A Case of Warthin’s Tumor Together with IgG4-Related Sialadenitis

Warthin’s tumor is the second most frequent neoplasm next to pleomorphic adenoma in the salivary gland. The tumor contains the epithelial oncocyte cells with the presence of rich-mitochondria and their surrounding abundant lymphocytes. A relatively new disease entity of IgG4-related disease frequently occurs in the salivary gland. However, the coexistence of Warthin’s tumor and IgG4-related disease is scarcely observed. We have recently experienced a rare case of Warthin’s tumor with IgG4-related sialadenitis. A 51-year-old man presented to our hospital, complaining of a mass with right submandibular tenderness and spontaneous pain. A computed tomography scan of the cervical region revealed a suspicion of lymph node proliferative disease, including malignant lymphoma. Elevated serum levels of IL-2R: 1843 U/ml (reference value 122 - 496 U/ml), IgG: 3430 mg/dl (reference value 861 - 1747 mg/dl), and IgG4: 3140 mg/dl (reference value 11 - 121 mg/dl) were observed. Other laboratory data showed within normal ranges. The cervical tumor was diagnosed as Warthin’s tumor by the findings of fine-needle aspiration cytology and biopsy examination. Immunohistochemistry revealed numerous IgG4- and IgG-positive cells with fibrosis surrounding the epithelial component of Warthin’s tumor, suggesting IgG4-rerated sialadenitis. Finally, we diagnosed the cervical tumor as Warthin tumor with IgG4-related sialadenitis. This is the second report describing a case of Warthin’s tumor with possible involvement of IgG4-related sialadenitis.

Interleukin-13 promotes cellular senescence through inducing mitochondrial dysfunction in IgG4-related sialadenitis

Immunoglobulin G4-related sialadenitis(IgG4-RS)is an immune-mediated fibro-inflammatory disease and the pathogenesis is still not fully understood.The aim of this study was to explore the role and mechanism of interleukin-13(IL-13)in the cellular senescence during the progress of IgG4-RS.We found that the expression of IL-13 and IL-13 receptorα1(IL-13Rα1)as well as the number of senescent cells were significantly higher in the submandibular glands(SMGs)of IgG4-RS patients.IL-13 directly induced senescence as shown by the elevated activity of senescence-associatedβ-galactosidase(SA-β-gal),the decreased cell proliferation,and the upregulation of senescence markers(p53 and p16)and senescence-associated secretory phenotype(SASP)factors(IL-1βand IL-6)in SMG-C6 cells.Mechanistically,IL-13 increased the level of phosphorylated signal transducer and activator of transcription 6(p-STAT6)and mitochondrial-reactive oxygen species(mt ROS),while decreased the mitochondrial membrane potential,ATP level,and the expression and activity of superoxide dismutase 2(SOD2).Notably,the IL-13-induced cellular senescence and mitochondrial dysfunction could be inhibited by pretreatment with either STAT6 inhibitor AS1517499 or mitochondria-targeted ROS scavenger Mito TEMPO.Moreover,IL-13 increased the interaction between p-STAT6 and c AMP-response element binding protein(CREB)-binding protein(CBP)and decreased the transcriptional activity of CREB on SOD2.Taken together,our findings revealed a critical role of IL-13 in the induction of salivary gland epithelial cell senescence through the elevated mitochondrial oxidative stress in a STAT6–CREB–SOD2-dependent pathway in IgG4-RS.

IgG4-related sclerosing cholangitis and chronic sclerosing sialadenitis mimicking cholangiocarcinoma and neck malignancy

To the Editor:IgG4-related sclerosing cholangitis（IgG4-SC）has re cently been recognized as a biliary manifestation of IgG4-related disease（IgG4-RD）.Type 3 IgG4-SC pre sented biliary strictures in both the porta hepatis and the distal common bile duct（CBD）.;Its manifestation especially in the absence of autoimmune pancreatitis,is extremely rare and very similar to that of cholangiocarci noma（CC）.

Oral manifestations of hepatitis C virus infection

Extrahepatic manifestations (EHMs) of hepatitis C virus (HCV) infection can affect a variety of organ systems with significant morbidity and mortality. Some of the most frequently reported EHM of HCV infection, involve the oral region predominantly or exclusively. Oral lichen planus (OLP) is a chronic inflammatory condition that is potentially malignant and represents cell-mediated reaction to a variety of extrinsic antigens, altered self-antigens, or super antigens. Robust epidemiological evidence support the link between OLP and HCV. As the virus may replicate in the oral mucosa and attract HCV-specific T lymphocytes, HCV may be implicated in OLP pathogenesis. Sjögren syndrome (SjS) is an autoimmune exocrinopathy, characterized by dryness of the mouth and eyes and a multitude of other systemic signs and symptoms. SjS patients have also an increased risk of non-Hodgkin lymphoma. Patients with chronic hepatitis C do frequently have histological signs of Sjögren-like sialadenitis with mild or even absent clinical symptoms. However, it is still unclear if HCV may cause a disease mimicking SjS or it is directly responsible for the development of SjS in a specific subset of patients. Oral squamous cell carcinoma is the most common oral malignant tumour and at least in some part of the world could be linked to HCV.

Clinical significance of hypoechoic submandibular gland lesions in type 1 autoimmune pancreatitis

To assess the role of ultrasonography of submandibular glands (SGs) in the diagnosis of type 1 autoimmune pancreatitis (AIP).METHODSThirty-seven patients who were definitively diagnosed with type 1 AIP according to the international consensus diagnostic criteria (ICDC) for AIP at our institution between December 1990 and April 2016 were retrospectively reviewed. Findings by physical examination, ultrasonography, and scintigraphy of SGs were analyzed to reach a diagnosis based on the ICDC for AIP. The efficacy of corticosteroid treatment in the resolution of hypoechoic lesions in SGs was also evaluated by assessment with ultrasonography before and after treatment in 18 cases.RESULTSThe sensitivity of multiple hypoechoic lesions in SGs by ultrasonography for the diagnosis of sialadenitis in type 1 AIP (84%) was higher than that of physical examination (46%), scintigraphy (28%), and SGs thickness (49%). Ultrasonographic evidence of hypoechoic lesions in SGs improved the definitive diagnosis of sialadenitis and type 1 AIP by the ICDC criteria in 11 (30%) and 2 (5.4%) cases, respectively. Multiple hypoechoic lesions in SGs were resolved or disappear by corticosteroid administration in 14 of 16 cases with hypoechoic lesions in SGs, whereas the ultrasonographic findings in the remaining 2 cases with hypoechoic lesions in SGs and the 2 cases with homogenous SG parenchyma remained unchanged after corticosteroid administration.CONCLUSIONSG ultrasonography to detect multiple hypoechoic lesions might be useful for type 1 AIP diagnosis by improving diagnostic accuracy together with the ICDC sialadenitis criteria.

Multi-organ IgG4-related disease continues to mislead clinicians: A case report and literature review

BACKGROUND Immunoglobulin G4-related disease(IgG4-RD)is a multisystemic mass forming immune-mediated disease that affects almost every organ and is a diagnostic challenge for every clinician.There is a lack of adequate epidemiological data worldwide,and evidence-based treatment recommendations are not yet established.We report the first case of IgG4-RD from Lithuania and the Baltic Sea region presented with thyroiditis,orbital myositis,orbitopathy,uveitis,scleritis,sialadenitis,autoimmune pancreatitis and prostatitis.CASE SUMMARY A 54-year-old Caucasian male was admitted to our tertiary Centre complaining of severe weight loss,diarrhoea,abdominal pain,salivary gland swelling,sicca symptoms and diplopia.On examination,bilateral palpable masses in the projection of major salivary glands,severe protrusion of the left eyeball and cachexia were noted.The patient was previously diagnosed with autoimmune thyroiditis and endocrine ophthalmopathy.The magnetic resonance imaging(MRI)of the head revealed enlarged extraocular muscles indicating orbital myositis.The biopsy from the salivary gland mass indicated sialadenitis.Abdominal MRI showed signs of autoimmune pancreatitis,and a serological test revealed the elevated serum IgG4 concentration.The patient was then diagnosed with IgG4-RD and successfully treated with prednisolone.There was a significant clinical,serological and radiological improvement after one month of treatment and no signs of relapse within twenty months.However,it took almost 18 years and the efforts of eight different medical specialists to establish the correct diagnosis.CONCLUSION A comprehensive approach to the patient is essential to improving the recognition of rare immune system conditions,such as IgG4-RD.

Sialendoscopy: A Review of 133 Cases

Objective: The aim is to review the effectiveness of sialendoscopy in treating various salivary gland disorders related to the duct. Methods: A total of 133 patients who underwent sialendoscopy were included in this study. Data was collected from case records of patients and was analysed. A detailed history examination was taken and the operative findings were analysed. Causes of obstructive sialadenitis were evaluated and treated. Results: A total of 159 glands were subjected to sialendoscopy and pathology was identified in 149 glands. Forty one submandibular glands had calculi and twelve had non-calcular obstruction. Fifteen parotid glands had calculi and 81 had non-calcular obstruction, of which stricture was the most common. Calculi retrieval or dilation of stricture was achieved with a sialendoscope in 112 glands. In 23 patients, the calculi were retrieved by combined approach. In three patients, the calculi were fragmented with intra luminal Holmium laser and the fragments were removed. All these patients had a good relief from their symptoms. Duct perforation was seen in two patients and a false passage was formed in one. Conclusion: Sialendoscopy was a safe and effective procedure for managing ductal pathologies of salivary glands.