American Journal of Surgical Pathology最新文献

{"title":"PRAME Expression in Merkel Cell Carcinoma.","authors":"Elisabeth Miller, Andrew Biesemier, David M Coomes, Shyam S Raghavan","doi":"10.1097/PAS.0000000000002288","DOIUrl":"10.1097/PAS.0000000000002288","url":null,"abstract":"<p><p>Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine tumor of the skin. Risk factors include extensive sun damage, infection with Merkel cell polyomavirus, and an immunocompromised state. PRAME, also known as preferentially expressed antigen in melanoma, is a cancer-testis antigen recently found to be a useful diagnostic tool in the workup of melanocytic neoplasms. However, the expression pattern of PRAME in Merkel cell carcinoma is unknown. In this study, we examine PRAME expression in Merkel cell carcinoma and explore its prognostic implications. The institutional archives at the University of Virginia were used to search for tumors classified as Merkel cell carcinoma from 2004 to 2022. All potential cases were reviewed to confirm the diagnosis, and electronic medical records were searched for clinical and demographic data. Tumors were subsequently immunostained for PRAME and Merkel cell polyomavirus. Cox proportional hazards regression models were used to estimate relative (all-cause) survival of PRAME positivity and MCPyV positivity in our study as well as MCC-specific survival of PRAME positivity. Univariate and multivariable models were created for each outcome related to all-cause survival. A total of 39 cases were included in the study. Twenty-eight percent (11 cases) demonstrated strong PRAME expression, and 27% of cases were positive for Merkel cell polyomavirus. There was no statistically significant correlation between PRAME expression and virus positivity. With respect to PRAME, the adjusted all-cause mortality hazard ratio was 11.4 (95% CI: 1.8, 70.8). The unadjusted MCC-specific hazard ratio was 4.6 (95% CI: 0.8, 27.5). The adjusted hazard ratio pertaining to Merkel cell polyomavirus infection was 0.25 (95% CI: 0.02, 2.96). In this limited cohort, PRAME expression appears to correlate with worse outcomes in Merkel cell carcinoma.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"1270-1276"},"PeriodicalIF":4.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141589478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Risk Factors of Lymph Node Metastasis and Prognosis in 891 Chinese Patients With Submucosal Early Gastric Carcinoma, Emphasizing Differences Between Gastric Cardiac and Noncardiac Origins.","authors":"Yuqing Cheng, Mingzhan Du, Yaohui Wang, Ting Li, Chongfang He, Xiaoli Zhou, Min Lin, Qin Huang","doi":"10.1097/PAS.0000000000002282","DOIUrl":"10.1097/PAS.0000000000002282","url":null,"abstract":"<p><p>Differences in risk factors (RF) of lymph node metastasis (LNM) and prognosis between submucosal early gastric cardiac (SEGCC) and noncardiac (SEGNCC) carcinomas remain unclear. In this study, we investigated and compared RF of LNM and prognosis in 891 patients with radical gastrectomy for SEGCC (n=217) or SEGNCC (n=674). Compared with SEGNCC, SEGCC displayed significantly higher proportion of elderly patients (70 y or above), the elevated macroscopic type, well/moderately differentiated tubular and low-grade papillary adenocarcinomas, as well as low-grade tumor budding, but lower prevalence of the depressed macroscopic type, poorly differentiated tubular adenocarcinoma, mixed adenocarcinoma, poorly cohesive carcinoma, lymphovascular invasion (LVI), perineural invasion, and high-grade tumor budding. By univariate analysis, significant RF for LNM of the cohort included female sex, poor differentiation, SM2 invasion, LVI, intermediate-grade and high-grade tumor budding, whereas tumor size, histology type, and perineural invasion were the significant RF for LNM in SEGNCC. By multivariate analysis, significant independent RF for LNM included female sex and LVI in SEGCC but were female sex, mixed adenocarcinoma, LVI, and high-grade tumor budding in SEGNCC. The 5-year overall survival was significantly worse in SEGCC than in SEGNCC for patients with LNM, but not for those without. For overall survival, LNM was the only significant independent RF in SEGCC, whereas age 70 years or above and LNM were independent RF in SEGNCC. The results of our study provided the clinicopathologic evidence for individualized clinical management strategies for these 2 groups of patients and suggested different pathogenesis mechanisms between SEGCC and SEGNCC.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"1293-1301"},"PeriodicalIF":4.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141722888","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inflammatory Giant Cell Carcinoma of the Lung: Clinicopathologic, Immunohistochemical, and Next-generation Sequencing Study of 14 Cases.","authors":"David I Suster, A Craig Mackinnon, Natali Ronen, Haider A Mejbel, Shuko Harada, Michael Michal, Saul Suster","doi":"10.1097/PAS.0000000000002285","DOIUrl":"10.1097/PAS.0000000000002285","url":null,"abstract":"<p><p>A distinctive histological variant of poorly differentiated, sarcomatoid, non-small cell lung carcinoma characterized by a discohesive population of giant tumor cells associated with prominent interstitial inflammatory cell infiltrates is described. The tumors occurred in 7 women and 7 men, 42 to 72 years of age (mean: 56 y). They predominantly affected the upper lobes and measured 1.3 to 9 cm in greatest diameter (mean: 4.6 cm). The tumor cells were characterized by large pleomorphic nuclei with prominent nucleoli, ample cytoplasm, and frequent abnormal mitoses, and were surrounded by a dense inflammatory cell infiltrate, often associated with emperipolesis. Immunohistochemical stains were positive in the tumor cells for cytokeratin AE1/AE3 and CK8/18 and negative for TTF1, napsin A, p40, and CK5/6. Next-generation sequencing was performed in all cases using the Oncomine Precision Assay; the most common abnormalities found included TP53 mutations (9 cases) and AKT1 amplification (8 cases), followed by KRAS mutations (4 cases) and MAP2K1/2 mutations (4 cases). Clinical follow-up was available in 13 patients. Three patients presented with metastases as the initial manifestation of disease; 8 patients died of their tumors from 6 months to 8 years (mean: 2.7 y); 3 patients were alive and well from 4 to 6 years; and 2 patients had metastases when last seen but were lost to follow-up thereafter. The importance of recognizing this distinctive and aggressive variant of non-small cell lung carcinoma lies in avoiding confusion with a sarcoma or other types of malignancy.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"1215-1223"},"PeriodicalIF":4.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141578725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Pathology of Pulmonary Disease After Pediatric Hematopoietic Stem Cell Transplantation.","authors":"Nahir Cortes-Santiago, Gail Deutsch, Kalyani R Patel, Manuel Silva-Carmona, Carolyn Henderson, Sarah E Sartain, Saleh Bhar, Jennifer Pogoriler","doi":"10.1097/PAS.0000000000002267","DOIUrl":"10.1097/PAS.0000000000002267","url":null,"abstract":"<p><p>Pulmonary complications continue to cause significant morbidity and mortality in posthematopoietic stem cell transplantation (HSCT) settings. The histopathology of pulmonary diseases in the post-HSCT context is poorly characterized, especially in the pediatric population. We sought to characterize the pathologic spectrum of pulmonary disease post-HSCT in a pediatric cohort. Fifty-six specimens, including 53 biopsy specimens, corresponding to 53 patients, were identified. Biopsy slides were reviewed and assigned to diagnostic categories (infectious, graft-versus-host disease, vasculopathy, indeterminate, and others) by consensus among 3 pediatric pulmonary pathologists, taking into consideration pathologic, clinical, radiologic, and laboratory findings. The most common diagnostic category was infection (n=20). Vasculopathy, mostly in the form of fibromyxoid intimal expansion, was very common in the entire cohort (n=26) and was the sole finding in a small subset of patients (n=5), with particularly poor outcomes. A subset of biopsies remained indeterminate (n=10), and the findings in this cohort were dominated by acute lung injury. The latter group had a poor prognosis, with a short biopsy-to-death interval. The overall clinicopathologic concordance was 40%, most commonly agreeing in the infectious category. Finally, wedge biopsies led to a change in management in 69% of cases versus 23% of limited procedures (i.e., core needle biopsies). Our results suggest that while infectious complications continue to be common post-HSCT, other findings such as vasculopathy and acute lung injury portend a particularly poor prognosis and should be actively sought and reported.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"1201-1214"},"PeriodicalIF":4.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141787077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Comprehensive Clinicopathologic and Molecular Reappraisal of GLI1 -altered Mesenchymal Tumors with Pooled Outcome Analysis Showing Poor Survival in GLI1 - amplified Versus GLI1- rearranged Tumors.","authors":"Carla Saoud, Abbas Agaimy, Josephine K Dermawan, Jie-Fu Chen, Marc K Rosenblum, Brendan C Dickson, Nooshin Dashti, Michael Michal, Kemal Kosemehmetoglu, Nasir Ud Din, Karen Albritton, Narasimhan P Agaram, Cristina R Antonescu","doi":"10.1097/PAS.0000000000002272","DOIUrl":"10.1097/PAS.0000000000002272","url":null,"abstract":"<p><p>GLI1 -altered mesenchymal tumor is a recently described distinct pathologic entity with an established risk of malignancy, being defined molecularly by either GLI1 gene fusions or amplifications. The clinicopathologic overlap of tumors driven by the 2 seemingly distinct mechanisms of GLI1 activation is still emerging. Herein, we report the largest series of molecularly confirmed GLI1 -altered mesenchymal neoplasms to date, including 23 GLI1- amplified and 15 GLI1 -rearranged new cases, and perform a comparative clinicopathologic, genomic, and survival investigation. GLI1- rearranged tumors occurred in younger patients (42 vs. 52 y) and were larger compared with GLI1 -amplified tumors (5.6 cm vs. 1.5 cm, respectively). Histologic features were overall similar between the 2 groups, showing a multinodular pattern and a nested architecture of epithelioid, and less commonly spindle cells, surrounded by a rich capillary network. A distinct whorling pattern was noted among 3 GLI1 -amplified tumors. Scattered pleomorphic giant cells were rarely seen in both groups. The immunoprofile showed consistent expression of CD56, with variable S100, CD10 and SMA expression. Genomically, both groups had overall low mutation burdens, with rare TP53 mutations seen only in GLI1- amplified tumors. GLI1 -amplified mesenchymal tumors exhibit mostly a single amplicon at the 12q13-15 locus, compared with dedifferentiated liposarcoma, which showed a 2-peak amplification centered around CDK4 (12q14.1) and MDM2 (12q15). GLI1 -amplified tumors had a significantly higher GLI1 mRNA expression compared with GLI1 -rearranged tumors. Survival pooled analysis of current and published cases (n=83) showed a worse overall survival in GLI1 -amplified patients, with 16% succumbing to disease compared with 1.7% in the GLI1- rearranged group. Despite comparable progression rates, GLI1 -amplified tumors had a shorter median progression-free survival compared with GLI1 -rearranged tumors (25 mo vs. 77 mo). Univariate analysis showed that traditional histologic predictors of malignancy (mitotic count ≥4/10 high-power fields, presence of necrosis, and tumor size ≥5 cm) are associated with worse prognosis among GLI1 -altered mesenchymal tumors.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"1302-1317"},"PeriodicalIF":4.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141454686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Additional Considerations on Aberrant BRG1 (SMARCA4) Expression in Small Cell Carcinoma of the Ovary, Hypercalcemic Type (SCCOHT).","authors":"Joanna Cyrta, Riwan Brillet, Enora Laas, Pierre-Alexandre Just, Mamy Andrianteranagna, Alexandra Leary, Anne Vincent-Salomon, Franck Bourdeaut, Julien Masliah-Planchon","doi":"10.1097/PAS.0000000000002296","DOIUrl":"10.1097/PAS.0000000000002296","url":null,"abstract":"","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"1335-1338"},"PeriodicalIF":4.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11404751/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141873973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevalence of S-methyl-5'-thioadenosine Phosphorylase (MTAP) Deficiency in Human Cancer: A Tissue Microarray Study on 13,067 Tumors From 149 Different Tumor Types.","authors":"Natalia Gorbokon, Niklas Wößner, Maximilian Lennartz, Sebastian Dwertmann Rico, Simon Kind, Viktor Reiswich, Florian Viehweger, Florian Lutz, Christoph Fraune, Andreas M Luebke, Claudia Hube-Magg, Anne Menz, Ria Schlichter, Till Krech, Andrea Hinsch, Eike Burandt, Guido Sauter, Ronald Simon, Stefan Steurer, Andreas H Marx, Patrick Lebok, David Dum, Sarah Minner, Frank Jacobsen, Till S Clauditz, Thilo Hackert, Faik G Uzunoǧlu, Lukas Bubendorf, Christian Bernreuther, Martina Kluth","doi":"10.1097/PAS.0000000000002297","DOIUrl":"10.1097/PAS.0000000000002297","url":null,"abstract":"<p><p>Loss of S-methyl-5'-thioadenosine phosphorylase (MTAP) expression is a common event in cancer leading to a critical vulnerability of cancer cells towards anti-cancer drugs. Homozygous MTAP deletions result in a complete expression loss that can be detected by immunohistochemistry (IHC). In this study, a tissue microarray containing 17,078 samples from 149 different tumor entities was analyzed by IHC, and complete MTAP loss was validated by fluorescence in situ hybridization. MTAP loss was observed in 83 of 149 tumor categories, including neuroendocrine neoplasms (up to 80%), Hodgkin lymphoma (50.0%), mesothelioma (32.0% to 36.8%), gastro-intestinal adenocarcinoma (4.0% to 40.5%), urothelial neoplasms (10.5% to 36.7%), squamous cell carcinomas (up to 38%), and various types of sarcomas (up to 20%) and non-Hodgkin lymphomas (up to 14%). Homozygous MTAP deletion was found in 90% to 100% of cases with MTAP expression loss in most tumor categories. However, neuroendocrine tumors, Hodgkin lymphomas, and other lymphomas lacked MTAP deletions. MTAP deficiency was significantly linked to unfavorable tumor phenotype in selected tumor entities and the presence of PD-L1 expression on tumor cells, absence of PD-L1 expression on immune cells, and a low density of CD8 + lymphocytes. In summary, MTAP deficiency can occur in various tumor entities and is linked to unfavorable tumor phenotype and noninflamed tumor microenvironment, but is not always related to deletions. MTAP IHC is of considerable diagnostic value for the detection of neoplastic transformation in multiple different applications.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"1245-1258"},"PeriodicalIF":4.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11404761/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141915914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reply to Letter by Cyrta et al, Entitled \"Additional Considerations on Aberrant BRG1 (SMARCA4) Expression in Small Cell Carcinoma of the Ovary, Hypercalcemic Type (SCCOHT)\".","authors":"Jasenka Mazibrada, Sabrina Croce, William D Foulkes, W Glenn McCluggage","doi":"10.1097/PAS.0000000000002295","DOIUrl":"10.1097/PAS.0000000000002295","url":null,"abstract":"","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":"1338-1340"},"PeriodicalIF":4.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142016151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epithelioid Fibrous Histiocytoma Is on a Continuum With Superficial ALK-rearranged Myxoid Spindle Cell Neoplasm: A Clinicopathologic Series of 35 Cases Including Alternate RET and NTRK3 Fusions.","authors":"Mia S DeSimone, Igor Odintsov, Harrison K Tsai, Brendan C Dickson, Ahmed K Alomari, Jason L Hornick, Christopher D M Fletcher, David J Papke","doi":"10.1097/PAS.0000000000002315","DOIUrl":"https://doi.org/10.1097/PAS.0000000000002315","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Anaplastic lymphoma kinase (ALK) rearrangements drive most examples of epithelioid fibrous histiocytoma (EFH) and have been reported in an emerging family of receptor tyrosine kinase (RTK) fusion-positive mesenchymal neoplasms, including superficial ones described under the rubric of \"superficial ALK-rearranged myxoid spindle cell neoplasm\" (SAMS). Here, we describe 35 superficial tumors with SAMS morphology, which occurred in 18 females (51%) and 17 males at a median age at presentation of 39 years (range: 6 to 82 y). Most tumors occurred on the lower extremity (25 tumors; 71%), followed by upper extremity (5; 14%), trunk (3; 9%), and face (2; 6%). Nine tumors were reported to have grown slowly before presentation, including &gt;10 years in 2 cases. Tumors occurred primarily in the dermis (32 tumors; 91%) or subcutis (3; 9%); 8 dermal tumors extended into the subcutis. Median tumor size was 1.3 cm (range: 0.5 to 8.0 cm). Clinical follow-up was available for 12 patients (34%; range: 2 mo to 21 y; median: 2.7 y), none of whom experienced metastasis. One incompletely resected tumor recurred locally at 19 months, and no other patients experienced recurrence. Histologically, tumors were characterized by bland spindle-to-ovoid cells showing whorled growth and myxoid-to-collagenous stroma. Recurrent features included an epidermal collarette (19/30; 63%), perivascular hyalinization (20/35; 57%), amianthoid collagen (14/35; 40%), and metaplastic ossification (2/35; 6%). Immunohistochemistry (IHC) demonstrated expression of ALK (24/31; 77%), CD34 (15/21; 71%), EMA (17/28; 61%), and S-100 (9/32; 28%). Eleven tumors showed hybrid morphologic features between EFH and SAMS; 9 of them (82%) showed cytomorphology typical of EFH but with whorled growth, myxoid stroma, and/or regions of spindle cell morphology. Two hybrid tumors showed sharp transitions between a region characteristic of EFH and a region characteristic of SAMS, with a concomitant sharp transition in EMA, CD34, and S-100 expression by IHC. Sequencing revealed ALK fusions in 15 of 19 tumors: 2 each with fusion partners FLNA, SQSTM1, and VCL, and 1 each with COL1A2, DCTN1, EML4, FXR1, MPRIP, PLEKHH2, PRKAR1A, SPECC1L, and TLN2. Thirteen of 14 ALK-rearranged tumors expressed ALK by IHC. Three tumors negative for ALK fusions instead harbored alternate RTK fusions (NCOA4::RET, TRIM27::RET, and VIM::NTRK3), and 1 tumor was negative for RTK alterations. CDKN2A/B deletions were found in 2 tumors with ALK fusions and both tumors with RET fusions. SAMS is on a morphologic and molecular genetic spectrum with EFH, with a similar body site distribution, frequent clinical presentation as an exophytic skin tumor, and invariably benign outcomes; we conclude that SAMS should be considered a histologic variant of EFH. Some morphologically typical examples harbor alternate RET and NTRK3 fusions, such that SAMS is not an appropriate designation for this morphologic class; instead, to highlight the clinicopathologi","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142339492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expanding the Molecular Spectrum of Carcinoma Ex Pleomorphic Adenoma: An Analysis of 84 Cases With a Novel HMGA2::LINC02389 Fusion.","authors":"Reydson Alcides de Lima-Souza, Albina Altemani, Michal Michal, Fernanda Viviane Mariano, Ilmo Leivo, Alena Skálová","doi":"10.1097/PAS.0000000000002307","DOIUrl":"https://doi.org/10.1097/PAS.0000000000002307","url":null,"abstract":"<p><p>Carcinoma ex pleomorphic adenoma (CXPA) is an aggressive epithelial and/or myoepithelial neoplasm that arises in association with a pleomorphic adenoma (PA). Its etiopathogenesis remains poorly understood, but it is believed that the development of this tumor is due to the accumulation of genetic, protein, metabolic, and epigenetic alterations in a PA. A retrospective review of the Salivary Gland Tumor Registry in Pilsen yielded 84 CXPA, namely 25/84 salivary duct carcinoma (SDC), 15/84 myoepithelial carcinoma (MC), 1/84 epithelial-myoepithelial carcinoma (EMC), and 1/84 adenoid cystic carcinoma (AdCC). All 84 CXPA cases were analyzed by next-generation sequencing (NGS) and/or fluorescence in situ hybridization (FISH). Forty-three tumors originally diagnosed as CXPA (43/84, 51.2%) showed some molecular alteration. Fusion transcripts were identified in 12/16 (75%) CXPA, including LIFR::PLAG1, CTNNB1::PLAG1, FGFR1::PLAG1, and a novel fusion, HMGA2::LINC02389. Most of the fusions were confirmed by FISH using PLAG1 (6/11) and HMGA2 (1/1) gene break probes. Split signals indicating gene break were identified by FISH for PLAG1 (12/17), HMGA2 (3/4), EWSR1 (7/22), and MYB (2/7). Concerning pathogenic mutations, only CXPA with epithelial differentiation (SDC) presented these alterations, including HRAS mutation (2/4), TP53 (1/4), PTEN (1/4), and ATK1 (1/4). In addition, amplifications in ERBB2 (17/35), MDM2 (1/4), and EWSR1 (1/7) were detected. A novel finding was the discovery of an HMGA2::LINC02389 fusion in 1 patient with EMC ex-PA. The present results indicate that molecular profiling of CXPA with myoepithelial differentiation (MC) tends to reveal chromosomal fusion events, whereas CXPA with epithelial differentiation (SDC) tends to have a higher frequency of pathogenic mutations and gene amplifications.</p>","PeriodicalId":7772,"journal":{"name":"American Journal of Surgical Pathology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142339493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}