The KAT6B::KANSL1 Fusion Defines a New Uterine Sarcoma With Hybrid Endometrial Stromal Tumor and Smooth Muscle Tumor Features
Neoplasms harboring a KAT6B/A::KANSL1 fusion were initially reported as benign (leiomyomas) and malignant (leiomyosarcomas, low-grade endometrial stromal sarcomas [LG-ESSs]) uterine neoplasms. However, they may represent an emerging entity characterized by clinical aggressiveness contrasting with a...
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description | Neoplasms harboring a KAT6B/A::KANSL1 fusion were initially reported as benign (leiomyomas) and malignant (leiomyosarcomas, low-grade endometrial stromal sarcomas [LG-ESSs]) uterine neoplasms. However, they may represent an emerging entity characterized by clinical aggressiveness contrasting with a rather reassuring microscopic appearance. Here, we aimed to confirm that this neoplasm is a distinct clinicopathologic and molecular sarcoma and identify criteria that should alert pathologists and lead to KAT6B/A::KANSL1 fusion testing in routine practice. Therefore, we conducted a comprehensive clinical, histopathologic, immunohistochemical, and molecular study, including array comparative genomic hybridization, whole RNA-sequencing, unsupervised clustering, and cDNA mutational profile analyses of 16 tumors with KAT6B::KANSL1 fusion from 12 patients. At presentation, patients were peri-menopausal (median, 47.5 years), and the primary tumors were located in the uterine corpus (12/12, 100%), with an additional prevesical location in 1 (8.3%) of 12 cases. The relapse rate was 33.3% (3/9). All tumors (16/16, 100%) showed morphologic and immunohistochemical features overlapping between leiomyoma and endometrial stromal tumors. A whirling recurrent architecture (resembling fibromyxoid-ESS/fibrosarcoma) was found in 13 (81.3%) of 16 tumors. All tumors (16/16, 100%) exhibited numerous arterioliform vessels, and 13 (81.3%) of 18 had large hyalinized central vessels and collagen deposits. Estrogen and progesterone receptors were expressed in 16 (100%) of 16 and 14 (87.5%) of 16 tumors, respectively. Array comparative genomic hybridization performed on 10 tumors classified these neoplasms as simple genomic sarcomas. Whole RNA-sequencing on 16 samples and clustering analysis on primary tumors found that the KAT6B::KANSL1 fusion always occurred between exons 3 of KAT6B and 11 of KANSL1; no pathogenic variant was identified on cDNA, all neoplasms clustered together, close to LG-ESS, and pathway enrichment analysis showed cell proliferation and immune infiltrate recruitment pathway involvement. These results confirm that the sarcomas harboring a KAT6B/A::KANSL1 fusion represent a distinct clinicopathologic entity, close to LG-ESS but different, with clinical aggressiveness despite a reassuring morphology, for which the KAT6B/A::KANSL1 fusion is the molecular driver alteration. |
doi_str_mv | 10.1016/j.modpat.2023.100243 |
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However, they may represent an emerging entity characterized by clinical aggressiveness contrasting with a rather reassuring microscopic appearance. Here, we aimed to confirm that this neoplasm is a distinct clinicopathologic and molecular sarcoma and identify criteria that should alert pathologists and lead to KAT6B/A::KANSL1 fusion testing in routine practice. Therefore, we conducted a comprehensive clinical, histopathologic, immunohistochemical, and molecular study, including array comparative genomic hybridization, whole RNA-sequencing, unsupervised clustering, and cDNA mutational profile analyses of 16 tumors with KAT6B::KANSL1 fusion from 12 patients. At presentation, patients were peri-menopausal (median, 47.5 years), and the primary tumors were located in the uterine corpus (12/12, 100%), with an additional prevesical location in 1 (8.3%) of 12 cases. The relapse rate was 33.3% (3/9). All tumors (16/16, 100%) showed morphologic and immunohistochemical features overlapping between leiomyoma and endometrial stromal tumors. A whirling recurrent architecture (resembling fibromyxoid-ESS/fibrosarcoma) was found in 13 (81.3%) of 16 tumors. All tumors (16/16, 100%) exhibited numerous arterioliform vessels, and 13 (81.3%) of 18 had large hyalinized central vessels and collagen deposits. Estrogen and progesterone receptors were expressed in 16 (100%) of 16 and 14 (87.5%) of 16 tumors, respectively. Array comparative genomic hybridization performed on 10 tumors classified these neoplasms as simple genomic sarcomas. Whole RNA-sequencing on 16 samples and clustering analysis on primary tumors found that the KAT6B::KANSL1 fusion always occurred between exons 3 of KAT6B and 11 of KANSL1; no pathogenic variant was identified on cDNA, all neoplasms clustered together, close to LG-ESS, and pathway enrichment analysis showed cell proliferation and immune infiltrate recruitment pathway involvement. These results confirm that the sarcomas harboring a KAT6B/A::KANSL1 fusion represent a distinct clinicopathologic entity, close to LG-ESS but different, with clinical aggressiveness despite a reassuring morphology, for which the KAT6B/A::KANSL1 fusion is the molecular driver alteration.</description><identifier>ISSN: 0893-3952</identifier><identifier>EISSN: 1530-0285</identifier><identifier>DOI: 10.1016/j.modpat.2023.100243</identifier><identifier>PMID: 37307879</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>endometrial stromal sarcoma ; KAT6B::KANSL1 fusion ; leiomyoma ; leiomyosarcoma ; RNA-sequencing ; uterine mesenchymal neoplasms</subject><ispartof>Modern pathology, 2023-10, Vol.36 (10), p.100243-100243, Article 100243</ispartof><rights>2023</rights><rights>Copyright © 2023. Published by Elsevier Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c362t-2b745551d0acc6dbf803f6e31472a93cfdc223b5f5c29b7a643025be049df84e3</citedby><cites>FETCH-LOGICAL-c362t-2b745551d0acc6dbf803f6e31472a93cfdc223b5f5c29b7a643025be049df84e3</cites><orcidid>0000-0002-6487-5418 ; 0000-0002-1674-1888</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925,64387</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37307879$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Trecourt, Alexis</creatorcontrib><creatorcontrib>Azmani, Rihab</creatorcontrib><creatorcontrib>Hostein, Isabelle</creatorcontrib><creatorcontrib>Blanchard, Larry</creatorcontrib><creatorcontrib>Le Loarer, François</creatorcontrib><creatorcontrib>Bourdon, Aurelien</creatorcontrib><creatorcontrib>Alame, Melissa</creatorcontrib><creatorcontrib>Nadaud, Béatrice</creatorcontrib><creatorcontrib>Mayer, Laetitia</creatorcontrib><creatorcontrib>Rebier, Flora</creatorcontrib><creatorcontrib>Larmonier, Claire</creatorcontrib><creatorcontrib>Moura, Madalena Souto</creatorcontrib><creatorcontrib>Soubeyran, Isabelle</creatorcontrib><creatorcontrib>Hartog, Cécile</creatorcontrib><creatorcontrib>Ray-Coquard, Isabelle</creatorcontrib><creatorcontrib>Treilleux, Isabelle</creatorcontrib><creatorcontrib>Devouassoux-Shisheboran, Mojgan</creatorcontrib><creatorcontrib>Croce, Sabrina</creatorcontrib><title>The KAT6B::KANSL1 Fusion Defines a New Uterine Sarcoma With Hybrid Endometrial Stromal Tumor and Smooth Muscle Tumor Features</title><title>Modern pathology</title><addtitle>Mod Pathol</addtitle><description>Neoplasms harboring a KAT6B/A::KANSL1 fusion were initially reported as benign (leiomyomas) and malignant (leiomyosarcomas, low-grade endometrial stromal sarcomas [LG-ESSs]) uterine neoplasms. However, they may represent an emerging entity characterized by clinical aggressiveness contrasting with a rather reassuring microscopic appearance. Here, we aimed to confirm that this neoplasm is a distinct clinicopathologic and molecular sarcoma and identify criteria that should alert pathologists and lead to KAT6B/A::KANSL1 fusion testing in routine practice. Therefore, we conducted a comprehensive clinical, histopathologic, immunohistochemical, and molecular study, including array comparative genomic hybridization, whole RNA-sequencing, unsupervised clustering, and cDNA mutational profile analyses of 16 tumors with KAT6B::KANSL1 fusion from 12 patients. At presentation, patients were peri-menopausal (median, 47.5 years), and the primary tumors were located in the uterine corpus (12/12, 100%), with an additional prevesical location in 1 (8.3%) of 12 cases. The relapse rate was 33.3% (3/9). All tumors (16/16, 100%) showed morphologic and immunohistochemical features overlapping between leiomyoma and endometrial stromal tumors. A whirling recurrent architecture (resembling fibromyxoid-ESS/fibrosarcoma) was found in 13 (81.3%) of 16 tumors. All tumors (16/16, 100%) exhibited numerous arterioliform vessels, and 13 (81.3%) of 18 had large hyalinized central vessels and collagen deposits. Estrogen and progesterone receptors were expressed in 16 (100%) of 16 and 14 (87.5%) of 16 tumors, respectively. Array comparative genomic hybridization performed on 10 tumors classified these neoplasms as simple genomic sarcomas. Whole RNA-sequencing on 16 samples and clustering analysis on primary tumors found that the KAT6B::KANSL1 fusion always occurred between exons 3 of KAT6B and 11 of KANSL1; no pathogenic variant was identified on cDNA, all neoplasms clustered together, close to LG-ESS, and pathway enrichment analysis showed cell proliferation and immune infiltrate recruitment pathway involvement. These results confirm that the sarcomas harboring a KAT6B/A::KANSL1 fusion represent a distinct clinicopathologic entity, close to LG-ESS but different, with clinical aggressiveness despite a reassuring morphology, for which the KAT6B/A::KANSL1 fusion is the molecular driver alteration.</description><subject>endometrial stromal sarcoma</subject><subject>KAT6B::KANSL1 fusion</subject><subject>leiomyoma</subject><subject>leiomyosarcoma</subject><subject>RNA-sequencing</subject><subject>uterine mesenchymal neoplasms</subject><issn>0893-3952</issn><issn>1530-0285</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><recordid>eNp9kEtv1DAQgC1ERZeWf4CQj1yyjF959IC0lC5F3ZbDbsXRcuyJ6lUSb-0E1AP_nVRZOPY0mplvZjQfIe8ZLBmw_NN-2QV3MMOSAxdTCbgUr8iCKQEZ8FK9JgsoK5GJSvFT8jalPQCTquRvyKkoBBRlUS3In90D0pvVLv9ycXGzuttuGF2PyYeefsXG95iooXf4m94PGKeUbk20oTP0px8e6PVTHb2jV70LHQ7Rm5Zuhzi1W7obuxCp6R3ddiFM7O2YbIvH-hrNMEZM5-SkMW3Cd8d4Ru7XV7vL62zz49v3y9UmsyLnQ8brQiqlmANjbe7qpgTR5CiYLLiphG2c5VzUqlGWV3VhcimAqxpBVq4pJYoz8nHee4jhccQ06M4ni21regxj0rzkSgHkEiZUzqiNIaWIjT5E35n4pBnoZ_F6r2fx-lm8nsVPYx-OF8a6Q_d_6J_pCfg8Azj9-ctj1Ml67C06H9EO2gX_8oW_X7yVMA</recordid><startdate>20231001</startdate><enddate>20231001</enddate><creator>Trecourt, Alexis</creator><creator>Azmani, Rihab</creator><creator>Hostein, Isabelle</creator><creator>Blanchard, Larry</creator><creator>Le Loarer, François</creator><creator>Bourdon, Aurelien</creator><creator>Alame, Melissa</creator><creator>Nadaud, Béatrice</creator><creator>Mayer, Laetitia</creator><creator>Rebier, Flora</creator><creator>Larmonier, Claire</creator><creator>Moura, Madalena Souto</creator><creator>Soubeyran, Isabelle</creator><creator>Hartog, Cécile</creator><creator>Ray-Coquard, Isabelle</creator><creator>Treilleux, Isabelle</creator><creator>Devouassoux-Shisheboran, Mojgan</creator><creator>Croce, Sabrina</creator><general>Elsevier Inc</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-6487-5418</orcidid><orcidid>https://orcid.org/0000-0002-1674-1888</orcidid></search><sort><creationdate>20231001</creationdate><title>The KAT6B::KANSL1 Fusion Defines a New Uterine Sarcoma With Hybrid Endometrial Stromal Tumor and Smooth Muscle Tumor Features</title><author>Trecourt, Alexis ; 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However, they may represent an emerging entity characterized by clinical aggressiveness contrasting with a rather reassuring microscopic appearance. Here, we aimed to confirm that this neoplasm is a distinct clinicopathologic and molecular sarcoma and identify criteria that should alert pathologists and lead to KAT6B/A::KANSL1 fusion testing in routine practice. Therefore, we conducted a comprehensive clinical, histopathologic, immunohistochemical, and molecular study, including array comparative genomic hybridization, whole RNA-sequencing, unsupervised clustering, and cDNA mutational profile analyses of 16 tumors with KAT6B::KANSL1 fusion from 12 patients. At presentation, patients were peri-menopausal (median, 47.5 years), and the primary tumors were located in the uterine corpus (12/12, 100%), with an additional prevesical location in 1 (8.3%) of 12 cases. The relapse rate was 33.3% (3/9). All tumors (16/16, 100%) showed morphologic and immunohistochemical features overlapping between leiomyoma and endometrial stromal tumors. A whirling recurrent architecture (resembling fibromyxoid-ESS/fibrosarcoma) was found in 13 (81.3%) of 16 tumors. All tumors (16/16, 100%) exhibited numerous arterioliform vessels, and 13 (81.3%) of 18 had large hyalinized central vessels and collagen deposits. Estrogen and progesterone receptors were expressed in 16 (100%) of 16 and 14 (87.5%) of 16 tumors, respectively. Array comparative genomic hybridization performed on 10 tumors classified these neoplasms as simple genomic sarcomas. Whole RNA-sequencing on 16 samples and clustering analysis on primary tumors found that the KAT6B::KANSL1 fusion always occurred between exons 3 of KAT6B and 11 of KANSL1; no pathogenic variant was identified on cDNA, all neoplasms clustered together, close to LG-ESS, and pathway enrichment analysis showed cell proliferation and immune infiltrate recruitment pathway involvement. These results confirm that the sarcomas harboring a KAT6B/A::KANSL1 fusion represent a distinct clinicopathologic entity, close to LG-ESS but different, with clinical aggressiveness despite a reassuring morphology, for which the KAT6B/A::KANSL1 fusion is the molecular driver alteration.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>37307879</pmid><doi>10.1016/j.modpat.2023.100243</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0002-6487-5418</orcidid><orcidid>https://orcid.org/0000-0002-1674-1888</orcidid></addata></record> |
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subjects | endometrial stromal sarcoma KAT6B::KANSL1 fusion leiomyoma leiomyosarcoma RNA-sequencing uterine mesenchymal neoplasms |
title | The KAT6B::KANSL1 Fusion Defines a New Uterine Sarcoma With Hybrid Endometrial Stromal Tumor and Smooth Muscle Tumor Features |
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