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Concept: Parotid gland


The most common tumour of salivary gland is pleomorphic adenoma (PA). They are benign, painless, can grow into big tumours but usually do not affect nerves or lymph nodes. PA most commonly occurs in the parotid gland but it may involve submandibular, lingual and minor salivary glands also. They can attain giant proportions and weigh several kilograms. We report a giant PA arising in the submandibular gland and treated by complete surgical excision without any complication. A female patient presented with a tumour in the submandibular region and front of neck with a history of more than 18 years. The weight of the resected mass was 4.35 kg. Patient’s fear of surgery and lack of awareness were the main reasons for her long-standing swelling. Such giant PAs of the submandibular gland are very rare in medical literature.

Concepts: Mass, Sjögren's syndrome, Parotid gland, Salivary gland, Submandibular gland, Sublingual gland, Mumps, Serous fluid


Recurrent parotitis is a rare manifestation of Sjögren syndrome. The management of recurrent parotitis is challenging because conservative methods may be of limited efficacy and invasive approaches carry the risk of complications. Botulinum toxin has been shown to reduce salivary flow, and consequently, the results of its use in the management of recurrent parotitis have been encouraging. A 65-year-old female patient with recurrent parotitis due to Sjögren syndrome was referred to us, complaining of weekly bouts of inflammation. She required a course of antibiotics monthly to control bacterial superinfections. We treated her with onabotulinumtoxinA injections into both parotid glands at regular intervals. After her second injection cycle, she denied further inflammatory bouts, has not required antibiotics in more than 36 months, and denied any side effects. Botulinum toxin may be a safe and effective method of treating Sjögren syndrome-associated recurrent parotitis.

Concepts: Effectiveness, Sjögren's syndrome, Parotid gland, Mumps


A 32-year-old woman presented with a 6-week history of swelling of both parotid glands, dry eyes, and dry mouth. She reported having difficulty moving the right side of her face, and she felt tingling in the right side of her tongue.

Concepts: Mouth, Sjögren's syndrome, Right-wing politics, Tongue, Parotid gland, Glossopharyngeal nerve, Heerfordt's syndrome


We undertook a re-analysis of the Canadian data from the thirteen-country INTERPHONE case-control study (2001-2004), which evaluated the association between mobile phone use and risk of brain, acoustic neuroma, and parotid gland tumors. The main publication of the multinational INTERPHONE study concluded that “biases and errors prevent a causal interpretation”. We applied a probabilistic multiple-bias model to address possible biases simultaneously, using validation data from billing records and non-participant questionnaires as information on recall error and selective participation. Our modelling sought to adjust for these sources of uncertainty and to facilitate interpretation. For glioma, the odds ratio comparing highest quartile of use (over 558 lifetime hours) to non-regular users was 2.0 (95% confidence interval: 1.2, 3.4). The odds ratio was 2.2 (95% confidence interval: 1.3, 4.1) when adjusted for selection and recall biases. There was little evidence of an increase in the risk of meningioma, acoustic neuroma, or parotid gland tumors in relation to mobile phone use. Adjustments for selection and recall biases did not materially affect interpretation in our Canadian results.

Concepts: Epidemiology, Statistics, Brain tumor, Types of cancer, Neurology, Normal distribution, Mobile phone, Parotid gland


Each year, 500,000 patients are treated with radiotherapy for head and neck cancer, resulting in relatively high survival rates. However, in 40% of patients, quality of life is severely compromised because of radiation-induced impairment of salivary gland function and consequent xerostomia (dry mouth). New radiation treatment technologies enable sparing of parts of the salivary glands. We have determined the parts of the major salivary gland, the parotid gland, that need to be spared to ensure that the gland continues to produce saliva after irradiation treatment. In mice, rats, and humans, we showed that stem and progenitor cells reside in the region of the parotid gland containing the major ducts. We demonstrated in rats that inclusion of the ducts in the radiation field led to loss of regenerative capacity, resulting in long-term gland dysfunction with reduced saliva production. Then we showed in a cohort of patients with head and neck cancer that the radiation dose to the region of the salivary gland containing the stem/progenitor cells predicted the function of the salivary glands one year after radiotherapy. Finally, we showed that this region of the salivary gland could be spared during radiotherapy, thus reducing the risk of post-radiotherapy xerostomia.

Concepts: Ionizing radiation, Saliva, Radiation therapy, Sjögren's syndrome, Parotid gland, Salivary gland


Objectives. To investigate the expression of IL-34 in labial salivary glands (LSGs) of patients with primary SS (p-SS) and its role in inducing a pro-inflammatory monocyte phenotype.Methods. LSG biopsies were obtained from 20 patients with p-SS and 10 patients with non-Sjögren’s sicca syndrome (n-SS). The expression of IL-34, IL-1β, TNF-α, IL-17 and IL-23 was assessed by real-time PCR. IL-34 expression was also investigated in LSGs by immunohistochemistry. The frequencies of subpopulations of CD14(+) monocytes were evaluated by flow cytometry among isolated mononuclear cells from peripheral blood and salivary glands from both patients and controls. The role of recombinant IL-34 on isolated peripheral blood mononuclear cells was also evaluated.Results. IL-34 m-RNA was overexpressed in the inflamed salivary glands of p-SS and associated with increased expression of TNF-α, IL-1β, IL-17 and IL-23p19. The increased expression of IL-34 was confirmed by immunohistochemistry in paraffin-embedded salivary glands from p-SS patients. IL-34 expression was accompanied by the expansion of pro-inflammatory CD14(bright)CD16(+) monocytes in the salivary glands. In vitro stimulation of peripheral blood mononuclear cells with IL-34 induced the expansion of both CD14(+)CD16(-) cells and CD14(bright)CD16(+) cells in p-SS and non-SS subjects.Conclusion. IL-34 seems to be involved in the pathogenesis of salivary gland inflammation in p-SS.

Concepts: Immune system, Inflammation, Monocyte, Atherosclerosis, Sjögren's syndrome, Glands, Parotid gland, Salivary gland


Mucoepidermoid carcinoma (MEC) is the most common salivary gland malignancy. Recent studies have shown that most MECs harbor gene fusions involving MAML2-an alteration that appears to be specific for MEC, a finding that could be diagnostically useful. While most cases of MEC are histologically straightforward, uncommon variants can cause considerable diagnostic difficulty. We present 2 variants of MEC for which MAML2 studies were crucial in establishing a diagnosis: a previously undescribed ciliated variant, and the recently described Warthin-like variant. All cases of ciliated and Warthin-like MEC were retrieved from the archives of The Johns Hopkins Hospital. Break-apart fluorescence in situ hybridization for MAML2 was performed on all cases. One ciliated MEC and 6 Warthin-like MECs were identified. The ciliated MEC presented as a 4.6 cm cystic lymph node metastasis originating from the tongue base in a 47-year-old woman. The Warthin-like MECs presented as parotid masses ranging in size from 1.2 to 3.3 (mean, 2.7 cm) in 4 women and 2 men. The ciliated MEC consisted of macrocystic spaces punctuated by tubulopapillary proliferations of squamoid cells and ciliated columnar cells. The Warthin-like MECs were comprised of cystic spaces lined by multilayered oncocytic to squamoid cells surrounded by a circumscribed cuff of lymphoid tissue with germinal centers. In these cases, the Warthin-like areas dominated the histologic picture. Conventional MEC, when present, represented a minor tumor component. MAML2 rearrangements were identified in all cases. Warthin-like MEC, and now a ciliated form of MEC, are newly described variants of a common salivary gland carcinoma. Unfamiliarity with these novel forms, unanticipated cellular features (eg, cilia), and morphologic overlap with mundane benign processes (eg, developmental ciliated cysts, Warthin tumor) or other carcinomas (eg, ciliated human papillomavirus-related carcinoma) may render these variants susceptible to misdiagnosis. These unusual variants appear to consistently harbor MAML2 fusions-a finding that establishes a clear link to conventional MEC and provides a valuable adjunct in establishing the diagnosis.

Concepts: Cancer, Carcinoma in situ, Lymph node, Anatomical pathology, Johns Hopkins Hospital, Lymphatic system, Lymph, Parotid gland


The schwannoma-like pleomorphic adenoma is a rare histopathological variant of the pleomorphic adenoma. Five previous reports with seven cases exist in English language literature. These tumors present in the parotid gland most commonly. Intraparotid schwannomas of the facial nerve and schwannomas with glandular differentiation have also been reported. A 60-year-old male presented with an asymptomatic swelling over the left angle of the mandible. The swelling had been present for about 12 years with a recent increase in size. CT imaging showed a hyperdense circumscribed mass of the superficial lobe of the parotid. The working diagnosis was that of a benign tumor of salivary gland or soft tissue origin. The mass was excised with careful preservation of the facial nerve. The 3.5 cm mass was submitted for histopathological examination. The well-circumscribed, encapsulated mass showed a predominant sheet-like proliferation of Antoni type A-like tissue, Foci of glandular differentiation with duct-like structures were also seen. Cytological atypia or mitotic activity were not seen. Nuclei of lesional cells diffusely and strongly expressed reactivity to p63. The final diagnosis was a schwannoma-like pleomorphic adenoma. No recurrence has been reported in the 15 months since the removal. Facial nerve function is unimpaired with a House Brackmann facial nerve function score of one. The potential for misdiagnosis in fine needle aspirate and incisional biopsies is real in cases of schwannoma-like pleomorphic adenoma. The diagnostic pitfalls include the schwannoma and leiomyoma. Schwannomas with glandular differentiation have also been reported and therefore a misdiagnosis may potentially occur in excised specimens. Careful application of immunohistochemistry may help in the differentiation of these lesions.

Concepts: Cancer, Oncology, Cranial nerves, Needle aspiration biopsy, Parotid gland, Salivary gland, Submandibular gland, Sublingual gland


The salivary duct cyst (SDC) is a reactive ductal ectasia most frequently seen in major salivary glands, and likely caused by obstruction. The aim of this study is to define the clinical and histopathologic spectrum of intraoral SDCs. Cases were retrieved from the archives of Harvard School of Dental Medicine/StrataDx, Inc. from January 2012 to August 2014. There were 177 cases of which 103 (58.2%) occurred in females, with a median age of 56 (range 2-95). Approximately half of cases (45.8%) presented in the area of the buccal mucosa, lower lip mucosa, or mandibular vestibule, and 23.2% presented in the floor of mouth. SDCs were lined at least focally by 1-2 layers of cuboidal/columnar epithelium in 85.3% of cases and showed varying degrees of metaplasia (oncocytic, mucous cell, squamous, ciliated, apocrine-like) in 68.4% of cases. Intraluminal mucous stasis was present in 41.8% of SDCs, incipient calcification was present within 4.5% of SDCs, and chronic obstructive sialadenitis was seen in 90.2% of cases. No cysts showed adenomatous ductal proliferations or true papillary structures with fibrovascular cores, although 41.2% exhibited reactive undulation of cyst lining. Thirty-nine ‘papillary oncocytic cystadenoma-like’ SDCs (22.0%) demonstrated complete oncocytic metaplasia and marked undulation. An additional seven such cysts (4.0%) had a ‘Warthin tumor-like’ lymphoplasmacytic infiltrate. Intraoral SDCs occur most commonly in the sixth decade of life in locations distinct from extravasation mucoceles, likely secondary to intraluminal obstruction. SDCs show diverse histopathology and certain phenotypic variants may be mistaken for papillary oncocytic cystadenoma or Warthin tumor.

Concepts: Mucous membrane, Mouth, Anatomical pathology, Histopathology, Glands, Parotid gland, Lip, Buccal mucosa


Polyomaviruses (PyVs) are known to infect a wide range of vertebrates and invertebrates and are associated with a broad spectrum of diseases, including cancers, particularly in immune-suppressed hosts. A novel polyomavirus, designated rat polyomavirus 2 (RatPyV2), was identified from a breeding colony of rats having X-linked severe combined immunodeficiency. Using a human panpolyomavirus immunohistochemistry test (P-PIT), RatPyV2 was initially detected in the parotid salivary gland of a colony member. Rolling circle amplification using DNA from harderian and parotid glands identified a novel 5.1-kb polyomavirus genome closely related to human Washington University (WU) and Karolinska Institute (KI) and vole polyomaviruses but notably divergent from Rattus norvegicus PyV1 (RnorPyV1; also designated RatPyV1). Further screening showed RatPyV2 inclusion body infection in the lung epithelium and variably in other respiratory, reproductive, and glandular tissues of 12/12 (100%) rats. IMPORTANCE Although P-PIT was developed to detect diseases associated with known human polyomaviruses, the identification of a new polyomavirus in rats suggests that it may have utility as a broad-based screen for new, as well as known polyomaviruses. Our findings suggest that RatPyV2 may be a commensal infection of laboratory rats that can lead to disseminated disease in T cell immune-deficient rats. Infection of the X-SCID rats with RatPyV2 and Pneumocystis carinii is a potential model for coinfection pathogenesis and treatment options during transplant preclinical studies.

Concepts: Gland, Glands, Parotid gland, Brown rat, Salivary gland