Histopathological evaluation of minor salivary gland papillary–cystic tumours: focus on genetic alterations in sialadenoma papilliferum and intraductal papillary mucinous neoplasm

Abstract

Aims Minor salivary gland tumours showing a predominant papillary–cystic structure are rare, and constitute a mixture of various types of neoplasm; thus, the histopathological assessment of these tumours poses a significant diagnostic challenge. We aimed to delineate the histological characteristics of these tumours and further mutational aspects with a particular focus on sialadenoma papilliferum (SP) and intraductal papillary mucinous neoplasm (IPMN). Methods and results We retrieved 28 papillary–cystic tumours of the minor salivary glands, and performed histological re‐evaluation and mutation analyses of several key oncogenes. The histological classifications were as follows: SP (n = 10), SP‐like intraductal papillary tumour (SP‐IPT) (n = 2), IPMN (n = 9), intraductal papilloma, cystadenoma, and cystadenocarcinoma (two, three and two respectively). Whereas SP typically consisted of a combination of exophytic squamous epithelium and endophytic intraductal papillary infoldings, SP‐IPT lacked the exophytic component. SP and SP‐IPT frequently harboured BRAF V600E mutations (75.0%), which were identified in both squamous and ductal components. IPMN was characterised by a well‐demarcated cystic lesion filled exclusively with a papillary proliferation of mucinous cells and a high rate of AKT1 E17K mutations (88.9%). Intraductal papillomas were unilocular cystic lesions with intraluminal papillary growth of bland columnar cells. In contrast, both cystadenomas and cystadenocarcinomas showed a multicystic appearance with a papillary configuration. Cystadenocarcinomas invaded the surrounding tissue and were composed of markedly atypical tumour cells. Conclusion The appropriate interpretation of histological findings and specific genetic alterations (e.g. BRAF V600E and AKT1 E17K in SP and IPMN) would be useful for the correct diagnosis of minor salivary gland papillary–cystic tumours.

A Rare Case of Intraductal Papilloma Arising from Minor Salivary Gland in the Floor of the Mouth

“…The lumen is partially or completely filled by branching papillary elements consisting of a fibrovascular core, and the epithelium that lines the cystic-like cavity is the same type of epithelium of papillary fronds, causing the mucus retention [ 2 – 5 , 7 ]. The presence of a varying degree of oncocytic metaplasia, as observed in the present case, is common in duct cysts arising from minor salivary glands [ 6 ].…”

“…Therefore, the present case is the third intraductal papilloma report that developed in the sublingual region, involving a minor salivary gland. Although with good prognosis and low recurrence rates, it is important to distinguish intraductal papillomas of other ductal neoplasms of salivary ductal origin, as papillary cystadenoma, cystadenocarcinoma, sialadenoma papilliferum, and inverted ductal papilloma [ 1 , 2 , 6 ].…”

“…In contrast with intraductal papilloma, cystadenoma and cystadenocarcinoma show a multicystic well-circumscribed lesion lined by papillary epithelium with variable size [ 2 , 6 ]. However, the cystadenocarcinoma is covered by a papillary epithelium with remarkable nuclear and structural atypia, some mitosis, and invasion of the surrounding tissue or infiltration of the adjacent salivary gland [ 6 ].…”

“…Additionally, sialadenoma papilliferum is characterized by a combination of exophytic projection of the surface squamous epithelium and inward papillary proliferation of duct epithelial cells [ 1 , 2 , 6 , 7 ]. The underlying glandular component forms papillary extensions surfaced by columnar or cuboidal cells or both, which is contiguous with underlying arborizing ductal structures and cystic spaces.…”

“…The underlying glandular component forms papillary extensions surfaced by columnar or cuboidal cells or both, which is contiguous with underlying arborizing ductal structures and cystic spaces. According to Nakaguro et al [ 6 ], based on histological and genetic aspects, sialadenoma papilliferum may be considered to be a counterpart of syringocystadenoma papilliferum of the skin.…”