. Notably, TRPS1 was expressed in 49% of MPNSTs and was absent in all schwannomas and neurofibromas. All MPNSTs showed TRPS1 labeling in &gt;50% of nuclei, with 95% of cases demonstrating diffuse labeling. Most cases (67%) showed weak TRPS1 immunoreactivity, while a smaller subset showed moderate (24%) or strong (9%) intensity staining. Analysis of publicly available gene expression datasets revealed higher levels of <em>TRPS1</em> mRNA in MPNSTs with PRC2 inactivation. In keeping with this finding, TRPS1 expression was more commonly observed in MPNSTs with loss of H3K27me3, suggesting a potential relationship between TRPS1 and the PRC2 complex. This study further broadens the spectrum of TRPS1-expressing tumors to include MPNST.</p></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"151 ","pages":"Article 105632"},"PeriodicalIF":2.7,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141859620","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}

{"title":"Heterogeneity or change in cell of origin in diffuse large B-cell lymphomas determined using hans algorithm","authors":"Akiko Miyagi Maeshima ,&nbsp;Hirokazu Taniguchi ,&nbsp;Yuka Takahashi ,&nbsp;Yuto Kaimi ,&nbsp;Tetsuro Ochi ,&nbsp;Haruhi Makino ,&nbsp;Shinichi Makita ,&nbsp;Noriko Iwaki ,&nbsp;Suguru Fukuhara ,&nbsp;Wataru Munakata ,&nbsp;Koji Izutsu","doi":"10.1016/j.humpath.2024.105630","DOIUrl":"10.1016/j.humpath.2024.105630","url":null,"abstract":"<div><p>This study aimed to analyze the heterogeneity or change in cell of origin (COO) in diffuse large B-cell lymphoma (DLBCLs) using the Hans algorithm including 156 patients with multiple DLBCL specimens. COO was detected via immunohistochemical staining for CD10, BCL6, and MUM1. The COO of the main tumor at initial diagnosis was germinal center B-cell (GCB) and non-GCB type in 50 (32%) and 106 (68%) patients, respectively. It did not change in 126 patients (81%). However, it changed in 30 patients (19%), from GCB to non-GCB in 12 patients and vice versa in 18 patients. The COO was heterogeneous or changed in 14% of simultaneous samples at other sites during the initial diagnosis, in 7% of primary refractory sites, and in 20% of samples obtained in the relapse phase other than the primary site. Changes in CD10, BCL6, and MUM1 expression were observed in 15%, 23%, and 24% samples, respectively. A low incidence of change in COO was observed in DLBCL with CD10⁺/BCL6⁺/MUM1^- (4%), CD10^-/BCL6^-/MUM1⁺ (3%), and CD10^-/BCL6^-/MUM1^- (0%) patterns, whereas DLBCL with other patterns showed COO changes at rates of 20–37%. In conclusion, COO was heterogeneous or changed in 19% of DLBCL cases. The COO should be re-examined in other biopsy samples to determine the optimal treatment.</p></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"151 ","pages":"Article 105630"},"PeriodicalIF":2.7,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141787914","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}

{"title":"Salivary gland amyloidosis: Proteomic identification and clinicopathologic characterization of 57 cases","authors":"April Chiu ,&nbsp;Surendra Dasari ,&nbsp;Samih H. Nasr ,&nbsp;Angela Dispenzieri ,&nbsp;Linda N. Dao ,&nbsp;Joanna C. Dalland ,&nbsp;Matthew T. Howard ,&nbsp;Daniel P. Larson ,&nbsp;Karen L. Rech ,&nbsp;Jason D. Theis ,&nbsp;Julie A. Vrana ,&nbsp;Ellen D. McPhail","doi":"10.1016/j.humpath.2024.105628","DOIUrl":"10.1016/j.humpath.2024.105628","url":null,"abstract":"<div><p>Salivary gland amyloidosis is an uncommon diagnosis. Most studies have focused on minor salivary gland biopsies as a surrogate site for diagnosing systemic amyloidosis, while only few studies have investigated major salivary gland amyloidosis. We retrospectively identified 57 major and minor salivary gland amyloidosis cases typed using a proteomics-based method between 2010 and 2022. Frequency of amyloid types, clinicopathologic features, and distribution patterns of amyloid deposits were assessed. The indication for salivary gland biopsy/resection (known in 34 cases) included suspected amyloidosis (N = 14; 41.2%), lesion/mass (N = 12; 35.3%), swelling/enlargement (N = 5; 14.7%), and rule out Sjogren syndrome (N = 3; 8.8%). Concurrent pathology was reported in 16 cases, and included chronic sialadenitis (N = 11), extranodal marginal zone lymphoma (N = 3), plasma cell neoplasm (N = 1), and pleomorphic adenoma (N = 1). We identified 3 types of amyloidosis: immunoglobulin light chain/AL (N = 47; 82.5%); immunoglobulin heavy chain/AH (N = 1; 1.8%), and transthyretin/ATTR (N = 9; 15.8%). The patterns of amyloid deposits (assessed in 35 cases) included: 1) Perivascular and/or periductal distribution (N = 18; 51.4%); 2) Mass formation (N = 9; 25.7%); 3) Stromal micronodule formation (N = 7; 20.0%); and 4) Diffuse interstitial involvement (N = 1; 2.9%). We also identified one case of AL amyloidosis localized to the major salivary gland, where only 6 other cases with adequate staging workup to exclude systemic amyloidosis were previously reported. In conclusion, salivary gland amyloidosis is an uncommon diagnosis but may be underrecognized due to low index of suspicion. Most cases of salivary gland amyloidosis are AL type, but a minority are ATTR. Therefore, proteomics-based typing remains essential for treatment and prognosis.</p></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"151 ","pages":"Article 105628"},"PeriodicalIF":2.7,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141727133","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}

{"title":"Small bowel pyloric metaplasia is associated with lower rates of earlier recurrence of Crohn's disease after resection","authors":"Jennifer Y. Ju ,&nbsp;David J. Escobar ,&nbsp;Yue Xue ,&nbsp;Adam L. Booth ,&nbsp;Jessica Nguyen ,&nbsp;Guang-Yu Yang","doi":"10.1016/j.humpath.2024.105629","DOIUrl":"10.1016/j.humpath.2024.105629","url":null,"abstract":"<div><p>Recurrence within one or two years is common after Crohn's disease (CD) resection. In this study, we seek to identify histologic features in CD resections that may predict earlier (≤18 months) recurrence to potentially guide post-operative management. A single-institution, retrospective review was performed on patients with first-time CD bowel resection specimens (2002–2007). Patient demographics and CD course were also documented. Slides were reviewed for inflammatory distribution and composition, small bowel (SB) pyloric metaplasia (PM), and presence and characteristics of submucosal fibrosis and granulomas. In our cohort, 14 of 41 patients experienced earlier clinical or endoscopic recurrence after initial resection. In the 38 patients who underwent SB resection (3 were colon only), PM was less common in those with earlier recurrence (6/12 [50%]) compared to those with later (&gt;18 months) or no known recurrence (22/26 [85%]) (<em>P</em> = 0.045). PM was present even in patients with &lt;1 year of known CD. Additionally, therapy with anti-tumor necrosis factor (TNF) prior to surgery was more common in earlier recurrence patients (7/14 [50%]) than later or no recurrence patients (4/27 [15%]) (<em>P</em> = 0.026). There was no significant difference in age, sex, smoking status, duration of CD, post-operative CD medication, distribution or features of inflammation, granulomas, or fibrosis. Overall, our results indicate that SB PM and pre-surgical anti-TNF therapy are possible helpful clinicopathologic features to evaluate for recurrence risk.</p></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"151 ","pages":"Article 105629"},"PeriodicalIF":2.7,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141727134","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}

{"title":"The utility of the lineage specific immunohistochemical stains SATB2, CDX2, and villin, and the mucin glycoproteins MUC2, MUC5AC, and MUC6 to distinguish pulmonary invasive mucinous adenocarcinoma from metastatic colorectal carcinoma","authors":"Vilasinee Rerkpichaisuth ,&nbsp;Ryan P. Lau ,&nbsp;Cherise Meyerson ,&nbsp;Gregory A. Fishbein","doi":"10.1016/j.humpath.2024.105627","DOIUrl":"10.1016/j.humpath.2024.105627","url":null,"abstract":"<div><h3>Context</h3><p>The lungs are a common site of tumor metastasis. While morphology and immunophenotype can help differentiate primary from metastatic tumors, distinguishing pulmonary invasive mucinous adenocarcinoma (PIMA) from metastatic colorectal adenocarcinoma (CRC) may occasionally be challenging due to overlapping morphological and immunohistochemical features. Lineage-specific markers such as CDX2, TTF-1, and napsin A are helpful with pulmonary non-mucinous adenocarcinoma (PNMA), however they are non-specific and insensitive when applied to PIMA. SATB2 is a newer marker that distinguishes CRC from upper gastrointestinal and pancreaticobiliary tumors; its utility in distinguishing CRC from PIMA has not been fully elucidated.</p></div><div><h3>Objective</h3><p>To evaluate the performance of lineage-specific and mucin glycoprotein immunostains in distinguishing PIMA and CRC.</p></div><div><h3>Design</h3><p>We stained tissue microarrays comprising 34 PNMA, 31 PIMA, and 32 CRC with CK7, CK20, SATB2, CDX2, villin, TTF-1, napsin A, and gel-forming mucins MUC2, MUC5AC, and MUC6.</p></div><div><h3>Results</h3><p>PIMA showed significant (&gt;50% of cells) expression of SATB2 (6%), CDX2 (6%), villin (74%), TTF-1 (13%), and napsin A (23%). However, significant CK7 expression was seen in nearly all PIMA (30/31) and none of the metastatic CRC.</p></div><div><h3>Conclusion</h3><p>Our results suggest that CK7 remains one of the most useful markers for distinguishing primary PIMA from metastatic CRC. Expression of the mucin glycoproteins MUC5AC and MUC6 and lack of expression of MUC2 favored a diagnosis of PIMA, but expression of these markers was too heterogeneous to be of clinical utility. To our knowledge this is the only study comparing the immunohistochemical profile of PIMA and metastatic CRC in lung metastasectomy specimens.</p></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"151 ","pages":"Article 105627"},"PeriodicalIF":2.7,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0046817724001291/pdfft?md5=72000903a7f481d57e2596f7d9b4d7b1&pid=1-s2.0-S0046817724001291-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141727135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TPPP-BRD9 fusion-related gallbladder carcinomas are frequently associated with intracholecystic neoplasia, neuroendocrine carcinoma, and a distinctive small tubular-type adenocarcinoma commonly accompanied with a syringomatous pattern","authors":"Burcin Pehlivanoglu ,&nbsp;Juan Carlos Araya ,&nbsp;Scott Lawrence ,&nbsp;Juan Carlos Roa ,&nbsp;Serdar Balci ,&nbsp;Jesper B. Andersen ,&nbsp;Asif Rashid ,&nbsp;Ann W. Hsing ,&nbsp;Bin Zhu ,&nbsp;Yu-Tang Gao ,&nbsp;Jill Koshiol ,&nbsp;Volkan Adsay","doi":"10.1016/j.humpath.2024.07.001","DOIUrl":"10.1016/j.humpath.2024.07.001","url":null,"abstract":"<div><p>A fusion between tubulin polymerization-promoting protein (<em>TPPP</em>), a regulatory cytoskeletal gene, and the chromatin remodeling factor, bromodomain-containing protein 9 (<em>BRD9</em>), <em>TPPP-BRD9</em> fusion has been found in rare cancer cases, including lung and gallbladder cancers (GBC). In this study, we investigated the histopathological features of 16 GBCs previously shown by RNA sequencing to harbor the <em>TPPP-BRD9</em> fusion. Findings in the fusion-positive GBCs were compared with 645 GBC cases from the authors’ database. Among the 16 <em>TPPP-BRD9</em> fusion-positive GBC cases, most were females (F:M = 7:1) of Chinese ethnicity (12/16), whereas the remaining cases were from Chile. The histopathological examination showed the following findings: 1) Intracholecystic neoplasm (ICN) in 7/15 (47% vs. 7% 645 reference GBCs, p &lt; 0.001), all with gastro-pancreatobiliary phenotype, often with clear cell change, and in the background of pyloric gland metaplasia and extensive high-grade dysplasia. 2) Neuroendocrine carcinoma (NEC) morphology: 3 cases (27% vs. 4.6% in the reference database, p = 0.001) showed a sheet-like and nested/trabecular growth pattern of monotonous cells with salt-and-pepper chromatin characteristic of NECs. Two were large cell type, one had prominent clear cell features, a rare finding in GBNECs; the other one had relatively bland, well-differentiated morphology, and the remaining case was small cell type. 3) Adenocarcinoma identified in 8 cases had a distinctive pattern characterized by widely separated small, round tubular units with relatively uniform nuclei in a fashion seen in mesonephric adenocarcinomas, including hobnail-like arrangement and apical snouts, reminiscent of tubular carcinomas of the breast in many areas. In some foci, the epithelium was attenuated, and glands were elongated, some with comma shapes, which along with the mucinous/necrotic intraluminal debris created a “syringoid” appearance. 4) Other occasional patterns included the cribriform, glomeruloid patterns, and metaplastic tubular-spindle cell pattern accompanied by hemorrhage. In conclusion, <em>TPPP-BRD9</em> fusion-positive GBCs often develop through intracholecystic neoplasms (adenoma-carcinoma sequence) of gastro-pancreatobiliary lineage, appear more prone to form NEC morphology and have a propensity to display clear cell change. Invasive adenocarcinomas arising in this setting often seem to display a distinctive appearance that we tentatively propose as the <em>TPPP-BRD9</em> fusion-positive pattern of GBC.</p></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"150 ","pages":"Pages 67-73"},"PeriodicalIF":2.7,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141554642","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}