Spindle cell sarcoma with KIAA1549‑BRAF resembling infantile fibrosarcoma morphologically: A case report and literature review

Abstract

Infantile fibrosarcoma (IFS) commonly harbors ETS variant transcription factor 6 (ETV6)-neurotrophic receptor tyrosine kinase 3 (NTRK3) fusion. However, the recent accessibility to clinical next-generation sequencing (NGS) has revealed ETV6-NTRK3 negative spindle cell sarcomas resembling IFS morphologically, involving NTRK1/2, MET, RET and BRAF. The present report describes a pediatric case of spindle cell sarcoma with KIAA1549-BRAF resembling IFS morphologically. A 20-month-old female patient was referred to Kobe Children's Hospital (Kobe, Japan) for the treatment of intrathoracic spindle cell sarcoma. Pathologically, the intrathoracic tumor cells were composed of spindle cells with focal hemagiopericytomatous pattern. In immunohistochemistry analysis, the intrathoracic tumor cells focally expressed desmin and WT-1 and were negative for pan-tropomyosin receptor kinase (TRK), S-100 and CD34. Fluorescence in situ hybridization analysis for ETV6 and capicua transcriptional repressor revealed negative split signals. Although the patient was initially diagnosed with IFS morphologically, KIAA1549-BRAF fusion transcript was detected by comprehensive genomic profiling with NGS using intrathoracic tumor tissues and confirmed by reverse transcription-PCR. Chemotherapy induced a reduction in the tumor size. At present, the patient is alive with the disease and has been receiving therapy for 8 months since the initiation of chemotherapy. Review of BRAF-altered spindle cell sarcomas resembling IFS morphologically revealed the inconsistency in immunohistochemical expression patterns and the diversity of BRAF fusion genes and mutations. Therefore, the elucidation of genomic profiling by NGS may assist in making an appropriate diagnosis and selecting novel alternative therapies in ETV6-NTRK3-negative spindle cell sarcomas resembling IFS morphologically.

KIAA1549-BRAF Gene Fusion Spindle Cell Sarcoma With Infantile Fibrosarcoma-Like Pattern in a Pediatric Patient: A Case Report

“…Immunohistochemically, the previous cases of spindle cell sarcomas with KIAA1549-BRAF alteration have reported focal expression of Desmin while other markers such as Pan-cytokeratin (AE1/AE3), SMA, Myogenin, CD34, and S100 were all negative [9,10]. Patchy expression of SMA was observed in our case, while other immunostains were negative.…”

“…Clinically, unlike IFS which commonly involves the extremities, BRAF-rearranged sarcomas commonly arise in axial location and have been reported in older children, adolescents, and adults [3,5,7,12]. Our patient with KIAA1549-BRAF spindle cell sarcoma presented with thigh mass which was found in two patients according to previous reports [9,10]. Indeed, only one patient with KIAA1549-BRAF translocation sarcoma in the previous study had evidence of neurofibromatosis type 2, at the time of presentation [10].…”

“…We as well as Fujikawa et al and Nagy et al have observed that pediatric KIAA1549-BRAF rearranged sarcoma is usually a localized tumor with indolent biological behavior and generally treated with initial tumor resection and/or chemotherapy [9,10]. There have been no published reports of this tumor metastasizing to other organs or spreading to the lymph nodes, which points to a favorable outcome.…”

“…Penning et al reported the first case of pediatric spindle cell sarcoma with KIAA1549-BRAF gene fusion in 2021 [8]. Recently, two cases of pediatric spindle cell sarcoma with KIAA1549-BRAF gene rearrangement resembling IFS morphologically were described [9,10]. To our knowledge, this is the fourth case to be reported of spindle cell sarcoma with KIAA1549-BRAF gene fusion in a female child.…”