Brian Cox, MD
Christopher Amling, MD, FACS
BASICS
DESCRIPTION
• Granulomatous prostatitis is inflammation of the prostate associated with granuloma formation
• Often confused with carcinoma of the prostate
– Similar findings on digital rectal exam (DRE); has the findings of a “prostate nodule"
– Similar elevations in prostate-specific antigen (PSA)
– Similar findings on transrectal ultrasound (TRUS) and magnetic resonance imaging (MRI) images
– Can be due to infectious and noninfectious etiologies
EPIDEMIOLOGY
Incidence
N/A
Prevalence
• 0.8–1% of benign inflammatory prostatic specimens
• Reported up to 4–10% of prostatitis cases
• Reported in 1.3–40% of post-Bacillus Calmette–Guérin (post-BCG) patients
RISK FACTORS
• Age: Mean age 62 yr (range 18–86 yr) (1)
– Typically 50–70 yr of age
• Infections:
– Bacterial, viral, fungal, parasitic, Mycobacterium, and sexually transmitted diseases (STDs)
– Human immunodeficiency virus (HIV) infection may increase risk for tuberculosis (TB) prostatitis
– Infectious etiologies make up ∼15–20% of granulomatous prostatitis cases
• Iatrogenic causes:
– Transurethral resection of prostate (TURP)
– BCG instillation for bladder cancer—up to 40% may develop granulomatous prostatitis after BCG.
– Iatrogenic etiologies make up ∼75% of granulomatous prostatitis cases
• Systemic granulomatous diseases:
– Wegener granulomatosis, Churg–Strauss syndrome, sarcoidosis, rheumatoid arthritis, polyarteritis nodosa, malakoplakia
– These make up a minority of granulomatous prostatitis cases
• Idiopathic: No specific cause identified
– Theory: Ductal/acinar obstruction causes prostatic secretions to leak into the stroma and cause granulomatous reaction
– Idiopathic etiologies make up a significant proportion of granulomatous prostatitis cases
Genetics
N/A
PATHOPHYSIOLOGY
• Specific subtype:
– Caused by identifiable infectious agent (mycobacterium, fungi, syphilis, brucellosis, virus, parasites)
It is often associated with systemic TB
With HIV, TB may cause prostatic abscess
• Nonspecific subtype:
– Usually an incidental finding on biopsy
Reported 0.3–3.0%
• Iatrogenic:
– After TURP- or TRUS-guided biopsy, necrotizing lesions may resemble lesions associated with rheumatoid diseases
• Eosinophilic subtype:
– Very rare, may suggest allergic etiology
– Associated with systemic condition (asthma, Wegener granulomatosis, Churg–Strauss syndrome
• Autoimmune based:
– HLA-DR15–linked T-cell–mediated response against PSA
ASSOCIATED CONDITIONS
• Prostate cancer can be coincident with granulomatous prostatitis in 10–14% of biopsy specimens (2)
• May be associated with systemic conditions
– Asthma, Wegener granulomatosis, Churg–Strauss syndrome, sarcoidosis, rheumatoid arthritis, polyarteritis nodosa, malakoplakia
GENERAL PREVENTION
N/A
DIAGNOSIS
HISTORY
• Often asymptomatic
• Previous urinary tract infection (UTI) or STD:
– Syphilis, TB, or other infectious etiology
– Often associated with UTI 2–3 m prior to onset of symptoms
• History of lower urinary tract symptoms (LUTS)
– Voiding symptoms including urgency, frequency, dysuria
– Obstructive voiding symptoms, including acute urinary retention
• Systemic granulomatous disease:
– If associated with systemic vasculitis or granulomatous disease, may have constitutional signs/symptoms
• History of prostate surgery or bladder cancer:
– BCG or TURP can cause granulomatous prostatitis
• Fever, chills, or other constitutional signs:
– Suggest infectious, systemic etiology
PHYSICAL EXAM
• DRE may be normal or abnormal
• Abnormal DRE:
– Indurated gland with/without nodule
– Tender or nontender
• TB prostatitis should be suspected if a draining perineal fistula is present
ALERT
• Digital Rectal Exam (DRE) cannot differentiate between prostate nodules due to granulomatous prostatitis and prostate cancer.
• Biopsy is required to differentiate these 2 etiologies.
DIAGNOSTIC TESTS & INTERPRETATION
Lab
• Urinalysis may be unremarkable
• Urine cultures
– Are often sterile
• Elevated erythrocyte sedimentation rate (ESR), acid phosphatase, serum eosinophils may be present
• PSA may rise transiently
• If evidence of TB/mycotic disease, appropriate testing includes:
– AFB stain of urine and semen
– TB cultures (may take up to 10 wk)
– Polymerase chain reaction (PCR): Genomic amplification of Mycobacterium Tuberculosis DNA
High sensitivity/specificity
Rapid: Takes 48 hr
Imaging
• TRUS
– Limited utility except to direct biopsy
– Appears as focal hypoechoic area
– Difficult to discern granulomatous prostatitis and prostate cancer
• MRI
– Limited utility
– Difficult to discern granulomatous prostatitis from prostate cancer on MRI
Diagnostic Procedures/Surgery
TRUS-guided prostate biopsy is needed for pathologic diagnosis
Pathologic Findings
• Histologically granulomatous prostatitis appears as noncaseating granulomas, prominent macrophage infiltrates with occasional multinucleated giant cells (Langerhan cells) which are characteristic of granulomas
– Immunohistochemistry for cytokeratin (CAM 5.2) may stain glands positive but not the macrophage infiltrate
– Macrophage infiltrate stains for macrophage marker CD68
• Fibrosis replaces parenchyma
• BCG therapy related
– Caseating or noncaseating granulomas located next to benign prostatic glands (not engulfing them)
– Usually AFB negative
DIFFERENTIAL DIAGNOSIS
• Nodular DRE (neoplasm/malignant):
– Lymphoma, primary, and secondary
– Prostatic adenocarcinoma
– Sarcoma, small-cell carcinoma, and other rare tumors and metastases
– Urothelial carcinoma
– Granulomatous prostatitis
Infectious, iatrogenic, etc. (See Risk Factors)
• Nodular DRE (benign):
– Prostatic calculus/calcification
– Ejaculatory duct cyst
– Scarring/fibrosis from prior surgery or infection
TURP, prostate biopsy
– Granulomatous prostatitis
• Rectal wall lesions (thrombosed hemorrhoid, carcinoma, etc.)
TREATMENT
GENERAL MEASURES
• Majority of granulomatous prostatitis symptoms resolve spontaneously including those that are BCG related (3 – 5)
• DRE changes and PSA elevation may persist
• Use antibiotics as indicated for UTI
• Symptom control:
– Sitz baths, fluids, anti-inflammatory α-blockers, and other symptomatic medications
• Temporary transurethral urinary catheterization if acute urinary retention or severe symptoms are present
• TRUS biopsy is indicated for:
– Differentiating granulomatous prostatitis from prostate carcinoma
– Consider rebiopsy if PSA remains elevated or DRE remains abnormal several months after treating symptomatic granulomatous prostatitis
MEDICATION
First Line
• Antibiotics as indicated for documented UTI
• Anti-TB medications for TB prostatitis:
– Use only if documented TB cause
– Isoniazid, rifampin, pyrazinamide, and either ethambutol or streptomycin for initial regimen, then change based on TB isolate sensitivities
– Pyridoxine (Vitamin B6) 25–50 mg/d to prevent isoniazid neuropathy
Second Line
N/A
SURGERY/OTHER PROCEDURES
• Majority of symptomatic cases of granulomatous prostatitis resolve spontaneously
• Reserve TURP or prostatectomy for refractory cases
– Reported in up to 10% of cases in some series
ADDITIONAL TREATMENT
Radiation Therapy
N/A
Additional Therapies
Corticosteroids and antihistamines have been recommended in idiopathic cases
Complementary & Alternative Therapies
N/A
ONGOING CARE
PROGNOSIS
• Majority of symptomatic cases of granulomatous prostatitis resolve spontaneously
• DRE findings may persist for months/years
• PSA elevation may last up to 3 mo
COMPLICATIONS
• Acute urinary retention
• Possible transmission of infectious etiology to sexual partner
• Possible infertility
• Possible undetected prostate cancer
FOLLOW-UP
Patient Monitoring
Rebiopsy may be indicated if DRE remains abnormal or PSA remains elevated after treatment to avoid missing coincident prostate cancer (reported in 10–14% of cases)
Patient Resources
Prostatitis Foundation. http://www.prostatitis.org/
REFERENCES
1. Stillwell T, Engen DE, Farrow GM. The clinical spectrum of granulomatous prostatitis: A report of 200 cases. J Urol. 1987;138:320–323.
2. Oppenheimer J, Kahane H, Epstein JI. Granulomatous prostatitis on needle biopsy. Arch Pathol Lab Med. 1997;121:724–729.
3. Uzoh CC, Uff JS, Okeke AA. Granulomatous Prostatitis. BJU Int. 2007;99(3):510–512.
4. Eyre RC, Aaronson AG, Weinstein BJ. Palisading granulomas of the prostate associated with prior prostatic surgery. J Urol. 1986;136:121–122
5. Lafontaine PD, Middleman BR, Graham SD Jr, et al. Incidence of granulomatous prostatitis and acid-fast bacilli after intravesicular BCG therapy. Urology. 1997;49:363–366.
ADDITIONAL READING
• Humphrey PA. Prostate Pathology, ASCP Press: Chicago. 2003;87–95.
• Warrick J, Humphrey PA. Nonspecific granulomatous prostatitis. J Urol. 2012;187:2209–2210.
See Also (Topic, Algorithm, Media)
• BCG Sepsis/BCGosis
• Prostate, Nodule
• Prostatitis, General
• Prostatitis, Granulomatous Image 
• Prostatitis, Tuberculosis
• Tuberculosis, Genitourinary, General Considerations
CODES
ICD9
• 135 Sarcoidosis
• 446.4 Wegener’s granulomatosis
• 601.8 Other specified inflammatory diseases of prostate
ICD10
• D86.9 Sarcoidosis, unspecified
• M31.30 Wegener’s granulomatosis without renal involvement
• N41.4 Granulomatous prostatitis
CLINICAL/SURGICAL PEARLS
• Majority of symptomatic cases of granulomatous prostatitis resolve spontaneously.
• Up to 40% of patients may develop granulomatous prostatitis after intravesical BCG.
• DRE changes and PSA elevation may persist for months.
• TRUS-guided prostate biopsy is needed for pathologic diagnosis.
• Rebiopsy may be indicated if DRE remains abnormal or PSA remains elevated after treatment to avoid missing coincident prostate cancer (reported in 10–14% of cases).