{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T08:25:41Z","timestamp":1786955141679,"version":"build-2736575974"},"reference-count":44,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"9","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:p>\n                    Mismatch repair-deficient (dMMR) sarcomas are rare and incompletely characterized. Here, we studied 39 sarcomas with high microsatellite instability (MSI-H) and\/or biallelic MMR gene inactivation (21\n                    <jats:italic toggle=\"yes\">MSH2<\/jats:italic>\n                    , 9\n                    <jats:italic toggle=\"yes\">MLH1<\/jats:italic>\n                    , 4\n                    <jats:italic toggle=\"yes\">PMS2<\/jats:italic>\n                    , 4\n                    <jats:italic toggle=\"yes\">MSH6<\/jats:italic>\n                    , 1\n                    <jats:italic toggle=\"yes\">EPCAM<\/jats:italic>\n                    ). All tumors evaluated with immunohistochemistry (IHC; n = 36) showed loss of MMR protein expression. Eight sarcomas were index neoplasms among the 15 patients with documented Lynch syndrome. Eighteen of 1531 sarcomas (1.2%) in our sequencing database were dMMR, with enrichment in pleomorphic rhabdomyosarcoma (PRMS; 1\/5), uterine leiomyosarcoma (LMS; 7\/124; 5.6%), and unclassified\/undifferentiated pleomorphic sarcoma (UPS; 6\/259; 2.3%). MMR IHC screening of independent cases confirmed MMR deficiency in PRMS (2\/20), uterine LMS (2\/20), and unclassified\/UPS (1\/20). Two histologic patterns were identified among unclassified\/UPS. Ten tumors, designated \u201cdistinctive lobulated inflammatory sarcoma\u201d (DLIS), showed lobular architecture, florid inflammation, and histiocytoid, variably pleomorphic neoplastic cells. All 6 patients with DLIS and follow-up (median: 6.0 y; range: 3 mo to 8.6\u00a0y) were alive with no evidence of disease (ANED), and 2 DLIS responded completely to immune checkpoint inhibition. A morphologically different group of 6 unclassified high-grade sarcomas showed sheets of epithelioid-to-rhabdoid cells with eosinophilic cytoplasm; among 5 patients with follow-up (median: 1.1\u00a0y; range: 4 mo to 6.9\u00a0y), only 1 was ANED. Surprisingly, all 3 PRMS patients with follow-up (median: 5.7 y; range: 4.2 to 8.3\u00a0y) were ANED, including 2 with complete responses of metastases to systemic therapy. We conclude that PRMS, uterine LMS, and unclassified\/UPS showed sufficiently prevalent MMR deficiency to justify prospective MMR IHC screening for Lynch syndrome and to identify patients who might benefit from immune checkpoint inhibition. Histologic subtyping of unclassified sarcomas predicted prognosis and therapeutic response. We propose universal MMR IHC screening of (1) PRMS, (2) uterine LMS, (3) unclassified\/UPS, and (4) any sarcoma in a patient with a personal or family history of Lynch syndrome.\n                  <\/jats:p>","DOI":"10.1097\/pas.0000000000002579","type":"journal-article","created":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T07:00:37Z","timestamp":1781247637000},"page":"1029-1045","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":0,"title":["Clinicopathologic Study of 39 Mismatch Repair-deficient Sarcomas Demonstrates Recurrent Histologic Patterns and Supports Universal Screening of Pleomorphic Rhabdomyosarcoma, Uterine Leiomyosarcoma, and Undifferentiated and Unclassified Sarcomas"],"prefix":"10.1097","volume":"50","author":[{"given":"Igor","family":"Odintsov","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of California San Francisco, San Francisco, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan A.","family":"Nowak","sequence":"additional","affiliation":[{"name":"Department of Pathology, Brigham and Women\u2019s Hospital, and Harvard Medical School"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther","family":"Baranov","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania School of Medicine, Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thierry","family":"Alcindor","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Candace L.","family":"Haddox","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vinayak","family":"Venkataraman","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lynette M.","family":"Sholl","sequence":"additional","affiliation":[{"name":"Department of Pathology, Brigham and Women\u2019s Hospital, and Harvard Medical School"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzanne","family":"George","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leona A.","family":"Doyle","sequence":"additional","affiliation":[{"name":"Department of Pathology, St. Vincent\u2019s University Hospital and University College Dublin, Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Redston","sequence":"additional","affiliation":[{"name":"Department of Pathology, Brigham and Women\u2019s Hospital, and Harvard Medical School"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7746-3546","authenticated-orcid":false,"given":"David J.","family":"Papke","sequence":"additional","affiliation":[{"name":"Department of Pathology, Brigham and Women\u2019s Hospital, and Harvard Medical School"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2026,6,12]]},"reference":[{"key":"R1-20260817","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1038\/s41436-019-0596-9","article-title":"Cancer risks by gene, age, and gender in 6350 carriers of pathogenic mismatch repair variants: findings from the Prospective Lynch Syndrome 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