{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,13]],"date-time":"2026-09-13T17:26:17Z","timestamp":1789320377051,"version":"build-2803163510"},"reference-count":33,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T00:00:00Z","timestamp":1778112000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T00:00:00Z","timestamp":1778112000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Histopathology"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      Dedifferentiated liposarcoma (DDLPS) is a typically non\u2010lipogenic malignant neoplasm that arises from progression of an underlying atypical lipomatous tumour\/well\u2010differentiated liposarcoma (ALT\/WDLPS) and is classically defined by amplification of chromosome 12q15, including\n                      <jats:italic>MDM2<\/jats:italic>\n                      and frequently cyclin\u2010dependent kinase 4 (\n                      <jats:italic>CDK4<\/jats:italic>\n                      ). Detection of\n                      <jats:italic>MDM2<\/jats:italic>\n                      amplification by fluorescence in situ hybridization (FISH) and\/or MDM2 protein expression immunohistochemistry (IHC) has, therefore, become central to the diagnosis of DDLPS, particularly in small biopsies from the retroperitoneum. Rare exceptions to this paradigm have been described, but the clinicopathologic and molecular spectrum of\n                      <jats:italic>MDM2<\/jats:italic>\n                      non\u2010amplified DDLPS remains poorly characterized. We report a series of\n                      <jats:italic>MDM2<\/jats:italic>\n                      non\u2010amplified DDLPS to better define their diagnostic features, genomic alterations and clinical behaviour.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Pathology archives from 2010 to 2025 were queried for cases diagnosed as DDLPS. Inclusion criteria required a high\u2010grade sarcoma arising in a histologically confirmed ALT\/WDLPS background, absence of MDM2 overexpression by IHC and lack of\n                      <jats:italic>MDM2<\/jats:italic>\n                      amplification by FISH and\/or single nucleotide polymorphism array. Clinicopathologic features, immunophenotype, treatment and outcomes were reviewed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Among 253 cases of DDLPS identified during the study period, four (1.6%) fulfilled criteria for\n                      <jats:italic>MDM2<\/jats:italic>\n                      \u2010negative DDLPS. All tumours arose in the retroperitoneum or intra\u2010abdominal soft tissues and demonstrated high\u2010grade sarcoma morphology with an associated WDLPS component on resection. Despite the absence of\n                      <jats:italic>MDM2<\/jats:italic>\n                      amplification, all cases showed strong CDK4 expression by IHC. Molecular analysis revealed recurrent alterations involving cell\u2010cycle regulation, including\n                      <jats:italic>CDK4<\/jats:italic>\n                      copy number gain in all cases and loss of\n                      <jats:italic>CDKN2A<\/jats:italic>\n                      in three. Two cases harboured\n                      <jats:italic>TP53<\/jats:italic>\n                      alterations. Clinically, outcomes were heterogeneous, ranging from aggressive disease with rapid recurrence and death within months to prolonged disease\u2010free survival exceeding 5\u2009years.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      <jats:italic>MDM2<\/jats:italic>\n                      non\u2010amplified DDLPS represents a rare subset of DDLPS that appear to be driven by alternative mechanisms of cell\u2010cycle dysregulation, most commonly involving\n                      <jats:italic>CDK4<\/jats:italic>\n                      gain and\n                      <jats:italic>CDKN2A<\/jats:italic>\n                      loss, with occasional\n                      <jats:italic>TP53<\/jats:italic>\n                      alterations. Awareness of this variant is critical to avoid misclassification as other high\u2010grade sarcomas, particularly on limited biopsies, and underscores the importance of integrating morphology, IHC and broad genomic profiling in diagnostically challenging retroperitoneal sarcomas.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/his.70174","type":"journal-article","created":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T05:19:41Z","timestamp":1778217581000},"page":"347-356","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Clinicopathologic evaluation of dedifferentiated liposarcoma lacking\n                    <i>MDM2<\/i>\n                    amplification"],"prefix":"10.1111","volume":"89","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-3512-8635","authenticated-orcid":false,"given":"Charlotte I","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Pathology Massachusetts General Hospital and Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6242-5595","authenticated-orcid":false,"given":"Soma","family":"Jobbagy","sequence":"additional","affiliation":[{"name":"Department of Pathology Massachusetts General Hospital and Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9810-9095","authenticated-orcid":false,"given":"Anne B","family":"Giersch","sequence":"additional","affiliation":[{"name":"Department of Pathology Brigham and Women's Hospital and Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8968-9710","authenticated-orcid":false,"given":"Jonathan B","family":"Greer","sequence":"additional","affiliation":[{"name":"Department of Surgical Oncology Massachusetts General Hospital and Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2071-5137","authenticated-orcid":false,"given":"Kevin X","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology Massachusetts General Hospital and Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0181-886X","authenticated-orcid":false,"given":"Gregory M","family":"Cote","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Massachusetts General Hospital and Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8568-1591","authenticated-orcid":false,"given":"Yin P","family":"Hung","sequence":"additional","affiliation":[{"name":"Department of Pathology Massachusetts General Hospital and Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9671-7211","authenticated-orcid":false,"given":"G Petur","family":"Nielsen","sequence":"additional","affiliation":[{"name":"Department of Pathology Massachusetts General Hospital and Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6826-0226","authenticated-orcid":false,"given":"Ivan","family":"Chebib","sequence":"additional","affiliation":[{"name":"Department of Pathology Massachusetts General Hospital and Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,7]]},"reference":[{"key":"e_1_2_10_2_1","volume-title":"WHO classification of Tumours: Skin tumours","author":"WHO Classification of Tumours Editorial 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