Oral sialadenoma papilliferum with kras mutation in a patient with linear nevus sebaceous syndrome.

Linear nevus sebaceous syndrome (LNSS) is a rare neurocutaneous syndrome part of the epidermal nevus syndromes group, characterized by the presence of sebaceous nevi and other extracutaneous lesions genetically related to RAS family gene mutations. Sialadenoma papilliferum (SP) is a rare benign intraoral neoplasm which is usually BRAF or HRAS mutated. We report a case of a young female girl diagnosed with a LNSS who developed a SP which had a KRAS mutation. This is the first case of SP with a KRAS mutation in the context of a LNSS.

Pulmonary sialadenoma papilliferum and its mimics: what you need to know.

Pumonary salivary gland-type tumours (SGT) represent a small but distinct group of primary lung neoplasms. These types of tumours originate from the submucosal bronchial glands of the tracheobronchial tree. Pulmonary SGTs differ greatly in the incidence of individual tumours from salivary gland tumours of the head and neck. Additionally, the vast majority of pulmonary SGT are malignant. Recently, pathological diagnosis has significantly improved with the application of molecular diagnostic technologies. However, the current knowledge of benign SGTs is limited; moreover, tumour diversity and overlapping morphological features of SGT represent diagnostic challenges such as correct tumour categorisation and their accurate differentiation from malignant lesions. Compounding this inherent difficulty has been the recent introduction of new variants, including sialadenoma papilliferum (SP). Pulmonary SP is very rare, with limited reports available, and most of the initial diagnoses rendered so far were incorrect, resulting in inappropriate treatment. Several cases of SP have recently been reported. This review will serve to update practicing pathologists on the morphology, immunophenotype and molecular characteristics of SP and its mimics.

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

Sialadenoma papilliferum (SP) is a rare benign tumor usually occurring in the minor salivary glands. Only two cases of malignant transformation of SP and an occasional case of dysplasia in SP have been reported in the literature till now. We report a case of SP of a minor salivary gland in a middle-aged male where the exophytic component retained the histomorphological features of SP while the endophytic component displayed characteristics of a mucoepidermoid carcinoma. Malignant change in sialadenoma papilliferum is an extremely rare phenomenon that requires further research and documentation. Careful evaluation of morphologic features and reporting of more such cases is required to delineate the clinical behavior of this unusual tumor.

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

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.

Bronchial Sialadenoma Papilliferum in a 10-Year-Old Boy.

Sialadenoma papilliferum (SP) is a rare salivary gland tumor mostly reported in the oral cavity. Here we describe a bronchial SP in the left upper lobe bronchus of a 10-year-old boy. At bronchoscopy, a well-circumscribed polypoid lesion protruding into the bronchial lumen was identified. The tumor was excised, but eventually, the patient had to undergo a sleeve resection after 2 recurrences. Pathology revealed a papillocystic lesion with exophytic and endophytic components. The cells lining the exophytic surface and papillary structures were columnar and squamous, and the cells lining endophytic cystic and papillary structures were cuboidal to columnar, all of which were diffusely reactive with antibodies to SOX10 protein. The presence of basal cells was demonstrated by p63 immunoreactivity. The cells failed to immunohistochemically express BRAF V600E. Fluorescence in situ hybridization analysis revealed no MAML2 or RET gene rearrangement. The patient is alive 24 years after resection with no additional recurrences. Bronchial SP needs to be recognized and distinguished from other benign and malignant salivary gland and pulmonary neoplasms so that patients can receive appropriate treatment and follow-up.

Sialadenoma papilliferum-like intraductal papillary tumour: an emerging entity with intercalated duct differentiation showing MAPK pathway activation in both ductal and myoepithelial cells.

Sialadenoma papilliferum-like intraductal papillary tumour (SP-IPT) is a recently described salivary gland tumour that shows identical morphology to sialadenoma papilliferum (SP) except for the lack of an exophytic papillary component. However, the immunohistochemical phenotypes and molecular profiles of SP-IPT remain unclear. This study aims to report new cases of SP-IPT and to determine its cellular differentiation and molecular basis. After histopathological review, four cases of SP-IPT were retrieved. Immunohistochemical staining was performed to analyse the expression patterns of cytokeratin 7 (CK7), p63, smooth muscle actin (SMA), vimentin, S100, mammaglobin, androgen receptor, SOX10, BRAF V600E-mutated protein, and phosphorylated ERK. Sanger sequencing was performed to determine the mutation status of the BRAF, KRAS, NRAS, and HRAS genes. All four cases affected the posterior mandible with a mean age of 62 years and a male-to-female ratio of 3:1. Histologically, all cases consisted of multiple tubular and cystic structures with varying sizes and shapes. The tubulocystic components were lined by a double or few-layered epithelium frequently showing a micropapillary pattern. The outer layer consisted of a rim of myoepithelial cells, which were CK7+/p63+/SMA+/vimentin+/S100+/SOX10+. The inner ductal cells were CK7+/S100+/SOX10+, consistent with intercalated duct differentiation. All cases harboured BRAF V600E mutations, but no other mutations were detected. The BRAF V600E-mutated protein and phosphorylated ERK were expressed in both ductal and myoepithelial cells. These findings demonstrate the immunohistochemical and molecular similarities between SP-IPT and SP and the role and extent of MAPK pathway activation in the pathogenesis of SP-IPT.

Sialadenoma papilliferum-like intraductal papillary tumor with unveiling BRAF V600E and PIK3CA H1047R mutations: Case report with molecular analysis and literature review.

INTRODUCTION: Sialadenoma papilliferum (SP), a rare minor salivary gland tumor, shares morphological and genetic similarities with syringocystadenoma papilliferum. Recent studies have identified BRAF V600E or HRAS mutations in SP, suggesting its neoplastic nature. Despite being uncommon, SP poses diagnostic challenges due to its resemblance to other lesions like squamous papilloma. The emergence of sialadenoma papilliferum-like intraductal papillary tumor (SP-IPT) further complicates its classification, emphasizing the need for thorough investigation. CASE PRESENTATION: A 50-year-old male presented with a left palatal lesion histologically diagnosed as SP-IPT. Surgical resection revealed characteristic features, including papillary projections into cystically dilated ductal spaces. Immunohistochemistry confirmed positivity for pan-keratin AE1/AE3, cytokeratin 7, SOX10, and BRAF V600E. Whole-exome sequencing identified BRAF V600E and PIK3CA H1047R mutations. No recurrence was observed three months post-excision. DISCUSSION: SP-IPT's diagnostic complexity stems from its resemblance to SP without an exophytic papillary component. However, shared BRAF mutations suggest a close relationship between the two entities. Similarities with skin adnexal tumors underscore the importance of molecular markers in tumor classification. The identification of PIK3CA mutation in SP-IPT adds to its molecular diversity, warranting further investigation into its clinical significance. CONCLUSION: This study presents a case of SP-IPT with unique histological and molecular features, highlighting its diagnostic and therapeutic challenges. The co-occurrence of BRAF V600E and PIK3CA H1047R mutations suggests a distinct molecular profile in SP-IPT, necessitating further research to elucidate its biological behavior and clinical implications.

Uncommon case of cytopathological features of sialadenoma papilliferum.

Sialadenoma papilliferum, a benign and rare salivary gland neoplasm, accounts for 0.4%-1.2% of all salivary gland tumors and occurs primarily in minor salivary glands of the oral cavity. Here, we report a case of sialadenoma papilliferum and its associated cytological findings. A papillary tumor was incidentally detected on the palate of an 86-year-old Japanese man. Conventional oral exfoliative cytology was performed; the cytology smear exhibited epithelial clusters composed of atypical epithelial cells with a high nuclear/cytoplasm ratio and arranged in sheet or small papillary-like projections. Cytoplasmic vacuoles were also observed in the papillae. It was difficult to make a definitive diagnosis due to the presence of uncommon cytological features. The excisional biopsy specimen revealed histological features characteristic of sialadenoma papilliferum. Mutational analysis detected BRAFV600E mutation, which confirmed the diagnosis of sialadenoma papilliferum. To the best of our knowledge, no prior cytomorphological evaluations of sialadenoma papilliferum have been reported in detail. Oral exfoliative cytology specimens from salivary gland tumors can demonstrate uncommon cytomorphological features. A differential diagnosis of sialadenoma papilliferum can be based on the observation of mildly atypical epithelial cells that form small papillary-like structures.

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

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.

Spectrum of salivary gland diseases: A 24-year single-institution retrospective study.

Introduction: Salivary glands are exocrine glands and are classified as major and minor salivary glands. Salivary gland pathologies are classified as neoplastic and non-neoplastic. The neoplasms of salivary glands can be benign or malignant. Aim: The aim of the study was to describe the frequency of various salivary gland diseases reported in our institution from 1997 to 2021. Methodology: This was a 24-year retrospective study of salivary gland lesions processed and reported by the Department of Oral Pathology and Microbiology. Data regarding age, gender, site, and diagnosis were obtained and studied. Results: Amongst the total 5928 biopsied cases reported, 6% were salivary gland pathologies. Two hundred sixty-six were non-neoplastic lesions and 81 were neoplastic. The most common non-neoplastic lesion was mucous extravasation cyst. The most common neoplastic lesion was pleomorphic adenoma. Conclusion: The frequency of occurrence of salivary gland lesions in the last 24 years of this institution is almost similar to that stated in other published studies.

Case Report: Papillary Lesions at the Mouth Floor May Mimic Sialadenoma Papilliferum.

Salivary gland tumor Sialadenoma papilliferum (SialP) clinically resembles papillary epithelial lesions, such as squamous papilloma (SqP) or verrucous leukoplakia. Pathological sampling including an adequate depth of both the mucosa and submucosa layer is required for discrimination between the diseases. Though ductal proliferation in the submucosa is characteristic in SialP, papillary lesions arising at the mouth floor, specifically near the ductal orifice, are more problematic. Salivary gland ductal ectasia, along with the overlying papillary hyperplasia, may mimic the biphasic tumorous growth pattern of SialP, making discrimination extremely difficult. Further cellular dysplasia in the papillary mucosal lesion raises the possibility of malignant transformation in a known benign lesion, SialP. Herein, we present a case of SqP at the mouth floor which mimicked both clinical and pathological features of SialP and compared it with a definite case of SialP. Moreover, we discuss major differential points that clinicians and pathologists should consider during diagnosis of oral papillary lesions arising near the salivary glands.

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

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.

Sialadenoma Papilliferum.

Sialadenoma papilliferum (SP) is a rare, benign salivary gland neoplasm sharing similar histopathologic features and harboring the same genetic alterations, BRAF V600E or HRAS mutations, with syringocystadenoma papilliferum. SP most commonly occurs in the hard palate and in older adults. Clinically, SP is most likely to be diagnosed as a squamous papilloma. Microscopically, SP shows an exophytic papillary epithelial proliferation and a contiguously endophytic ductal proliferation. Two distinct subtypes are identified: classic SP and oncocytic SP. Conservative surgical treatment seems to be adequate with a low recurrence. SOX10 immunohistochemistry and BRAF analysis may be useful in differential diagnosis.

Salivary Sialadenoma Papilliferum Consists of Two Morphologically, Immunophenotypically, and Genetically Distinct Subtypes.

Papillary salivary gland neoplasms are rare tumors usually arising in the minor salivary glands of the oral cavity. Their classification has been historically confusing due to overlapping histologic features, but molecular analysis may clarify these entities. Sialadenoma papilliferum (SP) is a peculiar member of this group that demonstrates both an endophytic ductal and an exophytic squamous component. SP closely resembles syringocystadenoma papilliferum of the skin, a tumor which has recently been shown to harbor BRAF V600E or HRAS mutations. We sought to perform histologic and immunophenotypic analysis of a group of SP, along with BRAF and HRAS mutational analysis. We collected 13 SP cases from 7 females and 6 males ranging from 2 to 91 years (mean 62.8). Five exophytic ductal papillomas were also analyzed as controls. Histological analysis was performed along with immunohistochemistry for CK7, p63, and SOX10. BRAF VE1 immunohistochemistry was done in all tumors, and BRAF V600E and HRAS Sanger sequencing was successfully performed in all but two cases. Histologic analysis revealed that SP consisted not only of classic SP (9 of 13 cases) but also an oncocytic variant (4 of 13 cases) characterized by a glandular component that uniformly exhibited abundant granular cytoplasm and prominent nucleoli. By immunohistochemistry, all SP demonstrated luminal CK7 and basal p63 expression, but SOX10 was expressed only in conventional SP (9 of 9 cases). BRAF VE1 immunohistochemistry was positive in 9 of 9 conventional SP but 0 of 4 oncocytic SP; staining was present in both the exophytic and endophytic components. BRAF V600E mutational status was confirmed by Sanger sequencing in 11 cases (7 conventional and 4 oncocytic). The exophytic ductal papillomas were negative for BRAF mutations, and all tumors tested were negative for HRAS mutations. In summary, we demonstrated that SP consists of two variants: (1) conventional SP which is SOX10-positive and harbors BRAF V600E mutations similar to syringocystadenoma papilliferum of the skin; and (2) an oncocytic variant which is SOX10-negative and negative for BRAF mutations. We also demonstrated that both the endophytic glandular component and exophytic squamous components of conventional SP harbor BRAF V600E mutations and are therefore neoplastic.

Sialadenoma papilliferum of the bronchus: a rare tumour of salivary gland origin.

Sialadenoma papilliferum is a benign salivary tumour which rarely occurs in the bronchial tree. Up to now, only four cases of pulmonary papillary sialadenoma have been reported in the literature. We discuss the case of a male patient with an accidental finding of a middle lobe nodule. The patient underwent a minimally invasive anatomical resection of the lobe to remove the lesion; the postoperative course was regular, and he was healthy at the last follow-up.

Sialadenoma papilliferum of the hard palate: A rare case report.

Sialadenoma papilliferum (SP) is a rare benign salivary gland tumor with unclear cell origin. This report presents a new case of SP of the hard palate occurring in a 50-year-old female. The lesion was completely excised, and the microscopic features were consistent with SP. The knowledge of this rare entity contributes to proper diagnosis and prevents unnecessary radical surgery and treatment.

Sialadenoma Papilliferum: Analysis of Seven New Cases and Review of the Literature.

Sialadenoma papilliferum (SP) is a rare benign salivary gland neoplasm that comprises from 0.4 to 1.2% of all salivary gland tumors. The tumor is so named because of its microscopic resemblance to the syringocystadenoma papilliferum, an uncommon benign tumor of sweat gland origin. The purpose of this paper is to report the clinical and microscopic features of seven new cases of SP and combine them with cases previously reported in the English language literature to further define this unusual lesion. Combining our cases with acceptable cases from the literature, the palate (especially the hard palate) was the most common site, with 80% of the cases occurring in this location. Other locations in decreasing order were buccal mucosa, upper lip, retromolar pad, and parotid gland. Age at diagnosis ranged from 18 to 87 years with a peak in the 6th decade and an average age of 56.4 years. Microscopically, the lesions demonstrated a papillary surface morphology, and the papillary projections varied from long and pointed to short and blunted. The supporting connective tissue contained a variable number of convoluted ductal structures, which often fused with the overlying surface epithelium. The ductal structures exhibited papillary infoldings and were lined by a double layer of epithelium consisting of basal cell layer and a luminal layer of cuboidal-to-columnar ductal cells. Immunohistochemical reactivity with p63 and p40 indicated that the basal cell layer was comprised predominantly of neoplastic myoepithelial cells. The luminal cells were immunoreactive with epithelial membrane antigen characteristic of ductal cell differentiation. Conservative surgical treatment was accomplished in most cases and appears to be adequate treatment as only two recurrences were documented. Several case reports of purported malignant transformation in SP have been reported in the literature, but in our opinion, there is insufficient evidence in the publications to unequivocally determine whether any of the malignancies truly originated within a pre-existing SP.

Oral Squamous Papilloma of Edentulous Mouth Interfering with Denture Retention.

Soft tissue overgrowths inside oral cavity can present with wide range of clinical manifestations and some of them can asymptomatic. Oral squamous papilloma is one of that asymptomatic lesion described in the literature with extremely low virulence and infectivity rate. Soft tissue overgrowths can sometimes interfere with denture retention. Here we report a case of squamous papilloma in a 60 years old edentulous female who presented with loss of denture retention.

Sialadenoma papilliferum in the buccal mucosa detected on 18F-fluorodeoxyglucose-positron emission tomography.

An incidental discovery of an accumulation of 18F-fluorodeoxyglucose (FDG) in the oral cavity of patients with malignant tumours on FDG positron emission tomography (PET) can pose a problem regarding the differential diagnosis of metastatic lesions. Large accumulations can often be found even when tumours in the salivary or thyroid gland are benign, so FDG-PET is limited in its ability to differentiate between benign and malignant disease. This report describes a rare case of sialadenoma papilliferum in the buccal mucosa that was discovered incidentally on FDG-PET in a patient with multiple metastases to bone after an operation for rectal cancer.

The First Successful Case of Transoral Robotic Surgery in a Patient with Sialadenoma Papilliferum.

INTRODUCTION: Sialadenoma papilliferum (SP) is a rare benign tumor, which originates from the minor salivary gland. It occurs at sites that have minor salivary glands, such as the palate, retromolar pads, buccal mucosa, and lips. The most common location for tumor development is on the hard palate. A differential diagnosis consists of ruling out other salivary gland tumors. Transoral robotic surgery (TORS) is a new technology used in head and neck surgery within certain centers around the world. CASE REPORT: Herein, we present the first successful case of SP tumor removal by TORS. CONCLUSION: This particular case highlights the identification of this rare tumor in an unusual location. Furthermore, it demonstrates the utilization of TORS, leveraging the superior visualization to obtain excellent local control with minimal acute and long-term morbidity, in comparison to conventional transoral surgical approaches.