KRAS mutant tenosynovial giant cell tumor in a pediatric patient: a case report

Abstract

Tenosynovial giant cell tumors (TSGCT) are a group of rare, benign soft tissue tumors with common histologic and cytogenetic features, with a median age of diagnosis being 47 years. Generally divided into localized and diffuse subtypes, TSGCTs are typically driven by overexpression of macrophage colony stimulating factor receptor-1 (CSF1R). Treatment of TSGCT is tumor resection, followed by radiation therapy in cases of incomplete resection. Even when the tumor is completely removed, recurrence rates can be as high as 30% in some anatomical locations. Here we report the identification of a previously undescribed KRAS p.G12D activating mutation within a pediatric TSGCT patient, who clinically presented with an enlarging right lower extremity mass pathologically consistent with TSGCT. The patient continues to be in remission three years after complete surgical removal. KRAS mutations are usually found in adult cancers, such as lung and pancreatic, as well as giant cell lesion of the jaw. This case demonstrates the utility of integrative clinical sequencing in identifying lesions with aggressive potential and aiding in complex diagnoses.

Keywords: KRAS; case report; integrative clinical sequencing; pediatric oncology; tenosynovial giant cell tumor (TSGCT).

Figure 1

HE stain 2×, showing well circumscribed tumor within skeletal muscle fibers.

Figure 2

Tumor microscopic photomicrograph. (A) HE stain, 20× magnification, revealing epithelioid mononuclear cells admixed with histiocytes and multinucleated tuton-type giant cells (arrow); (B) 10× magnification admixed epithelioid neoplastic cells with foamy histiocytes and occasional spindled cells.

Figure 3

High magnification (40×), HE stain showed epithelioid cells with eccentric nuclei eosinophilic cytoplasm and slight nuclear atypia (rhabdomyocyte-like).

Figure 4

CD163 immunostain, 10× magnification. Diffuse reactivity indicating histiocytic differentiation of this tumor.

Figure 5

Desmin immunostain, 10× magnification showing unusual diffuse expression that had been reported in subset tenosynovial giant cell tumor, a potential pitfall with rhabdomyosarcoma.

Figure 6

Myogenin immunostain 10× magnification, is negative with rare scattered cell staining (arrows).

Figure 7

Expression profiles of selected genes from 10-year-old TSGCT patient (in red), in the context of gene expression in our pan-cancer cohort comprising 3,959 samples. TSGCT, tenosynovial giant cell tumor.