SP is a subtype of intraductal papilloma, a rare benign tumor commonly found in middle-aged men with hard palate, accounting for approximately 80 percent. It can also occur in the parotid gland, submandibular gland, nasopharynx and esophagus 2, 4, 10, 16-30. Clinically, there are generally no obvious clinical symptoms with mostly painless growth, but sometime papillary erythema or pedicled lumps, occasional ulcers 31-41. Grossly, most of the lesions presents as a round to oval mass with white-colored and papillary surface, sharing about 80 percent.
Histologically, SP is formed by mucosal surface epithelium and ductal epithelium of the salivary gland which proliferate outward and inward simultaneously, with the characteristics of biphasic proliferation of squamous and ductal epithelium 9. Generally, SP has two components 3, 4: (1) superficial papillary structure: stratified squamous epithelium covered with incomplete keratinization, in addition to acanthosis or acanthosis cell edema; (2) ductal structure: the lumen-like structure lined by two layers of columnar and cuboidal cells is formed under the mucosa, and the ductal lumina can be mesh-like, fissure-like or expanded into a large cystic cavity. In addition, there are numerous inflammatory cells in the epithelial space, such as plasma cells and lymphocytes 3, 4. Immunohistochemistry showed that CK7 and CK8 were strongly expressed in columnar cells, and p63 was strongly positive in basal cells, but was negative in columnar cells from Table 2 and reported literatures, and some cases were positive for S-100 and GFAP, which indicate the convoluted ductal structures of SP include two cell types at least3, 5.
The Histogenesis of SP is still not fully understood 3, 5. There are several viewpoints as follows. Freedman, Lumerman, and Anuradha et al proposed that it may originate from the excretory tube cell, which is supposed to be a primitive precursor cell capable of multi-directional differentiation 42, 43. According to Abrams and Finck, the lesion was of pleuripotential myoepithelial origin because the tumor cells revealed the immunoreactivity for SMA 12. Moreover, Asahina and others suggested that the lesion derived from the intercalated duct cell due to the presence of the tumour cells coexpressing cytokeratin, vimentin, and desmin 21. Conversely, Eversole and several authors considered SP as the result of focal hyperplasia after salivary duct obstruction rather than a true neoplasm. However, in our limited series of SP, BRAF V600E immunoexpression presented in both the proliferative ductal and squamous tumor elements, which confirmed by molecular analysis, suggested the neoplastic nature of both components, and the transition of ductal epithelium to squamous epithelium seen in SP indicated this tumour may originate in the excretory ducts. Although the cells of origin are not entirely clear at present, the histopathological, immunohistochemical and molecular features of the fusion of the duct components with the surface epithelium seem to favor the origin of the excretory ducts 4, 44.
Although SP has been proposed as a distinct entity, it also needs to be differentiated from the following neoplasms. First of all, papillary squamous cell carcinoma, a papillary subtype of squamous cell carcinoma similar to the histopathological characteristics of SP, is characterized by an exophytic and papillary growth pattern. However, there is no glandular component with mucous cells in the lesion, and the squamous cell papilloma is mainly composed of the squamous epithelium, which manifests highly differentiated squamous cell carcinoma with keratinized beads structure, without downward extension of SP. Inverted ductal papilloma is another candidate for differential diagnosis, mainly composed of hyperplastic squamous epithelium under the mucosa that protrudes into connective tissue and connects with duct, but unlike SP with characteristic papillary surface configuration. Another antidiastole is highly differentiated mucoepidermoid carcinoma, which is rich in mucous cells, often forming a glandular cavity, and sometimes hyperplastic mucous cells form the papillary structure resembling that of SP, while mucoepidermoid carcinoma usually composed of epidermal-like cells, intermediate cells, mucus cells and other cell components 13. Wathin tumor shares papillary adenoid structure with characteristic double layer epithelium lining the glandular cavity liking SP should also be considered, but the interstitial of it is a lymphoid component associated with lymphoid follicle formation 14. Also papillary cystadenocarcinoma is a rare malignant tumour characterized by predominantly cystic growth and cell types that comprise the lining epithelium of cysts include most often cuboidal and columnar cells, which though resemble SP, neither exhibits squamous elements.
The current treatment of SP is conservative surgical resection 4, 45. In addition, oral robotic surgery (TORS) is a novel technique for head and neck surgery in some centers around the world46. Atarbashi-Moghadam proposed the first successful removal of SP tumors by TORS 15. The use of TORS provides better control of surgical procedures and reduced morbidity compared to traditional oral surgical procedures.
Although there have been a few reports of recurrence and malignant transformation, in which SP has reported that it can transformed into epithelial-muscle epithelial carcinoma, squamous cell carcinoma, and mucoepidermoid carcinoma, but malignant transformation is rare and not entirely convincing 4, 15, 31, 47. As the results of the statistics show that the prognosis of this lesion is very good, we believe that SP does not have malignant potential 13, 44.
Summarily, SP is a rare, benign and exophytic tumor of salivary gland neoplasm that commonly occurs in the hard palate in middle aged males with a painless and slow growing lesion. Characteristic of this tumor is its exophytic growth pattern, with multiple papillary surface fronds and deeper ductlike structures, which may be continuous with the surface epithelial component. In this study, we added another five cases of SP to the literature and discussed the clinicopathologic features of the 70 described cases of this unusual neoplasm. Although to identify the cell of origin of SP is difficult, we conclude that SP is a neoplastic lesion arising from the excretory ducts by immunophenotypic feature and molecular analysis, and virtually has no potentially malignant features mostly with good prognosis, which should be distinguished from other malignant tumours and avoided resultant overtreatment.