Case report: Tenosynovial giant cell tumor

Abstract

Tenosynovial giant cell tumor (TGCT) is a rare type of tumor that originates from the synovium of joints and tendon sheaths. It is characterized by recurring genetic abnormalities, often involving the CSF1 gene. Common symptoms include pain and swelling, which are not specific to TGCT, so MRI and a pathological biopsy are needed for an accurate diagnosis. We report the case of a 45-year-old man who experienced painful swelling in his right hip for six months. Initially, this was diagnosed as Erdheim-Chester disease. However, whole exome sequencing (WES) and RNA-Sequencing revealed a CSF1::GAPDHP64 fusion, leading to a revised diagnosis of TGCT. The patient was treated with pegylated interferon and imatinib, which resulted in stable disease after three months. Single-cell transcriptome analysis identified seven distinct cell clusters, revealing that neoplastic cells expressing CSF1 attract macrophages. Analysis of ligand-receptor interactions showed significant communication between neoplastic cells and macrophages mediated by CSF1 and CSF1R. Our findings emphasize the importance of comprehensive molecular analysis in diagnosing and treating rare malignancies like TGCT.

Keywords: CSF1 fusion transcript; RNA sequencing (RNA-seq); molecular tumor board (MTB); single cell sequencing (scRNA-seq); tenosynovial giant cell tumor (TGCT).

Figure 1

MRT images of the affected femoral head in the transverse plane (A) and frontal plane (B). Tumor tissue with a predominance of infiltrating foamy macrophages, cleft-like spaces (arrows), and multinucleated giant cells (arrowheads) in hematoxylin and eosin stainings (C) and immunostaining for CD68 (D). Original magnifications 200x, bar indicates 200 µm.

Figure 2

scRNA-seq analysis of cellular composition of bone marrow from Tenosynovial Giant Cell Tumor patient. Single-cell suspension from tenosynovial giant cell tumor patient analyzed by scRNA-seq. (A) UMAP plot of seven distinct cell clusters. (B) Violin plots of marker gene expression for the seven distinct clusters. (C) Relative pathway enrichment. Red indicates positive, whilst blue indicates negative enrichment.