Histopathology最新文献

{"title":"Expanding the spectrum of low-grade sinonasal adenocarcinoma with biphasic seromucinous differentiation and activating HRAS/AKT1 mutations.","authors":"Viktoria S Hadnagy, Meike Körner, Matthias Rössle, Patrick Dubach, Gunther Pabst, Alexandra Kotulova, Stefan Weder, Robert Seifert, Elisabeth J Rushing, David Holzmann, Martin Hüllner, Sandra N Freiberger, Niels J Rupp","doi":"10.1111/his.15251","DOIUrl":"10.1111/his.15251","url":null,"abstract":"<p><strong>Aims: </strong>Low-grade non-intestinal-type sinonasal adenocarcinoma (LGSNAC) is a rare heterogeneous and poorly characterised group of tumours, distinct from intestinal- and salivary-type neoplasms. Therefore, further characterisation is needed for clearer biological understanding and classification.</p><p><strong>Methods and results: </strong>Clinical, histological and molecular characterisation of four cases of biphasic, low-grade adenocarcinomas of the sinonasal tract was performed. All patients were male, aged between 48 and 78 years, who presented with polypoid masses in the nasal cavity. Microscopically, virtually all tumours were dominated by tubulo-glandular biphasic patterns, microcystic, focal (micro)papillary, oncocytic or basaloid features. Immunohistochemical staining confirmed biphasic differentiation with an outer layer of myoepithelial cells. Molecular profiling revealed HRAS (p.G13R, p.Q61R) mutations, and concomitant AKT1 (p.E17K, p.Q79R) mutations in two cases. Two cases showed potential in-situ/precursor lesions adjacent to the tumour. Follow-up periods ranged from 1 to 30 months, with one case relapsing locally after 12 and > 20 years.</p><p><strong>Conclusion: </strong>This study further corroborates a distinct biphasic low-grade neoplasm of the sinonasal tract with seromucinous differentiation. Although morphological and molecular features overlap with salivary gland epithelial-myoepithelial carcinoma, several arguments favour categorising these tumours within the spectrum of LGSNAC.</p>","PeriodicalId":13219,"journal":{"name":"Histopathology","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141456442","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":"Histopathological assessment of the viability of hepatic alveolar echinococcosis.","authors":"Selina Robers, Michael Reinehr, Lillemor Haibach, Eva Furrer, Annina Cincera, Philipp Andreas Kronenberg, Ramon Marc Eichenberger, Peter Deplazes, Ansgar Deibel, Beat Müllhaupt, Achim Weber","doi":"10.1111/his.15280","DOIUrl":"10.1111/his.15280","url":null,"abstract":"<p><strong>Aims: </strong>Infections by the larval stage of the tape worms Echinococcus multilocularis and Echinococcus granulosus s.l. are potentially fatal zoonoses affecting humans as dead-end hosts. Histopathological evaluation of hepatic echinococcosis is an integral part of patient management, including the distinction between alveolar (AE) and cystic echinococcosis (CE), which are associated with different disease courses and treatments. To improve histopathological assessment of Echinococcus lesions, we aimed to develop robust criteria to evaluate their viability and decay.</p><p><strong>Methods and results: </strong>Histomorphological criteria for determining parasitic viability based on the morphology of parasite structures and different stages of their decay were defined based on a clinically and molecularly defined cohort comprising 138 specimens from 112 patients (59 AE and 53 CE); 618 AE lesions were assessed for histopathological viability comparing haematoxylin and eosin (H&E) staining with mAbEm18 and mAbEm2G11 immunostaining. Moreover, parasite viability was systematically mapped in cross-sections of five additional AE lesions. Protoscoleces in CE and AE displayed variable states of degeneration. Albendazole had no significant effect on the morphology of parasite structures. Viability assessment revealed high agreement between H&E and mAbEm18, but not mAbEm2G11 staining, suggesting mAbEm18 staining as reliable for parasite viability assessment. H&E and mAbEm18 staining displayed a central-peripheral gradient of parasite viability and decay across parasitic lesions, with decayed cystic lesions located more towards the lesion centre while the most viable cystic lesions were located more peripherally.</p><p><strong>Conclusions: </strong>Histopathological criteria corroborated by mAbEm18 staining provide a simple and reliable tool to assess the viability of AE lesions, knowledge of which is a valuable decision-making tool for further treatment.</p>","PeriodicalId":13219,"journal":{"name":"Histopathology","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141751564","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 evolving molecular characterisation, histological criteria and nomenclature of adenoid ameloblastoma as a World Health Organisation tumour type.","authors":"Edward W Odell, Carolina Cavalieri Gomes, Selvam Thavaraj","doi":"10.1111/his.15270","DOIUrl":"10.1111/his.15270","url":null,"abstract":"<p><p>Adenoid ameloblastoma (AA) was recently recognised as a separate tumour type in the most recent World Health Organisation (WHO) classification of head and neck tumours. This decision has been considered controversial by several groups, who have described AA as a subtype of ameloblastoma, a hybrid odontogenic tumour or to fall within the spectrum of other recognised odontogenic tumours, including dentinogenic ghost cell tumour and adenomatoid odontogenic tumour. Here we review the reasons for the WHO decision to classify AA as a separate tumour type. We also critique molecular and histological findings from recent reports published since the WHO classification. While acknowledging that the classification of tumours is constantly evolving, the balance of current evidence suggests that AA should remain a distinct tumour type, and not a subtype of ameloblastoma, pending further molecular characterisation.</p>","PeriodicalId":13219,"journal":{"name":"Histopathology","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141456445","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":"Prediction of molecular subclasses of uveal melanoma by deep learning using routine haematoxylin-eosin-stained tissue slides.","authors":"Farhan Akram, Daniël P de Bruyn, Quincy C C van den Bosch, Teodora E Trandafir, Thierry P P van den Bosch, Rob M Verdijk, Annelies de Klein, Emine Kiliç, Andrew P Stubbs, Erwin Brosens, Jan H von der Thüsen","doi":"10.1111/his.15271","DOIUrl":"10.1111/his.15271","url":null,"abstract":"<p><strong>Aims: </strong>Uveal melanoma has a high propensity to metastasize. Prognosis is associated with specific driver mutations and copy number variations, and these can only be obtained after genetic testing. In this study we evaluated the efficacy of patient outcome prediction using deep learning on haematoxylin and eosin (HE)-stained primary uveal melanoma slides in comparison to molecular testing.</p><p><strong>Methods: </strong>In this retrospective study of patients with uveal melanoma, 113 patients from the Erasmus Medical Centre who underwent enucleation had tumour tissue analysed for molecular classification between 1993 and 2020. Routine HE-stained slides were scanned to obtain whole-slide images (WSI). After annotation of regions of interest, tiles of 1024 × 1024 pixels were extracted at a magnification of 40×. An ablation study to select the best-performing deep-learning model was carried out using three state-of-the-art deep-learning models (EfficientNet, Vision Transformer, and Swin Transformer).</p><p><strong>Results: </strong>Deep-learning models were subjected to a training cohort (n = 40), followed by a validation cohort (n = 20), and finally underwent a test cohort (n = 48). A k-fold cross-validation (k = 3) of validation and test cohorts (n = 113 of three classes: BAP1, SF3B1, EIF1AX) demonstrated Swin Transformer as the best-performing deep-learning model to predict molecular subclasses based on HE stains. The model achieved an accuracy of 0.83 ± 0.09 on the validation cohort and 0.75 ± 0.04 on the test cohort. Within the subclasses, this model correctly predicted 70% BAP1-mutated, 61% SF3B1-mutated and 80% EIF1AX-mutated UM in the test set.</p><p><strong>Conclusions: </strong>This study showcases the potential of the deep-learning methodology for predicting molecular subclasses in a multiclass manner using HE-stained WSI. This development holds promise for advanced prognostication of UM patients without the need of molecular or immunohistochemical testing. Additionally, this study suggests there are distinct histopathological features per subclass; mainly utilizing epithelioid cellular morphology for BAP1-classification, but an unknown feature distinguishes EIF1AX and SF3B1.</p>","PeriodicalId":13219,"journal":{"name":"Histopathology","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141476515","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":"Defining angioinvasion and lymphatic invasion in papillary thyroid carcinoma: morphological criteria, utility of D2-40/CD31/ERG immunohistochemistry and correlation with clinicopathological characteristics.","authors":"Bin Xu, Dibisha Roy, Rene Serrette, Ronald Ghossein","doi":"10.1111/his.15285","DOIUrl":"10.1111/his.15285","url":null,"abstract":"<p><strong>Aims: </strong>While CAP and ICCR protocols mandate the separation of angioinvasion (AI) and lymphatic invasion (LI) in thyroid carcinoma, distinction between them can be difficult. Because the presence of AI is used to stratify patients with papillary thyroid carcinoma (PTC), there is a need to accurately diagnose AI and LI.</p><p><strong>Methods and results: </strong>AI and LI were evaluated in 162 cases of PTC (n = 155) and high-grade differentiated thyroid carcinoma, papillary phenotype (HGDTCp, n = seven) using haematoxylin and eosin (H&E), D2-40 and CD31/ERG. In encapsulated carcinomas, vascular invasion (VI) was only of AI nature. Infiltrative carcinomas showed LI (46 of 131, 35%) and AI (19 of 131, 16%). The frequency of nodal metastasis (NM) and large volume of NM was 93 and 85%, respectively, in tumours with LI, and 39 and 26%, respectively, in those without LI. Luminal red blood cells and smooth muscle in the wall of large-calibre vessels were not reliable criteria to exclude LI and were seen in 23 and 6% of LI, respectively. LI was an independent predictor for NM, whereas AI is an independent predictor for distant metastasis at presentation in PTC/HGDTCp.</p><p><strong>Conclusion: </strong>VI in encapsulated carcinomas, including follicular variant PTC, is only of AI nature, confirming the position of this variant as a close entity to follicular carcinoma rather than classic PTC, whereas infiltrative PTC/HGDTCp may have LI or, less frequently, AI. As no morphological features reliably distinguish LI from AI, D2-40 and CD31/ERG immunostains should be considered for separating AI from LI when dealing with vascular invasion in an infiltrative PTC.</p>","PeriodicalId":13219,"journal":{"name":"Histopathology","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141731123","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":"Diagnostic approach to hepatic vascular lesions: a paediatric perspective.","authors":"Juan Putra, Grace E Kim","doi":"10.1111/his.15250","DOIUrl":"10.1111/his.15250","url":null,"abstract":"<p><p>The pathological evaluation of hepatic vascular lesions in children requires special consideration. Inconsistent terminology, rarity of pathology specimens and overlapping pathological features between various lesions may pose a serious diagnostic challenge. In this review, we highlight the importance of using the International Society for the Study of Vascular Anomalies (ISSVA) classification scheme to characterise these lesions. Selected entities are discussed, including hepatic vascular tumours exclusively seen in the paediatric age group, hepatic infantile haemangioma and hepatic congenital haemangioma. Vascular malformations, with emphasis on their syndromic associations (venous malformation in blue rubber bleb naevus syndrome) and complications (hepatocellular nodules in Abernethy malformation) are also covered.</p>","PeriodicalId":13219,"journal":{"name":"Histopathology","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141456441","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":"Can thyroid histomorphology identify patients with PTEN hamartoma tumour syndrome?","authors":"Melad N Dababneh, Laura Rabinowitz, Gilman Plitt, Charis Eng, Christopher C Griffith","doi":"10.1111/his.15278","DOIUrl":"10.1111/his.15278","url":null,"abstract":"<p><strong>Aims: </strong>The phosphatase and tensin homologue (PTEN) hamartoma tumour syndrome (PHTS) is a genetic disorder with variable clinical presentation and increased lifetime risk of multiorgan malignancies. The thyroid gland is commonly affected with follicular nodular disease (FND) and follicular cell-derived carcinomas. Histopathological and immunohistochemical assessment of thyroid disease in PHTS is essential to identify patients at-risk.</p><p><strong>Methods and results: </strong>In all, 30 PHTS patients with available thyroidectomy specimen material (2000-2023) and 31 control patients with FND and \"adenomatous nodules\" were retrieved. Histologic criteria, including the frequency of adenomatous-type nodules versus hyperplastic-type nodules, background and nodular lipomatous metaplasia, chronic lymphocytic thyroiditis, cytoplasmic clearing of follicular cells in nodules, nodule-in-nodule appearance, and spectrum of nuclear atypia between nodules were evaluated in both cohorts and a Thyroid Histomorphologic PHTS Score (THiPS) system was established with a cutoff of 4 points or higher being considered concerning for PHTS. In all, 27 PHTS (90%) and five control (16.1%) cases had THiPS ≥4. A PTEN immunohistochemical stain was evaluated in 25 cases of each cohort and showed nuclear and cytoplasmic loss of expression in all or most of the nodules of 24/25 PHTS cases. In 3/25 control cases, two with THiPS ≥4, had loss of expression in one to multiple nodules. Conventional papillary thyroid carcinomas in PHTS patients retained PTEN cytoplasmic expression.</p><p><strong>Conclusions: </strong>Our study supports that, although not specific, the finding of multiple histologic features is found more frequently in patients with PHTS compared to the non-PHTS control group. The THiPS system has high sensitivity for thyroid specimens from patients with PHTS.</p>","PeriodicalId":13219,"journal":{"name":"Histopathology","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141476494","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":"Clinicopathologic and molecular study of superficial CD34-positive fibroblastic tumours mimicking atypical fibrous histiocytoma (dermatofibroma).","authors":"Craig B Wakefield, Fredrik Mertens, Christopher D M Fletcher, William J Anderson","doi":"10.1111/his.15282","DOIUrl":"10.1111/his.15282","url":null,"abstract":"<p><strong>Aims: </strong>Superficial CD34-positive fibroblastic tumour (SCD34FT) is an uncommon but distinctive low-grade neoplasm of the skin and subcutis that shows frequent CADM3 expression by immunohistochemistry (IHC). In this study, prompted by an index case resembling 'atypical fibrous histiocytoma (FH)' that was positive for CADM3 IHC, we systematically examined a cohort of tumours previously diagnosed as 'atypical FH' by applying CADM3 and fluorescence in situ hybridization (FISH) for PRDM10 rearrangement, to investigate the overlap between these tumour types.</p><p><strong>Methods and results: </strong>Forty cases of atypical FH were retrieved, including CD34-positive tumours (n = 20) and CD34-negative tumours (n = 20). All tumours were stained for CADM3. All CADM3-positive tumours were evaluated by FISH to assess for PRDM10 rearrangement. Eleven CD34-positive tumours (11/20, 55%) coexpressed CADM3 and were reclassified as SCD34FT. None (0/20) of the CD34-negative atypical FH were CADM3-positive. Reclassified SCD34FT (10/11) arose on the lower extremity, with frequent involvement of the thigh (n = 8). Features suggestive of atypical FH were observed in many reclassified cases including variable cellularity, spindled morphology, infiltrative tumour margins, collagen entrapment, epidermal hyperpigmentation, and acanthosis. Variably prominent multinucleate giant cells, including Touton-like forms, were also present. An informative FISH result was obtained in 10/11 reclassified tumours, with 60% (6/10) demonstrating PRDM10 rearrangement.</p><p><strong>Conclusion: </strong>A significant subset of tumours that histologically resemble atypical FH, and are positive for CD34, coexpress CADM3 and harbour PRDM10 rearrangement, supporting their reclassification as SCD34FT. Awareness of this morphologic overlap and the application of CADM3 IHC can aid the distinction between SCD34FT and atypical FH.</p>","PeriodicalId":13219,"journal":{"name":"Histopathology","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141751563","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":"Quantitative comparison of immunohistochemical HER2-low detection in an interlaboratory study.","authors":"Maaike Anna Hempenius, Maran A Eenkhoorn, Henrik Høeg, David J Dabbs, Bert van der Vegt, Seshi R Sompuram, Nils A 't Hart","doi":"10.1111/his.15273","DOIUrl":"10.1111/his.15273","url":null,"abstract":"<p><strong>Aims: </strong>Recently, human epidermal growth factor 2 (HER2)-low (i.e. HER2 score 1+ or 2+ without amplification) breast cancer patients became eligible for trastuzumab-deruxtecan treatment. To improve assay standardisation and detection of HER2-low in a quantitative manner, we conducted an external quality assessment-like study in the Netherlands. Dynamic range cell lines and immunohistochemistry (IHC) calibrators were used to quantify HER2 expression and to assess interlaboratory variability.</p><p><strong>Methods and results: </strong>Three blank slides with a dynamic range cell line and an IHC calibrator were stained with routine HER2 assays by 35 laboratories. Four different antibody clones were used: 19 (54.3%) 4B5, six (17.1%) A0485, five (14.3%) DG44 (HercepTest) and five (14.3%) SP3. Laboratories used two different detection kits for 4B5 assays: 14 (73.7%) ultraView and five (26.3%) OptiView. Variability of HER2 expression in cell lines, measured with artificial intelligence software, was median (min-max) = negative core 0.5% (0.0-57.0), 1+ core 4.3% (1.6-71.3), 2+ core 42.8% (30.4-92.6) and 3+ core 96.2% (91.8-98.8). The calibrators DG44 and 4B5 OptiView had the highest analytical sensitivity, closely followed by 4B5 ultraView. SP3 was the least sensitive. Calibrators of A0485 assays were not analysable due to background staining.</p><p><strong>Conclusions: </strong>As assays were validated for detecting HER2-amplified tumours, not all assays and antibodies proved suitable for HER2-low detection. Some tests showed distinct expression in the negative cell line. Dynamic range cell line controls and quantitative analysis using calibrators demonstrated more interlaboratory variability than commonly appreciated. Revalidation of HER2 tests by laboratories is needed to ensure clinical applicable HER2-low assays.</p>","PeriodicalId":13219,"journal":{"name":"Histopathology","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141792355","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":"Detection of GRM1 gene rearrangements in chondromyxoid fibroma: a comparison of fluorescence in-situ hybridisation, RNA sequencing and immunohistochemical analysis.","authors":"Dianne Torrence, Josephine K Dermawan, Yanming Zhang, Chad Vanderbilt, Sinchun Hwang, Kerry Mullaney, Achim Jungbluth, Mamta Rao, Kate Gao, Purvil Sukhadia, Konstantinos Linos, Narasimhan Agaram, Meera Hameed","doi":"10.1111/his.15248","DOIUrl":"10.1111/his.15248","url":null,"abstract":"<p><strong>Aims: </strong>Chondromyxoid fibroma (CMF) is a rare, benign bone tumour which arises primarily in young adults and is occasionally diagnostically challenging. Glutamate metabotropic receptor 1 (GRM1) gene encodes a metabotropic glutamate receptor and was recently shown to be up-regulated in chondromyxoid fibroma through gene fusion and promoter swapping. The aim of this study was to interrogate cases of CMF for the presence of GRM1 gene rearrangements, gene fusions and GRM1 protein overexpression.</p><p><strong>Methods and results: </strong>Selected cases were subjected to testing by fluorescent in-situ hybridisation (FISH) with a GRM1 break-apart probe, a targeted RNA sequencing method and immunohistochemical study with an antibody to GRM1 protein. Two cases were subjected to whole transcriptomic sequencing. In 13 of 13 cases, GRM1 protein overexpression was detected by immunohistochemistry using the GRM1 antibody. Of the 12 cases successfully tested by FISH, nine of 12 showed GRM1 rearrangements by break-apart probe assay. Targeted RNA sequencing analysis did not detect gene fusions in any of the eight cases tested, but there was an increase in GRM1 mRNA expression in all eight cases. Two cases subjected to whole transcriptomic sequencing (WTS) showed elevated GRM1 expression and no gene fusions.</p><p><strong>Conclusion: </strong>GRM1 gene rearrangements can be detected using FISH break-apart probes in approximately 75% of cases, and immunohistochemical detection of GRM1 protein over-expression is a sensitive diagnostic method. The gene fusion was not detected by targeted RNA sequencing, due most probably to the complexity of fusion mechanism, and is not yet a reliable method for confirming a diagnosis of CMF in the clinical setting.</p>","PeriodicalId":13219,"journal":{"name":"Histopathology","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141418730","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}