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Sarcomas With RAD51B Fusions Are Associated With a Heterogeneous Phenotype.

Hsin-Yi Chang1, Josephine Dermawan2, Aarti Sharma3

  • 1Department of Pathology and Laboratory Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.

Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc
|December 23, 2023
PubMed
Summary
This summary is machine-generated.

RAD51B-rearranged sarcomas are rare uterine and extrauterine tumors. These aggressive neoplasms present with diverse morphologies and fusion partners, often leading to poor clinical outcomes.

Keywords:
PEComaRAD51Bfusionleiomyosarcomauterus

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Area of Science:

  • Oncology
  • Pathology
  • Genetics

Background:

  • RAD51B-rearranged sarcomas are rare neoplasms with heterogeneous morphology.
  • Previously reported cases exclusively involved the uterus, including perivascular epithelioid cell tumors (PEComas) and leiomyosarcomas (LMS).

Purpose of the Study:

  • To describe the morphologic, immunohistochemical, and molecular features of additional sarcomas with RAD51B rearrangement.
  • To include the first reported extrauterine example of such sarcomas.

Main Methods:

  • Morphologic and immunohistochemical analysis of 8 additional sarcomas.
  • Molecular analysis including targeted RNA sequencing and fluorescence in situ hybridization (FISH) for RAD51B rearrangements.
  • Targeted DNA sequencing for TSC gene alterations.

Main Results:

  • Eight additional sarcomas with RAD51B rearrangement were identified, including one extrauterine case.
  • Tumors exhibited diverse morphologies (spindle cell, epithelioid, undifferentiated) and high-grade cytologic atypia with high mitotic activity.
  • Immunohistochemistry showed features consistent with PEComa or LMS, or a nonspecific profile.
  • RNA sequencing identified various fusion partners (HMGA2, PDDC1, CEP170); FISH confirmed RAD51B rearrangements.
  • Clinical outcomes revealed aggressive behavior with recurrences, metastases, and deaths.

Conclusions:

  • RAD51B fusions define a spectrum of sarcomas with variable presentations, morphologies, and fusion partners.
  • These tumors predominantly occur in the uterus but can be extrauterine.
  • They present as LMS, PEComa, or undifferentiated phenotypes and are associated with an aggressive clinical course.