IgG4-related inflammatory pseudotumor of the renal pelvis involving renal parenchyma, mimicking malignancy

The first report indicating that serum IgG4 levels were elevated in patients with autoimmune pancreatitis and that pancreatic lesion of such patients showed infiltration of IgG4-positive plasma cells was published in 2001 [1]. Since then, reports have been published on the presence of IgG4-related lesion not only in the pancreas but also in other organs such as the bile duct, salivary glands, retroperitoneal tissue, and bone marrow. Thereafter, a new clinicopathologic entity called “IgG4-related systemic disease” was proposed [6].

In most cases, IgG4-related disease occurs in men (62 to 83%) and in those older than 50 years [7]. The disease can involve any organ, and the resultant symptoms are related to the affected site. Common sites involved by IgG4-related disease are the pancreas, hepatobiliary tract, salivary gland, orbit, and lymph node [7, 8]. The three key histopathologic findings of this disease are as follows: (1) dense lymphoplasmacytic infiltration, (2) storiform-type fibrosis, and (3) obliterative phlebitis [9]. If two of the three key histologic findings are present, the possibility of IgG4-related disease is strongly suggested pathologically. The most essential criterion to diagnose the disease is to the detection of IgG4-positive plasma cells in the lesion [7‐9]. Although there have been variety of suggested cut-off points, ranging from >10 to >50 IgG4-positive plasma cells per high-power field (HPF) [9], most researchers are in agreement with >50 per HPF [10]. The diagnosis can be further assisted by the ratio of IgG4-positive plasma cells to IgG-positive plasma cells. A ratio >40% is considered to be highly suggestive of the diagnosis [10]. Although the presence of the characteristic histopathologic features and IgG4-positive plasma cells can provide strong supportive evidence for the diagnosis of IgG4-related disease, the definitive diagnosis should be made only by careful correlation with the results of clinical and imaging studies [9].

Kidneys are not spared in IgG4-related disease. Most of the reported cases of IgG4-related disease involving the kidney have synchronous or metachronous involvement in other organs [3]. However, in the present case, IgG4-related disease occurred in the kidneys in isolation. Clinically, some patients show non-specific symptoms such as fever, fatigue, anorexia, or abdominal pain, while others do not present any symptoms and are detected incidentally during laboratory tests or imaging studies [11]. Laboratory findings of patients with IgG4-related renal disease usually reveal hypergammaglobulinemia, hypocomplimentemia, or impaired renal function [12]. Serum IgG4 levels are elevated in about 80% of the patients [3]. According to previous reports, the suggested critical point of serum IgG4 level is 135 mg/dl [13]. An elevated serum IgG4 level may provide much assistance although it is not a necessity for the diagnosis [9]. Additionally, the disease activity and the number of involved organs could correlate with the serum IgG4 level [9]. Urinalysis of IgG4-related renal disease usually shows mild abnormalities. We did not consider the possibility of IgG4-related disease before the surgery, and therefore the preoperative serum IgG4 level was not evaluated. And all other laboratory findings including urine analysis were in normal limits.

Since most of the IgG4-related renal disease shows radiologic abnormalities, imaging study plays an essential role [3]. IgG4-related renal disease most commonly presents as multiple low-density nodules in one or both kidneys [8]. These kidney lesions usually show low intensity in contrast CT scans. And T2-weighted MRI scans of the lesions are typically hypointense [14].

In rare cases, IgG4-related renal disease can affect the renal pelvis and forms a single unilateral mass, as observed in our present case. Such lesions can pose a diagnostic challenge, because they mimic malignant tumors of the renal pelvis, especially if there is no other organ involvement. To the best of our knowledge, this is the third case of isolated renal pelvic IgG4-related disease to be reported in the English literature [4, 5]. The clinical and radiologic features of the previously reported cases are summarized in Table 1. Imaging studies in the two previously reported cases showed hydronephrosis and soft tissue mass lesion around the renal pelvic region, raising the suspicion of malignant tumor. Further, Wang et al. [4] reported that the mass showed high glucose metabolism in positron emission tomography/CT (PET/CT), making the diagnosis more difficult. In one of the reported cases, surgical intervention could be avoided because of the evaluation for patient’s serum IgG4 level. Unfortunately, the other patient’s serum IgG4 level was not evaluated and she underwent radical surgery.

In our present case, the imaging findings strongly suggested that the mass lesion was a malignant tumor. The radiologist mainly suspected the mass to be urothelial carcinoma of the renal pelvis. Moreover, the patient did not present any urologic abnormalities, such as hematuria or proteinuria. Since, IgG4-related disease was not included in the differential diagnosis, neither evaluation of serum IgG4 level nor preoperative biopsy was performed. Therefore, the patient underwent unnecessary radical excision.

A renal pelvic mass arising from IgG4-related disease should be differentiated from genitourinary malignancy, metastatic cancer, and lymphomas to avoid unnecessary surgery. However, unfortunately, this differentiation on the basis of radiologic criteria alone is extremely difficult. Several reports have shown that IgG4-related kidney disease has been mistaken for malignant mass and diagnosed only after invasive operations [15]. More than 90% of patients with IgG4-renal disease have concurrent involvement in other organs such as pancreas and salivary gland, while isolated kidney lesion is uncommon [16]. Evaluating other organs for masses or fibrotic lesions could provide an important clue to the diagnosis of the IgG4-related disease. For the same reason, we should pay more attention to the patients’ medical history and check for evidence of other organ involvement. If there is evidence of other organ involvement in the past or present, we should examine the serum IgG4 level and perform preoperative biopsy.

In conclusion, we have presented a rare case of IgG4-related inflammatory pseudotumor affecting both the renal parenchyma and pelvis. In our case, preoperative biopsy or checking of the serum IgG4 levels was not performed due to lack of evidence for IgG4-related disease. This case emphasizes the importance of considering that IgG4-related diseases can involve the kidney and give rise to mass-like lesions and mimic renal malignancy.