A clinicopathologic and molecular reappraisal of myxoinflammatory fibroblastic sarcoma—A controversial and pathologically challenging low-grade sarcoma Journal Article
| Authors: | Hirose, T.; Chang, H. Y.; Saoud, C.; Lefkowitz, R. A.; Athanasian, E.; Antonescu, C. R. |
| Article 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. © 2025 Wiley Periodicals LLC. |
| Keywords: | adult; clinical article; controlled study; aged; middle aged; genetics; clinical feature; cancer recurrence; patient selection; disease free survival; follow up; cancer grading; neoplasm recurrence, local; gene amplification; cohort analysis; genetic association; transcription factor; pathology; oncology; carcinogenesis; transcription factors; sarcoma; oncogene; patient care; lung metastasis; fluorescence in situ hybridization; gene rearrangement; fibrosarcoma; tumor recurrence; gene fusion; transcription factor yap1; b raf kinase; braf; orthopedics; soft tissue neoplasms; soft tissue tumor; fibroblast growth factor receptor 1; fusion; braf gene; mgea5 gene; myxoinflammatory fibroblastic sarcoma; tgfbr3 gene; high throughput sequencing; cancer test; fgfr1 gene; very elderly; humans; human; male; female; article; tertiary care center; vgll3; vgll3 protein, human; maml2 gene; vgll3 gene; mgea; tgfbr3; ccnb3 gene; rragb gene; yap1 gene; zbtb47 gene |
| Journal Title: | Genes Chromosomes and Cancer |
| Volume: | 64 |
| Issue: | 1 |
| ISSN: | 1045-2257 |
| Publisher: | Wiley Periodicals, Inc |
| Date Published: | 2025-01-01 |
| Start Page: | e70018 |
| Language: | English |
| DOI: | 10.1002/gcc.70018 |
| PUBMED: | 39822017 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledge in the PDF -- Corresponding authors is MSK author: Cristina R. Antonescu -- Source: Scopus |
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