Introduction

Tuberculosis (TB) still remains a serious global health problem, especially in the developing world.[1] Genitourinary tuberculosis (GUTB) is the second most frequent form of extrapulmonary tuberculosis following lymph node tuberculosis with reported incidence ranging from 2% to 20%.[2,3] However isolated testicular involvement is very uncommon, and may occur as a result of either hematogenous or retrograde spread from the epididymis.[2] It predominantly affects middle-aged and elderly men. The clinical manifestations of tuberculous orchitis can be variable and and often presents as a unilateral testicular mass, resembling testicular neoplasms, chronic epididymo-orchitis, or sometimes even present as abscesses³. Because clinical and radiological findings are frequently non-specific, pre-operative diagnosis remains challenging in most cases. Microscopically, it may present with caseating granulomatous inflammation, but the microbiological diagnosis is hampered by the paucibacillary nature of the disease.[4] Xanthogranulomatous inflammation (XGI) is a rare chronic inflammatory condition comprising of foamy macrophages, chronic inflammatory cells admixed with giant cells. It is a rare inflammatory response in the testis[5], but is not uncommon in the kidneys and gallbladder.[6]

Here, we present a rare and diagnostically challenging case of tuberculous orchitis presented as a testicular abscess with an associated xanthogranulomatous inflammation which was confirmed by GeneXpert after negative Ziehl-Neelsen staining.

Case Presentation

A 56-year-old male presented with complaints of right-sided scrotal swelling for four months, associated with a wound over the swelling and purulent discharge. There was no significant past medical or surgical history. General condition of the patient was fair. Local examination revealed a right-sided scrotal swelling measuring approximately 10 × 7 cm. The swelling was firm in consistency. The overlying skin appeared erythematous with multiple discharging sinuses. Ultrasonography with Scrotal Doppler revealed a well-defined, thick-walled (~4 mm) organized heteroechoic collection with internal echogenic debris measuring approximately 9.5 × 6.9 × 6.7 cm (volume ~160 cc), expanding the right scrotal sac. Associated scrotal wall thickening and edema measuring up to 5 mm were noted. Complete blood counts were within normal range. Pus culture did not show any bacterial growth after 48 hours of incubation. Beta-HCG levels were within normal limits (>1.20m IU/m L). Based on clinical and radiological findings, scrotal exploration with debridement and orchidectomy was planned.

Gross Findings

Excised specimen was received in the Histopathology section of our department. Grossly the specimen showed grey brown to grey-white tissue pieces with hemorrhagic areas measuring 9.2 × 8 × 4.5 cm. Serial sectioning revealed greyish-yellow to grey white areas. (Figure 1)

Figure 1: Shows grey brown to grey white tissue with hemorrhagic areas (1A); Cut surface shows grey white to grey yellow areas

Figure 2: (2A)- Well formed granulomas are seen (arrows; 10X) with presence of Langhans giant cell and epithelioid cells (inset; 40X); (2B)- Sheets of foamy histiocytes are seen (10X; Inset – 40X); (2C)- Area of necrosis (10X), along with foci of dense mixed inflammatory infiltrate (Inset; 10X); (2D)- Unremarkable Seminiferous tubules (10X)

Microscopic Findings

Histopathological examination showed many well-defined epithelioid cell granulomas admixed with few Langhans-type giant cells within fibrocollagenous and fibroadipose tissue.(Figure 2A) In other sections, sheets of foamy histiocytes admixed with few lymphocytes, plasma cells were also seen.(Figure 2B) Also multiple foci of dense mixed inflammatory infiltrate comprising of viable and degenerated neutrophils, lymphocytes, histiocytes, and occasional plasma cells was noted. Areas of necrosis were also identified.(Figure 2C) Multiple congested and dilated thick- and thin-walled blood vessels were seen along with foci of granulation tissue.. Numerous unremarkable seminiferous tubules and epididymis were present (Figure 2D). Ziehl–Neelsen staining for acid-fast bacilli was negative. Based on the histopathological findings, a diagnosis of Granulomatous Orchitis with coexisting Xanthogranulomatous inflammation was made. Later M. Tuberculosis was detected by Gene expert. Hence Final diagnosis was Tuberculous orchitis with coexisting Xanthogranulomatous inflammation.

Discussion

Tuberculous orchitis is a rare benign inflammatory lesion that poses a significant diagnostic difficulty due to its close resemblance to neoplastic and inflammatory condition. The current case too provided a great diagnostic dilemma because of its atypical clinical presentation of large testicular abscess with numerous discharging sinuses and an initial impression of a chronic pyogenic infection. But, negative bacterial culture and normal tumor markers required further examination, highlighting the importance of considering atypical etiologies in chronic scrotal lesions.

Histopathological examination played important role in the diagnosis since it showed epithelioid cell granulomas admixed with Langhans-type giant cells and foci of necrosis, which were highly indicative of the tuberculous nature of the disease. Nonetheless, granulomatous orchitis has a broad differential diagnosis which includes idiopathic granulomatous orchitis, fungi, sarcoidosis, brucellosis, and syphilis.[4] The appearance of necrosis and clinical evidence of chronic infection in the current case were in support of a tuberculous etiology.

The negative Ziehl-Neelsen (ZN)-stain might have resulted in underdiagnosis justifying diagnostic drawback in this case. This may be attributed to the paucibacillary character of extrapulmonary tuberculosis, where bacillary load can fall below the sensitivity level of standard microscopy[4]. Comparatively, GeneXpert (CBNAAT) facilitated confirmation through the detection of Mycobacterium tuberculosis with low bacillary load. Past literature has shown that the sensitivity and specificity of GeneXpert is much higher than that of smear microscopy, especially in extrapulmonary and smear-negative cases.[7-9] Therefore, this case supports the significance of molecular diagnostics in the solution of histology-microbiology discordance.

The other characteristic that was notable in this case was the presence of large sheets of foamy histiocytes giving it a xanthogranulomatous appearance. Xanthogranulomatous inflammation is a rare chronic inflammatory reaction, which is characterized by lipid-laden macrophages, chronic inflammatory infiltrate, and tissue destruction, most commonly described in the kidney and gallbladder.[5-6] It is very rare in the testis where it can be confused with malignancy in presentation and radiographically. The pathogenesis is not yet clearly defined, but it is believed to be related to chronic infection, obstruction, and/or defective lipid metabolism.[5]

In the present case, of special interest was, coexistence of tuberculosis and xanthogranulomatous inflammation. It may be admissible that chronic tuberculous infection with underlying tissue destruction and necrosis resulted in the deposition of foamy histiocytes, which leads to a xanthogranulomatous reaction. This overlap can obscure the underlying etiology and further complicate diagnosis.

Clinically, both xanthogranulomatous orchitis and tuberculous orchitis are known to resemble testicular tumors and in many cases, orchidectomy is necessary to ascertain the diagnosis. Naeem M et al have emphasized that genitourinary tuberculosis often has non-specific imaging results and may resemble neoplastic conditions.[3] Likewise, Gongora E et al. referred to xanthogranulomatous orchitis as a rare disease that is usually treated surgically because of its tumor-like appearance.[5] But the coexistence of these two entities in the appearance of a large abscess with discharging sinuses is extremely uncommon and is rarely reported.

What is New in this Case:

This is a special case because of the co-existence of:

1. Tuberculous orchitis in the form of a large abscess with discharging sinuses simulating a chronic pyogenic infection.

2. Concomitant xanthogranulomatous inflammation, a very unusual testicular histological observation.

3. GeneXpert microbiological confirmation with negative Ziehl Neelsen staining, underscoring the importance of molecular tests in paucibacillary tuberculosis.

The case also underscores the significance of multidisciplinary diagnostic method that incorporates clinical, histopathological, and molecular methods in the assessment of atypical lesions of the testicles.

Conclusion

Tuberculous orchitis may also manifest as a testicular abscess and confuse with malignancy, especially in the endemic areas. The presence of xanthogranulomatous inflammation also makes diagnosis difficult. Diagnosis requires a high index of suspicion, histopathology, and even molecular techniques like GeneXpert, particularly in the cases of ZN-negative.

References

1. World Health Organization. Global Tuberculosis Report 2025. Available from https://www.who.int/teams/global-programme-on-tuberculosis-and-lung-health/tb-reports
2. Roddy K, Tobin EH, Leslie SW, Rathish B. Genitourinary Tuberculosis. 2024 Aug 16. In: Stat Pearls [Internet]. Treasure Island (FL): Stat Pearls Publishing; 2026 Jan–. PMID: 32491490.
3. Naeem M, Zulfiqar M, Siddiqui MA et al. Imaging manifestations of Genitourinary Tuberculosis. Radiographics. 2021;41(4):1123-43
4. Gopalaswamy R, Dusthackeer VNA, Kannayan S, Subbian S. Extrapulmonary Tuberculosis—An Update on the Diagnosis, Treatment and Drug Resistance. Journal of Respiration. 2021;1(2):141-164. https://doi.org/10.3390/jor1020015
5. Gongora E Silva RF, Pinto IC, Constantino ECN, Querichelli AFA, Spessoto LCF, Fácio FN Jr. Xanthogranulomatous orchitis: case report of a rare condition. AME Case Rep. 2019 Feb 14;3:4. doi: 10.21037/acr.2019.01.03.
6. Malek RS, Elder JS. Xanthogranulomatous pyelonephritis: a critical analysis of 26 cases and of the literature. J Urol. 1978 May;119(5):589-93. doi: 10.1016/s0022-5347(17)57559-x.
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8. Boehme CC, Nabeta P, Hillemann D et al. Rapid molecular detection of tuberculosis and rifampin resistance. N Engl J Med. 2010 Sep 9;363(11):1005-15. doi: 10.1056/NEJMoa0907847.
9. Azzouza AM, El-Sokkarya RTI, Wafib LS, Khalafa MGA. Role of GeneXpert in extrapulmonary tuberculosis. The Egyptian Journal of Chest Diseases and Tuberculosis. 2023;72:382-385. 10.4103/ecdt.ecdt_114_22.