Correspondence: Suresh T Chari M.D., Division of Gastroenterology and Hepatology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA. Email: email@example.com
IgG4-related disease is an idiopathic, systemic fibroinflammatory disease that can affect a wide variety of sites, including several in the genitourinary system. We describe a patient with steroid-responsive urinary symptoms and an abnormal digital rectal exam that were secondary to IgG4-related prostatitis. We discuss the importance of recognizing this condition and differentiating it from prostate cancer, which can present similarly.
IgG4-RD is a recently described inflammatory disease involving multiple organs. The best known manifestations of this entity include AIP and IgG4-related SC, but it has been reported in all organ systems, including the genitourinary tract. There are characteristic histopathological and immunohistochemical findings in IgG4-RD, and patients show a dramatic response to steroid therapy. We report the case of a patient with an abnormal digital rectal exam, steroid-responsive urinary symptoms and biopsy findings of IgG4-related prostatitis. We discuss the importance of recognizing this condition and differentiating it from prostate cancer to avoid unnecessary surgery.
A 55-year-old man presented for a medical examination. His medical history was notable for AIP diagnosed 7 years previously. He initially presented with obstructive jaundice and was found to have diffuse pancreatic enlargement on computed tomography imaging, an elevated serum IgG4 level of 1000 mg/dL (normal, 8–140 mg/dL), with resolution of jaundice and imaging abnormalities after steroid treatment, confirming a diagnosis of AIP. A total of 4 years later, a 3-cm mass in the tail of the pancreas was found with associated dilation of the main pancreatic duct and distal pancreatic atrophy. An endoscopic ultrasound fine-needle aspiration did not show evidence of malignancy, so he was retreated with steroids. The mass remained unchanged in size after 4 months of treatment, so the patient underwent distal pancreatectomy, which showed histological features of AIP without malignancy.
At the time of the medical examination, the patient lacked urinary symptoms, had a normal PSA level of 0.67 ng/mL (normal, <3.5) and elevated serum IgG4 level of 292 mg/dL. Palpation of his prostate revealed an approximately 60-g prostate without discrete nodules, but diffusely irregular and asymmetric. In the absence of a definite nodule, the patient's reluctance to proceed with biopsy and the low likelihood of rapid progression of disease if malignant, the decision was made to proceed conservatively and repeat a digital rectal exam in 3 months.
Before he returned for re-evaluation, the patient developed difficulties with nocturia and urinary hesitancy. Both of these symptoms resolved when he was given a course of oral prednisone for monoarticular gout. Although his PSA level was 0.45 ng/mL, his prostate remained asymmetric on palpation and a unilateral, irregular nodule was palpated. The decision was made to proceed with transrectal ultrasound-guided prostate biopsies (Fig. 1). Multiple core biopsies were taken from the right and left, and the specimens were interpreted as “benign prostatic tissue with mild to moderate chronic inflammation.”
Given his history of AIP, the prostate biopsies were reviewed again and IgG4 immunostaining was carried out. Histologically, there were typical changes of IgG4-RD including lymphoplasmacytic inflammation involving the stroma, but not the glands, storiform fibrosis, multiple foci of obliterative phlebitis and a large number (>40/hpf) of IgG4-positive staining cells; the IgG4/IgG ratio was 80% (Fig. 2).
Because of the patient's unstable comorbid diabetes mellitus and minimal urinary symptoms, he was not given additional steroid therapy. He continues to undergo annual follow up for prostate cancer screening and AIP surveillance.
IgG4-RD is a recently described fibroinflammatory disease with multiorgan involvement. It is characterized histologically by lymphoplasmacytic inflammation, storiform fibrosis, obliterative phlebitis and abundant IgG4-positive plasma cells at the affected sites. The most commonly involved organs are the pancreas (referred to as AIP) and biliary tract (referred to as IgG4-related SC). The list of other sites of involvement is growing and includes, orbit, salivary and lacrimal glands, lungs, and retroperitoneum.
Involvement of the genitourinary system is relatively uncommon, but IgG4-RD has been reported in kidneys, ureters, testes and the prostate. IgG4-related kidney disease is the best described, and includes tubulointerstitial nephritis, low-density cortical lesions and hypovascular renal masses. Tissue deposition of IgG4 in a small series of ureteral pseudotumors has been presented, although clinical evidence was not available to confirm IgG4-RD. Finally, a small number of paratesticular pseudotumors have been reported to be IgG4-related.[5, 6] Involvement of the prostate gland, currently referred to as IgG4-related prostatitis, is one of the most recently described manifestations of IgG4-RD.
Yoshimura et al. reported the first case of histologically-confirmed IgG4-related prostatitis. Their patient underwent transurethral prostate resection for benign prostatic hypertrophy, and developed systemic and pancreatobiliary manifestations of IgG4-RD within 6 months. Nishimori et al. reported two additional cases. One of the patients was retrospectively diagnosed 4 years after prostate resection, and no collateral evidence for AIP diagnosis was available. The other patient was incidentally noted to have increased uptake of FDG in the prostate on baseline positron emission tomography–computed tomography carried out at the time of AIP diagnosis. Interestingly, even though the patient did not have urinary symptoms, the FDG-avidity resolved after steroid treatment.
In a clinicopathological series, Uehara et al. showed that urinary symptoms improved after steroid therapy in three patients with standardized symptom reassessment. This small series illustrated several important points. First, two of the patients with elevated PSA levels and histological changes of IgG4-related prostatitis had synchronous prostate cancer. Thus, prostate cancer can occur in patients with IgG4-related prostatitis. Second, one patient had an abnormal PSA without histological evidence of cancer, indicating that IgG4-related prostatitis might be a cause of falsely elevated PSA levels. Finally, serum IgG4 levels in each of the patients with IgG4-prostatitis was markedly elevated (almost all were over 1000 mg/dL), suggesting that small, non-specific elevations in serum IgG4 carry less diagnostic significance.
We report the case of a patient with an abnormal digital rectal exam and history of steroid-responsive urinary symptoms. Biopsies were originally signed out descriptively, but in fact had changes diagnostic of IgG4-related prostatitis. IgG4-related prostatitis is the prostatic manifestation of IgG4-RD. The findings on histopathology and immunohistochemistry are similar to those seen in pancreas parenchyma. Although urinary symptoms often improve or resolve with steroid therapy, prostate biopsy is necessary to rule out synchronous malignancy in patients with suspected prostate cancer based on abnormal rectal examination or elevated PSA level. After excluding cancer, it is reasonable to provide close observation or medical therapy (i.e. oral steroids).