- Email: [email protected]
Granulomatous Disease of the Testis
!•
0022-5347 /80/1236-0868$02.00/0 Vol. 123, June Printed in U.S.A.
THE JOURNAL OF UROLOGY
Copyright© 1980 by The Williams & Wilkins Co.
GRANULOMATOUS DISEASE OF THE TESTIS ROBERT I. KAHN*
JACK W. MCANINCH
AND
From the Department of Urology, University of California School of Medicine and General Hospital, San Francisco, California
ABSTRACT
Granulomatous disease of the testis may have a specific cause or it may be: idiopathic. We found 3 specific agents as the cause of the disease in a retrospective review of 17 cases of granulomatous disease of the testis. Mycobacterium tuberculosis was the most common cause of subsequent granulomatous orchitis. The clinical presentations of the patients varied but several clues often were present that led to the diagnosis of granulomatous reaction_ The patients were treated with orchiectomy_ The acid-fast lipid of the tubercle bacillus and spermatozoa is suggested as a possible common denominator in the pathogenesis of the granulomatous reaction. In many cases a specific cause of granulomatous reaction is evident on clinical and pathological material. In other cases the etiology is obscure and the diagnosis must be pursued more aggressively. If the specific cause can be defined subsequent complete adjunctive chemotherapy can be given if necessary. The clinical presentation, diagnostic studies and treatment of granulomatous disease of the testis detailed herein provide some insight into the pathogenesis and etiology. MATERIALS AND METHODS
The cases were extracted from our pathology files of patients seen between 1940 and 1977 under the headings of granulomatous, tuberculous and xanthogranulomatous orchitis. Any cases of granulomatous disease of the epididymides alone or sperm granuloma were excluded. A total of 30 cases was found but the medical records for only 17 cases were available for review. Additional material for these cases was reviewed by examining several available microscopic sections. Information on longterm followup generally was not available. RESULTS
Clinical presentation. The patients ranged in age from 26 to 84 years old, with the majority being 40 to 70 years old. There were 14 white, 2 black and 1 oriental patient. The left testicle was involved in 11 instances and the right testicle was involved in 6. There were no cases of bilateral involvement. One patient had bilateral epididymal involvement but only the left testicle was affected by the same process. The duration of symptoms varied from 3 days to 4 years, with several patients having acute and chronic phases. The presenting clinical signs are summarized in table 1. Significant pain seemed to be almost universal in non-tuberculous orchitis and uncommon in the tuberculous form. Skin changes were just as common in tuberculous as in non-tuberculous disease. The only abnormal prostate glands were found in patients with tuberculous orchitis. Most patients with nontuberculous disease had abnormal epididymides but the epididymal examination was mentioned in only a few of the tuberculous cases. There was a wide range of other organ systems involved among the 11 cases of tuberculous orchitis recorded, with the same disease process usually at some point later in the patient's course. Only 1 patient had active renal tuberculosis, as observed by positive culture and excretory urogram (IVP). Five other patients had evidence of old renal tuberculosis, as observed by positive culture and negative IVP. There was evidence of either active (2 patients) or inactive (4 patients) pulmonary tubercu-
losis and 3 patients had signs of osseous tuberculosis. The patient with a recurrent hychtocele had no evidence of tuberculosis except on the tunica vi;lginalis. A specific cause of the disease could be assigned in 13 cases, including cases of granulomatous orchitis due to Mycobacterium tuberculosis, Mycobacterium avium and Phycomycetes circinella. Four other cases were labeled idiopathic. When a specific cause was identified the diagnosis was established by several clinical tests in addition to the pathology report (table 2). A diagnosis was made most frequently with a positive urine culture for acid-fast bacillus, a positive acid-fast bacillus tissue stain (fig. 1) or tissue culture. One case of tuberculous orchitis was established using Ziehl-Neelson staining of scrotal fistula drainage. Unfortunately, this test was not done in the remaining 5 cases with scrotal drainage. In 1 case of supposed idiopathic granulomatous orchitis a culture of prostate fluid showed Phycomycetes circinella to be the causal agent. The purified protein derivative tuberculin skin test was a useful diagnostic step in differentiating tuberculous from non-tuberculous orchitis. When the test was done posiHve results correlated well with the presence of Mycobacterium tuberculosis. Of 5 positive tests 4 were in patients with tuberculous disease, while of 6 negative tests 4 were in the non-tuberq1lous group; 1 of the remaining 2 in the tuberculous group was µnmunosuppressed. The patient with Mycobacterium avium h$.d a negative test and was tested with only second strength purified protein derivative but would otherwise have been expected,to be positive. An orchiectomy was done in 16 of 17 cases, with the remaining case being found at autopsy. An inguinal or inguinoscrotal incision was used in 10 of 13 patients. The remaining 3 patients TABLE
1. Clinical presentation of granulomatous orchitis in 17
cases Signs and Symptoms Hematocele Skin changes and/ or fistula Hydrocele* Mass or swelling lndurated prostate Fibrotic seminal vesicles Large or beaded vas deferens Nodular epididymist Pyuria Non-palpable testicle Soft testicle Significant pain Fever, chills Skin drainage Trauma Previous operation or instrumentation
No. Cases 1 6 2 13 2 2 3 6 9 3 1 8 4 5 4t 3
• Recurrent after hydrocelectomy. t When mentioned in physical examlllation. t 3 weeks to 10 years before clinical symptoms.
Accepted for publication August 10, 1979. • Requests for reprints: Urology, M-553, University of California, Sa11 Francisco, California 94143. 868
Tuberculous 0 4
2 8 2
1 1
Non-Tuberculous 1 2 0 5 0
1
3 2 3
2 4 4 0 0 5 2 2
2 2
2 1
2 5 3
1
869
GRANULOMATOUS DISEASE OF TESTIS TABLE
2. Efficacy of diagnostic tests to determine specific causal
agent in granulomatous reaction Pos. Test Acid-fast bacillus: Urine sn1ear Urine culture Tissue stain Sputum Gastric fluid Renal urine culture Scrotal drainage smear Tissue culture Prostate fluid culture
0 6
No. Cases Tested 3
5
10 8
3 0
4 J
0
2
1 3
1 3
purified protein derivative test was negative. A chest x-ray showed a questionable calcified lesion. Inguinal orchiectomy was done. The pathology specimen showed caseating granulomas. The patient was treated empirically with isoniazid and ethambutol. The fever resolved 5 days after orchiectomy but then returned. A preoperative urine culture showed Mycobac terium avium resistant to isoniazid and ethambutol, and sensitive to rifampin and streptomycin. The patient was treated with rifampin and streptomycin and the fever resolved. The pathologic specimens weighed from 45 to 138 gm, (normal 17 to 27 gm.) and measured from 2.5 cc to 10.5 X 4.5 X 6.6 cc. Gross and microscopic features are detailed in table 3. Microscopically, the specimens from patients with tuberculosis orchitis showed granulomas and caseous necrosis (fig. 2, A). In the non-tuberculous cases granulomas or xanthogranulomas were present but caseous necrosis and giant cells were less common or absent (fig. 2, B). DISCUSSION
FIG. l. Positive acid-fast bacillus tissue stain
were approached scrotally because of the nature of the preclinical problem, that is 1 hydrocele and 2 scrotal fistulas. The inguinoscrotal approach was used for the remainpwo,-·"·- with skin fistulas. The orchiectomies were done to ~""'""'"~ the possibility of tumor in 6 cases or tuberculosis in 8, or to treat unresolved inflammation, fistula or abscess in 6. If the tuberculous cases are considered separately there were 2 orchiectomies done before modern antituberculous chemotherapy 3 for draining a fistula or hydrocele in patients not yet u"""'''~,,vu as having tuberculosis and 5 to remove tumor or inflammation in a testicular mass. The only orchiectomies done ,-,uc,~,.,cu with a known diagnosis of tuberculosis were done effective antituberculous therapy was available. The orchiectomies done after this therapy was available were for 1) establishing the diagnosis of tuberculosis versus tumor versus other inflammation or 2) treating chronic local symptoms. Because only 1 orchiectomy was done in a medically treated with known tuberculosis after triple therapy was avau.arn,c it can be assumed that many other cases of tuberculous orchitis, and probably of epididymitis, were cured with alone coincidentally with the treatment of another focus. Although the exact number of these cases is unknown our select group represents those cases in which the of tuberculosis was not obvious and other entities must be considered. was the sole treatment in cases of idiopathic orchitis, In 10 cases of tuberculosis and in l case avium further triple chemotherapy was for at least 2 years. The results of followup examinations were not documented on the charts, so the effectiveness of therapy cannot be evaluated. However, the importance of adjunctive therapy and followup examination is illustrated in the following case report. UHm'UH>U
CASE REPORT
A 64-year-old white man was seen with a testicular mass and recurrent fever to 103F 4 years in duration. A second-strength
Granulomatous diseases of the testis encompass a group of diseases of different causes that resemble each other clinically and pathologically. Furthermore, these entities must be distinguished from other similarly presenting conditions, such as tumor. In 1926 Grunberg first described 3 cases of chronic orchitis with clinical manifestations of tumor that proved to be idiopathic granulomatous orchitis. 1 Little has been written on the clinical presentation of granulomatous diseases of the testis as a group. Case reports of idiopathic granulomatous orchitis scattered throughout the literature show that it usually is a disease of sudden onset in men in the sixth or seventh decade of life, and is associated with mild to moderate pain, swelling, occasional fever and skin changes. 2 However, other investigators have reported clinical presentations of either an asymptomatic mass or a mass with a chronic ache. 3 - 5 In the more acute version the symptoms fail to respond to antibiotic treatment and the testis is removed. In asymptomatic patients an inguinal orchiectomy is done to eliminate the possibility of tumor. The 6 cases of idiopathic granulomatous orchitis and other forms of non-tuberculous granulomatous orchitis displayed this variability in presentation, with I exception. None of the patients in the present series had any antecedent urinary complaints, 1.m: like the cases reported by Capers'3• 4 and Lynch and associates." Tuberculous orchitis is an entity rarely mentioned in the literature. It usually is described as an extension of the ongoing tuberculous process present in the epididymis. 6 Clinically, the condition is similar to other forms of granulomatous orchitis and should appear in the differential diagnosis of testicular masses. Several clinical clues often are present to make one suspect tuberculosis; that is 1) positive findings in the prostate, seminal vesicle or vas deferens, 2) hydrocele, 3) sterile pyuria and 4) evidence of tuberculosis elsewhere in the body. However, TABLE 3.
Pathologic characteristics of excised granulomatous testes Tuberculous
Gross characteristics: Diffuse Local Tunica thickened Cheesy material Creamy material Microscopic characteristics: Giant cells Caseous necrosis Coagulation necrosis Granuloma Xanthogranuloma Calcium Epididymal involvement*
* When mentioned in pathology report.
t Of 5 tuberculous cases. :j: Of 3 non-tuberculous cases.
Non-Tuberculous
4
2
4
4 I 0
2 6
6 11 0 11 0 I
4t
2
I
I 4 2 0
O:j:
870
KAHN AND MCANINCH
FIG. 2. A, typical tuberculous granulomatous reaction with caseation. B, granulomatous orchitis with typical epithelioid cell reaction replacing tubules.
only about half of the patients with tuberculous orchitis at some point in their history had other active tuberculosis and only 1 had evidence of active renal tuberculosis. In several cases the diagnosis of tuberculous orchitis was not obvious and was established only after thorough clinical and pathologic investigation. Examination of the scrotal drainage and tissue culture were most effective in diagnosing tuberculous orchitis. Multiple urine cultures and tissue stains for acid-fast bacillus also were important diagnostic tests. Frequently, if one of these was positive a diagnosis could be made with a borderline pathology report. Persistent, thorough clinical investigation also helped establish the diagnosis of unusual forms of granulomatous orchitis that otherwise would have been labeled idiopathic. The operative treatment of granulomatous diseases of the testis is dictated by the clinical presentation. In cases in which tumor is suspected strongly a standard radical orchiectomy must be done. Otherwise, an inguinoscrotal approach is recommended. This incision offers the advantages of cord control and the ability to treat local skin lesions simultaneously. Operative therapy probably is all that is necessary for idiopathic granulomatous orchitis. In cases strongly suspicious of tuberculosis antitubercular chemotherapy could be tried first, and orchiectomy could be reserved for cases in which there still was some doubt about the diagnosis or failure to respond to medical therapy. When Mycobacterium is isolated specific chemotherapy should be given for at least 2 years. Followup is important in all patients with mycobacterial granulomatous orchitis because of its multisystemic infectious nature.
The pathogenesis of genitourinary tuberculosis has been described by other investigators. 7 Renal tuberculosis is a result of hematogenous spread from another source. This lesion may progress or heal completely, depending on the response of the patient to therapy. Subsequently, prostatic tissue may become infected and act as a new focus for spread of the disease down the vas deferens to the seminal vesicles, epididymis and testis. In a large series of autopsies Medlar and associates reported the prevalence of renal lesions to be twice that of lesions in the prostate and 3 times that of lesions of the epididymis and seminal vesicles. 6 Testicular lesions were not mentioned. Their over-all incidence of genitourinary tuberculosis in patients with known tuberculosis was 7 per cent. Although tuberculous orchitis is believed to result from direct extension from the epididymis hematogenous spread rarely is suspected with diffuse involvement of the testis. In a series of about 400 cases of tuberculous epididymitis Borthwick reported on only 4 patients with diffusely involved testes. 7 Although equal numbers of diffusely and locally involved testes were seen in the present series there were no normal epididymides. This fact supports the concept of direct extension to the testis. The etiology of granulomatous orchitis remains obscure. Because granulomatous diseases of the testis have many common features the causes of the granulomatous reaction may have a common denominator. Some investigators compare the inflammatory reaction of extravasated sperm in sperm granulomas to granulomatous orchitis. 8 ' 9 Russell and Friedman produced sperm granulomas similar to those of granulomatous orchitis in experimental animals by severing the vas deferens and implanting it into the scrotal skin. 10 The case reported by Hubsmith and associates of early granulomatous orchitis described sperm invasion of the interstitial tissue of the epididymis. 11 They believed this invasion to be the initiating event that leads to subsequent granulomatous formation in the testis. To date, no intact sperm have been demonstrated in the lesions of granulomatous orchitis. In 1954 Berg extracted an acid-fast lipid from sperm heads that was similar spectroscopically to mycolid acid, a lipid found in the tubercle bacillus. 12 Phillips described a histochemical similarity between lipid extracted from sperm and lipid material seen on special lipid stains in specimens of granulomatous orchitis. 13 Two cases in our series had the features oflipid-laden epithelioid cells in the granuloma. Thus, the acid-fast lipid of the tubercle bacillus and spermatozoa! degradation products may be the common denominator in the pathogenesis of the granulomatous reaction. External or iatrogenic trauma was noted to be an important factor in 8 of 12 cases reported by Spjut and Thorpe. 14 Perhaps the trauma can set the stage for extravasation of sperm by direct injury or increased tubule pressure. Gow mentioned trauma as a factor allowing some tuberculous lesions to manifest clinically. 15 However, the trauma often is not related chronologically to the development of the lesion. 7 In this series 7 patients had had a history of trauma but it is unclear whether this fact had a role in the pathogenesis of the granulomatous lesion. REFERENCES 1. Grunberg, H.: Uber drei ungewonliche Fii.lle von chronischer Or-
2. 3. 4. 5. 6.
chitis unter dem klinischen Bilde eines Hodentumors. Frankfurt Zeitsch. Path., 33: 217, 1926. Morgan, A. D.: Inflammatory lesions simulating malignancy. Brit. J. Urol., suppl., 36: 95, 1964. Capers, T. H.: Granulomatous orchitis. Amer. J. Clin. Path., 34: 139, 1960. Capers, T. H.: Granulomatous orchitis with sperm granuloma of epididymis: a case report. J. Urol., 87: 705, 1962. Lynch, V. P., Eakins, D. and Morrison, E.: Granulomatous orchitis. Brit. J. Urol., 40: 451, 1968. Medlar, E. M., Spain, D. M. and Holliday, R. W.: Post-mortem
GRANULOMATOUS DISEASE OF TESTIS
compared with clinical diagnosis of genito-urinary tuberculosis in adult males. J. Urol., 61: 1078, 1949. Borthwick, W. M.: Pathogenesis of tuberculous epididymis. Edinburgh Med. J., 53: 55, 1946. Friedman, N. B. and Garske, G. L.: Inflammatory reactions involving sperm and the seminiferous tubules: extravasation, spermatic granulomas and granulomatous orchitis. J. Urol., 62: 363, 1949. Glassy, F. J. and Mostofi, F. K.: Spermatic granulomas of the epididymis. Amer. J. Clin. Path., 26: 1303, 1956. Russell, M. and Friedman, N. B.: Studies in general biology of sperm: experimental production of spermatic granuloma. J. U rol.,
871
65: 650, 1951. 11. Hubsmith, R. J., Garret, R. and Photos, C.: Granulomatous orchitis and epididymitis. J. Urol., 81: 301, 1959. 12. Berg, J. W.: An acid-fast lipid from spermatozoa. Arch. Path., 57: 115, 1954. 13. Phillips, D. E.: Lipid granulomata of the testis and epididymis. Brit. J. Urol., 33: 448, 1961. 14. Spjut, H.J. and Thorpe, J. D.: "Granulomatous orchitis". Amer. J. Clin. Path., 26: 136, 1956. 15. Gow, J. G.: Genito-urinary tuberculosis. Practitioner, 207: 609, 1971.
0022-5347 /80/1236-0868$02.00/0 Vol. 123, June Printed in U.S.A.
THE JOURNAL OF UROLOGY
Copyright© 1980 by The Williams & Wilkins Co.
GRANULOMATOUS DISEASE OF THE TESTIS ROBERT I. KAHN*
JACK W. MCANINCH
AND
From the Department of Urology, University of California School of Medicine and General Hospital, San Francisco, California
ABSTRACT
Granulomatous disease of the testis may have a specific cause or it may be: idiopathic. We found 3 specific agents as the cause of the disease in a retrospective review of 17 cases of granulomatous disease of the testis. Mycobacterium tuberculosis was the most common cause of subsequent granulomatous orchitis. The clinical presentations of the patients varied but several clues often were present that led to the diagnosis of granulomatous reaction_ The patients were treated with orchiectomy_ The acid-fast lipid of the tubercle bacillus and spermatozoa is suggested as a possible common denominator in the pathogenesis of the granulomatous reaction. In many cases a specific cause of granulomatous reaction is evident on clinical and pathological material. In other cases the etiology is obscure and the diagnosis must be pursued more aggressively. If the specific cause can be defined subsequent complete adjunctive chemotherapy can be given if necessary. The clinical presentation, diagnostic studies and treatment of granulomatous disease of the testis detailed herein provide some insight into the pathogenesis and etiology. MATERIALS AND METHODS
The cases were extracted from our pathology files of patients seen between 1940 and 1977 under the headings of granulomatous, tuberculous and xanthogranulomatous orchitis. Any cases of granulomatous disease of the epididymides alone or sperm granuloma were excluded. A total of 30 cases was found but the medical records for only 17 cases were available for review. Additional material for these cases was reviewed by examining several available microscopic sections. Information on longterm followup generally was not available. RESULTS
Clinical presentation. The patients ranged in age from 26 to 84 years old, with the majority being 40 to 70 years old. There were 14 white, 2 black and 1 oriental patient. The left testicle was involved in 11 instances and the right testicle was involved in 6. There were no cases of bilateral involvement. One patient had bilateral epididymal involvement but only the left testicle was affected by the same process. The duration of symptoms varied from 3 days to 4 years, with several patients having acute and chronic phases. The presenting clinical signs are summarized in table 1. Significant pain seemed to be almost universal in non-tuberculous orchitis and uncommon in the tuberculous form. Skin changes were just as common in tuberculous as in non-tuberculous disease. The only abnormal prostate glands were found in patients with tuberculous orchitis. Most patients with nontuberculous disease had abnormal epididymides but the epididymal examination was mentioned in only a few of the tuberculous cases. There was a wide range of other organ systems involved among the 11 cases of tuberculous orchitis recorded, with the same disease process usually at some point later in the patient's course. Only 1 patient had active renal tuberculosis, as observed by positive culture and excretory urogram (IVP). Five other patients had evidence of old renal tuberculosis, as observed by positive culture and negative IVP. There was evidence of either active (2 patients) or inactive (4 patients) pulmonary tubercu-
losis and 3 patients had signs of osseous tuberculosis. The patient with a recurrent hychtocele had no evidence of tuberculosis except on the tunica vi;lginalis. A specific cause of the disease could be assigned in 13 cases, including cases of granulomatous orchitis due to Mycobacterium tuberculosis, Mycobacterium avium and Phycomycetes circinella. Four other cases were labeled idiopathic. When a specific cause was identified the diagnosis was established by several clinical tests in addition to the pathology report (table 2). A diagnosis was made most frequently with a positive urine culture for acid-fast bacillus, a positive acid-fast bacillus tissue stain (fig. 1) or tissue culture. One case of tuberculous orchitis was established using Ziehl-Neelson staining of scrotal fistula drainage. Unfortunately, this test was not done in the remaining 5 cases with scrotal drainage. In 1 case of supposed idiopathic granulomatous orchitis a culture of prostate fluid showed Phycomycetes circinella to be the causal agent. The purified protein derivative tuberculin skin test was a useful diagnostic step in differentiating tuberculous from non-tuberculous orchitis. When the test was done posiHve results correlated well with the presence of Mycobacterium tuberculosis. Of 5 positive tests 4 were in patients with tuberculous disease, while of 6 negative tests 4 were in the non-tuberq1lous group; 1 of the remaining 2 in the tuberculous group was µnmunosuppressed. The patient with Mycobacterium avium h$.d a negative test and was tested with only second strength purified protein derivative but would otherwise have been expected,to be positive. An orchiectomy was done in 16 of 17 cases, with the remaining case being found at autopsy. An inguinal or inguinoscrotal incision was used in 10 of 13 patients. The remaining 3 patients TABLE
1. Clinical presentation of granulomatous orchitis in 17
cases Signs and Symptoms Hematocele Skin changes and/ or fistula Hydrocele* Mass or swelling lndurated prostate Fibrotic seminal vesicles Large or beaded vas deferens Nodular epididymist Pyuria Non-palpable testicle Soft testicle Significant pain Fever, chills Skin drainage Trauma Previous operation or instrumentation
No. Cases 1 6 2 13 2 2 3 6 9 3 1 8 4 5 4t 3
• Recurrent after hydrocelectomy. t When mentioned in physical examlllation. t 3 weeks to 10 years before clinical symptoms.
Accepted for publication August 10, 1979. • Requests for reprints: Urology, M-553, University of California, Sa11 Francisco, California 94143. 868
Tuberculous 0 4
2 8 2
1 1
Non-Tuberculous 1 2 0 5 0
1
3 2 3
2 4 4 0 0 5 2 2
2 2
2 1
2 5 3
1
869
GRANULOMATOUS DISEASE OF TESTIS TABLE
2. Efficacy of diagnostic tests to determine specific causal
agent in granulomatous reaction Pos. Test Acid-fast bacillus: Urine sn1ear Urine culture Tissue stain Sputum Gastric fluid Renal urine culture Scrotal drainage smear Tissue culture Prostate fluid culture
0 6
No. Cases Tested 3
5
10 8
3 0
4 J
0
2
1 3
1 3
purified protein derivative test was negative. A chest x-ray showed a questionable calcified lesion. Inguinal orchiectomy was done. The pathology specimen showed caseating granulomas. The patient was treated empirically with isoniazid and ethambutol. The fever resolved 5 days after orchiectomy but then returned. A preoperative urine culture showed Mycobac terium avium resistant to isoniazid and ethambutol, and sensitive to rifampin and streptomycin. The patient was treated with rifampin and streptomycin and the fever resolved. The pathologic specimens weighed from 45 to 138 gm, (normal 17 to 27 gm.) and measured from 2.5 cc to 10.5 X 4.5 X 6.6 cc. Gross and microscopic features are detailed in table 3. Microscopically, the specimens from patients with tuberculosis orchitis showed granulomas and caseous necrosis (fig. 2, A). In the non-tuberculous cases granulomas or xanthogranulomas were present but caseous necrosis and giant cells were less common or absent (fig. 2, B). DISCUSSION
FIG. l. Positive acid-fast bacillus tissue stain
were approached scrotally because of the nature of the preclinical problem, that is 1 hydrocele and 2 scrotal fistulas. The inguinoscrotal approach was used for the remainpwo,-·"·- with skin fistulas. The orchiectomies were done to ~""'""'"~ the possibility of tumor in 6 cases or tuberculosis in 8, or to treat unresolved inflammation, fistula or abscess in 6. If the tuberculous cases are considered separately there were 2 orchiectomies done before modern antituberculous chemotherapy 3 for draining a fistula or hydrocele in patients not yet u"""'''~,,vu as having tuberculosis and 5 to remove tumor or inflammation in a testicular mass. The only orchiectomies done ,-,uc,~,.,cu with a known diagnosis of tuberculosis were done effective antituberculous therapy was available. The orchiectomies done after this therapy was available were for 1) establishing the diagnosis of tuberculosis versus tumor versus other inflammation or 2) treating chronic local symptoms. Because only 1 orchiectomy was done in a medically treated with known tuberculosis after triple therapy was avau.arn,c it can be assumed that many other cases of tuberculous orchitis, and probably of epididymitis, were cured with alone coincidentally with the treatment of another focus. Although the exact number of these cases is unknown our select group represents those cases in which the of tuberculosis was not obvious and other entities must be considered. was the sole treatment in cases of idiopathic orchitis, In 10 cases of tuberculosis and in l case avium further triple chemotherapy was for at least 2 years. The results of followup examinations were not documented on the charts, so the effectiveness of therapy cannot be evaluated. However, the importance of adjunctive therapy and followup examination is illustrated in the following case report. UHm'UH>U
CASE REPORT
A 64-year-old white man was seen with a testicular mass and recurrent fever to 103F 4 years in duration. A second-strength
Granulomatous diseases of the testis encompass a group of diseases of different causes that resemble each other clinically and pathologically. Furthermore, these entities must be distinguished from other similarly presenting conditions, such as tumor. In 1926 Grunberg first described 3 cases of chronic orchitis with clinical manifestations of tumor that proved to be idiopathic granulomatous orchitis. 1 Little has been written on the clinical presentation of granulomatous diseases of the testis as a group. Case reports of idiopathic granulomatous orchitis scattered throughout the literature show that it usually is a disease of sudden onset in men in the sixth or seventh decade of life, and is associated with mild to moderate pain, swelling, occasional fever and skin changes. 2 However, other investigators have reported clinical presentations of either an asymptomatic mass or a mass with a chronic ache. 3 - 5 In the more acute version the symptoms fail to respond to antibiotic treatment and the testis is removed. In asymptomatic patients an inguinal orchiectomy is done to eliminate the possibility of tumor. The 6 cases of idiopathic granulomatous orchitis and other forms of non-tuberculous granulomatous orchitis displayed this variability in presentation, with I exception. None of the patients in the present series had any antecedent urinary complaints, 1.m: like the cases reported by Capers'3• 4 and Lynch and associates." Tuberculous orchitis is an entity rarely mentioned in the literature. It usually is described as an extension of the ongoing tuberculous process present in the epididymis. 6 Clinically, the condition is similar to other forms of granulomatous orchitis and should appear in the differential diagnosis of testicular masses. Several clinical clues often are present to make one suspect tuberculosis; that is 1) positive findings in the prostate, seminal vesicle or vas deferens, 2) hydrocele, 3) sterile pyuria and 4) evidence of tuberculosis elsewhere in the body. However, TABLE 3.
Pathologic characteristics of excised granulomatous testes Tuberculous
Gross characteristics: Diffuse Local Tunica thickened Cheesy material Creamy material Microscopic characteristics: Giant cells Caseous necrosis Coagulation necrosis Granuloma Xanthogranuloma Calcium Epididymal involvement*
* When mentioned in pathology report.
t Of 5 tuberculous cases. :j: Of 3 non-tuberculous cases.
Non-Tuberculous
4
2
4
4 I 0
2 6
6 11 0 11 0 I
4t
2
I
I 4 2 0
O:j:
870
KAHN AND MCANINCH
FIG. 2. A, typical tuberculous granulomatous reaction with caseation. B, granulomatous orchitis with typical epithelioid cell reaction replacing tubules.
only about half of the patients with tuberculous orchitis at some point in their history had other active tuberculosis and only 1 had evidence of active renal tuberculosis. In several cases the diagnosis of tuberculous orchitis was not obvious and was established only after thorough clinical and pathologic investigation. Examination of the scrotal drainage and tissue culture were most effective in diagnosing tuberculous orchitis. Multiple urine cultures and tissue stains for acid-fast bacillus also were important diagnostic tests. Frequently, if one of these was positive a diagnosis could be made with a borderline pathology report. Persistent, thorough clinical investigation also helped establish the diagnosis of unusual forms of granulomatous orchitis that otherwise would have been labeled idiopathic. The operative treatment of granulomatous diseases of the testis is dictated by the clinical presentation. In cases in which tumor is suspected strongly a standard radical orchiectomy must be done. Otherwise, an inguinoscrotal approach is recommended. This incision offers the advantages of cord control and the ability to treat local skin lesions simultaneously. Operative therapy probably is all that is necessary for idiopathic granulomatous orchitis. In cases strongly suspicious of tuberculosis antitubercular chemotherapy could be tried first, and orchiectomy could be reserved for cases in which there still was some doubt about the diagnosis or failure to respond to medical therapy. When Mycobacterium is isolated specific chemotherapy should be given for at least 2 years. Followup is important in all patients with mycobacterial granulomatous orchitis because of its multisystemic infectious nature.
The pathogenesis of genitourinary tuberculosis has been described by other investigators. 7 Renal tuberculosis is a result of hematogenous spread from another source. This lesion may progress or heal completely, depending on the response of the patient to therapy. Subsequently, prostatic tissue may become infected and act as a new focus for spread of the disease down the vas deferens to the seminal vesicles, epididymis and testis. In a large series of autopsies Medlar and associates reported the prevalence of renal lesions to be twice that of lesions in the prostate and 3 times that of lesions of the epididymis and seminal vesicles. 6 Testicular lesions were not mentioned. Their over-all incidence of genitourinary tuberculosis in patients with known tuberculosis was 7 per cent. Although tuberculous orchitis is believed to result from direct extension from the epididymis hematogenous spread rarely is suspected with diffuse involvement of the testis. In a series of about 400 cases of tuberculous epididymitis Borthwick reported on only 4 patients with diffusely involved testes. 7 Although equal numbers of diffusely and locally involved testes were seen in the present series there were no normal epididymides. This fact supports the concept of direct extension to the testis. The etiology of granulomatous orchitis remains obscure. Because granulomatous diseases of the testis have many common features the causes of the granulomatous reaction may have a common denominator. Some investigators compare the inflammatory reaction of extravasated sperm in sperm granulomas to granulomatous orchitis. 8 ' 9 Russell and Friedman produced sperm granulomas similar to those of granulomatous orchitis in experimental animals by severing the vas deferens and implanting it into the scrotal skin. 10 The case reported by Hubsmith and associates of early granulomatous orchitis described sperm invasion of the interstitial tissue of the epididymis. 11 They believed this invasion to be the initiating event that leads to subsequent granulomatous formation in the testis. To date, no intact sperm have been demonstrated in the lesions of granulomatous orchitis. In 1954 Berg extracted an acid-fast lipid from sperm heads that was similar spectroscopically to mycolid acid, a lipid found in the tubercle bacillus. 12 Phillips described a histochemical similarity between lipid extracted from sperm and lipid material seen on special lipid stains in specimens of granulomatous orchitis. 13 Two cases in our series had the features oflipid-laden epithelioid cells in the granuloma. Thus, the acid-fast lipid of the tubercle bacillus and spermatozoa! degradation products may be the common denominator in the pathogenesis of the granulomatous reaction. External or iatrogenic trauma was noted to be an important factor in 8 of 12 cases reported by Spjut and Thorpe. 14 Perhaps the trauma can set the stage for extravasation of sperm by direct injury or increased tubule pressure. Gow mentioned trauma as a factor allowing some tuberculous lesions to manifest clinically. 15 However, the trauma often is not related chronologically to the development of the lesion. 7 In this series 7 patients had had a history of trauma but it is unclear whether this fact had a role in the pathogenesis of the granulomatous lesion. REFERENCES 1. Grunberg, H.: Uber drei ungewonliche Fii.lle von chronischer Or-
2. 3. 4. 5. 6.
chitis unter dem klinischen Bilde eines Hodentumors. Frankfurt Zeitsch. Path., 33: 217, 1926. Morgan, A. D.: Inflammatory lesions simulating malignancy. Brit. J. Urol., suppl., 36: 95, 1964. Capers, T. H.: Granulomatous orchitis. Amer. J. Clin. Path., 34: 139, 1960. Capers, T. H.: Granulomatous orchitis with sperm granuloma of epididymis: a case report. J. Urol., 87: 705, 1962. Lynch, V. P., Eakins, D. and Morrison, E.: Granulomatous orchitis. Brit. J. Urol., 40: 451, 1968. Medlar, E. M., Spain, D. M. and Holliday, R. W.: Post-mortem
GRANULOMATOUS DISEASE OF TESTIS
compared with clinical diagnosis of genito-urinary tuberculosis in adult males. J. Urol., 61: 1078, 1949. Borthwick, W. M.: Pathogenesis of tuberculous epididymis. Edinburgh Med. J., 53: 55, 1946. Friedman, N. B. and Garske, G. L.: Inflammatory reactions involving sperm and the seminiferous tubules: extravasation, spermatic granulomas and granulomatous orchitis. J. Urol., 62: 363, 1949. Glassy, F. J. and Mostofi, F. K.: Spermatic granulomas of the epididymis. Amer. J. Clin. Path., 26: 1303, 1956. Russell, M. and Friedman, N. B.: Studies in general biology of sperm: experimental production of spermatic granuloma. J. U rol.,
871
65: 650, 1951. 11. Hubsmith, R. J., Garret, R. and Photos, C.: Granulomatous orchitis and epididymitis. J. Urol., 81: 301, 1959. 12. Berg, J. W.: An acid-fast lipid from spermatozoa. Arch. Path., 57: 115, 1954. 13. Phillips, D. E.: Lipid granulomata of the testis and epididymis. Brit. J. Urol., 33: 448, 1961. 14. Spjut, H.J. and Thorpe, J. D.: "Granulomatous orchitis". Amer. J. Clin. Path., 26: 136, 1956. 15. Gow, J. G.: Genito-urinary tuberculosis. Practitioner, 207: 609, 1971.