A Subset of FOXO1-Fusion Negative Rhabdomyosarcoma With Round Cell (Alveolar) and "Burkitt-Like" Morphology Is Associated With High Amplification of MYCL: A Report From the Children's Oncology Group.
AI interpretation is pending for this paper.
Open original publication →What the AI sees
Not AI summarized yet.
Research significance
Pending deeper interpretation.
Source abstract
OBJECTIVE: Alveolar rhabdomyosarcoma (ARMS) is a distinct histologic subtype of rhabdomyosarcoma, associated with the presence of a PAX3 or PAX7::FOXO1 gene fusion in approximately 80% of cases. Adverse outcomes for patients with ARMS are associated with the presence of a FOXO1 gene fusion; however, additional genetic markers are necessary to better characterize FOXO1-fusion negative ARMS. METHODS: We reviewed the histology of 306 diagnostic biopsies from participants enrolled in the recent Children's Oncology Group (COG) trial ARST1431. Ultra-low pass whole genome sequencing and custom panel sequencing were performed on all diagnostic biopsies with available material. RESULTS: Histologic review of diagnostic specimens from ARST1431 identified two cases with predominantly ARMS histology (small round cells with uniform, round nuclei) that were distinctive compared to other cases with ARMS histology due to the presence of: (a) distinctive large nucleoli with coarse chromatin, (b) amphophilic cytoplasm, (c) abundant karyorrhexis, and (d) admixed tingible body macrophages-all strongly resembling the histologic features of Burkitt lymphoma. Each case showed diffuse myogenin reactivity and lacked evidence of a FOXO1 gene rearrangement by FISH and expanded molecular testing. Tumor sites included the perianal region (2-year-old male) and upper extremity (1-year-old female). Sequencing studies identified high amplification (> 50 copies) of the MYCL proto-oncogene in both cases. Retrospective analysis of the amplification data available for ARST1431 identified one additional case in a 15-year-old male with high amplification of MYCL and similar histologic features that were more difficult to identify in a limited biopsy sample. The two former patients experienced recurrence and died of disease, while the third patient was alive without recurrence. CONCLUSIONS: We hypothesize that the distinctive histologic phenotype of these three cases is driven by high-level MYCL amplification (> 50 copies). With an incidence of 1.6% in this series, these unique histologic features may be useful to further identify and characterize FOXO1-fusion negative ARMS. Review of additional cases will be required to determine the clinical significance of this unique histologic pattern with MYCL amplification.