Glomangiopericytoma of the Nasal Cavity with CTNNB1 p.S37C Mutation: A Case Report and Literature Review

Abstract

Glomangiopericytoma (GPC) is a rare mesenchymal tumor arising from the nasal cavity or paranasal sinuses. GPC was categorized as a borderline and low-malignant-potential tumor by the World Health Organization in 2005 and accounts for less than 0.5% of all sinonasal tumors. We report a case of GPC in a 74-year-old woman with a history of recurrent epistaxis and nasal obstruction. A reddish tumor was seen in the right nasal cavity. Enhanced computed tomography showed a mass lesion occupying the right nasal cavity. The tumor, which originated from the nasal septum in the olfactory fissure area, was resected with 5-mm mucosal margins by endoscopic sinus surgery. Histologic examination revealed a uniform proliferation of oval-to-short spindle-shaped cells beneath the epithelium. Immunohistologic analysis demonstrated the tumor cells were positive for α-smooth muscle actin, β-catenin and Vimentin, and negative for AE1/AE3, Bcl-2, CD34, CD117, Factor VIIIR Ag, S-100 protein, or STAT6. The percentage of Ki-67-positive cells was approximately 5%. Genetic analysis using next-generation sequencing revealed a missense mutation in the CTNNB1 gene (c.110C > G, p.S37C). While other CTNNB1 mutations have been described in GPC; this is the first report of this specific mutation. The mutation was confirmed using Sanger sequencing.

Keywords: CTNNB1; Endoscopic sinus surgery (ESS); Glomangiopericytoma (GPC); Next-generation sequencing (NGS).

Fig. 1

Nasal endoscopic examination showed a reddish tumor in the right nasal cavity (a). CT scan revealed a mass occupying the right nasal cavity, with strong enhancement (b, c). FDG-PET/CT showed slight uptake by the tumor (d)

Fig. 2

Histopathologic examination revealed that the tumor extended with a diffuse growth pattern beneath the epithelium (HE, a). Oval-to-short spindle-shaped cells with uniform proliferation and stromal bleeding were observed (HE, b). Immunohistologic analysis showed tumor cells with cytoplasmic staining for α-smooth muscle actin (SMA) (c) and Vimentin (d). Diffuse staining of tumor cells for CD99 (e) and nuclear staining for β-catenin (f) were observed. Tumor cells were not stained for STAT6 (g). The percentage of Ki-67-positive cells was approximately 5% (h). Magnification ×20 (a), ×400 (b–h)

Fig. 3

Targeted genomic DNA sequences determined using next-generation sequencing were compared between tumor and peripheral blood samples with a read depth of 700 and 1800, respectively. A CTNNB1 mutation was identified in exon 3 with a C to G base change at nucleotide 110 (c.110C > G), leading to substitution of serine for cysteine at position 37 (p.S37C) of the protein product. The image was produced using the free software Golden Helix GenomeBrowse (http://goldenhelix.com) and modified (a). The mutation (c.110C > G) was confirmed using Sanger sequencing (b)

Fig. 4

Twenty-three reported types of mutation in the CTNNB1 gene in cases of glomangiopericytoma as reported by Lacosta et al. [21], Haller et al. [23], Anzai et al. [8], and Suzuki et al. [24]. Mutations were combined with that identified in the present case and shown as a bar graph. One patient reported by Haller et al. harbored two mutations (p.G34E and p.S37F)