Fusion‐positive salivary gland carcinomas

Abstract

Salivary gland tumors are a rare, heterogeneous group of neoplasms that pose significant diagnostic challenges for the histopathologist. Histopathological diagnosis relies primarily on morphological assessment, with ancillary special stains and immunohistochemistry. In recent years, new defining genomic alterations have been characterized in these tumors. In particular, they include gene fusions which have shown to be tightly tumor‐type specific, and thus valuable for use in diagnostically challenging cases. These discoveries also help in refining tumor classification. Furthermore, such genetic alterations may have prognostic as well as potentially therapeutic implications in the era of personalized medicine. This review aims at providing a summary of the most recent updates in this field.

Myoepithelial carcinoma of the parotid gland with a novel CTCF::NCOA2 fusion

“…A variety of gene fusions have been described in salivary gland neoplasms such as secretory carcinoma (ETV6::NTRK3), hyalinizing clear cell carcinoma (EWSR1::ATF1), intraductal carcinoma (NCOA4::RET), mucoepidermoid carcinoma (CRTC1::MAML2 or CRTC3::MAML2), adenoid cystic carcinoma (MYB::NFIB or MYBL1:: NFIB), microsecretory adenocarcinoma (MEF2C::SS18) and carcinoma ex pleomorphic adenoma (PA) (PLAG1 and HMGA2 rearrangements). 1,2 Rearrangements affecting the pleomorphic adenoma gene 1 (PLAG1) and high-mobility group AT-hook 2 gene (HMGA2) have been observed in PAs and myoepithelial carcinoma ex-PA, but recently TGFBR3::PLAG1 fusions have been shown in a subset of myoepithelial carcinoma arising de novo. Myoepithelial carcinoma usually exhibits low mutational load, frequent recurrent oncogenic fusions, and copy number alterations (CNA).…”

Detection of salivary gland and sinonasal fusions by a next‐generation sequencing based, ligation‐dependent, multiplex RT‐PCR assay

“…Recently, several recurrent gene fusions have been described in SGSN tumours (over 100 at this time). [1][2][3][4][5][6][7] These molecular alterations have improved the knowledge about their molecular pathology and their classification, which can serve as powerful diagnostic tools and have a clinical impact in the management through potential therapeutic targets. Diagnosis of SGSN tumours neoplasms is often challenging due to their high morphological diversity, and overlaps have caused many laboratories to switch to NGS-based screening techniques to cover all possible fusions.…”

“…1 These neoplasms may pose diagnostic difficulties due to overlapping morphologic features, the rarity of some tumours, and particularly in the context of limited sampling. In recent years, over 100 gene fusions have been found in SGSN tumours, [1][2][3][4][5][6][7] many being recurrent in a specific subtype. Next-generation sequencing (NGS) techniques are increasingly used as a diagnostic tool to detect a wide range of gene fusions instead of conventional molecular technics like reverse-transcription polymerase chain reaction (RT-PCR) and fluorescence in situ hybridization (FISH).…”

New entity of microsecretory adenocarcinoma of salivary glands: first case with recurrence and metastases — proof of malignancy

“…It exhibits uniform microcystic tubules with unilayered, cuboideal epithelium and PAS-positive luminal secretion and a consistent, but not specific immunophenotype (co-expression of CK14, CK18, S100, SOX10, p63 and negativity for p40, mammaglobin, and calponin) [1][2][3]. On molecular basis, MSA is characterized by an obviously obligate and specific MEF2C::SS18 gene fusion, which can be detected using RT-PCR or FISH [1,4,5].…”