Case report: EWSR1-TFCP2 in an adolescent represents an extremely rare and aggressive form of intraosseous spindle cell rhabdomyosarcomas

Abstract

The WHO Classification of Tumors of Soft Tissue and Bone subdivides rhabdomyosarcomas (RMS) into alveolar, embryonal, pleomorphic, and spindle cell RMS. Advances in molecular genetic diagnostics have made it possible to identify new RMS subgroups within traditional morphological entities. One of these subgroups comprises rare tumors characterized by epithelioid and spindle cell morphology, highly aggressive clinical course with pronounced tendency to intraosseous growth, and the presence of pathognomonic recurring genetic aberrations- chimeric genes/transcripts EWSR1::TFCP2, FUS::TFCP2, or MEIS1::NCOA2. Starting from 2018, only 26 reported cases of RMS have been assigned to this subgroup. The rarity of such tumors hampers their correct diagnostics for both anatomic pathologists and molecular oncologists. Here we describe a clinical case of intraosseous spindle cell RMS expressing EWSR1::TFCP2 fusion gene, encountered for the first time in our practice, in a 16-year-old female patient presenting with mandibular lesion. The diagnostic process took considerable time and involved RNA sequencing; a high-throughput method of molecular genetic research. The tumor was extremely aggressive, showing resistance to polychemotherapy, radiation therapy, and crizotinib targeted therapy, with the fatal outcome.

Clinicopathological features of rhabdomyosarcoma with novel FET::TFCP2 and TIMP3::ALK fusion: report of two cases and literature review

“…(2018) 2 . A total of 43 cases of this molecular subtype have been reported to date 2–17 . This tumour is characterised by an onset age ranging from 11 to 86 years (average age = 30 years).…”

TFCP2‐rearranged epithelioid and spindle cell rhabdomyosarcoma in the bladder: A rare case in an 8‐year‐old female child

“…[2][3][4][5][6][7][8][9][10][11][12][13][14] Tumor sites include bones (n = 34) especially craniofacial bones, chest wall (n = 1), peritoneum (n = 1), neck (n = 1), inguinal soft tissue (n = 1), and bladder (n = 1). [2][3][4][5][6][7][8][9][10][11][12][13][14] The clinical characteristics of the 12 pediatric cases include an evident female predilection (10 females and two males); all patients were older than 10 years except ours with an average age of 15 years at diagnosis; primary sites were craniofacial bones (n = 10), femur (n = 1), and bladder (n = 1); all the tumors but one with available tumor size information extended 5 cm in maximum diameter with an average of 6.0 cm. 2,8,[12][13][14] Histologically, most tumors displayed a mixed spindle cell and epithelioid pattern with vesicular nuclei, high mitotic activity, and tumor necrosis.…”

“…[2][3][4][5][6][7][8][9][10][11][12][13][14] The clinical characteristics of the 12 pediatric cases include an evident female predilection (10 females and two males); all patients were older than 10 years except ours with an average age of 15 years at diagnosis; primary sites were craniofacial bones (n = 10), femur (n = 1), and bladder (n = 1); all the tumors but one with available tumor size information extended 5 cm in maximum diameter with an average of 6.0 cm. 2,8,[12][13][14] Histologically, most tumors displayed a mixed spindle cell and epithelioid pattern with vesicular nuclei, high mitotic activity, and tumor necrosis. Histopathology usually had an immunoprofile such as desmin, myogenin, MyoD1, cytokeratin, and ALK expression.…”

“…TFCP2 rearrangement is useful for the diagnosis, with partner genes FUS(24/39, 61.5%)and EWSR1(15/39, 38.5%). [2][3][4][5][6][7][8][9][10][11][12][13][14] However, EWSR1 was involved in four of five extraskeletal tumors. An internal deletion of the ALK gene leading to ALK upregulation and ALK overexpression was frequently observed and gave a clue for ALKtargeted therapy.…”

“…9 For the nine pediatric cases with specific outcome data, six died of disease with overall survivals of 8, 11, months. 8,[12][13][14] In summary, we present the first reported case of TFCP2rearranged epithelioid and spindle cell RMS in the bladder and also the youngest patient for this tumor. For some refractory RMS, genetic tests may indicate a targeted therapy which may be beneficial for such patients and improve their prognoses.…”