Clinico-Pathological and Clinical Outcomes of Soft Tissue Sarcoma With FUS-TFCP2 or EWSR1-TFCP2 Fusions - A Case Series From North India

Sep 29, 2026

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Tumours with FUS-TFCP2 or EWSR1-TFCP2 mutations are currently classified under rhabdomyosarcomas, and are extremely rare. Histopathology shows spindled to epithelioid cells, often with a predilection for gnathic bone involvement and an aggressive clinical course. A four-patient North India case series describes adults recruited over 2.5 years with these TFCP2 mutations, including prior misdiagnoses and treatment response to chemotherapy and radiation.

LanguageEnglish

CategoryHealthcare

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Pages15

Reading Time38 min

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Abstract

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Review began 11/21/2025 Review ended 12/03/2025 Published 12/05/2025 © Copyright 2025 Agarwal et al. This is an open access article distributed under the terms of the Creative Commons Attribution License CC-BY 4.0. , which permits unrestricted use , distribution , and reproduction in any medium , provided the original author and source are credited. DOI: 10.7759/cureus.98552 Open Access Case Report Clinico-Pathological and Clinical Outcomes of Soft Tissue Sarcoma With FUS-TFCP2 or EWSR1-TFCP2 Fusions: A Case Series From North India Karishma Agarwal 1 , Sameer Rastogi 2, Sunil Pasricha 3, Yamini Dharmashaktu 4, Aditi Aggarwal 1 1. Radiation Oncology, Max Super Speciality Hospital, Saket, New Delhi, IND 2. Oncology, All India Institute of Medical Sciences, New Delhi, New Delhi, IND 3. Pathology, All India Institute of Medical Sciences, New Delhi, New Delhi, IND 4. Nuclear Medicine, All India Institute of Medical Sciences, New Delhi, New Delhi, IND Corresponding author: Sameer Rastogi, [samdoc_mamc@yahoo.com](samdoc_mamc@yahoo.com) Abstract Tumours with FUS-TFCP2 or EWSR1-TFCP2 mutations are classified under rhabdomyosarcomas at present. These tumours are exceedingly rare and on pathology show spindled to epitheloid cells, with a predisposition for gnathic bone involvement, with an aggressive outcome. We hereby present a total of four patients harbouring a FUS-EWSR1 TFCP2 mutation recruited over a period of 2 .5 years. All four reported cases are males with median age of 26 .5 years (range 22-37 years) . Primary site in all four cases was bone, with three being of head and neck origin and one with a primary in femur. Three of our patients were misdiagnosed outside. All of our patients received chemotherapy at some point and three out of four cases received radiation with a good response (two patients with palliative doses of radiation also responded well) . All four patients arealive at follow-up, two on treatment for metastatic disease. This is the first Indian case series reporting the clinicopathological details in patients with TFCP2 mutations. Categories: Pathology, Radiation Oncology, Oncology Keywords: ewsr1 mutation, fus-tfcp2 mutation, ihc panel, ngs panel, radiotherapy, rhabdomyosarcoma, sarcoma, soft tissue sarcoma, tfcp2 mutation, treatment of sarcoma Introduction Soft tissue sarcomas account for less than 1% of adult head and neck malignancies, of which 2-5% represent rhabdomyosarcomas (RMS) [1] . Rhabdomyosarcomas ofthe head and neck are encountered more frequently in children and adolescents with adults being affected in less than 10% cases [2] . Major histological subtypes of RMS are embryonal (ERMS), alveolar (ARMS), pleomorphic (PRMS), and spindle cell/sclerosing rhabdomyosarcoma. ERMS and ARMS are more commonly seen in the paediatric age group. ARMS are commonly seen in adolescents, typically characterized by FOXO1 gene rearrangement, and are clinically more aggressive than ERMS [3] . Spindle cell RMS was traditionally included as a variant of ERMS but it is now classified separately in the latest World Health Organization (WHO) classification (5th Edition, 2020) . Spindle cell rhabdomyosarcoma might harbour gene fusions involving VGLL2-related fusions or MYOD1-L 122R mutations. Recent advances in molecular diagnostics have led to the identification of an exceedingly rare tumour currently sub-classified under RMS and carries FUS-TFCP2 or EWSR1-TFCP2 fusions. As known, EWSR1 and FUS proteins are members of the FET (FUS, EWS, TAF15) RNA binding family, this variant is also known as FET-TFCP2 RMS [4] . These tumors have a monomorphic proliferation of spindle to epithelioid cells, with a high propensity for bony involvement especially in gnathic bones, with an extremely aggressive clinical course [5] . These tumours commonly show diffuse immuno-expression of cytokeratin (CK) and anaplastic lymphoma kinase (ALK), which poses a diagnostic challenge. The treatment protocol for

FAQs

What genetic alterations define the tumours in this case series?

The series focuses on soft tissue sarcomas harboring FUS-TFCP2 or EWSR1-TFCP2 fusions (TFCP2 mutations).

How were the cases diagnosed in terms of pathology and molecular testing?

Pathology was reviewed by expert sarcoma pathologists, and all patients had next-generation sequencing (NGS) performed using a sarcoma panel.

What treatments were used and what clinical responses were reported?

All patients received chemotherapy at some point; three of four also received radiation and showed good response, including two who received palliative-dose radiation. All were alive at follow-up.

Sep 29, 2026

Uploaded by Pentious