Concurrent Identification of Novel EGFR-SEPT14 Fusion and ETV6-RET Fusion in Secretory Carcinoma of the Salivary Gland

Abstract

Salivary gland secretory carcinoma, also termed mammary analogue secretory carcinoma (MASC), is a recently described salivary gland neoplasm with characteristic histomorphologic findings similar to those of secretory carcinoma of the breast and harboring recurrent ETV6-NTRK3 fusions. Recent findings have expanded the molecular profile of salivary gland secretory carcinoma to include multiple novel ETV6 fusion partners, including RET, MET, and MAML3. Here, we report a case of cystic MASC with cribriform and papillary histology harboring two gene fusions, ETV6-RET and EGFR-SEPT14, identified by targeted RNA sequencing. The presence of the rearrangements was confirmed by FISH, RT-PCR, and Sanger sequencing. This is the first EGFR-SEPT14 fusion reported in secretory carcinoma as a single event or in association with an ETV6 rearrangement. This finding adds to the expanding molecular profile of this tumor entity, and may translate into novel treatment strategies.

Keywords: EGFR–SEPT14; ETV6 fusion; Mammary analogue secretory carcinoma; Salivary gland carcinoma; Secretory carcinoma.

Fig. 1

MRI shows right cystic parotid lesion (2 × 2 × 1.6 cm) with subtle wall enhancement and thickening posteriomedially

Fig. 2

Secretory carcinoma of the salivary gland. Cyst wall with infiltrating glands showing focal cribriform and papillary architecture (a). Tumor cells are round, monomorphic, and have ample eosinophilic cytoplasm (b). Invasive gland surrounded by demosplastic stroma (c). Tumor cells are immunoreactive for S-100 (d), GATA3 (e), and mammaglobin (f)

Fig. 3

ETV6–RET and EGFR–SEPT14 translocations. Archer FusionPlex Custom Solid Panel demonstrates ETV6–RET translocation (ETV6 breakpoint, exon 6; RET breakpoint, exon 12) and EGFR–SEPT14 translocation (EGFR breakpoint, exon 24; SEPT14 breakpoint, exon 7) (a). RT-PCR amplification with 2 sets of primers verifies EGFR–SEPT14 fusion by both gel electrophoresis (b) [M, DNA ladder; Lane 1, amplified 237 bp fusion gene; Lane 2, HAPMAP Normal RNA control; Lane 3, water] and Sanger sequencing (c)