Sarcomas with RAD51B fusions are associated with a heterogeneous phenotype Journal Article
| Authors: | Chang, H. Y.; Dermawan, J.; Sharma, A.; Dickson, B.; Turashvili, G.; Torrence, D.; Nucci, M.; Chiang, S.; Oliva, E.; Kirchner, M.; Stenzinger, A.; Mechtersheimer, G.; Antonescu, C. |
| Article Title: | Sarcomas with RAD51B fusions are associated with a heterogeneous phenotype |
| Abstract: | RAD51B-rearranged sarcomas are rare neoplasms that exhibit a heterogeneous morphology. To date, 6 cases have been reported, all involving the uterus, including 4 perivascular epithelioid cell tumors (PEComas) and 2 leiomyosarcomas (LMS). In this study, we describe the morphologic, immunohistochemical, and molecular features of 8 additional sarcomas with RAD51B rearrangement, including the first extrauterine example. All patients were women with a median age of 57 years at presentation. Seven tumors originated in the uterus, and one in the lower extremity soft tissue, with a median tumor size of 12 cm. Histologically, 4 tumors showed predominantly spindle cell morphology with eosinophilic fibrillary cytoplasm, with or without nuclear pleomorphism, whereas 2 tumors exhibited pleomorphic epithelioid cells, featuring clear to eosinophilic, granular cytoplasm. Two neoplasms exhibited undifferentiated cytomorphology, including one with uniform small blue round cells. All tumors showed high-grade cytologic atypia and high mitotic activity (median: 30/10 high-power fields), whereas coagulative necrosis was noted in 6 cases and lymphovascular invasion in 2. By immunohistochemistry, 2 showed myoid and melanocytic markers in keeping with PEComa, whereas 4 cases were only positive for smooth muscle markers consistent with LMS (including 3 myxoid). The remaining 2 cases had a nonspecific immunoprofile. Five cases tested by targeted RNA sequencing (Archer FusionPlex, Illumina TruSight) showed different fusion partners (HMGA2, PDDC1, and CEP170). RAD51B rearrangements were identified by FISH in the remaining 3 cases. Targeted DNA sequencing in 2 cases was negative for TSC gene alterations. Clinical outcome, available in 5 patients (median follow-up, 19 months), revealed 3 local recurrences, 2 lung metastases, and 4 deaths due to disease. Our results expand the spectrum of sarcomas with RAD51B fusions, demonstrating variable clinical presentations, morphologic spectrum, and fusion partners. These tumors have a predilection for a uterine location, with either LMS, PEComa, or undifferentiated phenotypes, and are associated with an aggressive clinical course. © 2023 United States & Canadian Academy of Pathology |
| Keywords: | immunohistochemistry; adult; clinical article; controlled study; human tissue; aged; middle aged; unclassified drug; mutation; disease course; clinical practice; phenotype; cell structure; sarcoma; lung metastasis; fluorescence in situ hybridization; gene fusion; soft tissue sarcoma; spindle cell; leiomyosarcoma; loss of function mutation; uterus; smooth muscle; regulator protein; fusion; pecoma; perivascular epithelioid cell tumor; clinical outcome; coagulative necrosis; lymph vessel metastasis; very elderly; dna sequencing; human; female; article; rna sequencing; rad51b; lower limb; epithelioid histiocyte; rad51b protein |
| Journal Title: | Modern Pathology |
| Volume: | 37 |
| Issue: | 2 |
| ISSN: | 0893-3952 |
| Publisher: | Nature Research |
| Date Published: | 2024-02-01 |
| Start Page: | 100402 |
| Language: | English |
| DOI: | 10.1016/j.modpat.2023.100402 |
| PUBMED: | 38141829 |
| PROVIDER: | scopus |
| PMCID: | PMC11251009 |
| DOI/URL: | |
| Notes: | Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PDF -- MSK corresponding author is Christina Antonescu -- Source: Scopus |
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