HistopathologyPub Date : 2025-04-04DOI: 10.1111/his.15454
Winston Y Lee, Young S Kim, Aimin Li, Jack Reid, Julia Davidson, Alexandra C Hristov, Anamarija M Perry, Lorinda Soma, Joo Y Song
{"title":"Expanding the use of T cell receptor beta constant 1 immunohistochemistry in formalin-fixed paraffin-embedded tissues in assessing T cell clonality in mature and immature T cell neoplasms.","authors":"Winston Y Lee, Young S Kim, Aimin Li, Jack Reid, Julia Davidson, Alexandra C Hristov, Anamarija M Perry, Lorinda Soma, Joo Y Song","doi":"10.1111/his.15454","DOIUrl":"https://doi.org/10.1111/his.15454","url":null,"abstract":"<p><strong>Aims: </strong>Demonstration of clonality is important in the diagnosis of a T cell neoplasm. Allelic exclusion of T cell receptor beta constant chains (TRBC) ensures restricted TRBC1 or 2 expression in T cells. Here, we extend the applicability of TRBC1 immunohistochemistry (IHC) in assessing T cell clonality in formalin-fixed paraffin-embedded (FFPE) tissue sections, with a particular focus on peripheral T cell lymphoma and lymphoblastic lymphoma/leukaemia.</p><p><strong>Methods and results: </strong>TRBC1 and CD3 IHCs were performed on benign lymph nodes (BLN; n = 21), mature T cell lymphomas (TCL; n = 34), thymic tissues (n = 12) and T lymphoblastic lymphoma/leukaemia (T-ALL; n = 21). TRBC1 usage in CD3+ cells [TRBC1/CD3(%)] was scored manually and computationally. Non-restricted TRBC1 patterns in reactive T cells, as measured by TRBC1/CD3(%), are normally distributed (BLN average = 59.4%; thymocyte average = 58.5%). TRBC1 staining patterns, as measured by TRBC1/CD3(%), distribute into three clusters, reflecting the monotypic populations (TRBC1+ and TRBC1-) at two ends and a third cluster with a non-restricted pattern (due to increased reactive T cells). Based on the distribution patterns, we suggest TRBC1/CD3(%) ≤ 0.25 and ≥ 0.75 as a guide to establish monotypic patterns in mature T cells. Our T-ALL cohort, selected for high blast burden, exhibits monotypic TRBC1 patterns.</p><p><strong>Conclusion: </strong>TRBC1 IHC is a useful tool that can complement molecular TCR gene rearrangement studies in assessing clonality in mature and immature T cell populations, and can be compatible with decalcified tissue.</p>","PeriodicalId":13219,"journal":{"name":"Histopathology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143779866","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}
HistopathologyPub Date : 2025-04-04DOI: 10.1111/his.15423
Meaghan Polack, Gabi W van Pelt, Davita H van den Heuvel, Elma Meershoek Klein-Kranenbarg, Annet G H Roodvoets, Hein Putter, Augustinus S L P Crobach, Iris D Nagtegaal, Koen C M J Peeters, Rob A E M Tollenaar, J Han J M van Krieken, Wilma E Mesker
{"title":"The tumour-stroma ratio as predictive aid towards a biopsy-based treatment strategy in rectal carcinoma.","authors":"Meaghan Polack, Gabi W van Pelt, Davita H van den Heuvel, Elma Meershoek Klein-Kranenbarg, Annet G H Roodvoets, Hein Putter, Augustinus S L P Crobach, Iris D Nagtegaal, Koen C M J Peeters, Rob A E M Tollenaar, J Han J M van Krieken, Wilma E Mesker","doi":"10.1111/his.15423","DOIUrl":"https://doi.org/10.1111/his.15423","url":null,"abstract":"<p><strong>Aims: </strong>Tumour-stroma ratio (TSR) scores of biopsy material in rectal carcinoma (RC) could aid a biomarker-based, upfront and personalised treatment strategy selection for RC patients. In a large retrospective, multicentre cohort, we aimed to validate the predictive value of biopsy-scored TSR on neoadjuvant therapy response, and secondarily, disease-free and overall survival (DFS, OS).</p><p><strong>Methods and results: </strong>Scanned haematoxylin and eosin-stained RC biopsy slides were collected from Leiden University Medical Center (N = 116) and from the clinical PROCTOR-SCRIPT (N = 142) and RAPIDO (N = 271) trials. TSR was scored per protocol and categorised as stroma-low (≤ 50%) or stroma-high (> 50%). Major response was defined as tumour regression grade (TRG) 1 + 2 by Mandard, including pathological complete response. Ultimately, a large and varied cohort with 373 RC patients was established. Locally advanced RC was more often stroma-high (P < 0.001). We subsequently observed significantly lower major response rates in the stroma-high RC after a neoadjuvant treatment approach (hazard ratio = 0.63, 95% confidence interval = 0.41-0.99; P = 0.044). Despite correction for well-known risk factors in Cox hazard regression analysis, such as (y)pTNM substages or residual tumour status, the TSR had no singular significant influence on DFS nor OS in multivariate analysis (P = 0.438; P = 0.934, respectively).</p><p><strong>Conclusions: </strong>Biopsy-scored TSR can predict neoadjuvant therapy efficacy, as RC patients with stroma-high biopsies show less major response. However, patient survival is multifactorial, although response is an important predictor, influenced by TSR. Scoring TSR on RC biopsy material is a reliable histological parameter, implementation of which in treatment guidelines could improve upfront selection for a watch-and-wait strategy.</p>","PeriodicalId":13219,"journal":{"name":"Histopathology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143779870","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}
HistopathologyPub Date : 2025-03-31DOI: 10.1111/his.15453
Meejeong Kim, Miseon Lee, Ahwon Lee, Byung-Ock Choi, Woo-Chan Park, Sung Hun Kim, Jieun Lee, Jun Kang
{"title":"Correlating p53 immunostaining patterns with somatic TP53 mutation and functional properties of mutant p53 in triple-negative breast cancer.","authors":"Meejeong Kim, Miseon Lee, Ahwon Lee, Byung-Ock Choi, Woo-Chan Park, Sung Hun Kim, Jieun Lee, Jun Kang","doi":"10.1111/his.15453","DOIUrl":"https://doi.org/10.1111/his.15453","url":null,"abstract":"<p><strong>Aims: </strong>Immunohistochemical (IHC) staining of p53 is a potential marker for TP53 mutations in various cancers. However, criteria for predicting TP53 mutations in triple-negative breast cancer (TNBC) using p53 IHC staining are not yet established. We aim to correlate p53 IHC expression patterns with TP53 mutation status in TNBC.</p><p><strong>Methods and results: </strong>A total of 113 TNBC cases were analysed for p53 IHC staining pattern and somatic TP53 mutation using whole-exome sequencing. Functional properties of TP53 mutations were determined using the National Cancer Institute (NCI) TP53 database. P53 IHC patterns were categorized as nuclear overexpression (n = 58), null pattern (n = 40), wildtype (n = 15), cytoplasmic (n = 5), and subclonal (n = 5). The cutoff for predictive p53 nuclear overexpression was determined to be 80%, which strongly correlated with TP53 mutations. Notably, p53 overexpression had a positive predictive value (PPV) of 83% for missense or in-frame mutations, while the null pattern showed a PPV of 85% for detecting nonsense, frameshift, or splicing mutations. P53 overexpression was significantly linked to missense mutations within the DNA-binding domain (DBD) exhibiting gain-of-function (GOF) or dominant-negative effect (DNE). Cases exhibiting cytoplasmic expression correlated with nonsense or frameshift mutations in the DBD, nuclear localization signal (NLS), or splice sites. Cases with subclonal p53 staining patterns were associated with TP53 mutations.</p><p><strong>Conclusion: </strong>Our study proposes newly defined criteria for interpreting p53 immunostaining patterns in TNBC, potentially allowing for the prediction of TP53 mutation types and their functional implications.</p>","PeriodicalId":13219,"journal":{"name":"Histopathology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143752364","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}
HistopathologyPub Date : 2025-03-31DOI: 10.1111/his.15452
Alexander J Neil, Dingani Nkosi, Ju-Yoon Yoon, David L Kolin, Lynette M Sholl
{"title":"Molecular and immunohistochemical characterization of ERBB2 activating mutations in low-grade serous ovarian carcinoma.","authors":"Alexander J Neil, Dingani Nkosi, Ju-Yoon Yoon, David L Kolin, Lynette M Sholl","doi":"10.1111/his.15452","DOIUrl":"https://doi.org/10.1111/his.15452","url":null,"abstract":"<p><strong>Aims: </strong>Low-grade serous carcinoma (LGSC) of the ovary presents unique therapeutic challenges due to its resistance to platinum-based chemotherapies and a tendency to present at an advanced stage. Approximately 50% of LGSC possess activating mutations in KRAS, NRAS, and BRAF, a finding associated with better overall survival. However, many tumours lack obvious driver alterations against which to direct targeted treatment strategies, necessitating further investigation into molecular drivers of LGSC and their impact on clinical outcomes.</p><p><strong>Methods and results: </strong>We conducted a retrospective analysis of 84 LGSC patients who underwent tumour-only targeted next-generation sequencing at our institution. Molecular data were correlated with clinical outcomes, HER2 immunohistochemistry, and supplemented with additional tumour sequencing data from the AACR GENIE cohort v15.1 (n = 295). Approximately 5% of LGSC cases across the combined cohort harboured activating alterations in ERBB2 (n = 17/369), which encodes the HER2 receptor tyrosine kinase. These alterations were mutually exclusive of other MAP kinase pathway mutations and included exon 20 insertions (n = 6), extracellular domain/transmembrane domain missense alterations (n = 4), and exon 16 skipping mutations (n = 7). ERBB2 exon 16 emerged as a mutational hotspot in LGSC when compared to other tumour types. Immunohistochemistry revealed variable HER2 expression patterns that were independent of ERBB2 mutational status. In our institutional cohort, patients with RAS/RAF mutant tumours (n = 38) showed better overall survival compared to RAS/RAF wildtype tumours (n = 35). No tumours in our internal cohort (n = 84) harboured ERBB2 amplifications.</p><p><strong>Conclusion: </strong>As the landscape of HER2-directed therapies continues to evolve, these findings suggest that ERBB2 alterations and HER2 expression may represent a potential therapeutic target in LGSC.</p>","PeriodicalId":13219,"journal":{"name":"Histopathology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143751734","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}
HistopathologyPub Date : 2025-03-25DOI: 10.1111/his.15445
Peipei Zhu, Xueying Zeng, Lirui Yang, I Weng Lao, Lin Yu, Qianming Bai, Xiaoyan Zhou, Jian Wang
{"title":"RAF1-rearranged spindle cell neoplasm: a clinicopathological and molecular genetic study of six cases with review of the literature.","authors":"Peipei Zhu, Xueying Zeng, Lirui Yang, I Weng Lao, Lin Yu, Qianming Bai, Xiaoyan Zhou, Jian Wang","doi":"10.1111/his.15445","DOIUrl":"https://doi.org/10.1111/his.15445","url":null,"abstract":"<p><strong>Aims: </strong>RAF1-rearranged spindle cell neoplasm represents a rare but distinctive entity in the category of kinase-altered spindle cell neoplasms . We describe herein a cohort of six additional cases of RAF1-rearranged spindle cell neoplasm to further broaden its clinicopathological and molecular spectrum.</p><p><strong>Methods and results: </strong>The clinicopathological features, immunophenotypes and molecular profiles of six RAF1-rearranged spindle cell neoplasms were assessed. A comprehensive review of the literature was performed. There were two males and four females with age at presentation ranging from 0 to 65 years (median = 17 years). Three tumours arose in the lower extremities, two in the head and neck region and one in the ileum. Morphological examination showed spindle cell tumours with variable cellularity and atypia, displaying solid growth (n = 4), infantile fibrosarcoma-like (n = 1) and malignant peripheral nerve sheath tumour-like (n = 1) patterns respectively. Using immunohistochemistry, three cases co-expresssed CD34 and S100. Targeted RNA sequencing identified PDZRN3::RAF1, FMR1::RAF1, PTPRG::RAF1, QKI::RAF1, SPPL2A::RAF1 and ERC1::RAF1 fusion in one case each. RAF1 rearrangements were subsequently substantiated by fluorescence in-situ hybridisation. Follow-up (14-48 months) in four patients showed no signs of local recurrence or distant metastasis.</p><p><strong>Conclusions: </strong>RAF1-rearranged spindle cell neoplasm encompasses a morphologically and molecularly diverse spectrum of mesenchymal tumours occurring in both children and adults. We describe an ileal lesion and two novel SPPL2A::RAF1 and ERC1::RAF1 fusions to further expand its clinicopathological and genetic spectrum.</p>","PeriodicalId":13219,"journal":{"name":"Histopathology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143709698","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}
HistopathologyPub Date : 2025-03-25DOI: 10.1111/his.15449
Valentina Angerilli, Francesca Galuppini, Stefano Brignola, Gianluca Businello, Beatrice Filippin, Gianmaria Pennelli, Jessica Gasparello, Paola Parente, Angelo Paolo Dei Tos, Stefano Realdon, Alberto Fantin, Edoardo Vincenzo Savarino, Matteo Fassan
{"title":"Predictors of neoplastic progression in gastroesophageal lesions indefinite for dysplasia.","authors":"Valentina Angerilli, Francesca Galuppini, Stefano Brignola, Gianluca Businello, Beatrice Filippin, Gianmaria Pennelli, Jessica Gasparello, Paola Parente, Angelo Paolo Dei Tos, Stefano Realdon, Alberto Fantin, Edoardo Vincenzo Savarino, Matteo Fassan","doi":"10.1111/his.15449","DOIUrl":"https://doi.org/10.1111/his.15449","url":null,"abstract":"<p><strong>Aims: </strong>Current understanding of the risk of neoplastic progression in patients with Barrett's esophagus with indefinite for dysplasia (BE-IND) and gastric indefinite for dysplasia (G-IND) remains limited. This study aims to identify prognostic histological and clinicopathological factors for IND progression in the upper gastrointestinal tract.</p><p><strong>Methods and results: </strong>Patients with confirmed BE-IND and G-IND, no previous evidence of dysplasia/cancer and follow-up of ≥ 6 months were included. The rate of neoplastic progression was calculated and the multivariate Cox regression model adjusted for demographic and histological features was used to identify risk factors for progression. A total of 719 patients diagnosed with IND (158 BE-IND and 561 G-IND) were identified, 395 of whom were excluded. Progression rates were 4.4 per 100 person-year for BE-IND and 1.6 per 100 person-year for G-IND patients. Progression was observed only in IND of hyperproliferative intestinal metaplasia (HIM) type. Operative link for gastritis assessment (OLGA) stage (III-IV versus 0-II) was the only significant predictor of G-IND progression [hazard ratio (HR) = 47.82, confidence interval (CI) = 5%: 6.24-366.37, P < 0.001]. In BE-IND patients, lack of interval endoscopy significantly increased the risk for BE-IND (HR = 13.45, CI = 95%: 1.24-145.75, P = 0.032).</p><p><strong>Conclusion: </strong>IND is a challenging diagnosis for pathologists and implies an increased risk for neoplasia, especially in BE patients, without providing definitive information for patient management. This study highlights that neoplastic progression of IND lesions is primarily associated with HIM type. For BE-IND, interval endoscopy significantly reduces progression risk, while in G-IND, OLGA staging (III-IV) is a strong predictor of progression. These findings emphasise the importance of identifying HIM and using OLGA staging in G-IND for better risk stratification and follow-up strategies.</p>","PeriodicalId":13219,"journal":{"name":"Histopathology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143709630","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}
HistopathologyPub Date : 2025-03-24DOI: 10.1111/his.15444
Mélanie Legrand, Baptiste Louveau, Amélie Osio, Anne Tallet, Eduardo Calonje, Jean-Yves Scoazec, Arnaud de la Fouchardiere, Franck Tirode, Andreas Von Deimling, Klaus Busam, Ahmed Shah, Ashley Flaman, Fanélie Jouenne, Samia Mourah, Daniel Pissaloux, Sylvie Lantuejoul, Christopher A French, Keisuke Goto, Bernard Cribier, Carina A Dehner, Ahmed K Alomari, Christopher Dm Fletcher, John Hanna, Nicolas Macagno, Maxime Battistella, Thibault Kervarrec
{"title":"Primary cutaneous NUT adnexal carcinoma: morphologic, genetic and methylation analysis of seven new cases with comparison to extracutaneous NUT carcinoma and NUTM1-rearranged porocarcinoma.","authors":"Mélanie Legrand, Baptiste Louveau, Amélie Osio, Anne Tallet, Eduardo Calonje, Jean-Yves Scoazec, Arnaud de la Fouchardiere, Franck Tirode, Andreas Von Deimling, Klaus Busam, Ahmed Shah, Ashley Flaman, Fanélie Jouenne, Samia Mourah, Daniel Pissaloux, Sylvie Lantuejoul, Christopher A French, Keisuke Goto, Bernard Cribier, Carina A Dehner, Ahmed K Alomari, Christopher Dm Fletcher, John Hanna, Nicolas Macagno, Maxime Battistella, Thibault Kervarrec","doi":"10.1111/his.15444","DOIUrl":"https://doi.org/10.1111/his.15444","url":null,"abstract":"<p><p>NUT carcinoma is a rare malignant neoplasm characterised by recurrent NUTM1 rearrangements, initially reported in the midline. Recently, 10 cases of cutaneous NUT carcinoma with adnexal differentiation harbouring BRD3::NUTM1, NSD3::NUTM1, BRD4::NUTM1 or BRD3::NUTM2B fusions have been reported. Accordingly, 'NUT adnexal carcinoma' (NAC) has been introduced as a provisional tumour entity to the fifth edition of the WHO Classification of Skin Tumours.</p><p><strong>Aims: </strong>We report the histopathological, molecular genetic and epigenetic features of seven additional cases of NAC.</p><p><strong>Methods and results: </strong>The cohort consisted of four female and three male patients with a median age of 58 years. Follow-up was available for six cases, and documented diffuse metastatic spreading leading to death at 18 months after diagnosis for one case. Histopathological examination in all cases revealed dermal/subcutaneous neoplasms composed of poorly differentiated cells with large irregular vesicular nuclei and at least focally prominent nucleoli. All cases showed areas of duct/gland formation. Using immunohistochemistry, all tumours showed diffuse NUT expression with co-expression of SOX10 in five cases. P63 and P40 were diffusely positive in one case and confined to the periphery of the tumour nests in five cases. Molecular analysis showed BRD4::NUTM1 fusions (n = 3), BRD3::NUTM1 fusions (n = 3) and NSD3::NUTM1 (n = 1). Although being close to this latter group, methylation and transcriptional analysis revealed that NAC formed a unique cluster distinct from extracutaneous NUT carcinoma and NUTM1-rearranged porocarcinoma.</p><p><strong>Conclusions: </strong>Our results further support the existence of primary cutaneous NAC and suggest that it may represent an entity distinct from extracutaneous NUT carcinoma.</p>","PeriodicalId":13219,"journal":{"name":"Histopathology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143691983","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":"Inflammatory bowel disease-associated serrated lesions with dysplasia are frequently associated with advanced neoplasia: supporting a unified classification approach.","authors":"Dorukhan Bahceci, Anita Sejben, Lindsay Yassan, Gregory Miller, Xiaoyan Liao, Huaibin Mabel Ko, Marcela Salomao, Masato Yozu, Gregory Y Lauwers, Won-Tak Choi","doi":"10.1111/his.15448","DOIUrl":"https://doi.org/10.1111/his.15448","url":null,"abstract":"<p><strong>Aims: </strong>Inflammatory bowel disease (IBD)-associated serrated lesions are categorized into three distinct subtypes: traditional serrated adenoma (TSA)-like lesion, sessile serrated lesion (SSL)-like lesion, and serrated lesion, not otherwise specified (NOS). Although the risk of neoplastic progression of serrated lesions without dysplasia has not been shown to exceed that of sporadic cases, the clinicopathologic features of the three serrated subtypes with dysplasia remain poorly understood in the context of IBD.</p><p><strong>Methods and results: </strong>We analysed 87 serrated lesions with dysplasia (collectively referred to as serrated dysplasia) identified endoscopically in 58 IBD patients, including 51 (59%) TSA-like dysplasia, 24 (28%) SSL-like dysplasia, and 12 (14%) serrated dysplasia NOS. Inclusion criteria required all three serrated subtypes to show morphologic evidence of dysplasia and to be located within areas of colitis. We also compared the clinicopathologic features of serrated dysplasia with those of 239 conventional (adenomatous) dysplastic lesions from 149 IBD patients. The cohort included 39 (67%) men and 19 (33%) women, with a mean age of 54 years and a mean IBD duration of 20 years. Most patients had ulcerative colitis (n = 41; 71%) and pancolitis (n = 48; 83%). The majority of serrated lesions with dysplasia had a polypoid or visible endoscopic appearance (n = 73; 84%), with a mean size of 1.4 cm, and were found in the left colon (n = 66; 76%). Most lesions (n = 73; 84%) demonstrated low-grade dysplasia at the time of biopsy diagnosis, whereas high-grade dysplasia (HGD) was identified in the remaining 14 (16%) lesions. SSL-like dysplasia was more frequently associated with ulcerative colitis (94%) compared to TSA-like dysplasia (67%) and serrated dysplasia NOS (56%) (P = 0.042). Although only seven (12%) patients had a concurrent history of primary sclerosing cholangitis, it was exclusively identified in the TSA-like dysplasia group (19% versus 0% in both the SSL-like dysplasia group and the serrated dysplasia NOS group; P = 0.017). Serrated dysplasia NOS more commonly demonstrated HGD at the time of biopsy diagnosis (42%) compared to TSA-like dysplasia (12%) and SSL-like dysplasia (13%) (P = 0.022). Serrated dysplasia NOS was also more frequently associated with synchronous and/or metachronous nonconventional dysplasia (60%) compared to TSA-like dysplasia (16%) and SSL-like dysplasia (9%) (P = 0.037). Serrated dysplasia, regardless of subtype, was associated with high rates of advanced neoplasia (HGD or colorectal cancer) at the previous biopsy site or in the same colonic segment during follow-up. Within a mean follow-up time of 13 months, advanced neoplasia was detected in 50% of the TSA-like dysplasia group, 67% of the SSL-like dysplasia group, and 100% of the serrated dysplasia NOS group (P = 0.622). Moreover, at least one-third of patients in each group (58% in the TSA-like dysplasia group, 44% in th","PeriodicalId":13219,"journal":{"name":"Histopathology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656810","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":"HIV-negative primary effusion lymphoma: a series of seven cases.","authors":"Chang-Yao Chu, Bipin Thingujam, Shu-Hsien Wang, Ya-Ping Chen, Hsueh-Yin Cheng, L Jeffrey Medeiros, Kung-Chao Chang","doi":"10.1111/his.15446","DOIUrl":"https://doi.org/10.1111/his.15446","url":null,"abstract":"<p><strong>Aims: </strong>Primary effusion lymphoma (PEL) is a rare aggressive, human herpesvirus-8 (HHV8)-associated neoplasm of post-germinal centre B cell origin. It usually presents as a serous effusion in human immunodeficiency virus (HIV)-positive patients. PEL is rarely reported in HIV-negative patients.</p><p><strong>Methods and results: </strong>wWe report seven cases of HIV-negative elderly men diagnosed with PEL in a single institution. Clinical information and laboratory characteristics were collected. All patients were men, with a mean age of 76 years (range = 60-93) and presented with pleural effusions (n = 6), pericardial effusion (n = 1) and/or ascites (n = 2); two patients had multiple effusions. Extracavitary tissue involvement was present in one patient, who was also a liver transplant recipient. All patients had a decreased blood lymphocyte fraction, with a zero CD4+ count in one. The tumour cells in cytology of effusions showed a moderate amount of cytoplasm, perinuclear hof (a focal area of clearing) and irregular nuclear outlines with coarse chromatin and prominent nucleoli. Immunohistochemically, PEL cells were positive for HHV8 latent nuclear antigen (7 of 7), CD45 (3 of 3), CD30 (4 of 4), MUM1/IRF4 (2 of 2) and were negative for CD3 and CD20 in all seven cases. CD138 was positive in six of seven cases. Epstein-Barr virus (EBV) was detected in two of seven cases by in-situ hybridisation. B cell clonality by polymerase chain reaction (PCR) was positive in two cases with adequate materials available. Conventional cytogenetic analysis showed complex karyotypes in three of five cases, with recurrent +8, +12 and t(4;12)(q27;q21), and one case with +7. Six of seven patients died of disease with a mean survival of 5.4 months (range = 0.4-11.2 months).</p><p><strong>Conclusions: </strong>PEL can arise in immunocompetent, older patients, in this series all men, and behaves aggressively. These neoplasms are similar to their HIV-positive counterparts with anaplastic cytomorphology, HHV8 infection and a plasmablastic immunophenotype. The aetiology of PEL is uncertain, but may be related to physiological immunodeficiency associated with ageing.</p>","PeriodicalId":13219,"journal":{"name":"Histopathology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656801","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}