P27 Lymphoma-mimicker of IgG4-related dacryoadenitis and sialadenitis

Case report - Introduction Major salivary gland (sialadenitis) and lacrimal gland (dacryoadenitis) involvement can be a common feature of IgG4-related disease. There can be involvement of lacrimal and parotid gland which was previously called as Mikulicz disease and/or submandibular gland enlargement which was previously called Küttner tumour. These were previously mistakenly considered to be subcategories of Sjogren’s syndrome, but are now classified as IgG4-related disease. Here we discuss a case report of a patient who presented with bilateral dacryoadenitis and unilateral submandibular gland enlargement which initially was thought to be IgG4-related disease but turned out to be low-grade lymphoma. Case report - Case description A 15-year-old boy presented with 6-month history of bilateral eyelid swelling. The swelling was more on the lateral side of the eyelids and was painless. It had come on suddenly over a couple of days. No history of weight loss, dry eyes, dry mouth, joint issues or skin rashes or any other symptoms. Physical examination revealed bilateral ptosis, no visual impairment and systemic examination revealed an enlarged right submandibular gland. He had initially been to a local hospital where he had investigations which included autoimmune screen including ANA, ENA, ANCA, dsDNA, serum ace and complement levels which were all negative. C1 esterase inhibitor was normal. Routine bloods including complete blood count, urea and electrolytes, thyroid stimulating hormone and erythrocyte sedimentation rate were within normal limits. Urine albumin to creatinine ratio was not raised. Hepatitis serology including Hepatitis B & C and HIV was negative. Ultrasound abdomen was unremarkable. CT scan of orbits showed bilateral enlarged lacrimal glands with patchy post contrast enhancement and the glands extending up to insertion of lateral rectus muscle. CT chest some enlarged axillary lymph nodes and nodes in lung query infective etiology. CT abdomen and pelvis was unremarkable. Ultrasound neck showed right submandibular node enlargement with colour doppler showing increased vascularity. Fine needle aspirate of the submandibular gland showed reactive lymphoid hyperplasia. He was given two short courses of steroids and each time the swelling rapidly responded to the steroids but recurred on cessation of the steroids. IgG subset analyses revealed elevated IgG4 levels of 1152mg/dl. The differential here was IgG4-related disease but as there was no clear tissue diagnosis a core biopsy of the right submandibular gland was done. This revealed tissue suspicious of low grade (extranodal marginal zone and mucosa-associated lymphoid tissue [MALT]) lymphoma and excision biopsy was performed for definitive diagnosis. Case report - Discussion IgG4-related disease is an immune mediated fibroinflammatory condition which can affect a variety of organs and can present as tumour-like enlargement and/or organ dysfunction. The pathological findings in IgG4-related disease are lymphoplasmocytic infiltrates of IgG4-positive cells along with increased levels of serum IgG4 levels. Salivary and lacrimal glands can be commonly affected and present as enlargement, which is usually painless and bilateral. The combination of lacrimal gland enlargement with both parotid and submandibular gland enlargement is called IgG4-related Mikulicz disease. Apart from salivary glands, another commonly affected organ is the pancreas which can present as a pancreatic mass and painless jaundice, sclerosing cholangitis, retroperitoneal fibrosis, aortitis and periaortitis. Less commonly it can affect thyroid, kidney and lungs. Early recognition, diagnoses and treatment is important due to the fibroinflammatory nature of the disease. Malignancy is always in the differential and should be excluded. Steroids are the mainstay of treatment. If patients experience flare, rituximab can be added. Diagnosis should be confirmed with biopsy but histopathological findings are never alone diagnostic of IgG4-related disease and should be interpreted with clinical, serological and radiological findings. Case report - Key learning points Although this patient had typical presentation of IgG4-related disease with painless enlargement of salivary and lacrimal glands and elevated IgG4 serum levels, biopsy was imperative to get to the diagnoses of low-grade lymphoma and fine needle aspirate was not adequate. As mentioned above, biopsy in IgG4-related disease will confirm the diagnosis provided there are other supporting features (radiological and serological). However, it is imperative for excluding other important diseases like lymphoproliferative disorders.

DEMOGRAPHIC STUDY OF SALIVARY GLAND SWELLING

Introduction: Salivary glands, major and minor, comprise a complex anatomic and physiologic “organ” system-producing enzyme, lubrication, mixing agent and immune factors. Salivary gland swellings can be broadly classified into inflammatory, non- inflammatory and neoplastic swellings like calculi, benign tumours such as pleomorphic adenoma, oncocytoma, warthin’s tumour or malignant tumours like adenocarcinoma, adenoid cystic carcinoma and undifferentiated carcinoma. Connective tissue diseases like haemangioma, lymphangia, neurofibroma and other auto immune diseases like Sjogren’s syndrome, Mikulicz disease etc. Appropriate therapeutic management may be planned earlier, whether it is local excision for a benign neoplasm, radical surgery for a malignant one or any other alternate treatment. With non-neoplastic lesions, metastasis and lymph proliferative disorders, conservative management, chemotherapy or radiotherapy might be respectively preferable. Material and Methods: 40 cases of salivary gland swelling are studied, which were analyzed and conclusion drawn. The statistics have been compared with different standard studies conducted on same subject by various authors around world. Associated medical conditions like diabetes, hypertension and anemia were managed and controlled before surgery with the patient’s advice. As a part of general work up of surgery in all patients, hemoglobin level, bleeding time, clotting time, urine, sugar albumin, microscopy, chest screening, ECG, Blood urea, serum Creatinine, RBS was estimated. Specific investigations like FNAC, X-rays of Mandible were done for all patients in the study group. Demographic profile of all the study population was recorded. Results: Age of the patients varied from 9 years to 80 years. Average age of the patient was 40.6 years. The case of lowest age group i.e., 9 years was of non-inflammatory swelling and the case of highest age i.e., 80 years was of tumor swelling. Out of 40 cases 15(35%) cases was of male and 25(65%) cases of female. In this study, all cases presented with, symptoms of swelling (100%), 65% (26) presented with pain. 55 % (22) presented with tenderness. Three cases were with deep lobe involvement (11.4%), 19 cases of ear lobe elevation (47.5%). Facial nerve paralysis occurred in one case (2.8%). Conclusion: Diagnosis of the salivary gland tumors must be considered in any patient presenting with salivary gland swelling. Salivary gland swelling occur more commonly in 3rd and 4th decades of life and seen most common in females. Keywords: salivary gland, tumour, benign, malignant

Serum immunoglobulin G4 in Sjögren’s syndrome: a pilot study

Immunoglobulin IgG4 plays a role in the pathogenesis of the Mikulicz disease previously considered a form of primary Sjögren's syndrome (pSS). We investigated serum levels of IgG4, total IgG, C3, and C4 serum complementary components in patients suspected of Sjögren’s syndrome. Basic laboratory and immunological tests, including IgG4 and IgG concentration, were performed on 20 healthy and 68 suspected of pSS individuals. We distinguished: group I: 48 pSS patients; group II (sicca): 20 patients with dryness without pSS. We revealed: statistical differences between groups I and II concerning hypergammaglobulinemia, ESR, RF, ANA, Ro, and La antibodies; lower IgG4 levels and IgG4/IgG ratio in group I compared to healthy individuals (p < 0.0435; 0.0035, respectively); no significant differences in the concentrations of IgG4 and IgG4/IgG ratio between sicca and control groups. significantly lower (p < 0.0002) C4 levels in group I compared to other groups; significant differences in C4 concentration and IgG4/IgG ratio between three groups (p = 0.0002 and p = 0.0090, respectively); a weak negative correlation between C4 and IgG (r =− 0.274) in the whole database; weak positive correlation between C4 and IgG4/IgG ratio (r = 0.237); a negative correlation of IgG4, IgG4/Ig ratio and C4 with focus score (r = − 0.281; r = − 0.327; r = − 0.406, respectively). IgG4 serum levels were significantly decreased compared to healthy subjects. IgG4 and C4 levels correlated with infiltrations in minor salivary glands. Hypergammaglobulinemia and decreased serum C4 component levels are typical for pSS.

An old disease, a new diagnosis; A 49 year-old man with nephrotic syndrome

Background: IgG4-related disease (IgG4-RD) is a systemic immune-mediated disease that typically manifests as fibro-inflammatory masses that can affect nearly any organ system. Case Report: We present here a case of a 49-year old man with forgotten old disease (Mikulicz disease) with membranous nephropathy (MN). Conclusions: This entity is currently included within the spectrum of IgG4-related disease. The development of renal disease shortly after the suspension of rituximab suggests another probable pathway involved. To our knowledge the transforming growth factor may be responsible for existing pattern of fibrosis in this disease. The lack of response or at least partial response to rituximab can be explained by greater involvement of regulatory T lymphocyte in the pathophysiology of this entity.

IgG4-related hypophysitis presenting as diabetes insipidus with tubulo-interstital nephritis and mediastinal lymphadenopathy

Summary IgG4-related disease (IgG4-RD) is a rare but increasingly recognised condition, emerging as a clinical entity following the observation of the associations of autoimmune pancreatitis. IgG4-RD is characterised by extensive infiltration of IgG4-positive plasma cells into multiple organs and raised serum IgG4 levels. Clinical manifestations of IgG4 disease classically include autoimmune pancreatitis, lacrimal or salivary gland infiltration (formerly known as Mikulicz disease) and retroperitoneal fibrosis. More rarely, IgG4 disease can cause pituitary hypophysitis. Although most frequently described in middle-aged males, the epidemiology and pathogenesis of the disease remain largely undefined. Nevertheless, an understanding of the wide variety of clinical manifestations of this multi-system condition is undeniably important given the often excellent outcomes following treatment. We describe an unusual presentation of IgG4 disease with isolated diabetes insipidus secondary to pituitary hypophysitis. The patient in question subsequently developed chest pain secondary to mediastinal lymphadenopathy and tubulo-interstitial nephritis leading to renal dysfunction. He was successfully treated with oral steroids and had regular follow-up, and remains well at follow-up 2 years later. Learning points IgG4 disease, although rare, is increasing in prevalence largely due to increased recognition of its clinical manifestations, including autoimmune pancreatitis, lacrimal or salivary gland infiltration, retroperitoneal fibrosis and, more rarely, lymphocytic hypophysitis presenting as diabetes insipidus. IgG4 disease is highly treatable, and symptoms may show complete resolution with administration of steroids, highlighting the importance of correct and timely diagnosis. Causes of lymphocytic hypophysitis are varied and not distinguishable radiologically. Given the difficulty in biopsying the pituitary, careful attention must be paid to the systemic clinical presentation to provide clues as to the underlying disorder.

IgG4-Related Disease and Retroperitoneal Fibrosis

IgG4-related disease (IgG4-RD) has been observed to affect almost every organ system, with consistent histopathologic findings across systems. IgG4-RD can mimic malignant, infectious, and inflammatory disorders; accordingly, consideration of the histopathologic features of tissue biopsies and rigorous clinicopathologic correlations are essential to avoid misdiagnosis. Since the early 2000s, IgG4-RD has increasingly been recognized as a cause of what was previously referred to as “idiopathic” retroperitoneal fibrosis (RPF), and this IgG4-related RPF is now considered to comprise an important subset of IgG4-RD. This review includes an overview of IgG4-RD and discusses the pathology, pathophysiology, and clinical manifestations of IgG4. IgG4-related RPF is also discussed in this review, with topics including IgG4-related RPF versus RPF of other causes, the differences between RPF and other subsets of IgG4-RD, and treatment of both IgG4-RD and IgG4-related RPF. Figures show the histopathology features of IgG4-RD, immunostaining of tissue for IgG4, IgG4-related RPF and chronic periaortitis, “Mikulicz disease”, IgG4-RD of the lung, IgG4-related renal disease, and type 1 (IgG4-related) pancreatitis. The table lists conditions known previously by other names that often fall within the spectrum of IgG4-RD. This review contains 7 highly rendered figures, 1 table, and 66 references.