Sarcomas with RAD51B fusions are associated with a heterogeneous phenotype

• Verfasst von: Chang, Hsin-Yi [VerfasserIn]
• Verfasst von: Dermawan, Josephine [VerfasserIn]
• Verfasst von: Sharma, Aarti [VerfasserIn]
• Verfasst von: Dickson, Brendan [VerfasserIn]
• Verfasst von: Turashvili, Gulisa [VerfasserIn]
• Verfasst von: Torrence, Dianne [VerfasserIn]
• Verfasst von: Nucci, Marisa [VerfasserIn]
• Verfasst von: Chiang, Sarah [VerfasserIn]
• Verfasst von: Oliva, Esther [VerfasserIn]
• Verfasst von: Kirchner, Martina [VerfasserIn]
• Verfasst von: Stenzinger, Albrecht [VerfasserIn]
• Verfasst von: Mechtersheimer, Gunhild [VerfasserIn]
• Verfasst von: Antonescu, Cristina [VerfasserIn]
• Titel: Sarcomas with RAD51B fusions are associated with a heterogeneous phenotype
• Verf.angabe: Hsin-Yi Chang, Josephine Dermawan, Aarti Sharma, Brendan Dickson, Gulisa Turashvili, Dianne Torrence, Marisa Nucci, Sarah Chiang, Esther Oliva, Martina Kirchner, Albrecht Stenzinger, Gunhild Mechtersheimer, Cristina Antonescu
• E-Jahr: 2024
• Jahr: February 2024
• Umfang: 11 S.
• Illustrationen: Illustrationen
• Fussnoten: Online verfügbar: 21. Dezember 2023, Artikelversion: 4. Januar 2024 ; Gesehen am 25.06.2024
• Titel Quelle: Enthalten in: Modern pathology
• Ort Quelle: London : Nature Publishing Group, 1988
• Jahr Quelle: 2024
• Band/Heft Quelle: 37(2024), 2 vom: Feb., Artikel-ID 100402, Seite 1-11
• ISSN Quelle: 1530-0285
• DOI: doi:10.1016/j.modpat.2023.100402
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: fusion
• Sach-SW: leiomyosarcoma
• Sach-SW: PEComa
• Sach-SW: RAD51B
• Sach-SW: uterus
• K10plus-PPN: 1892169460

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.