Chondroid Soft Tissue Tumors With FOS::PABPN1 Fusion - A New Entity? - About Two Cases

Sep 22, 2026

Soft tissue tumors with chondroid matrix remain difficult to classify diagnostically, despite progress in molecular pathology. Molecular diagnostics have revealed recurrent gene fusions in several chondroid neoplasms, mainly involving FN1. Here, two young patients with small deep peri-osseous nodules are described, showing well-circumscribed lobulated tumors with fibro-cartilaginous and spindle cell areas and RNA-sequencing-confirmed FOS::PABPN1 in-frame fusion, with WIF1 overexpression.

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CategoryHealthcare

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Abstract

Introduction

Materials and Methods

Immunohistochemistry

RNA Sequencing

Genes, Chromosomes and Cancer Chondroid Soft Tissue Tumors With FOS::PABPN1 Fusion: A New Entity? About Two Cases Jinane Kharmoum1,2 | Alexendra Meurgey1,3 | Daniel pissaloux1,3 | Sanae Chaib1,2 | Nicolas Macagno4,5 | Mariame Chraibi2 | Franck Tirode3 | Marie Karanian1,3 1Department of Biopathology, Centre Leon Berard, Lyon, France | 2Preclinical Basic Sciences Laboratory, Faculty of Medicine and Pharmacy of Tangiers, Abdelmalek Essaadi University, Tetouan, Morocco | 3Centre de Recherche en Cancérologie de Lyon, INSERM U1052-CNRS UMR5286, Centre Léon Bérard, Université Lyon 1, Lyon, France | 4Department of Pathology and Neuropathology, La Timone Hospital, Marseille, France | 5INSERM MMG, Aix Marseille University, Marseille, France Correspondence: Jinane Kharmoum ([j.kharmoum@uae.ac.ma](j.kharmoum@uae.ac.ma)) Received: 23 May 2026 | Revised: 1 July 2026 | Accepted: 13 July 2026 Keywords: Chondroid neoplasm | FOS::PABPN1 | gene fusion | RNA sequencing | soft tissue tumor | synovial chondromatosis ABSTRACT Soft tissue tumors with chondroid matrix represent a heterogeneous group with persistent diagnostic challenges. Advances in molecular diagnostics have identified recurrent gene fusions in several chondroid neoplasms, predominantly involving FN1. Here, we report two cases of chondroid tumors harboring a novel FOS::PABPN1 fusion. The patients were young and presented with small, deep, peri-osseous nodules located in the extremities. Histologically, the tumors were well-circumscribed and lobulated. Both cases presented fibro-cartilaginous and spindle cell areas. No cytonuclear atypia, mitoses, or necrosis were observed. Immunohistochemistry (performed in Case 2) revealed positivity for S100, CD34, and FOS, with negativity for MDM2, HMGA2, PLAG1, and desmin. RNA sequencing identified an identical in-frame FOS::PABPN1 fusion transcript in both tumors. Unsupervised transcriptomic clustering positioned the cases near synovial chondromatoses and other chondroid lesions, despite the absence of FN1 rearrangements. Massive overexpression of the WIF1 (Wnt Inhibitory Factor1) gene was also observed. To our knowledge, this is the first description of FOS rearrangement in mesenchymal tumors exhibiting chondroid differentiation. The FOS::PABPN1 fusion expands the spectrum ofFOS-altered neoplasms beyond osteoblastic and vascular lesions and defines a potential new molecular subset of benign chondroid tumors. These findings highlight the utility of RNA sequencing in the diagnosis ofchondroid neoplasms in order to identify rearrangement (ofFN1, THBS1 or FOS) or IDH1/2. The consistent upregulation of WIF1 may represent a potential diagnostic biomarker. 1 | Introduction Mesenchymal tumors are a diagnostic dilemma for pathologists. Advances in histopathology and molecular biology have significantly improved the classification of soft tissue tumors [1–4] . These advances have led to the emergence of molecular biology as a vital tool in diagnosing different types of soft tissue tumors [2]. These techniques have helped in moving beyond morphological classification of soft tissue tumors and adopting a comprehensive approach wherein molecular biology acts as one of the primary diagnostic hallmarks. Soft tissue tumors with chondroid matrix are a diverse group of neoplasms, and diagnostic difficulties are encountered in precisely determining the type of matrix and its non-specificity [5] . Advances in molecular biology investigations have helped in discovering new molecular biology subclasses of chondroid mesenchymal neoplasms, such as calcified chondroid mesenchymal neoplasms (CCMN) with FN1 fusions [6] . Recently characterized acral fibrochondromyxoid tumors bearing THBS1::ADGRF5 fusions and acral chondromyxoid tumor with a TCF4::ERG gene fusion have also This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the ori

FAQs

What molecular finding is shared by the two reported cases?

Both tumors harbor an identical in-frame FOS::PABPN1 fusion transcript identified by RNA sequencing.

What immunohistochemistry markers were reported for the tumors?

Case 2 showed positivity for S100, CD34, and FOS, with negativity for MDM2, HMGA2, PLAG1, and desmin.

Why is RNA sequencing emphasized in this study?

The study highlights RNA sequencing as a useful diagnostic approach to detect gene rearrangements in chondroid neoplasms, including FOS, FN1, THBS1, or IDH1/2.

Sep 22, 2026

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