Plexiform Neurofibroma of the Submandibular Salivary Gland: A Rare Tumour

A 15 year old boy presented with swelling in the submandibular region. X ray of the part showed faint radio opaque shadow. A provisional diagnosis of sialadenitis with sialiolithiasis was made. Excised mass was reported histopathologically as plexiform neurofibroma of submandibular salivary gland. Plexiform neurofibroma of the salivary gland is a rare benign tumour, often present in the parotid gland. It is very rare in submandibular salivary gland. It is a slow growing, locally infiltrating tumour.     

Unusual case of a projecting intraoral giant sialolith

Sialolithiasis is the most common disease of the salivary glands. This report describes the case of a patient who had an unusually large submandibular gland ductal sialolith that had protruded out into the oral cavity.     

Immunohistochemical Reactivity of Prostate-Specific Membrane Antigen in Salivary Gland Tumors

Prostate-specific membrane antigen (PSMA) is a transmembrane glycoprotein that is overexpressed in the prostate gland and prostate cancer. PSMA has been recently used in positron emission tomography/computed tomography (PET/CT) imaging and targeted alpha-radiation therapy (TAT) for prostate cancer. Recently, the tubarial gland, a type of minor salivary gland that is described as a new organ situated in the pharynx, is reported to express PMSA. Here, we studied the expression of PSMA in common benign and malignant salivary gland tumors. We performed immunohistochemistry for PSMA in 55 salivary gland tumors comprising 10 pleomorphic adenomas, 10 Warthin tumors, 9 basal cell adenomas, 9 adenoid cystic carcinomas, 9 mucoepidermoid carcinomas, and 8 salivary duct carcinomas. PSMA was expressed in 97% of benign tumors and 77% of malignant tumors. Moreover, PSMA was expressed in 59% of normal salivary glands adjacent to the tumor. PSMA is relatively expressed in salivary gland tumors and salivary glands. Therefore, salivary gland neoplasm, and normal salivary gland, possibly demonstrate the accumulation of PSMA in PET/CT. Thus, we need to monitor the side effects in the salivary glands during TAT for prostate cancer.     

Mammary Lobular Carcinoma-Like Salivary Gland Carcinoma: Report of a Rare Case

Salivary and mammary glands are both exocrine organs sharing multiple tumorigenic processes. To the best of our knowledge, salivary gland tumors mimicking invasive lobular carcinoma of the breast have not yet been described. Herein, we report a case of a 62-year-old male who presented with progressive facial paralysis. Pathologic examination revealed an ill-defined epithelial neoplasm exhibiting discohesive growth set within an extensively fibrotic stroma. Both perineural and intraneural invasion were present. E-cadherin and p120 immunostaining showed aberrant cytoplasmic expression. Targeted next-generation sequencing detected a frameshift mutation of the CTNNA1 gene as the only known pathogenic variant. The patient was treated with surgical resection, immunotherapy, and chemotherapy. Currently, he is alive with disease twenty months after disease onset.     

Epithelial Proliferation in Small Ducts of Salivary Cystadenoma Resembling Atypical Ductal Hyperplasia of Breast

Salivary gland cystadenomas are cystic neoplasms with diverse architecture and cytology. Cystadenomas may have a considerable intracystic epithelial component, but an epithelial proliferation in small ducts and cysts resembling atypical ductal hyperplasia of breast has not been documented. The patient was a 68-year-old man with a slow growing right submandibular mass. He has no recurrence 13 months after resection. The tumor was polycystic and measured 3.0 × 2.5 × 2.5 cm. The epithelium of the larger cysts was composed of flat, cuboidal, columnar, and apocrine-like cells. Many of the larger cysts showed “Roman bridges”, epithelial tufting, and papillae. The smaller cysts and ducts had apocrine-like cells forming secondary glandular lumens. The ductal cells were surrounded by clear myoepithelial cells. Nuclear pleomorphism and hyperchromasia was seen in the apocrine-like cells. Adjacent to the larger cysts, there was an adenomatoid proliferation of small ducts surrounded by myoepithelial cells. No mitotic activity, necrosis, or stromal invasion was identified. The ductal cells were diffusely positive for keratin 7 and androgen receptors with focal expression of keratin 19 and high-molecular weight keratin. S-100, estrogen and progesterone receptors, and BRST-2 were negative in the ductal cells. Recognition of a prominent intraductal epithelial component in cystadenomas is important to avoid a misdiagnosis of cystadenocarcinoma or low-grade salivary duct carcinoma. Cystadenomas join the list of salivary gland lesions with microscopic similarities to primary lesions of the breast.     

Multiple Malignant Salivary Gland Neoplasms: Mucoepidermoid Carcinoma of Palate and Adenoid Cystic Carcinoma of Floor of Mouth

Salivary gland tumors usually occur as single lesions. To have more than one tumor is unusual. We report a case of an adult male who presented with a mucoepidermoid carcinoma involving the minor salivary glands of the palate at age 57 years, followed by an adenoid cystic carcinoma of the floor of mouth at age 63 years. The patient later succumbed to non-Hodgkin lymphoma at age 72 years. There are 31 acceptable cases of multiple malignant salivary gland neoplasms reported in the world literature. Multiple malignant tumors of the same histologic type are more common than those of different histologic type. Bilateral acinic cell adenocarcinoma was the most frequent combination of multiple salivary gland malignancy, accounting for 14 cases (10 synchronous and four metachronous). All involved the parotid glands bilaterally with the exception of one case that involved parotid and submandibular gland. Polymorphous low-grade adenocarcinoma accounted for three of the four cases of multiple malignant tumors involving minor salivary glands. Individuals with a history of malignancy are at risk for the development of additional malignant tumors and should receive appropriate clinical follow-up.

P27/SKP-2 Histochemical Profile is Relevant to Malignant Salivary Gland Tumors (MST) Histogenesis and Tumor Grade

Malignant salivary gland tumors (MST) represent over more than 24 distinct morphological subtypes. Most high grade tumors arise from the excretory duct portion of the salivary gland apparatus; the remainder from the intercalated duct portion. Altered p27/skp-2 expression has been associated with tumor aggressiveness and histologic differentiation. In our study, we analyzed p27/skp-2 expression proteins on series of malignant salivary gland tumors in order to assess their value as a histogenetic marker, which is relevant to tumor grade. 61 MST cases were segregated by proposed histogenesis and immunohistochemistry was performed using antibodies directed against p27 and skp-2. MST of proposed intercalated duct origin (n = 27) showed strong p27 expression (n = 25/27; 93%) in the vast majority of cases and all cases weakly expressed skp-2. MST of proposed excretory duct origin (n = 32) showed strong p27 expression (n = 18/32; 56%) and moderately strong/strong skp-2 expression (n = 18/32; 56%), respectively, in over half the cases. MST of intercalated duct origin showed evident p27/skp-2 inverse correlation. Differences in p27/skp-2 expression among the MST subtypes correlated with histogenesis and tumor grade, which reinforces the notion that tumor behavior is relevant to the portion of the salivary gland unit from which they arise. MST of proposed intercalated duct origin strongly expressed p27, and not skp-2, unlike MST of proposed excretory duct origin. The immunohistochemical profile of high grade mucoepidermoid carcinoma was distinct from its low/intermediate grade counterparts, suggesting a separate identity. These results may influence future decision making when formulating workable MST categorization schemes. Further studies on a larger series of MST are warranted in order to support the value of our findings.     

Expression of Mucins in Different Entities of Salivary Gland Cancer: Highest Expression of Mucin-1 in Salivary Duct Carcinoma: Mucin-1 – highest expression in Salivary Duct Carcinoma

Therapeutic options for advanced salivary gland cancer (SGC) are rare. Therefore, it was the aim of this study to investigate the extent and intensity of Mucin-1 (MUC1), Mucin-16 (MUC16), and Mucin-5AC (MUC5AC) as potential molecular targets using immunohistochemistry. The medical records of all patients who underwent primary surgery for salivary gland cancer with curative intent in a tertiary referral center between 1990 and 2018 were reviewed. Immunohistochemical staining for MUC1, MUC16, and MUC5AC was performed for all patients with sufficient formalin-fixed paraffin-embedded material, and a semi-quantitative combined score derived from the H-score for the cytoplasmatic, the membranous and the apical membrane was built for the most common entities of SGC. 107 patients with malignancies of the parotid (89.7%) and the submandibular gland (10.3%) were included. The most common entities were mucoepidermoid carcinoma (MuEp; n = 23), adenoid cystic carcinoma (AdCy; n = 22), and salivary duct carcinoma (SaDu; n = 21). The highest mean MUC1 combined score was found in SaDu with 223.6 (±91.7). The highest mean MUC16 combined score was found in MuEp with 177.0 (±110.0). The mean MUC5AC score was low across all entities. A higher MUC1 combined score was significantly associated with male gender (p = 0.03), lymph node metastasis (p < 0.01), lymphovascular invasion (p = 0.045), and extracapsular extension (p = 0.03). SaDu patients with MUC16 expression showed a significantly worse 5-year progression-free survival than those without MUC16 expression (p = 0.02). This is the first study to give a comprehensive overview of the expression of MUC1, MUC16, and MUC5AC in SGC. Since advanced SGCs lack therapeutic options in many cases, these results warrant in vitro research on therapeutic targets against MUC1 in SaDu cell lines and xenograft models.     

Low-Grade Intraductal Carcinoma of the Parotid Gland: A Case Report and Literature Review

Low-grade intraductal carcinoma is a rare neoplasia with an excellent prognosis, previously classified as low-grade cribriform cystadenocarcinoma and low-grade salivary duct carcinoma. The tumor mainly occurs in the parotid gland and presents a ductal phenotype and an intraductal/intracystic growth pattern. It resembles intraductal breast lesions such as atypical ductal hyperplasia, papillary and cribriform ductal carcinoma in situ. Despite its infrequency, discriminating low-grade intraductal carcinoma from other salivary gland tumors is crucial, especially because of its favorable prognosis. A 74-year-old woman with a history of neurofibromatosis underwent a superficial parotidectomy to remove a sharply demarcated multi-cystic mass, diagnosed as category 4 at FNAC. The histological examination revealed a demarcated but unencapsulated lesion composed of a bigger cyst surrounded by several smaller cysts, lined by a monolayer or bilayer epithelium alternated with a cribriform proliferation, characterized by “Roman-bridges”, with occasional micro-papillae. A myoepithelial component, with a basal disposition, was present, confirmed by intense staining for protein p63 and SMA. Immunohistochemical stains showed intense, strong uniform positivity for pan-cytokeratin, protein S100, and SOX10. The Ki67 proliferation index was low (< 10%). A diagnosis of Low-grade Intraductal Carcinoma (LGIC) of the parotid was made. We performed a literature search in PUBMED for “Intraductal carcinoma”, “Low-grade Intraductal Carcinoma”, “Cribriform Cystadenocarcinoma”, “Salivary Duct Carcinoma”, and “Low-Grade Salivary Duct Carcinoma”. We selected 17 papers published between 1983 and 2020; the most affected anatomical site was the parotid gland (77/90), followed by minor salivary glands (6/90), the intraparotid lymph nodes (3/90) and the submandibular gland (4/90). Their main histopathological features are reported in the paper. Here we present a case report and a review of scientific literature on this topic to provide some essential diagnostic tools to discriminate this rare entity.     

An Update on Salivary Gland Pathology

Andrew G. Huvos was born in communist Budapest, Hungary, in March of 1934. At twenty-four he immigrated to New York City, working as a cytotechnologist at Delafield Hospital. Dr. Huvos attended the University of Gottingen Medical School in Germany, where he was awarded his MD degree. He completed a 1-year internship at New York Hospital, going on to Residency at Delafield Hospital and Fellowship at Presbyterian Hospital. Dr. Huvos ascended through the ranks to Attending Pathologist and Member at Memorial Hospital for Cancer and Allied diseases, at Memorial Sloan-Kettering Cancer Center (MSKCC) in New York City. Concurrently, he was appointed to Weill Medical College of Cornell University, where he was Professor of Pathology for over two decades. Dr. Huvos was an editorial referee for over half a dozen highly esteemed publications, including the New England Journal of Medicine and Cancer. He trained over a thousand oncological surgical pathology fellows, head and neck fellows, and surgeons. Dr. Huvos spent nearly 40 years at MSKCC and his career was accompanied by his authorship of 388 peer-reviewed publications and eighteen book chapters. His legacy leaves behind a generation of pathologists who have greatly benefited from his tutelage.     

Salivary Gland Tumors: Current Concepts and Controversies

This current review focuses on current concepts and controversies for select key salivary gland epithelial neoplasms. Rather than the traditional organization of benign and malignant tumors, this review is structured around select key topics: biphasic tumors, mammary analogue secretory carcinoma, and the controversy surrounding polymorphous low-grade adenocarcinoma and cribriform adenocarcinoma of (minor) salivary gland origin.     

Human Kallikrein 8 Expression in Salivary Gland Tumors

The human kallikrein 8 protein (KLK8) is expressed in many normal tissues including esophagus, skin, testis, tonsil, kidney, breast, and salivary gland, and is found in biological fluids including breast milk, amniotic fluid, seminal fluid and serum. It has also been shown to be a biomarker and prognostic factor for breast cancer. The aim of this study was to determine whether KLK8 is expressed in salivary gland tissues and salivary gland tumors (both benign and malignant), in order to compare normal with tumor tissues. Pleomorphic adenomas, adenoid cystic carcinomas, polymorphous low grade adenocarcinomas, acinic cell carcinomas, mucoepidermoid carcinomas, and adenocarcinomas NOS of both minor and major salivary glands were examined. The results of this study indicate that most salivary gland tumors show high levels of expression of KLK8.     

Expression of Mucins in Salivary Gland Mucoepidermoid Carcinoma

Mucoepidermoid carcinoma (MEC) is the most common malignant salivary gland tumour in both adults and children. Histological grading of MEC is subjective, but plays an important role in predicting patient prognosis. Epithelial mucin (MUC) status may aid in establishing a more accurate grade. This study aimed to investigate the expression of various mucins (MUC1, MUC2, MUC4 and MUC5AC) in MECs to determine a possible correlation with tumour grade. Fifteen cases of each tumour grade (low-, intermediate-, and high-grade) were retrieved from the pathology archives of the Department of Oral Pathology and Oral Biology at the University of Pretoria. The patients included 23 men and 22 women, and ranged from 13 to 85 years (mean 49.8 years). Sections from formalin-fixed paraffin-embedded (FFPE) tissue were used for fluorescence in situ hybridization (FISH) for MAML2 rearrangements and MUC immunohistochemical analysis. The percentage immunohistochemical expression of the neoplastic mucous cells was evaluated first, followed by the overall percentage expression of all tumour cells. The results indicated that MUC1 overexpression may be a reliable marker of high-grade MECs, whereas MUC4 overexpression may be more indicative of low-grade tumours. MUC5AC expression was considered an unreliable marker in determining grade. MUC2 was only expressed in a single case of MEC and may be considered a useful marker to exclude MEC as a diagnostic possibility. This study demonstrates that MECs show an altered MUC expression pattern that can be used for diagnostic purposes and to aid in establishing a more accurate tumour grade.     

My Journey into the World of Salivary Gland Sebaceous Neoplasms

As part of this symposium honoring Leon Barnes, the authors were asked to present the case from which they learned the most. I chose a cystic sebaceous lymphadenoma (SL) as my case presentation. This paper presents this unusual case, as well as several additional sebaceous tumors that came across my desk the first few years I was in practice. These interesting cases led me to thoroughly review the literature on sebaceous tumors of the salivary glands, resulting in several publications, the largest series of sebaceous tumors published at this time as well as a careful review of all cases in the literature. The author will also review the current and previous literature on the five types of salivary gland sebaceous tumors: sebaceous adenoma, SL (and non-sebaceous lymphadenoma), sebaceous carcinoma, sebaceous lymphadenocarcinoma, and sebaceous differentiation in other types of salivary gland lesions.