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.

Keywords: BRAF; Clinical features; Histopathology; Immunohistochemistry; Sialadenoma papilliferum.

Fig. 1

Anatomic location of sialadenoma papilliferum (94 cases)

Fig. 2

Age distribution of sialadenoma papilliferum (94 cases)

Fig. 3

Pathological manifestations of Sialadenoma papilliferum. a SP shows a biphasic growth pattern with an exophytic papillary component surfaced by a keratotic squamous epithelium (Green arrow) and an endophytic adenomatous component of the underlying lesion (Red arrow) (20x). b Papillary frond surfaced by stratified squamous epithelium is contiguous with columnar ductal epithelium (Red arrow) (100x). c The surface papillary structure of the lumen supported by thin fibrovascular core often protrudes into the lumen (Red arrow) (50x). d The ductal lumen is double-layered, lined by luminal cuboidal to columnar cells (Green arrow) and cuboidal to flattened basal cells (Red arrow) (400x). e Localized enlargement of the cyst and eosinophilic deposition in the lumen (Red arrow) (50x). f Mucinous cells in tumour area (Red arrow) (400x)

Fig. 4

Immunohistochemical performance of Pathological manifestations. a CK7 is strongly positive in the luminal cells (100x). b p63 shows strong positive staining in the basal cells (100x). c S-100 shows positive staining in the basal cells (Red arrow) (100x). d Ki67 ranges from 20 to 30% (100x). e The expression of BRAF V600E is observed in both the glandular and squamous components (Red arrow) (100x). f BRAF V600E immunohistochemistry in the third case shows a weak staining (100x)

Fig. 5

Molecular features of sialadenoma papilliferum. BRAF wild type (Red arrow); BRAF p.V600E c.1799 T > A (Green arrow). BRAF mutation is confirmed in three of four cases by Sanger sequencing