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Am. J. Trop. Med. Hyg., 77(4), 2007, pp. 714-718
Copyright © 2007 by The American Society of Tropical Medicine and Hygiene

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Scrotal Tuberculosis in Adult Patients: A 10-Year Clinical Experience

Ing-Kit Lee, Wen-Chou Yang, AND Jien-Wei Liu*
Division of Infectious Diseases, Department of Internal Medicine and Division of Urology, Department of Surgery, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Taiwan


ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Twenty-nine adults (mean age, 59.9 ± 13.5 years) with scrotal tuberculosis (TB) were retrospectively analyzed. The mean interval from emergence of symptoms suggestive of scrotal TB to diagnosis established was 142.44 ± 227.66 days. Scrotal TB was initially suspected in only five (17.2%) patients, and infection caused by bacteria other than Mycobacterium tuberculosis (55.2%) was the leading presumptive diagnosis. Of 28 patients with chest radiographs available, 7 (25%) disclosed active pulmonary TB, and 9 (32.1%) showed a TB scar. All patients received anti-TB chemotherapy; 20 (69%) additionally underwent surgery. Pathologic examination of resected tissue at therapeutic surgery, biopsy, or polymerase chain reaction assay of urine led to rapid diagnosis of scrotal TB. Although evidence of scrotal TB was easily obtainable, the lack of alertness made clinicians avert from the appropriate diagnostic approaches and rendered a delayed diagnosis. Our report underscores the urgent need for improving clinicians’ awareness of scrotal TB.


INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Tuberculosis (TB) is a worldwide health problem with particularly high prevalence in developing countries.1 Albeit rare, TB may develop in the scrotum in male patients.2,3 The differential diagnoses of a swollen scrotum include bacterial epididymo-orchitis, viral orchitis, hydrocele/spermatocele, testicular torsion, traumatic scrotum, or neoplasm (either germ cell or non–germ cell origin).2–7 The rarity of scrotal TB has limited clinicians’ awareness of TB involving this anatomic site, which may in turn lead to failure to make a timely diagnosis of scrotal TB in a patient with a swollen scrotum.4–7 Scrotal TB can be medically cured.2,3,8,9 However, misdiagnosis of scrotal TB may lead to otherwise avoidable epididymo-orchiectomy. Therefore, the importance of a comprehensive understanding of scrotal TB cannot be overemphasized.

We performed a study of patients with scrotal TB diagnosed over a 10-year period in a large medical center, with the objective to better understand the demographic, clinical, laboratory, and imaging characteristics of TB involving the scrotum. The information from this series may be valuable for clinicians inexperienced with this disease entity in improving diagnosis and management of scrotal TB.


MATERIALS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
Study population. This is a retrospective study of patients with scrotal TB hospitalized between 1995 and 2005 at the Chang Gung Memorial Hospital-Kaohsiung (CGMH-KS), a 2,500-bed medical facility serving as a primary care and tertiary referral center in southern Taiwan. The included patients were searched from the records in the clinical microbiology and pathology laboratories of the hospital. The medical charts of the patients with scrotal TB were reviewed for collection of their demographic, clinical, laboratory, and imaging information for analyses.

Definitions and statistical analysis. Scrotal TB was diagnosed in a patient when at least one of the following criteria was fulfilled: 1) the excised scrotal lump culture was positive for Mycobacterium tuberculosis; 2) urine culture was positive for M. tuberculosis and the patient was experiencing a swollen scrotum10; 3) the excised testicle or epidydimis specimen histopathologically showed granulomatous inflammation (with or without caseous necrosis) and acid-fast bacilli11; 4) the excised testicle or epidydimis specimen histopathologically showed granulomatous inflammation (with or without caseous necrosis) with a negative acid-fast stain, and the patient was cured under anti-TB chemotherapy11; and 5) urine specimen was positive for M. tuberculosis deoxyribonucleic acid (DNA) tested with polymerase chain reaction (PCR) in a patient who was experiencing a swollen scrotum.12

The regimen for the treatment of TB consisted of isoniazid (5 mg/kg), rifampicin (10 mg/kg), pyrazinamide (15–30 mg/ kg), and ethambutol (15–25 mg/kg).13,14 Because evidence-based guidelines on how long genital TB should be treated were not available,13,14 the length of anti-TB treatment of scrotal TB was at the clinician’s discretion, which was made according to clinical severity of the affected patient; the treatment length might be further modified in patients who were noncompliant to anti-TB drugs or had coexisting pulmonary TB. Because experts agree that virtually all forms of extra-pulmonary TB can be treated as pulmonary TB in terms of anti-TB regimen and treatment length,13 in this study, a patient was considered cured when his constitutional syndromes (if any) and scrotal lump improved when he completed at least 6 months of anti-TB therapy. Relapse of scrotal TB was defined as TB that clinically redeveloped in the scrotum after at least 3 months of disease-free interval after ≥6-month therapy for the prior scrotal TB.

Active pulmonary TB referred to chest-radiographic manifestations of a patient in question suggestive of TB involving the lung, which was confirmed based on either M. tuberculosis growth from sputum culture or favorable clinical and radiographic responses to anti-TB chemotherapy at follow-up if sputum culture was negative for M. tuberculosis.15 The presumptive diagnosis of a swollen scrotum referred to the tentative diagnosis made by a clinician on the patient’s initial presentation. In urinalysis, microscopic hematuria was defined as the presence of more than three red blood cells per high-power field (HPF),16 and sterile pyuria as more than five leukocytes per HPF if urine was negative for bacterial growth.17 The urine specimen for culture was processed in accordance with standard procedures.18 Data are presented as mean ± SD or median (range), where applicable. The time lapse between the start of different diagnostic measures and the establishment of diagnosis of scrotal TB were compared using the Mann-Whitney U test. A two-tailed P < 0.05 was considered statistically significant.


RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
During the study period, 1,370 cases of extrapulmonary TB were diagnoses in CGMH-KS. Among these cases, 29 were scrotal TB, which accounted for 2.1% of extrapulmonary TB. The demographic, clinical, laboratory, and imaging characteristics of the 29 included patients with scrotal TB are summarized in Tables 1Go and 2Go.


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TABLE 1
Demographic, clinical, and laboratory characteristics of the 29 patients with scrotal TB*
 

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TABLE 2
Symptoms and signs of the 29 patients with scrotal TB*
 
The mean age of these 29 patients was 59.9 ± 13.5 years. The most prevalent ages for development of scrotal TB fell in the 60- to 69-year group; patients in this age group accounted for 37.9% of all included subjects. The mean interval from emergence of symptoms suggestive of scrotal TB to diagnosis was 142.44 days. As for symptoms, a scrotal lump was universally found. Before the diagnosis of scrotal TB, 15 (51.7%) patients experienced a scrotal lump for at least 3 months; of note, 1 of them experienced an insidiously progressive enlarged painless scrotal lump for ~3 years. Scrotal TB was initially suspected in only five (17.2%) of the included patients. Infection (with or without abscess) caused by bacteria other than M. tuberculosis (55.2%) and neoplasm (20.7%) were the two leading presumptive diagnoses of the swollen scrotum.

Of the 22 patients with hemograms available, the mean peripheral leukocytes count was 7.1 ± 1.2 x 109/L (normal value, 3.5–11 x 109/L). Three of the included patients had a serology test for human immunodeficiency virus (HIV) infection, which were negative. Of 28 patients with chest radiographs available, active pulmonary TB was found in 7 (25%), and a TB scar on chest radiograph was seen in 9 (32.1%). Among the seven patients with active pulmonary TB, five had a sputum culture positive for M. tuberculosis (M. tuberculosis isolate from one patient was resistant to ethambutol). Of the 16 patients who received ultrasound studies of the swollen scrotum, the findings (various combinations of ultrasonographic findings might be found in the same patient) were as follows: focal scrotal lesion in 11 (68.7%) and diffuse lesion in 5 (31.3%); ultrasonographic heteroechogenicity of the scrotal lesion in 8 (50%), hypoechogenicity in 5 (31.3%), and hyperechogenicity in 3 (18.7%).

The diagnostic measures for scrotal TB used in the 29 included patients (the same patient might have received more than one diagnostic procedure) were detailed as follows. Histopathologic examination of the resected tissues from 20 patients who underwent therapeutic surgery (orchiectomy in 16 and epididymectomy in 4) for their swollen scrotum(s) revealed caseating granuloma and acid-fast bacilli in 17 patients (additional positive urine PCR for M. tuberculosis DNA in one of them), caseating granuloma without acid-fast bacilli in 2, and noncaseating granuloma in 1 (additional positive urine PCR for M. tuberculosis DNA). Remarkably, only 5 (25%) of 20 patients who underwent therapeutic surgery had specimens sent for culture for M. tuberculosis, and 4 (80%) of the specimens of these 5 patients subsequently grew M. tuberculosis; all isolates were susceptible to the prescribed anti-TB drugs. Among the 20 patients who underwent surgery, 10 had their urine sampled for culture for M. tuberculosis, which turned out to be positive in seven (70%); one of these seven patients had a chest radiography that showed a TB scar and the M. tuberculosis isolate was resistant to ethambutol. As for the other nine patients who did not undergo therapeutic surgery, two received scrotal lump biopsy, and their biopsied tissue disclosed granulomatous inflammation and Langhans giant cells; five had urine culture positive for M. tuberculosis (all isolates were susceptible to anti-TB drugs), and two had positive urine PCR for M. tuberculosis DNA.

The time lapses between the starts of different diagnostic measures and the establishment of diagnosis of scrotal TB are summarized in Table 3Go. Of note, significantly shorter time lapses were found in histopathology examination of resected tissues obtained at either therapeutic surgery or biopsy of scrotal lump (P < 0.001) and in urine TB-PCR analysis (P = 0.001) compared with culture of each of the specimens for M. tuberculosis in reaching a diagnosis of scrotal TB.


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TABLE 3
Time lapses between the starts of different diagnostic measures and the establishment of diagnosis of scrotal TB*
 
All of the patients received self-administered anti-TB chemotherapy once scrotal TB was diagnosed. Five (17.2%) patients were lost to follow-up, and 24 (82.8%; 17 patients underwent surgery and 7 did not) each finished 6- to 24-month anti-TB chemotherapy. Of note, one patient who received epididymectomy for scrotal TB underwent anti-TB chemotherapy, which was extended to 24 months because of concurrent active pulmonary TB and poor adherence to treatment. Of the 24 patients who completed anti-TB chemotherapy, 15 (62.5%) patients (11 patients underwent surgery and other 4 did not) with a median time of follow-up of 10 months (range, 3–36 months) were traceable in terms of outcomes. Among these 15 patients, a scrotal lump redeveloped over the previous operation site in one patient 9 months after epididymectomy and completion of 9-month anti-TB chemotherapy for his right scrotal TB; despite the fact that the microbiology data for this patient were not available, the redeveloped scrotal lump was cured when he finished another course of 18-month anti-TB chemotherapy with the same regimen as he previously took. Of the other 14 patients with traceable outcomes, their scrotal TB was cured.


DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
TB remains one of the leading infectious diseases worldwide.19 The incidence of genital TB (included prostate gland, seminal vesicle, and testis) in men was reported to account for 0.43–15% of extrapulmonary TB.2,6,8,20,21 The 2.1% scrotal TB among cases of extrapulmonary TB at a single medical center in this series did not necessarily reflect the incidence of scrotal TB in the general population in Taiwan, because patient population at a medical center might be biased by patient selection or referral patterns. As the number of new cases of TB continues to increase worldwide because of increasing migration from TB endemic areas and because of the global HIV epidemic,19 it is reasonable to believe that the incidence of scrotal TB will escalate in the future.

The finding that > 50% of patients in this series had chest radiographic manifestations suggestive of either active or inactive TB supports the notion that scrotal TB mainly results from hematogenous or lymphatic spread of M. tuberculosis from other affected sites, especially from the lung.2,3,8,9,22 In this series, the mean interval from emergence of symptoms suggestive of scrotal TB to diagnosis was 142.44 days. TB in general is clinically insidiously progressive, which may result from the lack of vigorous systemic inflammatory response in the host.23,24 This observation is supported by the normal mean peripheral WBC counts (7.1 x 109/L) in 22 patients with data available; one previous study that reported that normal erythrocyte sediment rates in substantial patients suffered from wrist TB substantiates this observation.23 A possible explanation for the attenuated systemic inflammatory response is the slow growth of M. tuberculosis that renders immunologic reaction localized in the host.23,24

Consistent with other series,10,12,25–27 our study showed that pathology and molecular biology diagnostics each play an important role in unfolding scrotal TB; our data additionally emphasized that these diagnostics are capable of leading to a rapid diagnosis of scrotal TB. Although evidence supporting the diagnosis of scrotal TB is easily obtainable as was shown in Results, the failure in making a rapid diagnosis of scrotal TB in these patients seems to be rooted in the lack of clinicians’ alertness to this disease entity and therefore averting from the appropriate diagnostic approaches. In this series, although the yield of culture for M. tuberculosis (80%) was high, only excised materials from one fourth of the patients with scrotal lumps who received therapeutic surgery were sent for culture. Another noteworthy figure is that scrotal TB was initially suspected in only 17.2% of patients presenting with a swollen scrotum in this series. These data underscore the urgent need for improving the current clinicians’ awareness of scrotal TB. Tissue culture is important because the growth of M. tuberculosis is the gold standard for diagnosis of TB. Furthermore, the availability of the isolated bacterium makes susceptibility testing possible. Susceptibility testing is particularly preferable in areas where multidrug-resistant M. tuberculosis was prevalent because it offers valuable guides to anti-TB therapy.23

As for imaging study, ultrasonography of scrotum was reported to be helpful in assessing of testicular and extratesticular lesions.28,29 The two frequent ultrasonographic findings in our patients were a focal scrotal lesion (68.7%) and heteroechogenicity (50%) of the target. However, these ultrasonograhic manifestations are non-specific for scrotal TB, and thereby fail to distinguish scrotal TB from other disease entities such as bacterial epididymo-orchitis, tumor, and infarction.28,29 Experience with applicability of magnetic resonance imaging (MRI) in diagnosis of scrotal TB is limited.30,31 Mattrey and others31 reported that MRI of scrotal TB showed a less inflammatory change and less hypervascularity compared with that of acute bacterial epididymitis. Further studies are needed to establish the role of MRI in the diagnosis of scrotal TB.

Ferrie and others9 reported that ~75% of patients with epididymal TB had abnormal intravenous pyelography (IVP), suggesting a concurrent urinary tract TB involvement. However, given the anatomic proximity and the physiologic relations between the urinary and genital systems, it stands to reason that an abnormal IVP suggestive of TB involving the urinary system may disclose clues to the potential concurrent scrotal TB.

In this series, reemergence of scrotal TB was found in one patient who had received an epididymectomy, followed by 9 months of anti-TB chemotherapy. This relapse might result from poor drug compliance or insufficient anti-TB treatment; infection caused by multidrug resistant M. tuberculosis is unlikely because his scrotal TB was eventually cured after receiving further anti-TB therapy with the same regimen for a further 18 months. Scrotal TB is medically curable.2,3,8,9 Sterility is one of the potential complications of surgical intervention for scrotal TB.32 The limitations of our report are that being retrospectively analyzed, our study fails to disclose the optimal therapeutic length for scrotal TB, which has not been established by controlled studies thus far.19

In summary, scrotal TB is rare. Underawareness may lead to a misdiagnosis and/or delayed diagnosis of scrotal TB. Clinicians should have a high suspicious index for scrotal TB when facing a patient (an elderly patient in particular) with a chronic scrotal lump, especially when his chest radiography suggests either active or inactive pulmonary TB. Because scrotal TB can be medically cured, biopsy of the scrotal lump for pathology study and/or urine PCR analysis for M. tuberculosis should be performed first for rapid diagnostic purposes, and unnecessary surgery may thereby be circumvented.

Received March 3, 2007. Accepted for publication June 18, 2007.

* Address correspondence to Jien-Wei Liu, Division of Infectious Diseases, Department of Internal Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, 123 Ta Pei Road, Niao Sung Hsiang, Kaohsiung Hsien 833, Taiwan. E-mail: 88b0{at}adm.cgmh.org.tw Back

Authors’ addresses: Ing-Kit Lee and Jien-Wei Liu, Division of Infectious Diseases, Department of Internal Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Taiwan. Wen-Chou Yang, Division of Urology, Department of Surgery, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Taiwan.

Reprint requests: Jien-Wei Liu, Division of Infectious Diseases, Department of Internal Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, 123, Ta Pei Road, Niao Sung Hsiang, Kaohsiung Hsien 833, Taiwan. E-mail: 88b0{at}adm.cgmh.org.tw.


REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

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