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CC BY 4.0 · Brazilian Journal of Oncology 2025; 21: s00451809888
DOI: 10.1055/s-0045-1809888
Case Report

Targeted Therapy in a Rare Spindle Cell Tumor with ETV6-NTRK3 Gene Fusion Rearrangement: A Case Report

Jessé Lopes da Silva 
1   Department of Clinical Oncology, Hospital da Força Aérea do Galeão, Rio de Janeiro, RJ, Brazil.
2   Division of Clinical Research and Technological Development, Instituto Nacional de Câncer (INCA), Rio de Janeiro, RJ, Brazil.
,
Andréa Rodrigues Cordovil Pires
3   Pathology Section, Fonte Medicina Diagnóstica, Niterói, Rio de Janeiro, RJ, Brazil.
,
Priscilla de Almeida Romeiro
1   Department of Clinical Oncology, Hospital da Força Aérea do Galeão, Rio de Janeiro, RJ, Brazil.
,
Felipe de Carvalho Caetano
4   Department of Pathology, Hospital da Força Aérea do Galeão, Rio de Janeiro, RJ, Brazil.
,
Carolina de Bustamante Fernandes 
5   Oncoclínicas&Co, São Paulo, SP, Brazil.
,
Sumara Abdo Lacerda Matedi 
6   Clínica de Medicina Nuclear Villela Pedras, Rio de Janeiro, RJ, Brazil.
,
Andréia Cristina de Melo 
2   Division of Clinical Research and Technological Development, Instituto Nacional de Câncer (INCA), Rio de Janeiro, RJ, Brazil.
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Funding The authors declare that they did not receive funding from agencies in the public, private or non-profit sectors to conduct the present study.
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Abstract

Introduction

Advances in genomic tools have significantly improved the classification of soft tissue tumors (STTs), enabling the identification of specific subsets characterized by recurrent fusions and genetic alterations involving the Raf-1 proto-oncogene, serine/threonine kinase (RAF1), B-Raf proto-oncogene, serine/threonine kinase (BRAF), and neurotrophic tyrosine receptor kinase (NTRK) genes. The present study aims to address the clinical challenge of diagnosing and managing a rare case of spindle cell tumor by examining the utility of molecular characterization, particularly focusing on NTRK rearrangements and their relationship with clinical outcomes. These tumors are defined by the coexpression of S100 and CD34 markers, lacking SOX-10 expression. Genetic changes can also be observed in STTs exhibiting spindle cell morphology, with fibroblastic or neural characteristics.

Case Description

The current report presents a rare case of a spindle cell tumor in a 15-year-old male patient. Comprehensive histopathological and molecular analyses revealed the tumor's distinct entity through the coexpression of S100 and CD34 markers and an unusual ETV6-NTRK3 gene rearrangement. The identification of the ETS variant transcription factor 6-neurotrophic receptor tyrosine kinase 3 (ETV6-NTRK3) gene fusion was critical for tailoring a personalized therapeutic approach using larotrectinib. Periodic imaging assessments during treatment demonstrated a significant tumor response, culminating in a complete metabolic response by fluorodeoxyglucose (FDG) positron-emission tomography-computed tomography (PET-CT).

Conclusion

This rare case underscores the importance of precise diagnostic criteria and advanced molecular testing in effectively managing rare STTs. The identification of the ETV6-NTRK3 rearrangement facilitated a successful personalized treatment strategy, highlighting the need for interdisciplinary collaboration in patient care. Integrating genomic insights into clinical practice is essential for managing complex spindle cell tumors and improving patient outcomes.

Keywords

sarcomas - rare diseases - S100 proteins - tyrosine kinase inhibitors

Ethical Approval

The present study, which was approved by the Human Research Ethics Committee at Hospital de Força Aérea do Galeão (HFAG) in Rio de Janeiro, Brazil (registration number CAAE 58431022.7.0000.5250), adhered strictly to Good Clinical Practice guidelines. Prior to any data collection, the participant provided written informed consent.


Data Availability

All data supporting the study findings are contained within the manuscript. Requests for additional data may be directed to the corresponding author.




Publication History

Received: 30 January 2025

Accepted: 10 April 2025

Article published online:
01 July 2025

© 2025. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution 4.0 International License, permitting copying and reproduction so long as the original work is given appropriate credit (https://creativecommons.org/licenses/by/4.0/)

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Bibliographical Record
Jessé Lopes da Silva, Andréa Rodrigues Cordovil Pires, Priscilla de Almeida Romeiro, Felipe de Carvalho Caetano, Carolina de Bustamante Fernandes, Sumara Abdo Lacerda Matedi, Andréia Cristina de Melo. Targeted Therapy in a Rare Spindle Cell Tumor with ETV6-NTRK3 Gene Fusion Rearrangement: A Case Report. Brazilian Journal of Oncology 2025; 21: s00451809888.
DOI: 10.1055/s-0045-1809888
 

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