Distribution and Frequency of Salivary Gland Tumours: An International Multicenter Study.

BACKGROUND: Salivary gland tumours (SGT) are a relatively rare group of neoplasms with a wide range of histopathological appearance and clinical features. To date, most of the epidemiological studies on salivary gland tumours are limited for a variety of reason including being out of date, extrapolated from either a single centre or country studies, or investigating either major or minor glands only. METHODS: This study aimed to mitigate these shortcomings by analysing epidemiological data including demographic, anatomical location and histological diagnoses of SGT from multiple centres across the world. The analysed data included age, gender, location and histological diagnosis from fifteen centres covering the majority of the world health organisation (WHO) geographical regions between 2006 and 2019. RESULTS: A total of 5739 cases were analysed including 65% benign and 35% malignant tumours. A slight female predilection (54%) and peak incidence between the fourth and seventh decade for both benign and malignant tumours was observed. The majority (68%) of the SGT presented in major and 32% in the minor glands. The parotid gland was the most common location (70%) for benign and minor glands (47%) for malignant tumours. Pleomorphic adenoma (70%), and Warthin's tumour (17%), were the most common benign tumours whereas mucoepidermoid carcinoma (26%) and adenoid cystic carcinoma (17%) were the most frequent malignant tumours. CONCLUSIONS: This multicentre investigation presents the largest cohort study to date analysing salivary gland tumour data from tertiary centres scattered across the globe. These findings should serve as a baseline for future studies evaluating the epidemiological landscape of these tumours.

Microsecretory Adenocarcinoma of Salivary Glands: An Expanded Series of 24 Cases.

Microsecretory adenocarcinoma (MSA) is a recently described salivary gland tumor with a characteristic histologic and immunophenotypic profile and recurrent MEF2C-SS18 fusions. Because only six cases of MSA have been published, its complete clinicopathologic spectrum is unclear, and its biologic behavior has not been documented. Here, we present an updated and expanded experience of 24 MSA cases. All cases of MSA were obtained from the authors' files. Immunohistochemistry for S100, SOX10, p63, p40, SMA, calponin, and mammaglobin was performed. Molecular analysis was performed by targeted RNA sequencing, SS18 break apart fluorescence in situ hybridization, and/or reverse transcriptase polymerase chain reaction for MEF2C-SS18 fusion. Clinical follow-up was obtained from medical records. A total of 24 MSA cases were collected, from 13 women and 11 men, ranging from 17 to 83 years (mean 49.5 years). The vast majority (23 of 24) arose in the oral cavity, with the palate (n = 14) and buccal mucosa (n = 6) as the most frequent subsites. Tumors showed consistent histologic features including: (1) microcystic tubules, (2) flattened intercalated duct-like cells, (3) monotonous oval hyperchromatic nuclei, (4) abundant basophilic luminal secretions, (5) fibromyxoid stroma, and (6) circumscribed borders with subtle infiltration. The tumors were very consistently positive for S100 (24 of 24), p63 (24 of 24), and SOX10 (14 of 14) and negative for p40 (0 of 21), calponin (0 of 12) and mammaglobin (0 of 16), while SMA (4 of 20) was variable. MEF2C-SS18 fusion was demonstrated in 21 of 24 cases; in the remaining 3 cases with insufficient RNA, SS18 break apart FISH was positive. Treatment information was available in 17 cases, all of which were managed with surgery only. In 14 cases with follow-up (1-216 months, mean 30), no cases recurred or metastasized. MSA is a distinct salivary gland neoplasm with remarkably consistent clinical, histologic, immunophenotypic, and genetic features that generally behaves in an indolent manner following surgery alone. These observations solidify MSA as a unique, low-grade salivary gland carcinoma that warrants inclusion in the next version of the WHO classification of head and neck tumors.

Next-generation sequencing analysis for detecting human papillomavirus in oral verrucous carcinoma.

OBJECTIVE: The etiology of oral verrucous carcinoma is unknown, and human papillomavirus 'involvement' remains contentious. The uncertainty can be attributed to varied detection procedures and difficulties in defining 'gold-standard' histologic criteria for diagnosing 'verrucous' lesions. Their paucity also hampers investigation. We aimed to analyze oral verrucous lesions for human papillomavirus (HPV) subtype genomes. STUDY DESIGN: We used next-generation sequencing for the detection of papillomavirus sequences, identifying subtypes and computing viral loads. We identified a total of 78 oral verrucous cases (62 carcinomas and 16 hyperplasias). DNA was extracted from all and sequenced at a coverage between 2.5% and 13%. RESULTS: An HPV-16 sequence was detected in 1 carcinoma and 1 hyperplasia, and an HPV-2 sequence was detected in 1 carcinoma out of the 78 cases, with viral loads of 2.24, 8.16, and 0.33 viral genomes per cell, respectively. CONCLUSIONS: Our results indicate no conclusive human papillomavirus involvement in oral verrucous carcinoma or hyperplasia.

Perineural invasion in adenoid cystic carcinoma of the salivary glands: a valid prognostic indicator?

Of malignant tumours with a propensity to invade the perineural space, adenoid cystic carcinoma of the salivary glands is perhaps the best known. However, it is not known if microscopic evidence of perineural invasion has true prognostic significance in adenoid cystic carcinoma. A review of the available data, which is the aim of this article, reveals the issue is not straightforward. There is a plethora of conflicting data which, on balance, suggest the answer is indeed in the affirmative, particularly if the nerve involved is above a certain size, or "named". Even if the data are equivocal, many head and neck surgeons and oncologists take account of histologically proved perineural invasion when planning treatment for adenoid cystic carcinoma.

Prognostic factors in malignant tumours of the salivary glands.

Salivary gland tumours are a relatively rare group of lesions best managed in specialist centres. We review some of the factors that influence their prognosis. Clinical stage is the most important, with large malignancies having a poor prognosis regardless of histological grade and other features such as perineural invasion. Even high grade neoplasms may do well when they are small. A helpful guide to the management of salivary cancers is the "4 cm" rule.

CD40 in human oral epithelia.

CD40 is a transmembrane glycoprotein belonging to the tumour necrosis factor receptor superfamily, which has a role in a number of biological functions, including the regulation of cell growth and division, and cell mediated immunity. Although originally described on leucocytes, principally B lymphocytes, there is now abundant evidence for the cellular diversity of CD40. The aim of this article is to review the available data on CD40 in oral epithelium, principally that lining the oral mucosa, but also that of the salivary glands.

The immunohistology of CD40 in human oral epithelium in health and disease.

BACKGROUND: CD40 has a role in the regulation of immune responses, cell proliferation and migration, and apoptosis. Little is known of its distribution in oral mucosal pathology. METHODS: Oral keratinocyte lines were tested for CD40 protein by Western blotting. Immunohistochemistry was used to stain paraffin sections of oral mucosa in health and in inflammatory, reactive, dysplastic and malignant disease. RESULTS: Western blotting confirmed the presence of CD40 in oral keratinocytes. CD40 was generally expressed by keratinocytes in the basal layer, with variable parabasal expression. Langerhans cells also stained positively. Expression was lost in nine of 33 (27%) epithelial dysplasias, seven of which were severe. Eighty-one percent of well, 69% of moderately and 50% of poorly differentiated oral squamous cell carcinomas (OSCC) expressed CD40. Overall, 45 of 65 (69%) OSCC were positive. The pattern of expression was unrelated to tumour differentiation. CONCLUSION: CD40 expression by basal and parabasal oral keratinocytes is physiological. Expression is lost in approximately one-third of oral epithelial dysplasias and OSCC. The significance of such loss remains unknown, but may be related to immunological or other abnormalities of keratinocyte homeostasis.

Expression of major histocompatibility complex class II and costimulatory molecules in oral carcinomas in vitro.

Recognition in the 1980 s that keratinocytes can express class II molecules of the Major Histocompatibility Complex (MHC) first raised the possibility that these cells might have an immunological function, and may even act as antigen presenting cells (APC). For effective T lymphocyte activation, APC require, in addition to MHC II, appropriate costimulatory signals. The aim of this study was to determine the expression of MHC class II and the co-stimulatory molecules CD40, CD80 and CD86 in keratinocytes derived from healthy oral mucosa and oral carcinomas. Using flow cytometry, it was confirmed that oral keratinocytes, switch on, expression of MHC class II molecules after stimulation with IFNgamma in vitro. All keratinocyte lines expressed CD40 constitutively; by contrast, CD80 and CD86 were universally absent. Loss of CD80 and CD86 may be one means whereby tumours escape immunological surveillance.

Oral nodular fasciitis: case report.

Nodular fasciitis is a reactive, non-neoplastic, myofibroblastic lesion that is thought to be a response of tissue to injury. Microscopically it mimics sarcoma, so accurate diagnosis is important to avoid over treatment. It has been reported at all anatomical sites, but is most common in the upper extremities. We present a rare case of nodular fasciitis of the soft tissues of the cheek.

Cheilitis glandularis: An unusual presentation in a patient with HIV infection.

Cheilitis glandularis is a rare disorder of unknown etiology characterized by inflammation of the minor salivary glands of the lower lip. The present report details the features of a patient who presented with cheilitis glandularis and was subsequently found to also have undiagnosed HIV infection.

Metastasising clear cell odontogenic carcinoma: a case report and review of the literature.

Primary odontogenic carcinomas are rare and examples which have metastasised are even more uncommon. We describe the first reported case of a clear cell odontogenic carcinoma which metastasised to distant bones, namely the 5th lumbar vertebra and hip, 3 years after initial diagnosis. The initial incisional biopsy was thought to represent a calcifying epithelial odontogenic tumour, but in the subsequent resection the tumour showed a prominent clear cell component admixed with squamous cells showing peripheral palisading, widespread infiltration and necrosis indicating a malignant neoplasm. Radiologically guided biopsy revealed a metastatic lesion in L5 vertebrae and left hip, confirmed by immunohistochemistry. The metastatic lesion had similar appearances to the first biopsy, and diagnosis was confirmed by comparison of histological features, immunohistochemistry and exclusion of a second primary lesion by clinical examination and imaging. The diagnosis of clear cell odontogenic carcinoma is a difficult one to make. The behaviour of these tumours is unpredictable. This case confirms that clear cell odontogenic carcinomas have the potential for distant metastasis and require long-term follow up.