{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T05:00:09Z","timestamp":1785214809309,"version":"3.55.0"},"reference-count":57,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T00:00:00Z","timestamp":1785196800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:p>\n                    Malignant phyllodes tumor (MPT) is a rare breast neoplasm with high recurrence rates and potential for heterologous sarcomatous differentiation. Malignant peripheral nerve sheath tumor (MPNST)-like differentiation in MPT is exceptionally rare and presents considerable diagnostic and therapeutic challenges. We report a case of a 24-year-old female with recurrent MPT exhibiting MPNST-like differentiation and integrated immunophenotypic and genomic characterization. The patient initially presented in November 2023 with a 3.8\u00a0cm right breast MPT treated by wide local excision. Five months later, ultrasound revealed local recurrence (5.8\u00a0cm), prompting right mastectomy in April 2024. Sixteen months after mastectomy, a 1\u00a0cm right chest wall nodule was identified and completely excised. Pathological examination revealed a high-grade spindle cell malignant neoplasm with MPNST-like morphology, brisk mitotic activity (&amp;gt;10 mitoses\/10 HPF), and a Ki-67 index of 80\u201390%. Immunohistochemistry demonstrated focal S100 positivity, partial SOX10 expression, complete loss of H3K27me3, and absent RB1 protein expression, with cytoplasmic \u03b2-catenin positivity supporting phyllodes stromal lineage. A structured differential diagnosis excluded metaplastic spindle cell carcinoma, monophasic synovial sarcoma, fibromatosis\/desmoid-type fibromatosis, myofibroblastic sarcoma, undifferentiated pleomorphic sarcoma, and primary\n                    <jats:italic>de novo<\/jats:italic>\n                    MPNST. Paired tumor\u2013normal whole-exome sequencing of the recurrent lesion identified a\n                    <jats:italic>TP53<\/jats:italic>\n                    truncating mutation (p.R342*) and an\n                    <jats:italic>RB1<\/jats:italic>\n                    frameshift mutation (p.S127Vfs*9), the latter concordant with RB1 protein loss by immunohistochemistry. The tumor was microsatellite stable and tumor mutational burden-low, with no reportable copy-number alterations, gene rearrangements or fusions, clinically significant germline variants, or reportable\n                    <jats:italic>SUZ12\/EED<\/jats:italic>\n                    alterations. These findings support molecular characterization of the recurrent lesion but do not establish clonal continuity with prior tumors or a definitive PRC2-driven mechanism. This case highlights the diagnostic value of integrating serial morphology, immunohistochemistry, and genomic profiling in recurrent MPT with rare MPNST-like differentiation. The combined findings of H3K27me3 and RB1 immunophenotypic loss,\n                    <jats:italic>TP53<\/jats:italic>\n                    truncation, and\n                    <jats:italic>RB1<\/jats:italic>\n                    frameshift mutation raise the possibility that chromatin-associated and cell-cycle alterations may contribute to neural crest-like heterologous differentiation, although this hypothesis requires further validation.\n                  <\/jats:p>","DOI":"10.3389\/fonc.2026.1802541","type":"journal-article","created":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T04:26:00Z","timestamp":1785212760000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Case Report: Recurrent malignant phyllodes tumor with malignant peripheral nerve sheath tumor-like differentiation and loss of H3K27me3\/RB1 expression"],"prefix":"10.3389","volume":"16","author":[{"given":"Meiqi","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Breast Surgery and Oncology, the Second Affiliated Hospital, Zhejiang University School of Medicine","place":["Hangzhou, China"]},{"name":"The Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, the Second Affiliated Hospital, Zhejiang University School of Medicine","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaonan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Hangzhou Linping District Integrated Traditional Chinese and Western Medicine Hospital","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jili","family":"Qiu","sequence":"additional","affiliation":[{"name":"Department of Breast Surgery and Oncology, the Second Affiliated Hospital, Zhejiang University School of Medicine","place":["Hangzhou, China"]},{"name":"The Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, the Second Affiliated Hospital, Zhejiang University School of Medicine","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingjie","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pathology, the Second Affiliated Hospital, Zhejiang University School of Medicine","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"51","DOI":"10.4048\/jbc.2024.0284","article-title":"Recent advances in Malignant phyllodes tumors of the breast","volume":"28","author":"Lee","year":"2025","journal-title":"J Breast Cancer"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.breast.2025.104491","article-title":"Phyllodes tumors 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