Sialadenoma papilliferum: clinicopathologic, Immunohistochemical, molecular analyses of new five cases and review of the literature

Abstract

Background Sialadenoma papilliferum (SP) is an extremely rare benign neoplasm of salivary glands. To explore and define the clinicopathological features of SP, we retrospectively analyzed 89 cases previously reported and five new cases. Methods The clinical features, histopathology, immunohistochemistry and molecular analysis of our cases were further performed and the related literatures were reviewed and analyzed. Results Combining 89 cases from the literature with our cases, the hard palate was the most common locations for SP. However, two of our cases were rarely located in the esophageal mucosa. Among all cases, the male gender was more affected, with the average age and median age of 61.8 and 62 years, respectively. Conventional histomorphologically, SP was characterized by complex papillary structures with a biphasic growth pattern of exophytic squamous component and endophytic glandular component. The glandular structures were lined by a double layer of epithelium composed of flattened or cuboidal basal cells and a cuboidal or columnar luminal cells formed papillary infoldings into the ductal lumina. Immunohistochemically, the luminal epithelial configurations showed strong expression of CK7 along the luminal cell membrane, while the basal myoepithelia displayed strong nuclear p63 expression. In both the glandular and squamous tumour components showed BRAF V600E-positive immunostaining and BRAF V600E mutation. Conclusion For the first time, we have comprehensively aggregated and analyzed 90 cases sialadenoma papilliferum from almost all previous publications, and further explored the clinicopathological features of SP; concordantly, this study demonstrated that SP shows a papillomatous growth pattern with exophytic and endophytic proliferation of ductal epithelium composed of double-layered cells harboring BRAF V600E mutation. Additionly, adequate treatment for SP is surgical excision, with a favorable prognosis in patients.

Activating HRAS mutation in a case of inverted ductal papilloma of the salivary gland

“…Little is known regarding the mutational landscape of benign papillary/cystic neoplasms of the salivary duct system, 2–5 and to our knowledge, this is the first reported case of IDP with an activating HRAS G13R mutation. Interestingly, HRAS Q61R mutation has been reported in a few examples of BRAF ‐mutated SP and AKT1 ‐mutated IPMN (Table 1).…”

“…Because of the lack of well‐reproducible categorization and overlap of histological features, accurate phenotyping of benign papillary/cystic neoplasms of the salivary duct system may be challenging, making their differential diagnosis difficult 2,3 . Table 1 presents a comparative summary of the key features of exo‐endophytic SP, exophytic EDP, IP, cystadenoma, IPMN and endophytic IDP 2–5,9–15 . In the present IDP, the appearance of the ductal opening was evidenced by exudation of exfoliated tumor cells on pressure.…”

“… 2,3 Although limited series of cases, EDP, IP and cystadenoma were reportedly HRAS wild‐types 2–4 . Considering these findings together, SP and IDP may be genetically characterized by activating mutations in MAP‐kinase genes 2–5 …”

“…Benign papillary or papillary/cystic neoplasms arising from the excretory duct epithelium of the minor salivary glands are uncommon, 1,2 and few reports have focused on their molecular characteristics 2 . Recently, three groups have genetically studied a series of sialadenoma papilliferum (SP), SP‐like intraductal papillary tumor (SP‐like tumor lacking an exophytic squamous papilloma component), 3 exophytic ductal papilloma (EDP), 4 intraductal papillary mucinous neoplasm (IPMN), intraductal papilloma (IP) and/or cystadenoma, 3–5 although no cases of inverted ductal papilloma (IDP) were included. Here, presenting a new case of oral IDP, we would like to extend the list of salivary gland tumors harboring an activating mutation in HRAS .…”

Sialadenoma papilliferum of a minor salivary gland with transformation to mucoepidermoid carcinoma

“…Majority of the reported cases had a benign clinical course though occasional cases documented recurrence. [ 1 2 ] The existence of malignant counterpart of SP has been debatable.…”