A novel low‐grade nasopharyngeal adenocarcinoma characterized by a GOLGB1‐BRAF fusion gene

Abstract

Nasopharyngeal adenocarcinoma is a rare malignancy that is classified into conventional/surface-and salivary-types. Herein we report the case of a 52-year-old male who presented with a right nasopharyngeal mass and right-sided hearing loss. Diagnostic imaging revealed a circumscribed 1.7 cm mass centred in the right anterolateral aspect of the nasopharynx. A biopsy showed a gland-forming neoplasm that was in continuity with the surface epithelium. The tumor exhibited a nested to micro-papillary architecture, with mild cytologic atypia. Immunohistochemistry demonstrated diffuse staining for CK7, SOX10, and p16; the abluminal layer was highlighted by CK5 and p63, while the luminal cells expressed CD117. The tumor was not amenable to subclassification and was diagnosed as a low-grade nasopharyngeal adenocarcinoma, not otherwise specified (NOS). Subsequent RNA sequencing was performed which identified a novel GOLGB1-BRAF fusion product. Based on its unique morphology and molecular findings, this is presumed to represent a novel subtype of nasopharyngeal adenocarcinoma. In addition to being of diagnostic relevance, this fusion may ultimately represent a potential therapeutic target.

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

“…Gene fusions are increasingly recognised in epithelial and mesenchymal tumours. Recently, several recurrent gene fusions have been described in SGSN tumours (over 100 at this time) 1–7,14–85 . 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.…”

“…These fusions cover 100% of the 29 head and neck histological entities known to be associated with gene fusion (listed in Table 1, Figure 2, Table S1). 1–7,14–85 Seven gene fusions are associated with secretory carcinomas (SC), three with mucoepidermoid carcinoma (MEC), six with adenoid cystic carcinoma (ACC), seven with intraductal carcinoma (IC), three with clear cell carcinoma (CCC), three with clear cell odontogenic carcinoma (CCOC), 18 with pleomorphic adenoma (PA) and carcinoma ex‐pleomorphic adenoma (CA ex PA), one with adamantinoma‐like Ewing Sarcoma (ALES), one with DEK::AFF2 sinonasal carcinoma (DAC), one with EWSR1::COLCA2 sinonasal sarcoma (ECSS), one with acinic cell carcinoma (AiCC), two with microsecretory carcinoma (miC), two with cribriform adenocarcinoma of minor salivary glands (CAMSG), three with salivary duct carcinoma (SDC), 14 with myoepithelioma (M), six with clear cell myoepithelial carcinoma (CCMC), four with myoepithelial carcinoma (MC), five with nasopharyngeal carcinoma (NPC), nine with NUT carcinoma, five with biphenotypic sinonasal sarcoma (BSNS), one with sinonasal squamous cells carcinoma (SNSC), one with low‐grade nasopharyngeal adenocarcinoma (LGNA), one with low‐grade sinonasal adenocarcinoma (LGSA), one with microcribriform adenocarcinoma (MicC), one with adenocarcinoma NOS (ACA, NOS), one with papillary‐cystic neoplasms of the middle ear, and nine with Ewing sarcoma. Some genes are implicated in several fusions, such as EWSR1 ( n = 16) in Ewing sarcoma, ALES, CCC, CCOC, CCMC, PLAG1 ( n = 12) in PA and CA ex PA, myoepithelioma, myoepithelial carcinoma, myoepithelial carcinoma (clear cells), NUTM1 ( n = 9) in NUT carcinoma, HMGA2 ( n = 6) in PA and CA ex PA, RET ( n = 6) in SC, IC, and SNLGA, ETV6 ( n = 5) in SC, SNLGA, and SNSC, MAML2 ( n = 3) in MEC and NC, ALK ( n = 4) in IC, SDC, and SC.…”

Effectiveness Treatment of a BRAF-ZKSCAN5 Fusion Gene Melanoma Case with Dabrafenib/Trametinib

“…In addition, the efficacy of the BRAF/MEK inhibitor for brain metastases from melanoma was also reported in BRAFi naive patients with an overall response rate of 67.3%, median overall survival of 20.0 months, and median progression-free survival of 7.5 months compared to previous treatment modalities [ 8 ]. Although there are some case reports of BRAF fusion genes in various tumors other than melanoma, no BRAF-targeted therapies for melanoma have been reported [ 9 , 10 ]. Previous basic research on melanoma cells reported that the efficacy of BRAF inhibitors is specific to the fusion gene type [ 11 ].…”

“…Although there are some case reports of BRAF fusion genes in various tumors other than melanoma, no BRAF-targeted therapies for melanoma have been reported [9,10]. Previous basic research on melanoma cells reported that the efficacy of BRAF inhibitors is specific to the fusion gene type [11].…”