Secondary Logo

Journal Logo

Your Diagnosis Please

Testicular Nodules in a 16-Year-Old Boy

Friedman, Bat-Chen MD*; Banai, Menachem PhD; Friedman, Boris MD; Neheman, Amos MD; Ephros, Moshe MD

Editor(s): Azimi, Parvin H. MD; Lee, Brian MD

Author Information
The Pediatric Infectious Disease Journal: February 2009 - Volume 28 - Issue 2 - p 168, 171-172
doi: 10.1097/INF.0b013e3181880a24
  • Free

A 16-year-old male from a village in northern Israel presented to the pediatric emergency department complaining of erythema, swelling, warmth, and tenderness of his left scrotum, which had gradually developed over a 3-week period. There was no history of trauma, fever, upper respiratory illness, or intestinal symptoms. The patient denied urinary complaints, urethral discharge, and sexual activity. Other than diabetes mellitus diagnosed at age 12, he had no active medical problems. Ten days before admission he was seen by an urologist and was treated with a 10-day course of cephalexin. When there was no improvement, the patient was referred to the pediatric emergency department.

The patient was a healthy-appearing adolescent male in no distress. His temperature was 37°C, heart rate was 113 beats/min, and blood pressure was 120/80 mm Hg. Physical examination was normal except for left scrotal swelling, erythema, tenderness, and warmth. There was no urethral discharge. Cremasteric reflex was present, and the right testis was normal.

White blood cell count was 8120/mm3 with 53% neutrophils, 40% lymphocytes, 4% monocytes, and 3% eosinophils. Hemoglobin was 12.1 g/dL, hematocrit was 34.5%, and platelet count was 345,000/mm3. ESR was 30 mm/h. Serum glucose was 362 mg%, urea was 31 mg%, and creatinine was 0.7 mg%; electrolytes, calcium, and liver function tests were normal. Urinalysis showed glycosuria with mild ketonuria without pyuria or hematuria. Serum α-fetoprotein and β-HCG were normal. Chest radiograph and abdominal ultrasound showed no abnormalities, but Doppler ultrasound of the testes revealed 3 hypoechoic lesions within the left testis, each about 1 cm in diameter. There was increased blood flow around but not within the lesions, and to the epididymis. Based on these findings, the patient was diagnosed with focal orchitis, hospitalized, and treated with intravenous cefuroxime. After 3 days of treatment, the scrotum remained swollen, but the tenderness, erythema, and warmth had diminished somewhat. He was then discharged with 10 days of oral cefuroxime. Two weeks later the patient returned with worsening scrotal swelling and was found to have enlargement of the testicular lesions by ultrasound. Because of suspected malignancy, surgical exploration and biopsy were recommended by the urologist. After additional history was obtained, the surgery was deferred, and additional tests were performed, which confirmed the diagnosis.


The patient reported intermittent consumption of homemade dairy products. In addition, his mother had been hospitalized with high fever and hepatosplenomegaly 2 months earlier. She had had 3 positive blood cultures and a positive serology for Brucella melitensis. Our patient's anti-Brucella antibody titer was 1:380 (Remel, Basingstoke, UK) and Rose Bengal test was also strongly positive, suggesting that the focal orchitis was due to brucellosis. Blood cultures were negative.

The patient was treated with an 8-week course of oral doxycycline and rifampin. After 3 weeks of therapy, the testicular tenderness and warmth diminished significantly, anti-Brucella antibody titer declined to 1:80, and a repeat ultrasound showed that although one of the testicular lesions had disappeared, the other 2 had become increasingly hypoechoic, suggesting progressive necrosis. Despite 8-weeks of therapy, the diameter of the remaining masses stabilized at 1.6 and 1.3 cm, and the patient continued to complain of intermittent scrotal pain. Over the ensuing 3 months, ultrasounds showed progressive enlargement of one of the masses; this occurred despite another 8-week course of therapy. Six months after presentation, the patient underwent left orchiectomy.

Pathologic examination of the resected tissue demonstrated extensive areas of necrosis surrounded by palisaded histiocytes, inflammatory cells, and fibrosis. Adjacent testicular tissue showed degenerative changes with hypospermatogenesis and areas of maturation arrest. Histochemical stains including PAS, Gram, methenamine silver, and Zeil-Neelsen were negative. Polymerase chain reaction (PCR)1 of the testicular tissue was positive for B. melitensis.

Brucellosis is a geographically widespread zoonotic disease that is particularly endemic to the Middle East and capable of multiorgan involvement and protean manifestations. The clinical presentation of brucellosis is variable and nonspecific: fever, malaise, anorexia, and fatigue may develop over several days or weeks.2,3 Localization of the infection may cause focal symptoms and signs involving almost any organ. Second only to osteoarticular involvement, involvement of the genitourinary system is seen in 2% to 20% of brucellosis patients, with epididymo-orchitis being the most common manifestation.4–6 In a study of 59 cases of Brucella epididymo-orchitis, scrotal pain and swelling were the most common symptoms (100%), followed by systemic fever (88%) and diaphoresis (73%). Lower urinary tract symptoms were infrequent (occurring in only 4%).5 Testicular involvement is usually unilateral6–8 and rarely is it the sole complaint as it was in the case of our patient.

Epididymo-orchitis in prepubertal males is almost always viral in etiology and patients rarely present with localized intratesticular lesions.9 Pyogenic bacterial orchitis is usually the result of the contiguous spread from an inflammatory process of the epididymis, and in children and nonsexually active adolescents, most cases are associated with UTI. Pathogens include Escherichia coli, Klebsiella spp., Pseudomonas aeruginosa, enteroccoci, staphylococci, or streptococci.9 Typically, pyogenic bacterial orchitis is associated with an acute onset of high fever, extreme testicular tenderness, and an ill appearing patient—inconsistent with the insidious clinical presentation in our patient. Uncommon etiologies such as Mycobacterium tuberculosis and blastomycosis must also be considered. Furthermore, it is important to consider the diagnosis of testicular cancer as prompt recognition may have a significant impact on survival. Distinguishing between focal testicular infection and a testicular neoplasm may be difficult because about 10% of patients with testicular neoplasms show signs of inflammation, and focal orchitis due to Brucella may manifest as a gradually enlarging testicular mass with minimal systemic signs.10–11

In brucellosis, routine laboratory studies can be nonspecific. White blood cell count is usually normal or low. Markers of inflammation (ESR, CRP) are not consistently abnormal and minor disturbances of hepatocellular enzymes are relatively common. Ultrasound may show scrotal thickening with diffuse epididymitis or, less frequently, well-defined hypoechoic lesions.7,8,10 Although important for diagnosis and management of focal epididymo-orchitis, ultrasound cannot differentiate granulomatous inflammation from neoplasia.8

Both culture and serologic tests can be used to establish the diagnosis of brucellosis. Isolation of the organism from blood culture or tissue provides definitive diagnosis; however, the sensitivity of blood culture in brucellosis is variable, with positive cultures ranging from 15% to 80%.2,12 Recent studies have demonstrated that the BACTEC 9240 blood culture system with pediatric Peds Plus/F (PPF) or adult Plus Aerobic/F (PAF) medium enables detection of Brucella within 1 week and precludes the need for longer incubation or subculturing negative blood culture vials.13 The BACTEC MYCO/F LYTIC (MFL) medium, which was specially developed for improved culturing of intracellular pathogens, offers no advantage for the detection of Brucella when compared with the PAF and PPF media.13 In addition to blood, a variety of other tissues may yield positive cultures including liver, joint, pleural, or cerebrospinal fluid. Bone marrow cultures are highly sensitive and may be justified in some cases.2

Agglutination tests remain the main diagnostic tool; however, indirect enzyme-linked immunosorbent assay (ELISA) has a greater sensitivity and specificity. The disadvantages of serology include inability to detect Brucella canis antibodies and possible cross reactivity with other pathogens such as Yersinia enterocolitica 0:9, Salmonella urbana, Francisella tularensis, E. coli 0116 and 0157, and Vibrio cholerae.2,3 The use of sequential antibody titers for follow-up and relapse prediction is limited because titers can remain high for prolonged periods.2

Molecular diagnosis provides a promising tool for detection and rapid diagnosis of infection with Brucella spp. Specific polymerase chain reaction (PCR) can be preformed on any body tissue and yield relatively rapid results. 16SrRNA gene sequence reveals genus-specific homology and has been used in clinical settings with proven high sensitivity.14 Recent advances include real-time PCR assays, which are practical, highly sensitive, and specific,15 but still require standardization and better definition of their specific clinical role.

Treatment of human brucellosis should be by combination therapy and current guidelines for treating children 8 years or older recommend doxycyline for a period of 6 weeks in combination with either streptomycin for 3 weeks or rifampin for 6 weeks.2,3 Other drugs used include trimethoprim-sulfamethoxazole, quinolones, and other aminoglycosides (eg, gentamicin). Treatment of Brucella epididymo-orchitis is challenging and there is no consensus on specific drugs, duration of treatment, or on the role of surgery.4,5,9,11 A minimum of 6 weeks of antibiotic treatment is associated with a high (25%) relapse rate,5 thus treatment will often be continued for significantly longer. Poor response to antibiotics is often noted with focal epididymo-orchitis, where necrotizing granulomatous orchitis tends to evolve, as seen in our patient. This rare manifestation often eventually requires orchiectomy as well as medical therapy for definitive cure.5,6,8

Sonography of left testis (saggital view) showing multiple focal hypoechoic lesions with increased blood flow surrounding, but not within, them.


1. Bardenstein S, Mandelboim M, Ficht TA, et al. Identification of the Brucella melitensis vaccine strain Rev. 1 in animals and humans in Israel by PCR analysis of the PstI site polymorphism of its omp2 gene. J Clin Microbiol. 2002;40:1475–1480.
2. Pappas G, Aritidis N, Bosilkovski M, et al. Brucellosis. N Engl J Med. 2005;352:2325–2336.
3. Franco MP, Mulder M, Gilman RH, et al. Human brucellosis. Lancet Infect Dis. 2007;7:775–786.
4. Ibrahim A, Awad R, Shetty D, et al. Genito-urinary complications of brucellosis. Br J Urol. 1988;21:283–289.
5. Navarro-Martinez A, Solera J, Corredoira J, et al. Epididymoorchitis due to Brucella mellitensis: a retrospective study of 59 patients. Clin Infect Dis. 2001;33:2017–2022.
6. Yetkin MA, Erdinc FS, Bulut C, et al. Epididymoorchitis due to brucellosis in central Anatolia, Turkey. Urol Int. 2005;75:235–238.
7. Ozturk A, Ozturk E, Zeyrek F, et al. Comparison of brucella and non-specific epididymoorchitis: gray scale and color Doppler ultrasonographic features. Eur J Radiol. 2005;56:256–262.
8. Salmeron I, Ramirez-Escobar MA, Puertas F, et al. Granulomatous epididymo-orchitis: sonographic features and clinical outcome in brucellosis, tuberculosis and idiopathic granulomatous epididymo-orchitis. J Urol. 1998;159:1954–1957.
9. Papatoris AG, Mpadra FA, Karamouzis MV, et al. Endemic brucellar epididymo-orchitis: a 10-year experience. Int J Infect Dis. 2002;6:309–313.
10. Kocak I, Dundar M, Culhaci N, et al. Relapse of brucellosis simulating testis tumor. Int J Urol. 2004;11:683–685.
11. Memish ZA, Venkatesh S. Brucellar epididymo-orchitis in Saudi-Arabia: a retrospective study of 26 cases and review of literature. BJU Int. 2001;88:72–76.
12. Yagupsky P. Detection of brucella in blood cultures. J Clin Microbiol. 1999;37:3437–3442.
13. Yagupsky P. Use of BACTEC MYCO/F LYTIC medium for detection of Brucella melitensis bacteremia. J Clin Microbiol. 2004;42:2207–2208.
14. Navarro E, Escribano J, Fernandez J, et al. Comparison of three different PCR methods for detection of Brucella spp in human blood samples. FEMS Immunol Med Microbiol. 2002;34:147–151.
15. Probert WS, Schrader KN, Khuong NY, et al. Real-time multiplex PCR assay for detection of Brucella spp., B. abortus, and B. melitensis. J Clin Microbiol. 2004;42:1290–1293.

testicular mass; brucellosis

© 2009 Lippincott Williams & Wilkins, Inc.