Human pathology最新文献

{"title":"PD-L1 expression and immune infiltration across molecular subtypes of endometrial cancer: An integrative-analysis of molecular classification and immune subtypes","authors":"Yanhui Zhang ,&nbsp;Baohui Ju ,&nbsp;Runfen Cheng ,&nbsp;Tingting Ding ,&nbsp;Jianghua Wu","doi":"10.1016/j.humpath.2024.105704","DOIUrl":"10.1016/j.humpath.2024.105704","url":null,"abstract":"<div><div>The immune subtypes of the tumor microenvironment in endometrial cancer (EC), associated with different molecular classifications, warrant further investigation to guide EC immunotherapy strategies. This study focused on programmed death-ligand 1 (PD-L1) expression (Clone SP263) and immune cell (IC) markers (CD3, CD8, CD68, CD20, CD21) in 110 EC cases. In this cohort, the molecular subtype distribution was: <em>POLE</em> mutation (POLEmut) 7.3% (8/110), mismatch repair-deficient (MMRd) 21.8% (24/110), p53 abnormal (p53abn) 14.5% (16/110), and non-specific molecular profile (NSMP) 56.4% (62/110). NSMP subtypes exhibited the lowest PD-L1+ cell densities and scores. POLEmut and MMRd subtypes showed higher IC densities, while p53abn and NSMP subtypes had lower IC densities and fewer tertiary lymphoid structures (TLS). Integrative analysis of immune subtypes with PD-L1 and CD8⁺ tumor infiltrating lymphocytes (TILs) revealed 62.5% of POLEmut and 45.8% of MMRd cases as TIME type Ⅰ (PD-L1⁺ &amp; CD8^high). Conversely, p53abn and NSMP cases were more heterogeneous, with 37.5% of p53abn cases in TIME type Ⅲ (PD-L1⁺ &amp; CD8^low) and 41.9% of NSMP cases in TIME type Ⅱ (PD-L1^- &amp; CD8^low). Higher CD8⁺ T cell density was a prognostic marker for disease-free survival in EC, including within NSMP (<em>p</em> &lt; 0.05). In summary, the four WHO molecular subtypes of EC exhibit distinct TIME subtypes, complementing molecular classification and providing insights for optimizing EC immunotherapy strategies.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"154 ","pages":"Article 105704"},"PeriodicalIF":2.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142812903","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":"BRAF V600E gene mutation is present in primary intraosseous Rosai-Dorfman disease","authors":"Lokman Cevik,&nbsp;Swati Satturwar,&nbsp;Dan Jones,&nbsp;Joel Mayerson,&nbsp;Steve Oghumu,&nbsp;O. Hans Iwenofu","doi":"10.1016/j.humpath.2024.105702","DOIUrl":"10.1016/j.humpath.2024.105702","url":null,"abstract":"","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"154 ","pages":"Article 105702"},"PeriodicalIF":2.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142817917","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":"Genetic alteration analysis of non-pediatric diffuse midline glioma, H3 K27-altered","authors":"Hanbin Jang ,&nbsp;Seyoung Moon ,&nbsp;Hyun Jung Kwon ,&nbsp;Sejoon Lee ,&nbsp;Gheeyoung Choe ,&nbsp;Kyu Sang Lee","doi":"10.1016/j.humpath.2024.105709","DOIUrl":"10.1016/j.humpath.2024.105709","url":null,"abstract":"<div><div>Diffuse midline gliomas with H3 K27-alteration (DMGH3) are lethal and inoperable brain tumors. Although DMGH3s mainly occur in pediatric patients, they have also occurred in adult patients. This study aimed to analyze the clinicopathological significance of targetable genetic alterations in non-pediatric DMGH3. Next-generation sequencing (NGS) was conducted on 18 non-pediatric DMGH3 patients to analyze additional genetic alterations. The median age at diagnosis was 35 years, and the mean follow-up duration was 762 days. Fourteen cases involved the thalamus-hypothalamus (77.8%). Histologic high-grade features (WHO histologic grade ≥ 3) were observed in 11 (61.1%) patients. <em>H3F3A</em> (H3 K27 M) alterations were identified in all 18 patients using immunohistochemistry and NGS. <em>TP53</em> mutations were found in 11 patients (61.1%), <em>FGFR1</em> or <em>PIK3CA</em> in 3 (16.7%), <em>ATRX</em> in 6 (33.3%), <em>NF1</em> in 4 (22.2%), and <em>KRAS</em> or <em>ATM</em> in 1 (5.6%). <em>TP53</em> mutations were significantly correlated with high-grade histological features and worse overall survival (OS) (P &lt; 0.05). Despite non-pediatric DMGH3 cases exhibiting superior OS compared to pediatric DMGH3 cases, <em>TP53</em> mutations were associated with poorer OS outcomes. Notably, <em>FGFR1</em> and <em>PIK3CA</em> mutations, which have been identified as potential targetable genes, were detected. In conclusion, non-pediatric DMGH3s showed predominant tumor localization within the thalamus and improved prognosis compared to those in pediatric cases, with <em>TP53</em> alterations correlating with high-grade histology and shorter survival. Genetic profiling, particularly identifying targetable mutations like <em>FGFR1</em> and <em>PIK3CA</em>, could inform personalized treatment strategies and improve patient outcomes.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"154 ","pages":"Article 105709"},"PeriodicalIF":2.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142864110","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 findings in a cohort of metastases to the stomach","authors":"Trevor Toussieng ,&nbsp;Brent K. Larson ,&nbsp;Miguel Burch ,&nbsp;Alexandra Gangi ,&nbsp;Jun Gong ,&nbsp;Maha Guindi ,&nbsp;Michael Kozak ,&nbsp;Keith Lai ,&nbsp;Danielle A. Hutchings ,&nbsp;Kevin M. Waters","doi":"10.1016/j.humpath.2024.105694","DOIUrl":"10.1016/j.humpath.2024.105694","url":null,"abstract":"<div><h3>Aims</h3><div>Metastatic tumors to the stomach can mimic primary gastric adenocarcinoma or be subtle and difficult to identify. The current study aimed to characterize the clinicopathology of metastases to the stomach to aid in diagnosis.</div></div><div><h3>Methods and results</h3><div>Forty-three metastatic tumors and 30 primary gastric adenocarcinoma cases were reviewed. Metastases originated from numerous primaries with the most common being mammary (n = 17) or melanoma (n = 9). The gastric metastasis represented the initial diagnosis for 9 (21%) cases without previous history of malignancy. The median age at diagnosis was similar (metastatic 66 years; primary 67.5 years; <em>P</em> = 0.42). The most common indication for procedure was abdominal pain (23%; <em>P</em> = 0.95) in metastases and melena (43%; <em>P</em> &lt; 0.01) in primaries. Procedural findings suggestive of metastasis over primary adenocarcinoma were multiple lesions (23% versus 0%; <em>P</em> = 0.01), non-mass forming mucosal changes (30% versus 0%; <em>P</em> &lt; 0.01), submucosal nodularity (14% versus 0%; <em>P</em> = 0.09), and absence of ulceration (9% versus 53%; <em>P</em> &lt; 0.01). Histologic findings less commonly seen in metastasis were mucosal layer involvement (86% versus 100%; <em>P</em> = 0.09), ulceration (40% versus 70%; <em>P</em> = 0.02), surface epithelial involvement/colonization by tumor (12% versus 60%; <em>P</em> &lt; 0.01), intestinal metaplasia (9% versus 53%; <em>P</em> &lt; 0.01), background dysplasia (0% versus 30%; <em>P</em> &lt; 0.01), and <em>Helicobacter pylori</em> infection (0% versus 20%; <em>P</em> &lt; 0.01). Lymphovascular invasion had similar prevalence (metastatic 23%; primary 20%; <em>P</em> = 0.70).</div></div><div><h3>Conclusions</h3><div>Metastasis to the stomach included a variety of primary sites and was not infrequently the initial diagnosis. Patient demographics were similar to primary adenocarcinoma. Multiple lesions, non-mass forming mucosal changes, and/or submucosal nodularity were more common in metastasis. Histologically, the absence of surface epithelial involvement, ulceration, intestinal metaplasia, background dysplasia, or <em>H. pylori</em> infection can raise suspicion for metastasis.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"154 ","pages":"Article 105694"},"PeriodicalIF":2.7,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142695479","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":"Genetic validation of a TSC2 immunohistochemistry assay in TSC/mTOR-pathway altered renal tumors","authors":"Amir Akbari ,&nbsp;Clarence Rachel Villanueva ,&nbsp;Ondrej Hes ,&nbsp;Sean R. Williamson ,&nbsp;Shivani Kandukuri ,&nbsp;Shivani Sharma ,&nbsp;Aggarwal Aditi ,&nbsp;Kristyna Pivovarcikova ,&nbsp;Pedram Argani ,&nbsp;Sambit K. Mohanty ,&nbsp;Kaushal Asrani ,&nbsp;Tamara L. Lotan","doi":"10.1016/j.humpath.2024.105693","DOIUrl":"10.1016/j.humpath.2024.105693","url":null,"abstract":"<div><div>Pathogenic mutations in the genes associated with tuberous sclerosis complex (TSC)/mTOR pathway are linked to histologically diverse renal cell neoplasms, including eosinophilic solid and cystic renal cell carcinoma (ESC RCC), low grade oncocytic tumor (LOT), eosinophilic vacuolated tumor (EVT), and xanthomatous giant cell renal cell carcinoma (XGC RCC). Here, we validate a TSC2 immunohistochemistry (IHC) assay by comparison to genomic data in these neoplasms. Automated TSC2 IHC was performed on formalin-fixed paraffin embedded (FFPE) tissues from 38 genetically-confirmed TSC/mTOR-associated renal tumors (6 ESCs, 16 EVTs, 13 LOTs, 2 XGC and 1 clear cell RCC) and visually scored in a semi-dichotomous fashion compared to internal control tissue. The positive predictive value (PPV) of TSC2 protein loss for underlying pathogenic mutation in <em>TSC2</em> was 92% (11/12), while the negative predictive value (NPV) of intact TSC2 by IHC for lack of underlying pathogenic mutation in <em>TSC2</em> was 81% (21/26). Intact TSC2 by IHC was 95% (21/22) specific for absence of underlying pathogenic <em>TSC2</em> mutation. All the cases lacking <em>TSC2</em> mutation with intact TSC2 protein had an underlying mutation in <em>TSC1</em>, <em>MTOR</em> or <em>PIK3CA</em>. Loss of TSC2 was 77% (10/13) sensitive for underlying <em>TSC2</em> truncation mutations and 33% (1/3) sensitive for underlying <em>TSC2</em> missense mutations. Overall, 73% (8/11) tumors with TSC2 IHC loss and underlying pathogenic alterations in <em>TSC2</em> showed heterogeneous protein loss, with rare interspersed positively staining tumor cells. These data support TSC2 IHC as a potentially useful assay for the diagnostic workup of renal tumors suspected to belong to the TSC/mTOR-associated subgroups.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"154 ","pages":"Article 105693"},"PeriodicalIF":2.7,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142686825","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":"Validation of Keratin 17 as a tissue biomarker in the diagnosis of upper tract urothelial carcinoma","authors":"Woodson Smelser ,&nbsp;Nam Kim ,&nbsp;Sholeh Jahanfard ,&nbsp;Mark Sarno ,&nbsp;Sam S. Chang ,&nbsp;Giovanna A. Giannico","doi":"10.1016/j.humpath.2024.105682","DOIUrl":"10.1016/j.humpath.2024.105682","url":null,"abstract":"<div><div>Upper tract urothelial carcinoma (UTUC) has a relatively low incidence but presents significant surveillance and treatment challenges. Therefore, novel biomarkers for the accurate detection of upper tract urothelial tumors are urgently needed. We evaluated the expression of Keratin 17 (KRT17), an oncoprotein implicated in the cell cycle progression of multiple human cancers and previously studied in bladder urothelial carcinoma, by immunohistochemistry in 139 UTUC cases, including noninvasive, invasive papillary urothelial carcinoma and urothelial carcinoma in situ. KRT17 expression pattern (basal/negative vs. nonbasal) and H-score were evaluated. The expression pattern was significantly different in normal (NL) compared to malignant urothelium. Nonbasal KRT17 expression was significantly higher in pTa (p &lt; 0.001) and invasive (pTinv) (p = 0.0023) urothelial carcinoma compared to NL, and in pTinv compared to pTa (p = 0.0391). Sensitivity and specificity for distinguishing benign from malignant tumors were 85% and 82, respectively, with an area under the curve of 0.83 (p &lt; 0.001). The KRT17 H-score was significantly higher in pTa and pTinv compared to NL (p &lt; 0.001 and p = 0.0035, respectively). Sensitivity and specificity for distinguishing benign from malignant carcinoma were 91% and 69%, respectively, with an AUC of 0.81 (p = 0.0010). KRT17 was not associated with tumor site, grade, or stage.</div><div>In summary, K17 is a sensitive and specific marker of neoplastic upper tract urothelium, and its potential use in routine diagnostics should be explored in larger studies.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"154 ","pages":"Article 105682"},"PeriodicalIF":2.7,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142644102","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":"Metastatic renal cell carcinoma with fibromyomatous stroma associated with tuberous sclerosis or MTOR, TSC1/TSC2-Mutations: A Series of 4 cases and a review of the literature","authors":"Sounak Gupta ,&nbsp;Michael R. McCarthy ,&nbsp;Melissa Y. Tjota ,&nbsp;Tatjana Antic ,&nbsp;John C. Cheville","doi":"10.1016/j.humpath.2024.105680","DOIUrl":"10.1016/j.humpath.2024.105680","url":null,"abstract":"<div><div>Renal cell carcinoma with fibromyomatous stroma (RCCfms) are characterized by a constellation of morphologic findings that include elongated tubules lined by cells with clear to pale eosinophilic cytoplasm and intersecting bands of smooth muscle stroma. Consistent immunohistochemistry findings in RCCfms include diffuse positivity for carbonic anhydrase 9 and variable expression of keratin 7. Molecular profiling of such tumors show either pathogenic alterations of the <em>ELOC</em> (<em>TCEB1</em>) gene, or alterations of <em>MTOR</em>, <em>TSC1</em>, and <em>TSC2</em>. <em>MTOR</em>, <em>TSC1</em>/<em>TSC2</em>-altered RCCfms (M/TSC-RCCfms) has been reported both in the sporadic setting and in association with tuberous sclerosis complex (TSC). The importance of accurate diagnosis of M/TSC-RCCfms includes prompting germline testing in the appropriate clinical context. In addition, it can lead to patient management strategies that are focused on the preservation of renal function, as TSC patients often have multifocal and bilateral disease. As diagnostic criteria for M/TSC-RCCfms have only been recently established, additional data are needed to understand the natural history of this disease. Herein, we report 6 patients with metastatic M/TSC-RCCfms, including four patients from our institutional archives (four males, aged 36–58 years at nephrectomy), and two additional cases reported in the literature. Five patients had TSC, and the sixth had an <em>MTOR</em>-altered RCCfms. The majority of patients (5/6, 83%) presented with regional lymph node involvement and one patient developed metastases to the lung. All patients were alive at last follow up (median follow-up of 85 months). Our report is intended to raise awareness regarding rare instances of metastatic behavior for M/TSC-RCCfms.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"153 ","pages":"Article 105680"},"PeriodicalIF":2.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142619274","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":"SALL4 expression is very rare in endometrial endometrioid and serous carcinoma","authors":"Meline Brouard,&nbsp;Mousa Mobarki,&nbsp;Michel Péoc'h,&nbsp;Georgia Karpathiou","doi":"10.1016/j.humpath.2024.105675","DOIUrl":"10.1016/j.humpath.2024.105675","url":null,"abstract":"","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"153 ","pages":"Article 105675"},"PeriodicalIF":2.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142499407","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":"Multinucleated tumor cells and micropapillary morphology appear to be predictors of poor prognosis in renal cell carcinoma with papillary and oncocytic features","authors":"Ting Zhao,&nbsp;Thomas Denize,&nbsp;Hanzhang Wang,&nbsp;Adam S. Fisch,&nbsp;Shulin Wu,&nbsp;Chin-Lee Wu,&nbsp;Kristine M. Cornejo","doi":"10.1016/j.humpath.2024.105677","DOIUrl":"10.1016/j.humpath.2024.105677","url":null,"abstract":"<div><div>Renal cell carcinoma with papillary and oncocytic features (RCC-PO) are poorly understood, partially due to conflicting results in multiple studies. The histological features that predict behavior of RCC-PO have not been elucidated. The aim is to review clinicopathologic features and to correlate clinical outcomes of patients with RCC-PO to further expand our knowledge on these heterogeneous tumors. An archival search was done for “RCC” and “papillary,” and tumors with &gt;50% papillary and oncocytic features were included. Clinicopathologic data including tumor size, grade, stage, molecular and immunohistochemical testing when performed, and follow-up data were collected. Using multivariate analyses, correlation between histological features, tumor stage and prognosis were analyzed. Sixty-one patients with RCC-PO were identified of which 49 (80%) were male with a median age of 65 (range: 36–93) years, and a mean tumor size of 5.2 (range: 1–21.5) cm. Micropapillary features were seen in 4, bizarre nuclei (at least 3 times larger or with irregular shape) in 6, multinucleated tumor cells (MTC) in 15, single or small clusters (SSC) (made of 2–3 tumor cells) located away from areas of necrosis in 16, and striking eosinophilic cytoplasmic inclusions in 3 tumors, respectively. Thirty-six (59%) tumors were high-grade (WHO/ISUP grade 3–4), and 23 (38%) had a high stage (≥pT3 or pN1). Tumors were positive for AMACR (15/16) and CK7 (13/17), with preserved FH (7/7) staining and were all negative for CD117 (0/7), ALK, TFE3, cathepsin K, Melan A, and HMB45 (0/4, each). Three tumors underwent chromosomal microarray (CMA) plus gene fusion assay, and FISH and germline testing for <em>FLCN</em> and <em>MET</em> gene alterations by PCR were done on 1 each. Ten (16%) patients had a local recurrence (LR) or metastasis after nephrectomy; 4 died of disease (2 had tumors with micropapillary features), with a median follow-up of 7 (range: 0.01–19) years. Tumors with micropapillary features showed significantly higher RCC-PO-related mortality (50% vs. 3.5%, p &lt; 0.001). In multivariable analysis, SSC correlated with a higher stage (HR: 11.95; p = 0.005); micropapillary features (HR: 18.42; p = 0.017) and MTC (HR: 180.22; p = 0.036) with presence of metastasis/LR; and micropapillary features with a higher RCC-PO-related mortality (HR: 60.35; p = 0.036). RCC-PO are cytogenetically heterogeneous with overlapping features of various renal neoplasms. Micropapillary features and MTC appear to be independent predictors of poor outcomes in these tumors.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"153 ","pages":"Article 105677"},"PeriodicalIF":2.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567881","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":"Clinically aggressive follicular cell-derived thyroid carcinoma: A comprehensive series with histomolecular characterization and discovery of novel gene fusions","authors":"Ziyad Alsugair ,&nbsp;Francoise Descotes ,&nbsp;Jonathan Lopez ,&nbsp;Hélène Lasolle ,&nbsp;Françoise Borson Chazot ,&nbsp;Jean-Christophe Lifante ,&nbsp;Myriam Decaussin-Petrucci","doi":"10.1016/j.humpath.2024.105674","DOIUrl":"10.1016/j.humpath.2024.105674","url":null,"abstract":"<div><div>Thyroid cancer rates are increasing, mostly with a good prognosis and less than 2 % of cases are more aggressive. Recent efforts focus on understanding molecular events predicting tumor aggressiveness and treatment targets in advanced thyroid cancer. This study concerned 57 patients with aggressive metastatic, and/or radioiodine-refractory thyroid carcinomas, excluding anaplastic cases. Molecular profiling, including next-generation sequencing and RNA sequencing, was conducted to dissect the complex molecular landscape of these aggressive tumors. Histopathological analysis indicated that papillary carcinomas and high-grade thyroid carcinomas were predominant. The molecular analysis revealed a spectrum of mutations, with prevalent occurrences of BRAF V600E, TERT promoter, and RAS mutations. RNA sequencing identified ten gene fusions, such as <em>NTRK</em> and <em>RET</em> fusions. Three novel fusions were discovered: <em>UGGT1::TERT</em>, <em>BTBD9::TERT</em>, and <em>TG::IGF1R</em>, potentially driving aggressive behavior. <em>UGGT1::TERT</em> was linked to radioiodine-refractory tall cell PTC, <em>BTBD9::TERT</em> to high-grade follicular PTC, and <em>TG::IGF1R</em> to oncocytic carcinoma. These findings underscore the importance of <em>TERT</em> alterations in aggressive phenotypes and offer insights into molecular mechanisms guiding targeted therapies. Further research is necessary to confirm their significance as diagnostic and prognostic markers in thyroid cancer.</div></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":"153 ","pages":"Article 105674"},"PeriodicalIF":2.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142552121","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}