Abundant IgG4-positive Plasma Cell Infiltration Research Articles

A case of intraductal papillary-mucinous carcinoma of the pancreas, invasive with a markedly elevated serum IgG4 concentration and swollen papilla of Vater due to abundant IgG4-positive plasma cell infiltration, suggesting an association with autoimmune pancreatitis

A case of intraductal papillary-mucinous carcinoma of the pancreas, invasive with a markedly elevated serum IgG4 concentration and swollen papilla of Vater due to abundant IgG4-positive plasma cell infiltration, suggesting an association with autoimmune pancreatitis

Autoimmune Pancreatitis with Gastric Cancer: Some IgG4-related Diseases May Be Paraneoplastic Syndrome

A 70-year-old man was referred to our department for the treatment of early gastric cancer. Contrast-enhanced computed tomography (CT) incidentally showed diffuse enlargement of the pancreas with a capsule-like rim, and blood tests showed elevated serum IgG4 levels, leading to a diagnosis of autoimmune pancreatitis (AIP). Endoscopic treatment for gastric cancer was performed, and pathological findings showed adenocarcinoma with abundant IgG4-positive plasma cell infiltration. Thereafter, the serum IgG4 levels normalized, and the findings of AIP disappeared on CT without steroid treatment. These findings suggest that the gastric cancer activated an IgG4-related immune response, resulting in the development of AIP.

Clinical course of pituitary function and image in IgG4-related hypophysitis.

A 76-year-old man had a hypopituitarism including adrenal insufficiency, hypogonadism and hypothyroidism. Based on various findings including the swelling of the pituitary gland, increase of serum IgG4 level and abundant IgG4-positive plasma cell infiltration in immunostaining of the pituitary gland, we diagnosed this subject as IgG4-related hypophysitis. In general, a high-dose glucocorticoid treatment is effective for IgG4-related disease. His clinical symptom, laboratory data and adrenal insufficiency were almost improved without any therapy. The serum IgG4 level was decreased and pituitary size was normalized with hydrocortisone as physiological replacement. This case report provides the possibility that IgG4 level is decreased spontaneously or with physiological dose of glucocorticoid therapy.Learning points:We performed the pituitary gland biopsy and histochemical examination glucocorticoid therapy in a subject with IgG4-related hypophysitis.This case report provides the possibility that IgG4 level is decreased spontaneously or with a physiological dose of glucocorticoid therapy. We reported the clinical course of IgG4-related hypophysitis without a high-dose glucocorticoid treatment, although there were a few reports about the retrospective examination.Although the patient had still higher IgG4 level compared to normal range, his clinical symptom disappeared and his laboratory data were improved.We should keep in mind the possibility of IgG4-related hypophysitis when we examine one of the uncertain causes of a hypopituitarism including adrenal insufficiency, hypogonadism and hypothyroidism.

Clinical research on benign lymphoepithelial lesions of lacrimal gland in 20 Chinese patients.

Background:Benign lymphoepithelial lesion (BLEL) is characterized by symmetric bilateral swelling of the lacrimal and salivary glands and considered a subtype of immunoglobulin G4 (IgG4)-related sclerosing disease, the etiology and pathogenesis of which has not been determined. The purpose of the present study was to analyze the clinical features of BLEL in the lacrimal gland and the relationship between the serum level of IgG4 and BLEL.Methods:Twenty consecutive patients with BLEL diagnosed in Department of Ophthalmology at Beijing Tongren Hospital, Capital Medical University between January 2012 and December 2013 were observed. The clinical features, imaging findings, laboratory tests, treatments and follow-up status of these 20 consecutive patients were analyzed.Results:In all 20 patients, the ratio of male to female was 1:4, the ages ranged from 28 to 57 years, the ratio of unilateral to bilateral eyes involvement was 1:4, and painless uncongested symmetrical swelling of the upper eyelid was the main clinical manifestation. Orbital magnetic resonance imaging (MRI) showed that all patients involved lacrimal gland, which were obviously enlarged with equal signals in T1W images and T2W images and obvious enhancement on contrast MRI. Extraocular muscles were involved in 5 patients, salivary gland in 8 patients, and frontal nerve in 3 patients. Serum IgG4 concentration was elevated in 18 patients. The treatment strategy mainly included surgery and steroid administration. Three patients were lost to follow-up, 17 patients reached complete response, and no recurrence was observed.Conclusions:Eyelid swelling is the typical symptom of BLEL. Most of the patients involved bilateral lacrimal glands. High serum IgG4 level and abundant IgG4-positive plasma cell infiltration are the important features, which can be found in most of BLEL patients. Surgery combined with glucocorticoids is an efficient treatment strategy.

Analysis of pancreatic endocrine function in patients with IgG4-related diseases, in whom autoimmune pancreatitis was ruled out by diagnostic imaging

IgG4-related disease (IgG4RD) is a newly recognized systemic disease characterized by the elevation of serum IgG4 levels and abundant IgG4-positive plasma cell infiltration into the involved organs. Few data exist regarding the relationship between diabetes or glucose intolerance and IgG4RD in the absence of obvious type 1 autoimmune pancreatitis (AIP). Therefore, we are characterizing pancreatic endocrine function in IgG4RD patients with no signs of type 1 AIP. 28 patients (12 men, mean age 62.1 years old) were diagnosed as having IgG4RD from serum IgG4 levels, histopathology and images. Diagnostic imaging ruled out obvious type 1AIP. We used 75g oral glucose tolerance tests (OGTT) and arginine tolerance tests (ATT) to evaluate pancreatic endocrine function. Patients' serum IgG4 and HbA1c levels were 603±437 mg/dL and 6.6±1.0%, respectively. The results of OGTT on 23 patients showed that 12 patients had diabetes, 4 had impaired glucose tolerance, and 7 had normal glucose tolerance. Interestingly, insulin secretion was preserved in most of the patients, even in diabetic patients, on OGTT and ATT. Glucagon hyperreactivity was observed in 10 of the 19 patients who underwent ATT. Twenty-three patients were treated for IgG4RD with glucocorticoids. Their HbA1c levels were significantly elevated during the first six months of treatment, but improved after twelve months in parallel with glucocorticoid therapy. These results demonstrate the high frequency of pancreatic endocrine dysfunction in IgG4RD even when there is no indication of AIP, thus revealing that pancreatic endocrine dysfunction frequently occurs in IgG4RD without obvious type 1 AIP.

Ultrasonography in Patients With Autoimmune Pancreatitis: Pancreatic and Extrapancreatic Features

Autoimmune pancreatitis (AIP) has been considered an extraordinary type of chronic pancreatitis, with characteristic abundant IgG4-positive plasma cell infiltration and accompanying sclerosis, and was recently recognized as the pancreatic manifestation of IgG4-related sclerosing disease. Diagnosis of AIP has been recently increased with increase in awareness, dramatic improvement of radiological examination such as CT and MRI, and immunologic diagnostic assay tool including IgG and IgG4. Many investigators have focused on the image findings of AIP on CT and MR and its differential diagnosis from the common bile duct (CBD) or pancreatic cancer.

Immunoglobulin G4‐related lung disease: Clinicoradiological and pathological features

Immunoglobulin G4 (IgG4)-related disease is a multi-organ disorder that can include the lungs. IgG4-related lung disease can present in various forms; the clinical, radiological and pathological features of patients with this disease have been assessed. Forty-eight patients suspected of having IgG4-related lung disease, with a high serum concentration of IgG4 and abundant IgG4-positive plasma cell infiltration into the intrathoracic organs, were retrospectively evaluated. Their clinical features, chest imaging findings and pathological findings were examined, with final diagnoses made by an open panel conference. Of the 48 patients, 18 with extrathoracic manifestations were diagnosed as having IgG4-related lung disease. Most of these patients were middle-aged to elderly men. IgG4-related lung disease was characterized by high serum concentrations of IgG and IgG4, normal white blood cell count and serum C-reactive protein concentration and a good response to corticosteroids. Common radiological findings included mediastinal lymphadenopathy and thickening of the perilymphatic interstitium, with or without subpleural and/or peribronchovascular consolidation. Pathological examination showed massive lymphoplasmacytic infiltration with fibrosis in and around the lymphatic routes, with distribution well correlated with radiological manifestations. The findings suggest that the intrathoracic manifestations of IgG4-related lung disease develop through lymphatic routes of the lungs and show various clinical characteristics. Because some lymphoproliferative disorders show similar findings, the correlation of clinicoradiological and pathological characteristics is crucial for the diagnosis of IgG4-related lung disease.

Isolated IgG4-related interstitial lung disease: unusual histological and radiological features of a pathologically proven case

IgG4-related lung disease is commonly associated with autoimmune pancreatitis. Recently, isolated IgG4-related interstitial lung disease (ILD) without other organ involvement has newly been reported in two cases with clinical features of nonspecific interstitial pneumonitis (NSIP).We report the first case of an isolated IgG4-related ILD in a 78-year-old man with dry cough and dyspnea, whose clinical findings proved to be different from NSIP. Serum IgG4 levels were increased. Chest CT scan revealed bilateral consolidations especially in the lower lobes, enlarged mediastinal and hilar lymph nodes and pleural effusions. Video-assisted thoracoscopic (VATS) lung biopsy revealed a pattern similar to usual interstitial pneumonia (UIP) and an abundant IgG4-positive plasma cell infiltration. He was effectively treated by steroid therapy.Increasing recognition of IgG4 related diseases has led to a growing number of new entities. The novel concept of isolated IgG4-related ILD as a pulmonary manifestation of a systemic IgG4-related disorder should be taken into account as a possible differential diagnosis of ILD and mass-forming lesions, even when no other organ manifestation is clinically apparent at the time of diagnosis. Lung specific diagnostic criteria and algorithms are required to enhance diagnostic accuracy in cases of possible IgG4-related ILD.

Isolated IgG4-related interstitial lung disease: unusual histological and radiological features of a pathologically proven case

IgG4-related lung disease is commonly associated with autoimmune pancreatitis. Recently, isolated IgG4-related interstitial lung disease (ILD) without other organ involvement has newly been reported in two cases with clinical features of nonspecific interstitial pneumonitis (NSIP). We report the first case of an isolated IgG4-related ILD in a 78-year-old man with dry cough and dyspnea, whose clinical findings proved to be different from NSIP. Serum IgG4 levels were increased. Chest CT scan revealed bilateral consolidations especially in the lower lobes, enlarged mediastinal and hilar lymph nodes and pleural effusions. Video-assisted thoracoscopic (VATS) lung biopsy revealed a pattern similar to usual interstitial pneumonia (UIP) and an abundant IgG4-positive plasma cell infiltration. He was effectively treated by steroid therapy. Increasing recognition of IgG4 related diseases has led to a growing number of new entities. The novel concept of isolated IgG4-related ILD as a pulmonary manifestation of a systemic IgG4-related disorder should be taken into account as a possible differential diagnosis of ILD and mass-forming lesions, even when no other organ manifestation is clinically apparent at the time of diagnosis. Lung specific diagnostic criteria and algorithms are required to enhance diagnostic accuracy in cases of possible IgG4-related ILD.

Risk of Cancer in Patients With Autoimmune Pancreatitis

Although simultaneous occurrences of autoimmune pancreatitis (AIP) and cancer are occasionally observed, it remains largely unknown whether cancer and AIP occur independently or these disorders are interrelated. The aim of this study was to examine the relationship between AIP and cancer. We conducted a multicenter, retrospective cohort study. One hundred and eight patients who met the Asian diagnostic criteria for AIP were included in the study. We calculated the proportion, standardized incidence ratio (SIR), relative risk, and time course of cancer development in patients with AIP. We also analyzed the clinicopathological characteristics of AIP patients with cancer in comparison with those without cancer. Of the 108 AIP patients, 18 cancers were found in 15 patients (13.9%) during the median follow-up period of 3.3 years. The SIR of cancer was 2.7 (95% confidence interval (CI) 1.4-3.9), which was stratified into the first year (6.1 (95% CI 2.3-9.9)) and subsequent years (1.5 (95% CI 0.3-2.8)) after AIP diagnosis. Relative risk of cancer among AIP patients at the time of AIP diagnosis was 4.9 (95% CI 1.7-14.9). In six of eight patients whose cancer lesions could be assessed before corticosteroid therapy for AIP, abundant IgG4-positive plasma cell infiltration was observed in the cancer stroma. These six patients experienced no AIP relapse after successful cancer treatment. Patients with AIP are at high risk of having various cancers. The highest risk for cancer in the first year after AIP diagnosis and absence of AIP relapse after successful treatment of the coexisting cancers suggest that AIP may develop as a paraneoplastic syndrome in some patients.

Refractory gastric ulcer with abundant IgG4-positive plasma cell infiltration: A case report

We describe a 77-year-old man with refractory gastric ulcer that worsened after Helicobacter pylori eradication therapy. Pathology showed marked infiltration of IgG4-positive plasma cells in the gastric lesions, which led us to suspect IgG4-related sclerosing disease. To the best of our knowledge, this is the first report of IgG4-related gastric ulcer without the main manifestation of autoimmune pancreatitis.

Multiple IgG4‐related sclerosing lesions in the maxillary sinus, parotid gland and nasal septum

IgG4-related sclerosing disease is recognized as a distinct clinicopathological entity. It is well known that this disease can occur in the salivary, lacrimal and pituitary glands, in the head and neck region. The nasal cavity is an extremely rare site of involvement of IgG4-related sclerosing disease. Herein is reported a case of multiple IgG4-related sclerosing lesions in the maxillary sinus, parotid gland and nasal septum. A 73-year-old Japanese man presented with nasal obstruction and tumors of the right maxillary sinus and parotid gland were detected, after which resections of these tumors were performed. One year after the last surgery, he noted swelling of the nasal septum, and the tumor was resected. These three tumors had similar histopathology, such as conspicuous fibrosclerotic changes with dense lymphoplasmacytic infiltration and occasional obliterative phlebitis. Immunohistochemistry indicated abundant IgG4-positive plasma cell infiltration and high ratios of IgG4-positive/IgG-positive plasma cells (>70%) in all three lesions. The diagnosis of multiple IgG4-related sclerosing lesions was made. The present case suggests that IgG4-related sclerosing lesion can occur in the maxillary sinus and nasal septum, and represents an extension of the spectrum of IgG4-related sclerosing disease.

IgG4-related hepatic inflammatory pseudotumor with sclerosing cholangitis: a case report and review of the literature

IntroductionInflammatory pseudotumor is rare benign mass composed of chronic inflammatory cell infiltration and proliferating fibrous tissue. Some cases of inflammatory pseudotumor show abundant infiltrating IgG4-positive plasma cells and obliterative phlebitis, which are the pathologic hallmarks of autoimmune pancreatitis.Case presentationA 77-year-old Japanese man was admitted to our hospital because of epigastric pain. A solitary mass with delayed enhancement by dynamic computed tomography was present in the left hepatic lobe. Endoscopic retrograde cholangiography showed only segmental stenosis of the left intrahepatic bile duct. No abnormal findings were detected in the pancreas. The patient was clinically diagnosed as having intrahepatic cholangiocarcinoma and underwent surgery. Histological examination of the hepatic mass and bile duct wall showed abundant IgG4-positive plasma cell infiltration with obliterative phlebitis. The final diagnosis was IgG4-related hepatic inflammatory pseudotumor with sclerosing cholangitis. Delayed enhancement by computed tomography is a characteristic feature of IgG4-related inflammatory pseudotumor similar to that of autoimmune pancreatitis.ConclusionIgG4-related hepatic inflammatory pseudotumor unassociated with autoimmune pancreatitis should be one of the entities considered for differential diagnosis of liver tumors. Delayed enhancement on computed tomography might be useful finding for diagnosing IgG4-related hepatic inflammatory pseudotumor.

IgG4+ to IgG+ Plasma Cells Ratio of Ampulla Can Help Differentiate Autoimmune Pancreatitis From Other “Mass Forming” Pancreatic Lesions

Autoimmune pancreatitis (AIP) shows a unique spectrum of histologic features and commonly presents with an abundant IgG4-positive (IgG4+) plasma cell infiltration. However, differentiating AIP from other mass lesions, particularly pancreatic cancer [invasive ductal carcinoma (IDC)] can be clinically challenging. In this study, we evaluated the validity of IgG4 and IgG immunohistochemistry of ampullary and periampullary tissue for the diagnosis of AIP. Our study group consisted of 14 resected AIP cases with appropriate ampullary sections. Superficial ampullary tissue and "shouldering" duodenal mucosa were evaluated for several histologic variables. Immunohistochemistry for IgG4 and IgG was performed. The number of IgG4 and IgG-positive plasma cells was counted and an IgG4+ to IgG+ plasma cells ratio (IgG4/IgG ratio) was evaluated. A control cohort was composed of IDC (n=30) and chronic pancreatitis (CP) (n=29). Although an overlap was present between the groups, the overall inflammation and number of plasma cells in and around the ampulla was significantly increased in AIP compared with CP and IDC. Furthermore, although there was some overlap in the crude number of IgG4+ plasma cells of the ampullary and duodenal tissue between AIP, IDC, and CP, an IgG4/IgG ratio, especially of the ampulla, seems diagnostically useful in differentiating AIP from other "mass forming" lesions. When a cut-off of 0.10 was applied, the diagnostic sensitivity and specificity of the ampullary IgG4/IgG ratio was 86% and 95%, respectively. In conclusion, evaluation of ampullary histology and IgG4/IgG ratio might be proven beneficial in discriminating AIP from other mass forming pancreatic lesions.

An autopsy case of autoimmune pancreatitis after a 6-year history of steroid therapy accompanied by malignant dissemination of unknown origin

Little is known about the long-term outcome of autoimmune pancreatitis (AIP), and whether AIP possesses malignant potential. We report herein a 68-year-old Japanese AIP patient who rapidly developed systemic malignant dissemination of unknown origin, resulting in death. The patient was diagnosed histopathologically as having AIP in 1999. After a 6-year history of 5 mg/day of prednisolone therapy, a sudden onset of abdominal pain and convulsive seizure occurred, and the patient died on the tenth hospital day owing to diffuse peritoneal disseminations and metastases in the bilateral lungs and brain. Autopsy disclosed that the primary site was renal cell carcinoma, detectable only by autopsy, originating in the left kidney. On microscopy, metastatic cells obtained from the brain, lung, and peritoneum were composed of pleomorphic malignant cells identical to those from the renal cell carcinoma. Unexpectedly, abundant IgG4-positive plasma cell infiltration, suggesting high activity of AIP in pancreatic parenchyma and around dilated bile ducts, was still observed.

Immunoglobulin G4-related sclerosing cholangitis in patients resected for presumed malignant bile duct strictures

Immunoglobulin (Ig) G(4)-related lymphoplasmacytic sclerosing pancreatitis has been described in the context of autoimmune pancreatitis mimicking distal cholangiocarcinoma. The aim of this study was to assess the occurrence of this entity in benign bile duct strictures in patients resected for presumed hilar cholangiocarcinoma. Of 185 patients who had undergone resection of proximal bile ducts on suspicion of hilar cholangiocarcinoma between January 1984 and June 2005, 32 (17.3 per cent) had a benign bile duct stricture on histopathological examination. After re-evaluation, further immunohistochemical analysis was performed on specimens from patients with features of autoimmune-like disease. The periductal stroma in 15 patients showed features of autoimmune-like disease (diffuse, moderate to severe lymphoplasmacytic infiltration with marked fibrosis). Abundant IgG(4)-positive plasma cell infiltration around the bile duct lesions was seen in two of these. Although not significant, patients with features of autoimmune-like disease on histological changes showed a higher incidence of recurrent biliary complications than those without (P = 0.250). Features of autoimmune-like bile duct disease were seen in almost half (15 of 32) of patients with benign hilar strictures resected for presumed hilar cholangiocarcinoma. Frank IgG(4)-related sclerosing disease was found in only two of the 15 patients with autoimmune-like bile duct disease.

Three Clinicopathological Subtypes of Autoimmune Pancreatitis Stratified By the Duodenal Papillary Findings and the Serum IgG4

Background: The majority of cases with autoimmune pancreatitis (AIP) respond well to steroid therapy, some cases show spontaneous remission, while others develop a refractory course. The clinical differences between these three types of AIP have not yet been fully elucidated. Aim: To study the clinicopathological differences among the three aforementioned types of AIP. Patients and Methods: Thirty-one consecutive patients of AIP who underwent ERCP between April 2001 and November 2007 were identified from our database. The patients were stratified by the serum IgG4 level into three subtypes. (Group A: IgG4 < 135 mg/dl; B:IgG4 135-1000 mg/dl; C: IgG4 > 1000 mg/dl). We conducted a retrospective review to determine whether the following factors might be useful in distinguishing among the three subgroups of patients with AIP; serological data, presence/absence of obstructive jaundice, presence/absence of sclerosing cholangitis affecting the hilar bile duct, duodenal papillary findings (presence/absence of swelling), distribution of the pancreatic swelling (local/diffuse), and presence/absence of complicating extrapancreatic lesions. The histopathological differences in the duodenal papilla were also examined. Results: There were 11, 17 and 3 patients, respectively, in Groups A, B and C. Group C showed a younger onset, with a higher frequency of bronchial asthma, sclerosing sialadenitis, sclerosing cholangitis and relapse. The results of univariate analysis revealed that group C patients were significantly younger (Group A, 68 years; B, 68 years; C, 50 years), and showed significantly higher frequencies of a swollen duodenal papilla (Group A, 9%; B, 76.4%; C, 100%) and diffuse pancreatic swelling (Group A, 0%; B, 52.9%; C, 100%) (p < 0.05). Histopathological examination revealed marked stromal lymphoplasmocytic infiltration with an abundance of IgG4-positive plasma cells (cells / high power field) in the duodenal papilla in group C (Group A, 3/HPF; B, 17/HPF; C, 25/HPF). Conclusions: Our results suggest that AIP can be classified into 3 subgroups; AIP cases showing spontaneous remission, those with typical AIP responding to steroid therapy, and those with refractory AIP showing high titers of serum IgG4, younger onset, and high frequencies of bronchial asthma, swelling of the duodenal papilla with abundant IgG4-positive plasma cell infiltration, sclerosing sialadenitis and diffuse pancreatic swelling. This last group of AIP patients should be distinguished from those with typical AIP and should be treated with great caution because of the high frequency of relapse in these patients. Towards this end, examination of the duodenal papilla may pay rich dividends.

Pathological classification of hepatic inflammatory pseudotumor with respect to IgG4-related disease

Recently, much attention has focused on IgG4-related disease, which is characterized by abundant IgG4-positive plasma cell infiltration and high serum IgG4 levels. IgG4-related disease sometimes manifests as tumorous lesions, and its relationship to inflammatory pseudotumor has been suggested. In this study, we examined clinicopathological features of a total of 16 cases of hepatic inflammatory pseudotumor (11 men and 5 women with an average age of 67 years) with respect to IgG4-related disease. The tumors could be pathologically classified into two types: fibrohistiocytic (10 cases) and lymphoplasmacytic (6 cases). Fibrohistiocytic inflammatory pseudotumors were characterized by xanthogranulomatous inflammation, multinucleated giant cells, and neutrophilic infiltration, and mostly occurred in the peripheral hepatic parenchyma as mass-forming lesions. In contrast, lymphoplasmacytic inflammatory pseudotumors showed diffuse lymphoplasmacytic infiltration and prominent eosinophilic infiltration, and were all found around the hepatic hilum. In addition, venous occlusion with little inflammation and cholangitis without periductal fibrosis were frequently observed in the fibrohistiocytic type, whereas obliterative phlebitis and cholangitis with periductal fibrosis were common features of the lymphoplasmacytic type. Interestingly, IgG4-positive plasma cells were significantly more numerous in the lymphoplasmacytic than fibrohistiocytic type. However, two of the fibrohistiocytic inflammatory pseudotumors had relatively many IgG4-positive plasma cells. In conclusion, hepatic inflammatory pseudotumor could be classified into two types based on clinicopathological characteristics. The lymphoplasmacytic type is unique, and could belong to the so-called IgG4-related diseases. In contrast, the fibrohistiocytic type might still be a heterogeneous group of disorders. This latter type seems pathologically different from IgG4-related disease, although cases with relatively abundant IgG4-positive plasma cells should be differentiated from IgG4-related disease with secondary histopathologic modifications.

Renal Lesions in IgG4-Related Systemic Disease

Recently, a new concept of IgG4-related systemic disease including autoimmune pancreatitis, characterized by a high serum IgG4 level and tissue infiltration by IgG4-positive plasma cells, has been proposed. Our aim was to investigate the renal involvement in this condition. We investigated the results of laboratory and imaging studies of the kidneys in 7 patients with IgG4-related systemic disease, and examined the renal histology in four of them. All patients showed elevated serum IgG4 levels, and 4 had autoimmune pancreatitis. The other three patients showed involvement of various extrapancreatic organs (lymphadenopathy, sialadenitis or renal insufficiency), and abundant IgG4-positive plasma cell infiltration was confirmed in their affected tissues. Six of the 7 patients showed some renal abnormalities. In one patient, hydronephrosis was observed accompanied by retroperitoneal fibrosis. Another patient showed multiple low-density areas in both kidneys by computed tomography, and gallium citrate scintigraphy showed gallium-67 accumulation in both kidneys, although renal function was normal. Four patients had tubulointerstitial nephritis. In two of them, the tubulointerstitial nephritis was diffuse. In one patient, marked diffuse but patchily distributed lymphoplasmacytic infiltration of the renal interstitium was observed. In another patient, computed tomography showed a tumor-like low-density mass; open biopsy of the mass showed aggregates of lymphocytes and plasma cells in the renal interstitium. Renal parenchymal lesions in IgG4-related systemic disease are due to dense lymphoplasmacytic infiltration of the renal interstitium, and the lesions vary from diffuse tubulointerstitial nephritis to tumor-like masses according to the distribution patterns of the infiltrating cells.