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Epithelioid noncaseating granulomatosis, extensively involving the rete testis, epididymis, tunica vaginalis, hilar soft tissue, and adjacent testicular parenchyma.


Sections show numerous noncaseating granulomas with tightly packed epithelioid cells, multinucleated histiocytes, and lymphocytes, diffusely involving the rete testis, epididymis, and parts of the testicular parenchyma. No fungal organisms were identified by PASD, GMS, and Mucicarmine stains. AFB is negative for mycobacteria. Immunohistochemistry for Treponema is also negative. OCT3/4 immunostain did not reveal evidence of germ cell neoplasia.


Granulomatous orchitis is a rare inflammatory process of the testis of unknown etiology. It is a rare entity and is seen more commonly in African Americans in a wide age range of 29-79 years old. It is characterized by the presence of non-specific granulomatous inflammation and admixed multinucleated giant cells without caseation. Bilateral testicular involvement has been reported. Granulomatous orchitis usually presents as a testicular mass mimicking malignancy. No definite etiological factor has been found to date; however, trauma, genitourinary tract infection, sperm extravasation, and autoimmune disease have been postulated as possible pathogenic mechanisms.

Differential diagnoses include non-neoplastic entities such as sarcoidosis, malakoplakia, sperm granuloma, and inflammatory etiologies including tuberculosis, brucellosis, lepromatous leprosy, and syphilis. Also, neoplastic entities need to be ruled out, including germ cell tumors and lymphoma. Genitourinary sarcoidosis is characterized by well-formed non-caseating granulomas. There is usually evidence of systemic disease, and sarcoidosis should remain a diagnosis of exclusion. Malakoplakia is a chronic inflammatory condition that involves the testes, which can resemble granulomatous orchitis. The distinctive histological feature in malakoplakia is a dense infiltrate of histiocytes associated with the destruction of seminiferous tubules and pathognomonic spherical, concentrically laminated Michaelis–Gutmann bodies. Because these contain calcium and iron, von Kossa and Perl's stains may help highlight these structures. Sperm granuloma is an exuberant reaction to sperm and occurs most commonly after vasectomy. Positive AFB stain in sperm may be misinterpreted as mycobacteria. Tuberculosis more often presents as epididymo-orchitis due to ascending infection from the prostate. Special stains for acid-fast bacilli may aid in demonstrating the organisms. Syphilitic orchitis is an inflammatory condition of the testes seen in the early or late phase of syphilis. Histologically, characterized by dense plasma cell infiltration with evidence of obliterative endarteritis and sclerosis or gummatous orchitis. Anti-treponema pallidum immunostain and Warthin Starry special stain may be used for confirmation of the diagnosis. Importantly, seminoma with associated granulomatous inflammation can closely mimic granulomatous orchitis. In such cases, the residual seminiferous tubules should be closely looked at for intratubular germ-cell neoplasia (IGCNU). Immunostains for OCT3/4 and CD117 may aid in confirming the diagnosis. Malignant lymphoma must also be considered in the list of differential diagnoses. The key histologic findings include the compression and obliteration of the tubules and testicular parenchyma by a proliferation of monotonous lymphocytes.


Histologic features

Ancillary studies


Clusters of tumor cells, evidence

of IGCNU in the background seminiferous tubules

CD117, OCT3/4


Sheets of monotonous atypical lymphoid cells

IHC and flow cytometry


Noncaseating granulomas



Histiocytic infiltrate,

Michaelis-Gutmann bodies

Von Kossa, Perl’s, PAS

Sperm granuloma

Foreign-body type

granulomas with sperm

AFB (false positive)


Caseating granulomas

AFB stain


Gumma, plasma cell infiltrate, obliterative endarteritis

Warthin Starry, IHC, PCR

Lepromatous lepra

Non-caseating granulomas, perivascular lymphocytic infiltrate

Fite stain


Noncaseating granulomas, interstitial lymphohisticytic inflammation




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Histopathology of Tumors, 2021, Christopher Fletcher

Hum Pathol. 45(4): 844-50.

Wegner et al. Eur Urol. 26(1):56-60.

Pathology Outlines “Granulomatous orchitis”

Anatomic Pathology 15(1):18-27.

Pathology Research and Practice 207(2011): 275–78.

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