Intraosseous Spindle Cell/Epithelioid Rhabdomyosarcoma with TFCP2 Rearrangement: A Recent Recognized Subtype with Partial Response to Alectinib

Abstract

Rhabdomyosarcoma affects mainly pediatric patients and is currently classified into four categories: embryonal, alveolar, pleomorphic, and spindle cell/sclerosing. Recently, a molecular group of spindle cell/sclerosing rhabdomyosarcoma demonstrated new fusion transcripts involving FET-family genes with TFCP2. In this report, we describe a rare case of spindle cell/sclerosing rhabdomyosarcoma in a 19-year-old woman, presenting as a destructive lesion involving the condyle of mandible. Next generation sequencing was performed, revealing a FUS::TFCP2 fusion and deletion of ALK gene. Alectinib therapy was initiated, which resulted in a favorable response for 4 months. However, the patient died due progression of the tumor. To make an accurate diagnosis and ensure appropriate patient management, it is necessary to be aware of this variant and use proper immunohistochemical stains when facing malignant mesenchymal bone lesions, expanding its differential diagnosis.

Spindle cell rhabdomyosarcomas: With TFCP2 rearrangements, and novel EWSR1::ZBTB41 and PLOD2::RBM6 gene fusions. A study of five cases and review of the literature

“…Anecdotal cases have been reported in which the combination of ALK inhibitors and radiotherapy resulted in disease stabilization. 29,36 This therapeutical option appears to be effective in primary TFCP2rearranged RMS where ALK gene alteration has been identified. However, recurrences or metastases of these tumours usually lacked any ALK-gene alterations.…”

“…However, recurrences or metastases of these tumours usually lacked any ALK-gene alterations. 15,26,29,33,36,39,41 Six patients were treated with a combination of CHT and/or RT and biological treatment (without surgery), in particular ALK inhibitors (including alectinib, crizotinib, and/or lorlatinib) or vascular endothelial growth factor inhibitors (pazopanib). These were used either alone or in combination in six and three cases, respectively.…”

“…Except for two patients who are alive with the disease, all others progressed despite treatment and died of the disease. 39 Thirteen TFCP2-rearranged SS-RMS harboured homozygous deletion of CDKN2A or CDKN2B (n = 12) or had amplification of CDKN2A and CDKN2B genes (n = 1), 14,15,36,[38][39][40] but none showed concurrent inactivation of TP53, associated with a worse outcome in other RMS types, mainly in pleomorphic RMS. 51 CDKN2A/B genes might be another potential target, but none of the cases reported in the literature were treated by CDK4/6 inhibitors that could be efficient drugs in tumours with a high CDK4 level.…”

“…Twenty-three articles reporting 66 cases of TFCP2rearranged SS-RMS (our three cases included) were found in the English literature. [13][14][15]19,[25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40] There were 39 female and 25 male patients (the gender was unknown in two cases). The average age at The tumours were composed of admixture of different cell phenotypes including spindle, epithelioid, and round cells.…”

“…Deletion of the ALK gene was found in 11 cases and two cases carried ALK gene amplification by RNA sequencing. [13][14][15]41 Thirteen cases harboured homozygous deletion of CDKN2A/B, 14,15,36,[38][39][40] including one case with chromothripsis of 1p and 3p chromosomes 14 case with concurrent loss of NF2 and MTAP genes. 38 One case carried amplification of the CDKN2A/B gene.…”