# Inflammatory and Nested Testicular Sex Cord Tumors: Clinical and Molecular Characterization

## TL;DR

This paper describes a new type of testicular tumor called IN-TSCT, characterized by specific genetic changes and distinct clinical features.

## Contribution

The paper identifies IN-TSCT as a distinct subtype of testicular tumor defined by EWSR1::ATF1 gene fusions and unique clinicopathologic features.

## Key findings

- IN-TSCT is associated with EWSR1::ATF1 gene fusions and lacks germ cell tumor markers.
- The tumor exhibits aggressive behavior in some cases, including metastasis.
- Molecular studies show fusion-driven oncogenesis with low tumor mutational burden.

## Abstract

Inflammatory and nested testicular sex cord tumor (IN-TSCT) is a recently characterized malignant neoplasm within the spectrum of testicular sex cord–stromal tumors. Previously misclassified as Sertoli cell tumor, not otherwise specified, or as seminoma, this entity has emerged as a distinct clinicopathologic and molecular subtype defined by recurrent EWSR1::ATF1 gene fusions and a potentially aggressive clinical course. Patients most commonly present with unilateral painless testicular enlargement, and radiologic findings are typically nonspecific. Histologically, tumors demonstrate solid and nested growth patterns, epithelioid cytology with eosinophilic to clear cytoplasm, prominent hyalinized stroma, and a conspicuous inflammatory infiltrate. Immunophenotypically, tumors express sex cord–stromal markers, including steroidogenic factor-1 (SF-1) and inhibin, and frequently co-express epithelial membrane antigen and CD30 while lacking germ cell tumor markers. Molecular studies indicate fusion-driven oncogenesis associated with low tumor mutational burden. Published cases suggest that IN-TSCT may exhibit aggressive clinical behavior, including metastatic spread in a subset of patients; however, the total number of reported cases remains very limited, and the true metastatic risk and prognostic spectrum have not yet been clearly defined. This review synthesizes the available literature to provide a comprehensive clinicopathologic and molecular overview of this emerging tumor entity.