Epithelial-Predominant Synovial Sarcoma With a Deceptive Neuroendocrine Phenotype

TL;DR

This paper describes a rare case of epithelial-predominant synovial sarcoma with unusual neuroendocrine features that mimicked a carcinoma.

Contribution

The study highlights a rare case of synovial sarcoma with neuroendocrine differentiation and genomic findings that may explain its progression.

Findings

The tumor showed high-grade epithelial features with neuroendocrine differentiation confirmed by synaptophysin and INSM-1 positivity.

RNA sequencing identified an SS18::SSX4 fusion gene, and FISH confirmed an SS18 rearrangement with amplification in the epithelial component.

Prominent ossification and tumor progression over time were observed despite initial stability.

Abstract

Synovial sarcoma (SS) is a tumor of uncertain lineage with a characteristic mixture of spindled and epithelial components that is subtyped as biphasic when both spindle and epithelial components are present and as monophasic when composed solely of spindle cells. Epithelial-predominant SS is extremely rare, and neuroendocrine differentiation within this component would be exceptional. Prominent ossification is another uncommon feature in SS, thought to portend a better prognosis. The hallmark genomic alteration in SS is t(X;18;p11;q11), resulting in the formation of an oncogenic fusion gene, usually SS18(SYT):: SSX1 or SS18::SSX2 and rarely SS18::SSX4. We herein describe a case of an epithelial-predominant SS arising in the right inguinal soft tissue of a 62-year-old woman. The mass is discovered incidentally on imaging and is peripherally calcified and stable during the first four years of follow-up, but later doubles in size. Microscopic examination reveals an epithelial-predominant malignant neoplasm forming glands and solid sheets, embedded in a variably cellular but mostly fibrotic-looking stroma. Prominent ossification is seen peripherally. The epithelial component is high-grade and shows neuroendocrine differentiation, further confirmed by positivity for synaptophysin and INSM-1. SS18::SSX4 is detected by RNA sequencing. Break-apart fluorescence in situ hybridization (FISH) performed separately on the epithelial and stromal components confirms an SS18 rearrangement, with the epithelial component additionally showing amplification of the region corresponding to the 5' end of SS18. We speculate that the latter finding could have played a role in the neuroendocrine transformation and progression of this tumor. Herein, we present a rare case of epithelial-predominant SS with unusual neuroendocrine differentiation mimicking a carcinoma.

Figures