Adamts18 Deficiency Causes Spontaneous SMG Fibrogenesis in Adult Mice

Chronic sclerosing sialadenitis of the submandibular gland (also known as Küttner tumor) is characterized by concomitant swelling of the submandibular glands secondary to strong lymphocytic infiltration and fibrosis. The pathogenesis of this disease has been unclear, but it is associated with immune disorders. ADAMTS18 is a member of the ADAMTS superfamily of extracellular proteinases. In this study, we showed that Adamts18 is highly expressed in submandibular salivary gland (SMG) during embryonic development and decreases but is retained in adult SMG tissue in mice. Adamts18 deficiency led to reduced cleft formation and epithelial branching in embryonic SMG before embryonic day 15.5 in mice. No significant histologic changes in the later stages of branching or the morphology of SMG were detected in Adamts18−/− mice. However, Adamts18 deficiency causes spontaneous SMG fibrogenesis and fibrosis in adult mice. At 8 wk of age, Adamts18−/− mice began to manifest the first signs of pathologic changes of mild fibrosis and CD11b+ cell infiltration in SMG tissues. At ≥8 mo, all male and female Adamts18−/− mice developed unilateral or bilateral SMG scleroma that is similar to patients with chronic sclerosing sialadenitis of the submandibular gland. Adamts18−/− mice also showed secretory dysfunction and severe dental caries. Histologically, SMG scleroma is characterized by progressive periductal fibrosis, acinar atrophy, irregular duct ectasis, and dense infiltration of IgG-positive plasma cells. A significant infiltration of CD4+ T lymphocytes and CD11b+ monocytes and macrophages was also detected in the SMG scleroma of Adamts18−/− mice. The levels of TGF-β1, IL-6, and IL-33 were significantly increased in Adamts18−/− SMGs, which induces chronic inflammation and myofibroblast activation, ultimately leading to fibrosis. This study indicates that Adamts18 regulates the early branching morphogenesis of embryonic SMG and plays a role in protecting from spontaneous SMG fibrogenesis via modulating local inflammation, autoimmune reaction, and myofibroblast activation in adult mice.

Reticular enhancement of the submandibular gland on contrast-enhanced magnetic resonance imaging in three cases with IgG4-related chronic sclerosing sialadenitis

The present case study reports contrast-enhanced magnetic resonance findings in three patients with histopathologically proven IgG4-related chronic sclerosing sialadenitis of the submandibular gland. All three patients presented with painless swelling of the submandibular region. The contrast-enhanced T1-weighted images showed reticular enhancement of the swollen submandibular gland. Radiological–pathological correlation revealed that the characteristic reticular enhancement corresponded to fibrosis and to inflammatory cell infiltration in the interlobular septa and in the periductal region of the submandibular gland.

Chronic sclerosing sialadenitis: report of a rare and atypical case

A Chronic Sclerosing Sialodenitis is a rare and benign lesion that preferentially affects a submandibular gland of male patients. Although its etiology is considered unknown, it is suggested that the secretion of IgG4 immunoglobulin may be useful for its manifestation. This pathology has specific clinical characteristics for malignant neoplasms of the salivary glands, where the recommended treatment is a surgical excision. The present study presents an atypical case of chronic sclerosing sialodenitis that involves a woman's soft palate, where there was a complete resolution of the clinical case, in which the conservative treatment was chosen by the use of medications.

Chronic sclerosing sialadenitis (Küttner's tumor): an uncommon cause of submandibular swelling

<p class="Noindentpara">Chronic sclerosing sialadenitis (CSS) or Küttner’s tumour, a rare benign condition affecting submandibular gland, is now believed to be a localised type of IgG4-related disease. It presents as an asymptomatic swelling. Histopathology is the gold standard for diagnosis. Here we discuss the same in a 55-year-old male presenting as a painless submandibular swelling.</p>

Chronic sclerosing sialadenitis IgG4-related in a boy with recurrent parotitis: a case report

BackgroundIgG4-related diseases are a group of immune-mediated diseases characterized by a lymphoplasmacytic infiltrate with a prevalence of IgG4-positive plasma cells, storiform fibrosis, obliterative phlebitis. Autoimmune pancreatitis, sialadenitis, dacryoadenitis and retroperitoneal fibrosis are the most frequent manifestations. IgG4-related sialadenitis usually affects submandibular glands and is very rare in children. We report here a case of an unexpected diagnosis of IgG4-related sialoadenitis in a boy previously diagnosed as affected by juvenile recurrent parotitis.Case presentationA six-year old boy presented to our centre with left parotid swelling about 4x3 cm, tender, soft in consistency, with the overlying skin red and warm. He had low-grade fever and a mild enlargement of left cervical lymph nodes. In the last two years he had five episodes of parotitis and a diagnosis of juvenile recurrent parotitis.. The general conditions were good, and the remainder of the physical examination was normal. At the ultrasonography left parotid was enlarged, inhomogeneous, with a colliquated intraparotid lymph node and no evidence of sialolithiasis. Laboratory tests were normal, except for an increase of white blood cells and positivity for IgM and IgG anti-VCA, with anti-EBNA e anti-EA I negative. The patient was treated with cephalosporins and azitromycin, but after 10 days the parotid became fluctuating and the patient underwent to drainage and biopsy of the gland. He was discharged after 3 days of observation, without any complications, and treated with a further course of cefpodoxime and betametasone, with a good clinical response.Investigations for aerobic and anaerobic bacteria, mycobacteria and Bartonella on the pus were negative. Histology showed marked fibrosis and histiocytic and lymphoplasmacellular infiltration. The plasma cells were polyclonal and mostly expressed IgG4 subclass immunoglobulins. The final diagnosis was chronic sclerosing sialadenitis IgG4-related in recurrent parotitis and recent EBV infection. ConclusionsThe interest of this case comes from the rarity of IgG4-related sialadenitis in children. It is not possible to argue with certainty that the previous episodes of parotitis were manifestations of a IgG4-related disease, due to the lack of histological data. Serum IgG4 in our patient were normal, as described in literature in 30% of cases.

Sialadenitis and Sialadenosis

In this chapter, the etiology and management of salivary gland inflammation (sialadenitis) and sialadenosis (sioalosis) are discussed. Causes of inflammatory disorders of the parotid gland include viral infections; bacterial infections; recurrent parotitis of childhood; papillary obstructive parotitis; granulomatous sialadenitis; autoimmune sialadenitis including Mickulicz disease, Sjogren's syndrome; and other autoimmune sialadenitis such as Wegener's granulomatosis, Kimura's disease, and chronic sclerosing sialadenitis. Sialadenosis is a chronic, diffuse, non-inflammatory, non-neoplastic disorder causing diffuse enlargement of salivary glands, usually the parotid glands. Grossly, there is only diffuse enlargement of the affected gland, and histologically, the condition is characterized by acinar hypertrophy and fatty infiltration. Patients present with painless, soft, and diffuse enlargement of both parotid glands. Treatment in the form of controlling the underlying disorder or withdrawing the incriminated drug helps sialosis to resolve.

Kuttner’s tumour: chronic sclerosing sialadenitis- a mimicker of malignancy

Background: Kuttner’s tumour is a condition of the submandibular gland which is underreported as a distinct entity. Also called as the chronic sclerosing sialadenitis it resembles a plasmocytic and lymphocytic inflammatory process and presents as a hard and painful mass which clinically mimics a malignancy and raises significant concerns. The objective of the present study was to evaluate cases of Kuttner’s tumor and discuss its clinical and pathological aspects to distinguish it from a definite malignancy and create a grown acceptance of the presence of such an entity in our setting.Methods: We collected 170 cases of submandibular swellings and evaluated in detail the clinical and pathological aspects of eight cases out of them which were later diagnosed to as Kuttner’s tumour.Results: The age of the patients varied between 23 to 61 years (mean age 42.5 years) with 3 males and 5 females. 6 patients reported with a firm to hard painless submandibular mass (5 left sided; 3 right sided) while 2 patients experienced intermittent discomfort. The mean duration of presentation of symptoms was 5.3 months. Fine needle aspiration cytology was done in 6 cases preoperatively. Following submandibular sialadenectomy histopathology showed salivary gland tissue with preserved lobular architecture, but with marked fibrosis, acinar atrophy, and a dense lymphoplasmacytic infiltrates.Conclusions: Kuttner’s tumor may be pre operatively distinguished from a malignancy with improved imaging and a good image guided FNA Cytology saving the clinician and the patient from a lot of dilemma. However, histopathology and immunohistochemistry would be the key in establishing the diagnosis.