Clinicopathologic Study of Sialadenoma Papilliferum of the Minor Salivary Glands: A Series of 8 New Cases With BRAF V600E Mutation-specific Immunohistochemical Analysis

Abstract

Introduction. Sialadenoma papilliferum (SP) is a rare benign neoplasm that usually arises in the minor salivary glands. Recently, it was demonstrated that SP shares similar molecular genetic alterations ( BRAF V600E or HRAS mutations) with its morphologic analog, syringocystadenoma papilliferum. Methods. We sought to perform clinicopathologic and immunophenotypic (BRAF V600E and SOX10) analyses on 8 new cases of SP. Results. The cases were from 4 males and 4 females, with ages ranging from 28 to 81 years (average: 64 years). The common locations were the hard palate (n = 3) and buccal mucosa (n = 3). Histopathologically, 7 cases were classic and 1 case was oncocytic. BRAF V600E immunohistochemistry (IHC) was positive in all classic SP, involving both the exophytic and endophytic components, but negative in the oncocytic SP. SOX10 was positive in the endophytic ductal cells of the evaluated classic SP but was negative in the oncocytic SP. Conclusions. We report 8 new cases of this rare salivary gland neoplasm, using BRAF V600E and SOX10 IHC to further support the following points: (1) the functional role of BRAF V600E mutation, RAS/mitogen-activated protein kinase signaling pathway in the pathogenesis of classic SP of salivary glands by IHC; (2) the analogous relationship between SP, syringocystadenoma papilliferum, and papillary seromucinous adenocarcinoma with sinonasal papilloma-like surface component (PSASP-like surface); (3) endophytic ductal component in classic SP arises from the intercalated ducts and not the excretory ducts; and (4) oncocytic SP is distinct from classic SP.

Salivary Duct Carcinoma with Rhabdoid Features of the Parotid Gland with No E-Cadherin Expression: A Report with Anti-HER2 Therapy and Review of the Literature

“…Mutations in PIK3CA, HRAS, and NRAS have been reported in classic SDC [19,20]. Many salivary gland neoplasms are known to have recurrent genetic alterations: PLAG1 (fusion partners CTNNB1, LIFR, ND4, NFIB, TGFBR3, FGFR1, and CHCHD7) in pleomorphic adenoma (PA), carcinoma ex-PA, and myoepithelial carcinoma [21][22][23][24][25]; HMGA2 (fusion partners FHIT, NFIB, WIF1, and TMTC2) in PA and carcinoma ex-PA [25][26][27]; MYB/MYBL1::NFIB in adenoid cystic carcinoma [28,29]; MAML2::CRTC1/3 in mucoepidermoid carcinoma [30]; PRKD1/2/3 (fusion partners ARID1A, DDX3X, PPP2R2A, PRKAR2A, SNX9, ATL2, and STRN3) in polymorphous adenocarcinoma/cribriform adenocarcinoma of the salivary gland [31][32][33][34][35][36]; ETV6 (fusion partners NTRK3, RET, and MET) in secretory carcinoma [37][38][39]; SS18 (fusion partners MEF2C and ZBTB7A) in microsecretory adenocarcinoma [40]; RET (fusion partners TRIM27/33 and NCOA4) in intraductal carcinoma [41,42]; HTN3-MSANTD3 and NR4A3 upregulation in acinic cell carcinoma [43][44][45]; AKT1 mutations in epithelia-myoepithelial carcinoma, intraductal papillary mucinous neoplasm, and salivary mucinous adenocarcinoma [46][47][48]; CTNNB1 mutations in basal cell adenoma and basal cell adenocarcinoma [49,50]; and BRAF mutations in sialadenoma papilliferum [51][52][53]. The majority of SDC-RF patients were treated with surgery alone or followed by chemoradiation or radiation therapy …”