{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T16:39:05Z","timestamp":1789663145517,"version":"4.0.1"},"reference-count":71,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,6,19]],"date-time":"2025-06-19T00:00:00Z","timestamp":1750291200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"\u201cScience for Children\u201d foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>In children without Down syndrome who have acute megakaryoblastic leukemia (AMKL), inv(16)(p13q24)\/CBFA2T3::GLIS2 is the most frequent genetic aberration. Pediatric CBFA2T3::GLIS2-positive AMKL is strongly associated with a poor prognosis and a high cumulative incidence of relapse. One of the key laboratory signs of CBFA2T3::GLIS2-positive AMKL is the RAM immunophenotype, which looks very similar to that of solid-tumor bone marrow (BM) infiltration. For this reason, in cases of isolated extramedullary involvement of CBFA2T3::GLIS2-positive AMKL, excluding solid tumors may be challenging. We report a case of a girl with isolated extramedullary CBFA2T3::GLIS2-positive AMKL relapse, which was misdiagnosed as secondary Ewing sarcoma. The morphological differential diagnosis between Ewing sarcoma and AMKL presented significant challenges owing to their overlapping histological features (small, round blue-cell morphology and similar growth patterns). The tumor cells\u2019 immunophenotype completely mirrored that at the initial diagnosis of AMKL. Additional cytogenetic and molecular studies confirmed the presence of the CBFA2T3::GLIS2 fusion, but no Ewing sarcoma-specific EWSR1, FUS and CIC fusion transcripts were found. Thus, extramedullary CBFA2T3::GLIS2-positive AMKL relapse was confirmed. The presented case demonstrates the difficulties in differential diagnosis between AMKL relapse and the development of a secondary tumor.<\/jats:p>","DOI":"10.3390\/ijms26125895","type":"journal-article","created":{"date-parts":[[2025,6,19]],"date-time":"2025-06-19T08:43:58Z","timestamp":1750322638000},"page":"5895","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Extramedullary Relapse of CBFA2T3::GLIS2-Positive Megakaryoblastic Leukemia Mimicking Secondary Ewing Sarcoma: An Exemplary Case for the Diagnostic Trap"],"prefix":"10.3390","volume":"26","author":[{"given":"Svetlana","family":"Lebedeva","sequence":"first","affiliation":[{"name":"Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, 1, S. Mashela St., Moscow 117998, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3450-0498","authenticated-orcid":false,"given":"Ekaterina","family":"Mikhailova","sequence":"additional","affiliation":[{"name":"Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, 1, S. Mashela St., Moscow 117998, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-4500-5453","authenticated-orcid":false,"given":"Sophia","family":"Bogacheva","sequence":"additional","affiliation":[{"name":"Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, 1, S. Mashela St., Moscow 117998, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dmitry","family":"Abramov","sequence":"additional","affiliation":[{"name":"Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, 1, S. Mashela St., Moscow 117998, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svetlana","family":"Kashpor","sequence":"additional","affiliation":[{"name":"Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, 1, S. Mashela St., Moscow 117998, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Druy","sequence":"additional","affiliation":[{"name":"Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, 1, S. 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Mashela St., Moscow 117998, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0889-6986","authenticated-orcid":false,"given":"Alexander","family":"Popov","sequence":"additional","affiliation":[{"name":"Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, 1, S. Mashela St., Moscow 117998, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1038\/ng.3772","article-title":"Pediatric non-Down syndrome acute megakaryoblastic leukemia is characterized by distinct genomic subsets with varying outcomes","volume":"49","author":"Branstetter","year":"2017","journal-title":"Nat. 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