Diagnosis of IgG4-related systemic disease by cytology of large pericardial effusion with fine needle aspiration

IgG4-related disease has characteristic features as follows; Serum IgG4 is prominently elevated, IgG4-positive plasma cells infiltrate in involved tissues and various mass-forming lesions with fibrosis, such as the autoimmune pancreatitis, salivary gland and retroperitoneum. As this disease comes to attention, the reports of IgG4-related disease have been increasing, but the pathogenesis and exact frequency of the disease remain unknown. We present the case of a 69 year-old male who was admitted to our hospital for evaluation of lower legs edema in July, 2010. He first noticed lower legs edema in 2009 and visited a local clinic, and was diagnosed deep vein thrombosis, received anti-coagulation therapy. However, his edema was getting worth and hydrocele testis was appeared. When he visited our office, he complained of trouble in walking with lower legs edema. On physical examination, his body temperature was 36.2 °C, blood pressure 152/82 mm Hg, and pulse rate 60 per minute. There was no murmur in his cardiac sounds and lungs were clear. On abdominal examination, it was slightly swelling but not any mass were noted. His trunk was edematous, especially in lower legs. The thyroid gland, salivary glands and lymph nodes were not palpable. He had never experienced dry eye and dry mouth. Laboratory findings were as follows: WBC 4390/μL, hemoglobin 10.6 g/dL, platelet 27.3×10/μL, BUN 10 mg/dL, creatinine 1.04 mg/dL, BNP 119.0 pg/mL, CRP b0.10 μg/L. Liver function test was normal. Urinalysis did not demonstrate any protein on dipstick. Rheumatoid factor, anti-nuclear antibody, anti SS-A and anti SS-B, antibodies and antineutrophil cytoplasmic antibody were all negative. IgG, IgA, IgM and IgE were 1769.0 mg/dL, 272.7 mg/dL, 74.8 mg/dL and 276 mg/dL, respectively. Serum level of IgG4 was elevated by 408 mg/dL. A chest radiograph revealed marked cardiomegaly. Echocardiography revealed marked pleural effusion with slightly collapsed right atrium. Computed tomography (CT) revealed also large pericardial effusion (Fig. 1A) and low density area around the aorta (Fig. 1B). The mass, which was suspected retroperitoneal fibrosis (RPF), compressed inferior vena cava and right urinary duct, and induced lower legs edema and right hydronephrosis. After admission, a ureteral stent was placed in order to treat the hydronephrosis. Lip biopsy was done, but there was no significant pathological change. Gallium scintigraphy showed no hot lesions. Autoimmune pancreatitis was ruled out by magnetic resonance pancreatic cholangiopancreatography. Then,we performedpericardiocentesis byfineneedle aspiration on 9 days after admission. The specimen was light yellow, cloudy, TP 5.2 g/dL, albumin 3.0 g/dL, IgG 1604.3 mg/dL, IgG4 451 mg/dL and abundant small sized lymphocytes, rich in IgG4-positive cells (Fig. 2). There was no malignancy. Culture of the pericardial fluid revealed no bacterial infection. Therefore, we diagnosed this case as IgG4-related disease and treated with prednisolone 50 mg/day. Then his edema was rapidly improved. One month after starting steroid therapy, the CT revealed disappearance of pericardial effusion and regression of retroperitoneal mass (Fig. 1C and D). To our knowledge, this is the first case report diagnosed by fine needle aspiration cytology of large pericardial effusion. The pathological characteristic of this disease is rich in IgG4-positive plasma cells with typical fibrosis or sclerosis in the tissue [1]. IgG4related disease sometimes shows retroperitoneal fibrosis (RPF) and caused hydronephrosis as in our case. A biopsy for the retroperitoneal mass is necessary to provide a definitive diagnosis, but is considerably invasive. The major reasons of pericardial effusion are idiopathic pericarditis, infection included tuberculosis and malignancy [2,3]. Secondary to malignancy are frequently observed in lung cancer, breast cancer, and malignant lymphoma. Malignant lymphoma is considered of differential diagnosis in both RPF and pericardial effusion. Fine needle aspiration of pericardial effusion is less invasive compared to retroperitoneal biopsy. Although Sugimoto et al. reported IgG4-related disease caused constrictive pericarditis diagnosed by pericardiectomy [4], pericardial effusion is not a major complication. We showed that the cytology of pericardial effusion was rich in IgG4-positive cells similar to serum, suggesting that IgG4-related disease caused pericardial exudation of the plasma cell. Thus, it is necessary to consider the possibility of IgG4-related disease in the differential diagnosis of pericardial effusion. A pericardiocentesis will be useful to diagnose a IgG4related disease. The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology [5].