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Indian J Urol. 2016 Apr-Jun; 32(2): 166–168.
PMCID: PMC4831511

Steroid-responsive IgG4-related disease with isolated prostatic involvement: An unusual presentation with elevated serum PSA


Autoimmune prostatitis is known to occur as a part of multisystem fibro-inflammatory disorder known as IgG4 related disease (IgG4 RD). The usual presentation is with symptoms of gastro-intestinal disease with prostatic involvement presenting as lower urinary tract symptoms. The disease responds to corticosteroids. We report an asymptomatic young man who was diagnosed to have IgG4 related prostatitis on TRUS-guided prostate biopsy done for elevated serum PSA, in the absence of any other systemic involvement. The treatment with steroid resulted in normalization of S PSA levels.

Keywords: Autoimmune, immunohistochemistry, PSA, prostatitis


IgG4-related disease (IgG4 RD) is considered to be a systemic disorder involving multiple organ systems including genitourinary system. Autoimmune prostatitis in these patients is a known clinical entity and usually a part of systemic conglomerate. Such patients present with lower urinary tract symptoms (LUTS) that have been reported to show a considerable response to corticosteroids. Isolated IgG4 prostatitis is extremely rare. We report the case of a young male, who was incidentally diagnosed with IgG4 autoimmune prostatitis on trans-rectal ultrasound (TRUS)-guided prostatic biopsy done for raised serum prostate-specific antigen (S PSA) levels, which subsequently normalized on steroid therapy.


A 45-year-old male patient presented to us with a single value of raised S PSA of 7.16 ng/ml. He did not give any history of LUTS, but complained of nonspecific generalized bony ache. The pain did not have a specific pattern or a characteristic feature. He was being evaluated for this complaint, on the lines of arthritis, at some other medical facility. His blood tests were normal (serum calcium, serum phosphate, serum PTH levels and antibodies negative). His roentgenograms and bone scan tests were unremarkable. He was also advised S PSA levels that turned out to be elevated and he was referred to us for further management.

His digital rectal examination was within normal limits with no signs of prostatitis. TRUS showed 37 g of homogenous and unremarkable prostate. We repeated the S PSA test after 4 weeks of the previous value and it showed a progressive pattern (S PSA = 10.47 ng/ml). Therefore, we planned a prostatic biopsy of this patient. A 12-core TRUS-guided prostatic biopsy was performed. The histopathologic examination (HPE) of tissue [Figure 1] revealed stromal aggregate of lymphoplasmacytic cells, periductal condensation of plasma cells with intraepithelial infiltration and destruction, and dense fibro-collagenous tissue with intense plasma cell infiltration. The features were suggestive of autoimmune prostatitis. On further immunohistochemistry evaluation, plasma cells showed IgG4 positivity.

Figure 1
(a) Intense chronic inflammation and fibrocollagenous stroma (×40, H and E), (b) resolutions of ducts with intense inflammation (×200, HE), (c) stromal aggregate of lymphoplasmacytic cells (×200, HE), (d) periductal condensation ...

Subsequently, serum IgG4 levels were obtained that was found raised (3.18g/L). We also advised an abdomino-pelvic contrast CT scan keeping in mind the systemic nature of the disease and association of IgG4 prostatitis with pancreatitis. However, it showed normal findings with no abnormalities in the pancreas with mild enlargement of prostate [Figure 2]. The patient was counseled regarding the absence of any prostatic malignancy but the need for regular follow up. As no specific urological symptoms were present, no active treatment from urological point of view was advised. But, to evaluate effect on S PSA levels, corticosteroids were started. We observed a steady decline in S PSA levels after starting medication 2 and 4 weeks (4.16 and 3.22 ng/ml, respectively) later. The patient is on regular follow-up till date with normal S PSA levels on corticosteroids.

Figure 2
Pelvic tomogram showing the prostatic volume


IgG4-RD is a systemic fibro-inflammatory disease involving single or multiple organ systems at the same time. The pancreas is found to be the most commonly involved organ followed by biliary tract.[1] Involvement of genitourinary system is relatively uncommon, but IgG4-RD has been reported affecting kidneys, ureters, testes, and prostate.[2]

A relatively recent description of this disease affecting prostate gland is in the form of auto-immune prostatitis. In 2006, the first case of IgG4-related prostatitis was reported by Yoshimura et al. in a sample of TURP specimen.[3] Two additional cases were incidentally diagnosed by Nishimori et al.[4] Elevated S PSA and synchronous prostatic cancers have also been found in patients affected by this disease, thereby necessitating the need for regular follow-ups.[5]

A prominent feature in such cases is marked elevation of serum IgG4 levels. The characteristic features on histopathology are lympho-plasmacytic inflammation, storiform fibrosis, obliterative phlebitis and abundant IgG4-positive plasma cells at the affected sites. The criteria laid down by Deshpande et al.[6] for HPE diagnosis was mainly described in pancreas, but prostatic tissue specimens are also evaluated on similar guidelines. Being a rare entity to be encountered in prostatic tissue, coupled with the patchy distribution of the IgG4-positive B or plasma cellular infiltrate, the HPE confirming the diagnosis still remains a challenge for pathologists in this part of Asian continent, hence requiring final confirmation on immunohistochemistry. A recently published comprehensive diagnostic guideline for IgG4-related disease by the Japanese IgG4-related disease study group has been tabulated in Table 1.[7,8]

Table 1
Japanese IgG4-related disease study group comprehensive diagnostic guideline

Buijs et al.[9] studied 117 patients suffering from IgG4-related pancreaticobiliary disease. Nine of these patients, with LUTS, showed characteristic histopathological features of IgG4-RD in prostatic tissue. They were of the opinion that urological symptoms might even precede the onset of gastrointestinal symptoms in such patients. These patients with co-existing pancreaticobiliary disease and LUTS have found to be benefited by treatment with steroids.[10] The organ involvement, in IgG4-RD, might strongly mimic malignancy in pancreaticobiliary organs and this has been found true for prostatic involvement as well. Till recently, serum IgG4 has been considered to be the best marker to diagnose IgG4-RD and to distinguish it from malignancy.[11] However, several authors have questioned the use of this serum marker in diagnostic criteria because of its limited sensitivity and specificity. Carruthers et al.,[12] in their most recent work, analysed 380 patients to evaluate the sensitivity, specificity and positive and negative predictive values of elevated serum IgG4 concentrations for the diagnosis of IgG4-RD and concluded that a substantial number of patients with histology-positive IgG4-RD do not have elevated serum IgG4 and multiple non-IgG4-RD conditions are associated with elevated serum IgG4, leading to poor specificity and low-positive predictive value for this test.

Our case is peculiar in a number of ways. This is possibly the first reported case of IgG4-related prostatitis from Indian subcontinent. The affected individual is of relatively younger age group contrary to much common sixth decade of life. The patient had no other organs affected till he was diagnosed with this pathology, representing an isolated involvement of prostate by the disease process. Abdomino-pelvic computed tomogram showed mild prostatic enlargement. Majority of patients develop LUTS easily confounded with benign prostatic hyperplasia. Some have undergone even trans-urethral resection of prostate with favorable outcomes.[3] However, our case had no such symptoms. The patient had only mild elevation in serum IgG4 levels. Therefore, in the presence of strongly positive histology but the absence of significant “characteristic diffuse” organ enlargement and elevated serum IgG4 levels, our case fits into what is considered to be the “probable IgG4-related disease” as per comprehensive diagnostic criteria [Table 1]. Although no symptoms were present and diagnosis was an incidental finding, we started the patient on steroids, to evaluate the effect on S PSA levels. A progressive decline in the S PSA levels in response to steroids was evident (steroid-responsive isolated IgG4 prostatitis). The hypothesis stands that the pathogenic mechanism affects a lot number of organ systems; hence it is important to follow our case closely for early detection of any other pathology.

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Conflicts of interest

There are no conflicts of interest.


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