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Non-Specific Granulomatous Prostatitis
Vol. 118, July, Part 1 Printed in U.S.A.
THE JOURNAL OF UROLOGY Copyright © 1977 by The Williams & Wilkins Co.
NON-SPECIFIC GRANULOMATOUS PROSTATITIS MICHAEL J. O'DEA,* DANIEL B. HUNTING
AND
LAURENCE F. GREENE
From the Mayo Clinic and Mayo Foundation, Rochester, Minnesota
ABSTRACT
Between 1963 and 1972, 86 patients with non-specific granulomatous prostatitis were seen. Symptomatology was suggestive of a lower urinary tract infection in the majority of the cases. The most important feature on prostatic examination was the likelihood of confusion with prostatic carcinoma. Management by whatever means yielded uniformly good results. The natural history of this disease seems to be that of gradual resolution. Non-specific granulomatous prostatitis is a rare but important infectious process in the prostate-important because it often is confused with carcinoma. Its benign course is in marked contradistinction to carcinoma and to the specific forms of granulomatous prostatitis caused by known etiologic agents such as Mycobacterium tuberculosis, 1 Treponema pallidum, 2 various fungi 3 • 4 and Brucella abortus. 5 Between 1963 and 1972, 2,599 patients with prostatitis were seen at this clinic, 86 (3.3 per cent) of whom had histologically proved nonspecific granulomatous prostatitis and form the basis of our review.
while 20 patients were treated with antimicrobials alone for 2 to 4 weeks (table 6). One patient underwent radical prostatectomy because of associated carcinoma, 1 had a retropubic adenectomy and 2 with associated carcinoma had estrogen therapy. Followup information. Followup data were available in 67 of the 86 patients, with an average followup of 6 years (table 7). Of these 67 patients 57 had no further trouble. Seven patients had 1 exacerbation only that responded to antimicrobials and 3 patients continue to have mild persistent symptoms. Management of any type, including no treatment at all, produced similar results. In fact there were only 2 exacerbations in 17 patients who were followed for an average of 7 years and who did not have any form of treatment. There was no evidence for the development ofprostatic cancer in any patient followed.
CLINICAL FEATURES
Of the 86 patients 44 per cent were in the seventh decade of life, with an average age of61 years (table 1). Dysuria, pyrexia and frequency 3 to 4 weeks in duration were the most common symptoms noted (table 2). Progressive prostatism was experienced by 25 patients, while low back pain, epididymo-orchitis, hematuria, suprapubic pain, perineal discomfort and groin pain were less frequent presentations. Six patients were asymptomatic and the diseased prostate was detected by digital rectal examination during a routine physical examination. Previous recurrent non-specific prostatitis had occurred in 7 patients. Two patients had had a previous prostatic resection. Carcinoma was suspected in 45 of the 86 patients. In 20 of these cases an unequivocal diagnosis of carcinoma was made because of fixation, nodularity or hardness of the prostate (table 3). The prostate was considered benign in 27 cases, while in 14 cases non-specific granulomatous prostatitis was strongly suspected or mentioned as a differential to carcinoma because of a clinical history of symptoms referable to the lower urinary tract a few weeks in duration. Laboratory and roentgenologic studies indicated that the majority of patients had pyuria and microhematuria (table 4). Of the 28 patients who had organisms cultured from the urine, Escherichia coli was the most common organism, being found in 17 cases. Six patients had polymorphonuclear leukocytosis. Two of 48 patients had elevated serum alkaline phosphatase and the same 2 of 52 patients studied had elevated serum acid phosphatase. Both of these patients had associated prostatic carcinoma. Method of diagnosis. Diagnosis was made by transrectal needle biopsy in 51 of the 86 patients, by transurethral resection in 34 patients and by retropubic adenectomy in the remaining patient (table 5). Four patients had associated carcinoma. Management. Almost half of the patients underwent transurethral prostatic resection and were given antimicrobials,
DISCUSSION
Non-specific granulomatous prostatitis was first described by Tanner and McDonald in 1943. 6 The etiology i& obscure. Epstein, in a comprehensive review in 1967, considered the granulomatous reaction to be a response to tissue injury by a poorly soluble substance mediated through the accumulation and proliferation of reticuloendothelial cells. 7 It may arise either as a foreign body response to a colloidal substance or as a hypersensitivity reaction. Prostatic contents (for example prostatic secretions, corpora amylacea), bacterial products and urine have been suggested as etiologic agents. 8 These substances may be released into the periacinar space secondary to obstruction (caused by inflammation or inspissated corpora amylacea). Histologically, the stromal infiltrate contains epithelioid cells, lymphocytes, plasma cells and a few eosinophils, and scattered about are multinucleated giant cells (see figure). These lesions should be distinguished from another group of eosinophilic granulomatous lesions in the prostate, which exhibit fibrinoid necrosis, occur exclusively in patients suffering from bronchial asthma and are associated with a grave prognosis. These are better referred to as allergic granuloma of the prostate. 9 The rarity of this lesion has been well established by other authors. 10• 11 Low grade fever, dysuria, frequency and other symptoms suggestive of lower urinary tract infection are in keeping with the infectious concept of the disease. It is not surprising that a history of progressive prostatism was given in 25 of 86 patients, because the age groups are similar. The laboratory findings, when abnormal, provided corroborative evidence of an inflammatory rather than a malignant lesion. Associated carcinoma with raised serum alkaline and acid phosphatase levels was present in 2 patients. The upper part of the urinary tract was normal in the 62 patients in whom roentgenographic examination was performed. Among 63
Accepted for publication October 1, 1976. *Requests for reprints: Section of Publications, Mayo Clinic, Rochester, Minnesota 55901. 58
59
NON-SPECIFIC GRANULOMATOUS PROSTATITIS TABLE
1. Age distribution of 86 patients in series* No. Pts. 30-39 40-49 50-59 60-69 70-79 80-89
TABLE
7. Results of management in 67 patients with granulomatous
prostatitis
(%)
2
(2.5)
8
(9)
23 38 13 2
(27) (44)
Yrs. ofFollowup No. Pts. Transurethral resection and antimicrobials
(15)
33
Range
(av.)
1-11
(5)
(2.5)
No recurrence-28 cases Exacerbation- 4 cases Persistent symptoms-1
* Average age 61 years.
case TABLE
Antimicrobials only
2. Symptoms
15
1-11.5
(6)
No recurrence-12 cases Exacerbation-1 case Persistent symptoms-2 cases
7.5 6.5
(7.5) (6.5)
No recurrence No recurrence*
1-13
(7)
No recurrence -15 cases Exacerbation-2 cases
No. Pts. Dysuria Pyrexia Frequency Progressive prostatism Low back pain Epididymo-orchitis Hematuria Suprapubic pain Perinea! discomfort Groin pain None TABLE
Results
44 41 32 25 5 4
4
Retropubic adenectomy Radical retropubic prostatectomy* No treatment
1 1 17
* For associated carcinoma.
1 2 1 6
3. Impression on digital rectal prostatic examination No. Pts.
Ca Benign Granulomatous prostatitis Granulomatous prostatitis or Ca
45* 27 7
7
Total
86
* In 20 cases unc 1uivocal diagnosis was prostatic carcinoma. TABLE
4. Laboratory and roentgenologic findings No. Pts. Investi- No. Pts. WithPos. gated Findings
Pyuria Microscopic hematuria Urinary pathogens Leukocytosis Alkaline phosphatase levels Acid phosphatase levels Plain film of kidneys, ureters and bladder Excretory urogram
86 86 86 86 48 52 63 62
71
51 28 6
2 2
5* 0
Typical non-caseating granuloma with predominantly lymphocytic and plasma cell infiltration and prominent giant cell component. H & E, reduced from xlOO.
* Patients had prostatic calculi. TABLE
5. Method of diagnosis in 86 patients with granulomatous
prostatitis * No. Pts. Transrectal needle biopsy of prostate Transurethral resection Retropubic adenectomy
51 34 1
* Associated carcinoma in 4 patients. TABLE
6. Management of 86 patients with granulomatous prostatitis No. Pts.
Transurethral resection and antimicrobials Antimicrobials only Radical prostatectomy Retropubic adenectomy Estrogen No treatment
40 20 1 1 2 22
plain roentgenograms of the abdomen 5 revealed prostatic calculi. Misconstrued malignancy was the most important feature of digital rectal examination of the prostate, being the only consideration in 45 of the 86 patients and considered in the differential diagnosis in a further 7 patients. The management methods used for 82 patients included transurethral resection with antimicrobial therapy, antimi-
crobial therapy only for 2 to 4 weeks and no treatment. Admittedly, 24 patients with a history of progressive prostatism, who had a transurethral resection, were justifiably treated but when the followup data were analyzed results were essentially similar to any form of treatment or- more importantly- to no treatment whatever. The natural history of this disease seems to be that of gradual resolution. A further 3 patients were treated for concomitant carcinoma and 1 patient with severe obstructive symptoms from a grossly enlarged prostate had a retropubic adenectomy. In none of the 67 patients followed for an average of 6 years was there any evidence to suggest the development ofprostatic carcinoma. REFERENCES
1. Moore, R. A.: Tuberculosis of the prostate gland. J. Urol., 37: 372, 1937. 2. Thomson, L.: Syphilis of the prostate. Amer. J. Syphil., 4: 323, 1920. 3. Dreyfuss, M. L., Simon, S. and Sommer, R. I.: Granulomatous prostatitis due to Cryptococcus neoformans (Torula) with disseminated cryptococcosis and meningitis. N.Y. State J. Med., 61: 1589, 1961. 4. Gritti, E. J., Cook, F. E., Jr. and Spencer, H.B.: Coccidioidomycosis granuloma of the prostate: a rare manifestation of the disseminated disease. J. Urol., 89: 249, 1963. 5. Kelalis, P. P., Greene, L. F. and Weed, L.A.: Brucellosis of the
60
O'DEA, HUNTING AND GREENE
urogenital tract: a mimic of tuberculosis. J. Ural., 88: 347, 1962. 6. Tanner, F. H. and McDonald, J. R.: Granulomatous prostatitis: a histologic study of a group of granulomatous lesions collected from prostate glands. Arch. Path., 36: 358, 1943. 7. Epstein, W. L.: Granulomatous hypersensitivity. Prag. Allergy, 11: 36, 1967. 8. Schmidt, J. D.: Non-specific granulomatous prostatitis: classification, review and report of cases. J. Ural., 94: 607, 1965.
9. Kelalis, P. P., Harrison, E. G., Jr. and Greene, L. F.: Allergic granulomas of the prostate in asthmatics. J.A.M.A., 188: 963, 1964. 10. Kelalis, P. P., Greene, L. F. and Harrison, E. G., Jr.: Granulomatous prostatitis: a mimic of carcinoma of the prostate. J.A.M.A., 191: 287, 1965. 11. Towfighi, J., Sadeghee, S., Wheller, J.E. and Enterline, H. T.: Granulomatous prostatitis with emphasis on the eosinophilic variety. Amer. J. Clin. Path., 58: 630, 1972.
THE JOURNAL OF UROLOGY Copyright © 1977 by The Williams & Wilkins Co.
NON-SPECIFIC GRANULOMATOUS PROSTATITIS MICHAEL J. O'DEA,* DANIEL B. HUNTING
AND
LAURENCE F. GREENE
From the Mayo Clinic and Mayo Foundation, Rochester, Minnesota
ABSTRACT
Between 1963 and 1972, 86 patients with non-specific granulomatous prostatitis were seen. Symptomatology was suggestive of a lower urinary tract infection in the majority of the cases. The most important feature on prostatic examination was the likelihood of confusion with prostatic carcinoma. Management by whatever means yielded uniformly good results. The natural history of this disease seems to be that of gradual resolution. Non-specific granulomatous prostatitis is a rare but important infectious process in the prostate-important because it often is confused with carcinoma. Its benign course is in marked contradistinction to carcinoma and to the specific forms of granulomatous prostatitis caused by known etiologic agents such as Mycobacterium tuberculosis, 1 Treponema pallidum, 2 various fungi 3 • 4 and Brucella abortus. 5 Between 1963 and 1972, 2,599 patients with prostatitis were seen at this clinic, 86 (3.3 per cent) of whom had histologically proved nonspecific granulomatous prostatitis and form the basis of our review.
while 20 patients were treated with antimicrobials alone for 2 to 4 weeks (table 6). One patient underwent radical prostatectomy because of associated carcinoma, 1 had a retropubic adenectomy and 2 with associated carcinoma had estrogen therapy. Followup information. Followup data were available in 67 of the 86 patients, with an average followup of 6 years (table 7). Of these 67 patients 57 had no further trouble. Seven patients had 1 exacerbation only that responded to antimicrobials and 3 patients continue to have mild persistent symptoms. Management of any type, including no treatment at all, produced similar results. In fact there were only 2 exacerbations in 17 patients who were followed for an average of 7 years and who did not have any form of treatment. There was no evidence for the development ofprostatic cancer in any patient followed.
CLINICAL FEATURES
Of the 86 patients 44 per cent were in the seventh decade of life, with an average age of61 years (table 1). Dysuria, pyrexia and frequency 3 to 4 weeks in duration were the most common symptoms noted (table 2). Progressive prostatism was experienced by 25 patients, while low back pain, epididymo-orchitis, hematuria, suprapubic pain, perineal discomfort and groin pain were less frequent presentations. Six patients were asymptomatic and the diseased prostate was detected by digital rectal examination during a routine physical examination. Previous recurrent non-specific prostatitis had occurred in 7 patients. Two patients had had a previous prostatic resection. Carcinoma was suspected in 45 of the 86 patients. In 20 of these cases an unequivocal diagnosis of carcinoma was made because of fixation, nodularity or hardness of the prostate (table 3). The prostate was considered benign in 27 cases, while in 14 cases non-specific granulomatous prostatitis was strongly suspected or mentioned as a differential to carcinoma because of a clinical history of symptoms referable to the lower urinary tract a few weeks in duration. Laboratory and roentgenologic studies indicated that the majority of patients had pyuria and microhematuria (table 4). Of the 28 patients who had organisms cultured from the urine, Escherichia coli was the most common organism, being found in 17 cases. Six patients had polymorphonuclear leukocytosis. Two of 48 patients had elevated serum alkaline phosphatase and the same 2 of 52 patients studied had elevated serum acid phosphatase. Both of these patients had associated prostatic carcinoma. Method of diagnosis. Diagnosis was made by transrectal needle biopsy in 51 of the 86 patients, by transurethral resection in 34 patients and by retropubic adenectomy in the remaining patient (table 5). Four patients had associated carcinoma. Management. Almost half of the patients underwent transurethral prostatic resection and were given antimicrobials,
DISCUSSION
Non-specific granulomatous prostatitis was first described by Tanner and McDonald in 1943. 6 The etiology i& obscure. Epstein, in a comprehensive review in 1967, considered the granulomatous reaction to be a response to tissue injury by a poorly soluble substance mediated through the accumulation and proliferation of reticuloendothelial cells. 7 It may arise either as a foreign body response to a colloidal substance or as a hypersensitivity reaction. Prostatic contents (for example prostatic secretions, corpora amylacea), bacterial products and urine have been suggested as etiologic agents. 8 These substances may be released into the periacinar space secondary to obstruction (caused by inflammation or inspissated corpora amylacea). Histologically, the stromal infiltrate contains epithelioid cells, lymphocytes, plasma cells and a few eosinophils, and scattered about are multinucleated giant cells (see figure). These lesions should be distinguished from another group of eosinophilic granulomatous lesions in the prostate, which exhibit fibrinoid necrosis, occur exclusively in patients suffering from bronchial asthma and are associated with a grave prognosis. These are better referred to as allergic granuloma of the prostate. 9 The rarity of this lesion has been well established by other authors. 10• 11 Low grade fever, dysuria, frequency and other symptoms suggestive of lower urinary tract infection are in keeping with the infectious concept of the disease. It is not surprising that a history of progressive prostatism was given in 25 of 86 patients, because the age groups are similar. The laboratory findings, when abnormal, provided corroborative evidence of an inflammatory rather than a malignant lesion. Associated carcinoma with raised serum alkaline and acid phosphatase levels was present in 2 patients. The upper part of the urinary tract was normal in the 62 patients in whom roentgenographic examination was performed. Among 63
Accepted for publication October 1, 1976. *Requests for reprints: Section of Publications, Mayo Clinic, Rochester, Minnesota 55901. 58
59
NON-SPECIFIC GRANULOMATOUS PROSTATITIS TABLE
1. Age distribution of 86 patients in series* No. Pts. 30-39 40-49 50-59 60-69 70-79 80-89
TABLE
7. Results of management in 67 patients with granulomatous
prostatitis
(%)
2
(2.5)
8
(9)
23 38 13 2
(27) (44)
Yrs. ofFollowup No. Pts. Transurethral resection and antimicrobials
(15)
33
Range
(av.)
1-11
(5)
(2.5)
No recurrence-28 cases Exacerbation- 4 cases Persistent symptoms-1
* Average age 61 years.
case TABLE
Antimicrobials only
2. Symptoms
15
1-11.5
(6)
No recurrence-12 cases Exacerbation-1 case Persistent symptoms-2 cases
7.5 6.5
(7.5) (6.5)
No recurrence No recurrence*
1-13
(7)
No recurrence -15 cases Exacerbation-2 cases
No. Pts. Dysuria Pyrexia Frequency Progressive prostatism Low back pain Epididymo-orchitis Hematuria Suprapubic pain Perinea! discomfort Groin pain None TABLE
Results
44 41 32 25 5 4
4
Retropubic adenectomy Radical retropubic prostatectomy* No treatment
1 1 17
* For associated carcinoma.
1 2 1 6
3. Impression on digital rectal prostatic examination No. Pts.
Ca Benign Granulomatous prostatitis Granulomatous prostatitis or Ca
45* 27 7
7
Total
86
* In 20 cases unc 1uivocal diagnosis was prostatic carcinoma. TABLE
4. Laboratory and roentgenologic findings No. Pts. Investi- No. Pts. WithPos. gated Findings
Pyuria Microscopic hematuria Urinary pathogens Leukocytosis Alkaline phosphatase levels Acid phosphatase levels Plain film of kidneys, ureters and bladder Excretory urogram
86 86 86 86 48 52 63 62
71
51 28 6
2 2
5* 0
Typical non-caseating granuloma with predominantly lymphocytic and plasma cell infiltration and prominent giant cell component. H & E, reduced from xlOO.
* Patients had prostatic calculi. TABLE
5. Method of diagnosis in 86 patients with granulomatous
prostatitis * No. Pts. Transrectal needle biopsy of prostate Transurethral resection Retropubic adenectomy
51 34 1
* Associated carcinoma in 4 patients. TABLE
6. Management of 86 patients with granulomatous prostatitis No. Pts.
Transurethral resection and antimicrobials Antimicrobials only Radical prostatectomy Retropubic adenectomy Estrogen No treatment
40 20 1 1 2 22
plain roentgenograms of the abdomen 5 revealed prostatic calculi. Misconstrued malignancy was the most important feature of digital rectal examination of the prostate, being the only consideration in 45 of the 86 patients and considered in the differential diagnosis in a further 7 patients. The management methods used for 82 patients included transurethral resection with antimicrobial therapy, antimi-
crobial therapy only for 2 to 4 weeks and no treatment. Admittedly, 24 patients with a history of progressive prostatism, who had a transurethral resection, were justifiably treated but when the followup data were analyzed results were essentially similar to any form of treatment or- more importantly- to no treatment whatever. The natural history of this disease seems to be that of gradual resolution. A further 3 patients were treated for concomitant carcinoma and 1 patient with severe obstructive symptoms from a grossly enlarged prostate had a retropubic adenectomy. In none of the 67 patients followed for an average of 6 years was there any evidence to suggest the development ofprostatic carcinoma. REFERENCES
1. Moore, R. A.: Tuberculosis of the prostate gland. J. Urol., 37: 372, 1937. 2. Thomson, L.: Syphilis of the prostate. Amer. J. Syphil., 4: 323, 1920. 3. Dreyfuss, M. L., Simon, S. and Sommer, R. I.: Granulomatous prostatitis due to Cryptococcus neoformans (Torula) with disseminated cryptococcosis and meningitis. N.Y. State J. Med., 61: 1589, 1961. 4. Gritti, E. J., Cook, F. E., Jr. and Spencer, H.B.: Coccidioidomycosis granuloma of the prostate: a rare manifestation of the disseminated disease. J. Urol., 89: 249, 1963. 5. Kelalis, P. P., Greene, L. F. and Weed, L.A.: Brucellosis of the
60
O'DEA, HUNTING AND GREENE
urogenital tract: a mimic of tuberculosis. J. Ural., 88: 347, 1962. 6. Tanner, F. H. and McDonald, J. R.: Granulomatous prostatitis: a histologic study of a group of granulomatous lesions collected from prostate glands. Arch. Path., 36: 358, 1943. 7. Epstein, W. L.: Granulomatous hypersensitivity. Prag. Allergy, 11: 36, 1967. 8. Schmidt, J. D.: Non-specific granulomatous prostatitis: classification, review and report of cases. J. Ural., 94: 607, 1965.
9. Kelalis, P. P., Harrison, E. G., Jr. and Greene, L. F.: Allergic granulomas of the prostate in asthmatics. J.A.M.A., 188: 963, 1964. 10. Kelalis, P. P., Greene, L. F. and Harrison, E. G., Jr.: Granulomatous prostatitis: a mimic of carcinoma of the prostate. J.A.M.A., 191: 287, 1965. 11. Towfighi, J., Sadeghee, S., Wheller, J.E. and Enterline, H. T.: Granulomatous prostatitis with emphasis on the eosinophilic variety. Amer. J. Clin. Path., 58: 630, 1972.