Granulomatous prostatitis after intravesical immunotherapy mimicking prostate cancer.

Intravesical immunotherapy with attenuated strains of Mycobacterium bovis is a widely used therapeutic option in patients with non-muscle-invasive transitional cell carcinoma of the bladder. A rare complication of intravesical therapy with the Bacillus Calmette-Guérin vaccine is granulomatous prostatitis, which due to increasing levels of prostate-specific antigen and abnormalities found in transrectal examination of the prostate may suggest concomitant prostate cancer. A case of extensive granulomatous prostatitis in a 61-year-old patient which occurred after the first course of a well-tolerated Bacillus Calmette-Guérin therapy is presented. Due to abnormalities found in rectal examination and an abnormal transrectal ultrasound image of the prostate with extensive infiltration mimicking neoplastic hyperplasia a core biopsy of the prostate was performed. Histopathological examination revealed inflammatory infiltration sites of tuberculosis origin.

Case report

A 61-year-old patient attended a consultation in a urology clinic due to complaints associated with the lower urinary tract. Digital rectal examination (DRE) revealed a slightly enlarged non-painful prostate gland with normal density and smooth contours. Prostate-specific antigen (PSA) level was 2.1 ng/ml. A urine test revealed 10–15 red blood cells/hpf.

The patient reported polyuria during the day and nocturia as well as persistent urgency with a normal urine stream. In an abdominal ultrasound scan no abnormalities were found in the upper urinary tract. Due to the lack of effects of solifenacin therapy the patient was scheduled for a cystoscopy. A 5-millimeter papillomatous lesion was found near the left ureteral orifice. Transurethral en bloc electroresection of the lesion was performed. Samples from the suspicious posterior wall mucosa were also taken.

Histopathological examination of samples from the tumor revealed: “Urothelial carcinoma high-grade pT1, total resection of the lesion”. In addition, carcinoma in situ was diagnosed in samples taken from the posterior wall of the urinary bladder. The patient was scheduled for intravesical immunotherapy. Due to the size of the primary lesion (5 mm) and the radicality of the original resection no repeated transurethral electroresection of the tumor of the bladder (re-TURT) was performed.

Bacillus Calmette-Guérin (BCG) vaccine therapy was started 5 weeks after transurethral resection of the tumor (TURT). The vaccine was an attenuated strain of Mycobacterium bovis (Onco BCG 100 formulation, Biofarm, Lublin, Poland, containing at least 300 million live, attenuated mycobacteria of the Brazilian Moreau substrain dissolved in saline in 1 ampoule of 100 mg). An induction course was introduced – 6 instillations were administered in weekly intervals. After the first 2 doses the patient reported increases in body temperature of up to 37.5°C as well as urgency episodes.

After 6 weeks from the completion of the induction course cystoscopy and urine cytology were performed and no abnormalities were found.

During a follow-up visit in a urology clinic DRE revealed a very hard non-painful left prostatic lobe with an uneven surface, which was suspected of neoplastic hyperplasia. In line with the European Association of Urology Guidelines(, the patient was scheduled for a core biopsy of the prostate based on rectal examination results, despite a low PSA level (2.1 ng/ml in the pre-operative period). In the group of patients with PSA in the range of 2.1–3 ng/ml the risk of prostate cancer diagnosis is 23.9% (European Association of Urology Guidelines)(. The biopsy was conducted 3 months after BCG therapy completion.

Twelve samples in total were collected under local anesthesia, including heterogeneously hypoechoic foci located in the peripheral zone on the left side. Histopathological examination revealed multifocal low-grade prostatic intraepithelial neoplasia (LG-PIN) in the right lobe of the prostate, while prostatitis chronica granulomatosa cum necrosi coagulativa telarum was found in samples from the right lobe, indicating a serious suspicion of tuberculosis origin of the lesions. The patient received consultation in a tuberculosis clinic; however, no indications were found for anti-tuberculosis treatment.

The patient was prescribed with ofloxacin to be taken twice daily for 3 weeks. Eight months after TURT cystoscopy, DRE and TRUS were conducted and samples were taken from lesions with suspected cancer relapse. Rectal examination after 2 months from the biopsy revealed a non-painful, very hard left lobe of the prostate with an uneven surface. TRUS conducted in a reference center revealed an enlarged prostate of 45.6 ml in volume. The peripheral zone on the left, the apex of the prostate in the midline and the area of the membranous urethra on the left were hypoechoic (Fig. 1, 2, 3, 4, 5). Fine hyperechoic foci with the largest one characterized by reverberations (probably gas) were found (Fig. 6). Adenomatous enlargement of the transitional and central zones was observed. Seminal vesicles were without abnormalities.

Fig. 1

Transrectal ultrasound of the prostate. Endorectal 9 MHz end-fire probe. Sagittal view. Hypoechoic lesion (22 mm × 20 mm) located in the peripheral zone on the left corresponds with a hard nodule

Fig. 2

Transrectal ultrasound of the prostate. Endorectal 9 MHz end-fire probe. Transverse view. Bulky hypoechoic lesion originating from the peripheral zone of the left prostatic lobe

Fig. 3

Transrectal ultrasound of the prostate. Endorectal 9 MHz end-fire probe. Transverse view. Color Doppler examination demonstrating blood flow within the suspicious lesion

Fig. 4

Transrectal ultrasound of the prostate. Endorectal 9 MHz end-fire probe. Sagittal view. Hypoechoic lesion reaching beyond the midline part of the prostate

Fig. 5

Transrectal ultrasound of the prostate. Endorectal 9 MHz end-fire probe. Transverse view. Elastography mode. Hypoechoic lesion in grayscale is heterogeneously hard in elastography mode

Fig. 6

Transrectal ultrasound of the prostate. Endorectal 9 MHz end-fire probe. Transverse view. Reverberation bands found within the nodule

In line with the European Association of Urology Guidelines, due to the presence of a high-grade neoplasm in the original TURT the patient underwent cystoscopy every 3 months. Liquid-based urine cytology was also regularly performed due to the original diagnosis of carcinoma in situ.

In histopathological examination of samples taken during flexible cystoscopy low-grade intraurothelial neoplasia was found in a 1-millimeter sample taken from the neck/left wall and posterior wall. A relatively intense chronic inflammatory infiltration with epitheloid cell granuloma was observed in a sample from a polypous mucosa of the prostatic urethra.

In rectal examination performed 9 months after TURT the prostate was very hard on the left side. Transrectal ultrasound scan revealed a peripheral zone on the left side filled with hypoechoic foci with signs of extraprostatic infiltration (Fig. 7, 8). A core biopsy of the prostate was conducted under neurovascular bundle block. Three samples each were taken bilaterally from the base and four samples each were taken bilaterally from the apex (Fig. 9, 10).

Fig. 7

Transrectal ultrasound of the prostate. Endorectal 12 MHz probe. Transverse view. Extraprostatic infiltration at the prostatic apex on the left side

Fig. 8

Transrectal ultrasound of the prostate. Endorectal 12 MHz probe. Transverse view. Power Doppler image before the second biopsy

Fig. 9

Transrectal ultrasound of the prostate. Endorectal 12 MHz end-fire probe. Sagittal view. Biopsy of the suspicious lesion

Fig. 10

Transrectal ultrasound of the prostate. Endorectal 12 MHz end-fire probe. Sagittal view. Biopsy of the suspicious lesion infiltrating periprostatic fatty tissue

The histopathological report stated the following: “Inflammatione chronica partim granulomatosa et cum necrose focali in samples from the base of the left lobe. Inflammatione chronica partim granulomatosa et cum necrose focali in the apex of the left lobe” (Fig. 11).

Fig. 11

Core biopsy of the prostate. Necrosis (upper left) and two multinucleated Langhans-type giant cells (arrows) are visible

During a follow-up visit in a clinic 14 months after TURT rectal examination revealed a very hard, non-painful left lobe of the prostate. The patient did not report complaints associated with the lower urinary tract. Cystoscopy did not reveal any foci with suspected neoplastic hyperplasia. Blood PSA level was 2.4 ng/ml. The result of a liquid-based cytology of urine sediment was negative.

Discussion and conclusions

BCG therapy is currently the most effective immunotherapy method used for the treatment of non-muscle-invasive transitional cell carcinoma of the bladder. Due to the common use of this type of therapy urologists are aware of the most frequent adverse reactions occurring during the therapy, both local and systemic ones(.

Granulomatous prostatitis of tuberculosis origin is an exceptionally rare complication of intravesical therapy. In approximately 40% of cases an increased PSA level is observed as a result of intravesical instillations(. Symptomatic, mycobacterial prostatitis, which requires a 3-month antimycobacterial drug therapy, may be accompanied by symptoms of irritation in the lower urinary tract, pain in the perineum, episodes of hematuria towards the end of micturition, sterile purulent discharge from the urethra and compromised fertility. Histopathological assessment of samples taken from the prostate is recommended if elevated PSA levels persist for more than 3 months. However, no algorithm of optimal treatment has been determined for the cases in which granulomatous prostatitis with little or no symptoms is diagnosed(. Immunotherapy should be stopped and antimycobacterial treatment should be considered(.

In the present case the patient was referred for a core biopsy of the prostate due to a justified suspicion of concomitant bladder and prostate cancer. In the early follow-up period the presence of a hard or even very hard, non-painful lesion was determined already after an induction course of BCG, while no signs of prostatitis were observed.

Gray-scale, Doppler and elastography ultrasound scans showed a hypoechoic lesion with irregular contours, distinct blood flow and significantly increased density, which did not lose sonographic signs of malignant hyperplasia and even seemed to infiltrate the extraprostatic area despite the discontinuation of the intravesical therapy.

An atypical finding for a prostate ultrasound image were fine hyperechoic foci with reverberation bands dispersed in the hypoechoic lesion, which could have corresponded to necrotic foci found in biopsy specimens.

Unfortunately, transrectal ultrasound imaging does not offer sufficient ability to differentiate between hypoechoic lesions of inflammatory and/or neoplastic nature(.

Although rectal examination performed before the instillations demonstrated only enlargement of the prostate that suggested benign, adenomatous hyperplasia, unfortunately, a transrectal ultrasound scan was not performed at the time which could have been the point of reference for images of the prostate obtained after induction BCG therapy. Therefore, in our opinion, not only thorough physical examination, but also imaging of the prostate is justified in patients referred for intravesical therapy, since it allows for comparison of the condition of the prostate with the image from before the therapy.