A case of primary CNS embryonal rhabdomyosarcoma with PAX3-NCOA2 fusion and systematic meta-review

Abstract

Purpose: Primary central nervous system (CNS) rhabdomyosarcomais a rare mesenchymal tumor predominantly seen in children and associated with a poor outcome. We report a case of primary CNS rhabdomyosarcoma with PAX3-NCOA2 fusion and presenta systematic meta-review of primary CNS rhabdomyosarcoma to characterize this rare tumor. Methods: We present the case of a 6-year-old boy with primary CNS rhabdomyosarcoma in the posterior fossa. In a systematic meta-review, we compare the demographic data of primary CNS rhabdomyosarcoma with data of rhabdomyosarcoma at all sites from the SEER database and analyze clinical factors associated with survival outcome.Results: Our patient underwent gross total resectionand receivedvincristine, actinomycin-D, cyclophosphamide with early introduction of concurrent focal radiation and remained alive with no evidence of disease for 2 years after the end of therapy. Histopathological review revealed embryonaltype rhabdomyosarcoma, and whole-transcriptome analysis revealed PAX3 (EX6)-NCOA2 (EX12) fusion. In all, 77 cases of primary CNS rhabdomyosarcoma were identi ed through the meta-review. The demographic data of primary CNS rhabdomyosarcoma were similar to dataof rhabdomyosarcoma at all sites. Overall and event-free survival outcomes were available for 64 and 56 patients, respectively, with a 3-year OS of 29.5%and a 3-year EFS of 26.2%. The group that received trimodal treatment exhibited better survival outcomes, with a 3-year OS of 57.4%and a 3-year EFS of 46.3%.Conclusions: Primary CNS rhabdomyosarcoma shares common histological, molecular, and demographic features with non-CNS rhabdomyosarcoma. A trimodal treatment approach with early introduction of radiation therapy may result in favorable survival outcomes.

ZFP64::NCOA3 gene fusion defines a novel subset of spindle cell rhabdomyosarcoma

“…For example, fusions involving NCOA1 or NCOA2, with multiple potential partner genes, are regularly identified in either infantile or skeletal variants of spindle cell rhabdomyosarcomas. 3,6,15,16 However, to date, there have been no…”

“…Many of these events are extremely rare and found on the order of case reports; however, some genes have a recurring presence in this category. For example, fusions involving NCOA1 or NCOA2 , with multiple potential partner genes, are regularly identified in either infantile or skeletal variants of spindle cell rhabdomyosarcomas 3,6,15,16 . However, to date, there have been no prior reports of this tumor type harboring NCOA3 rearrangement.…”

Myxoid epithelioid smooth muscle tumor of the vulva: A distinct entity with MEF2D::NCOA2 gene fusion

“…In the gynecologic tract, NCOA2 fusions have been reported in the following: ESR1::NCOA2 in uterine tumors resembling ovarian sex cord tumors (UTROSCT) 12,13 and adenosarcoma 14 ; GREB1::NCOA2 in UTROSCT 12 and undifferentiated uterine sarcoma 15 ; and MEIS1::NCOA2 in spindle cell sarcomas [16][17][18] and adenosarcoma. 19 Other NCOA2 fusions in mesenchymal neoplasms include AHRR::NCOA2 and GTF2::NCOA2 in soft tissue angiofibromas 20,21 ; SRF:: NCOA2, TEAD1::NCOA2, and VGLL2::NCOA2 in congenital/infantile spindle cell rhabdomyosarcomas 22,23 ; MEIS1::NCOA2 in intraosseous rhabdomyosarcoma 24 ; PAX3::NCOA2 in primary CNS rhabdomyosarcoma 25 and biphenotypic sinonasal sarcoma 26 ; and HEY1::NCOA2 in mesenchymal chondrosarcoma. 27 A C11orf95::NCOA2 fusion has also been reported in an ependymoma-like tumor.…”