{"doi":"10.1002/gcc.70018","title":"A Clinicopathologic and Molecular Reappraisal of Myxoinflammatory Fibroblastic Sarcoma—A Controversial and Pathologically Challenging Low‐Grade Sarcoma","abstract":"PURPOSE: Myxoinflammatory fibroblastic sarcoma (MIFS) is a rare, low-grade sarcoma affecting with predilection the acral soft tissues of middle-aged adults. Clinically, MIFS is associated with a high rate of local recurrence but infrequent distant metastases. The diagnosis remains challenging due to their wide histologic spectrum and overlap with reactive, benign, and low-grade malignant lesions. Moreover, a significant limitation is that molecular confirmation is achieved in only a subset of cases, due to its broad range of genetic alterations which requires a multiplatform approach. Thus, a definitive diagnosis, especially at nonacral sites and in molecularly negative cases, remains uncertain. Our goal was to perform a detailed clinicopathologic and molecular reappraisal of MIFS managed at a single tertiary cancer center with dedicated orthopedic oncology expertise. Additionally, we examined potential outcomes correlating with specific genetic alterations. PATIENTS AND METHODS: A cohort of 33 patients (12 males, 21 females, median age 52 years) was selected. Tumors were tested by FISH, Archer, and/or targeted NGS. RESULTS: VGLL3 amplification was detected in 84%, BRAF fusions in 33% and combined TGFBR3/MGEA5 rearrangements in 32% of cases. Two novel fusions were detected, RRAGB::CCNB3 and FGFR1::ZBTB47. Other events included a YAP1::MAML2 fusion in two cases, one co-existing with a BRAF fusion. Overall, 8 (24%) patients recurred, 4 more than once, while 4 (12%) patients developed metastasis (3 locoregional, 1 pulmonary), all associated with VGLL3 gene amplification. CONCLUSION: Positive margin status was associated with increased recurrence and reduced disease-free survival (DFS, p = 0.02). Moreover, it emphasizes the impact of multiplatform molecular testing in confirming the diagnosis. The lack of both local recurrence and metastatic potential outside VGLL3 amplifications requires further investigation.","journal":"Genes Chromosomes and Cancer","year":2025,"id":530943,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9661,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1410864,"name":"Hsin‐Yi Chang","orcid":"0000-0002-2742-0676","position":1,"is_corresponding":false},{"id":884523,"name":"Carla Saoud","orcid":"0000-0002-4540-6990","position":2,"is_corresponding":false},{"id":889489,"name":"Robert A. Lefkowitz","orcid":"0000-0003-3884-9643","position":3,"is_corresponding":false},{"id":485212,"name":"Edward A. Athanasian","orcid":"0000-0003-1526-5506","position":4,"is_corresponding":false},{"id":35289,"name":"Cristina R. Antonescu","orcid":"0000-0002-9717-8205","position":5,"is_corresponding":false},{"id":1410863,"name":"Takeshi Hirose","orcid":"0000-0003-1588-9757","position":0,"is_corresponding":true}],"reference_count":19,"raw_metadata":null,"created_at":"2026-07-19T02:51:10.077559Z","pmid":"39822017","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}