Infectious Disease of the Testis
In more than 50% of cases, infections affect both the testis and the epididymis (orchioepididymitis). Infections can be divided into acute and chronic depending on the etiologic agent and the duration of infection. Germs reach testis and epididymis in several ways: hematogenous, retrograde if there is urine reflux seminal vesicle-epididymis, lymphatic, or direct from a trauma or wound. Germs that arrive by hematogenous route affect the testicle and produce orchitis. Infectious agents that reach through excretory ducts lead to epididymitis (Nistal et al. 2016).
Epididymitis and Acute Orchioepididymitis
Clinically, the epididymis or, where appropriate, the testicle are congestive, thickened, edematous with fibrinopurulent exudate. The most frequent etiology is bacterial, followed by viral and those caused by parasites.
In some cases, abscesses of the epididymis or of the testicle end up draining through a scrotal sinus associated with vascular inflammatory lesions. The viruses that most often produce orchioepididymitis are mumps, Coxsackie B virus, and cytomegalovirus. Mumps epididymitis is present in 85% of cases of mumps orchitis. Isolated epididymitis is rare. Most patients have a history of parotiditis 4–6 days before. Orchioepididymitis is bilateral in 20–30% of cases. Histologically, at the level of the epididymis only congestion and a lymphocytic intertubular infiltrate are seen. In the testics, the lesions are multifocal. The inflammatory infiltrate is acute, seminiferous epithelium is destroyed, and tubules are sclerosed. If the lesion is bilateral, the patient will probably be infertile and in those cases in which destruction is important, hypergonadotropic hypogonadism may occur. Cytomegalovirus epididymitis are frequent in patients with AIDS and in those who are undergoing immunosuppressive therapy by transplantation. Human papilloma virus has been identified by PCR in squamous metaplasia with dysplasia of the epididymis epithelium. Many other viral infections can produce orchioepididymitis.
Other acute epididymitis are caused by direct trauma or appear during treatment with certain drugs such as amiodarone.
Granulomas are very frequent in chronic inflammation of the testis and epididymis. When they are found, tuberculosis, syphilis, leprosy, brucellosis, sarcoidosis, malacoplaquia, fungi and parasites, and idiopathic granulomatous orchitis, among others, should be suspected.
Syphilis: In the congenital form, both testes are affected. An interstitial infiltrate similar to that of the acquired interstitial orchitis of the adult is observed. If left untreated, the testicles suffer atrophy and fibrosis. In adults, acquired orchitis is a complication of the tertiary stage of syphilis. Histologically, it adopts two interstitial and Gumma forms: In the interstitial form there is a dense inflammatory infiltrate rich in plasma cells. The seminiferous tubules undergo atrophy, while endoarteritis lesions and small gummas appear. The epididymis is not usually affected. In the gummatose form, necrosis develops, which may be multifocal with a yellowish color. In the necrosis, the silhouettes of necrotic seminiferous tubules can be observed and, surrounding it there are lymphocytes, plasma cells and, isolated giant cells. Spirochetes are easily detected by immunohistochemistry or PCR in paraffin material.
Leprosy: It is the lepromatous and borderline forms that most frequently affect the testicle and epididymis. The affectation is more frequently bilateral although the degree varies from one patient to another. Histology changes over time. First, perivascular lymphocytic inflammation predominates with histiocytes loaded with acid-fast bacilli, then the seminiferous tubules atrophy, Leydig cells stand out for forming large clusters and the vessels show endoarteritis. Finally, the testicle is replaced by fibrous tissue with isolated lymphocytes and macrophages with bacilli. In these cases, infertility is the rule.
Brucellosis: Brucellosis orchioepididymitis is common in Middle East and should be suspected in a patient with undulant fever, sweating, weight loss and headache. It may even be the first symptom (Bosilkovski et al. 2018). Histologically, there is lymphohistiocytic inflammation with occasional noncaseating granulomas. The diagnosis is made by clinical and laboratory criteria (high titers of brucella agglutination and/or reverse transcriptase PCR (rt-PCR) assay of urine.
Sarcoidosis: Sarcoidosis affects male genital tract asymptomatically and is discovered in 5% of the autopsies of these patients. The most frequent affectation is that of the epididymis. In 33% of cases, it is bilateral and the only symptom is an increase in the size of the epididymis. Noncaseating epithelioid granulomas may show multinucleated cells, Schauman bodies, and asteroid bodies. Before making the diagnosis, other granulomatous orchioepididymitis should be excluded.
Malacoplakia: The testicle and/or the epididymis are affected in 12% of cases of malacoplakia of the urogenital system. The testicles are enlarged and firm. When cut, testis and epididymis show a grayish-yellowish color and abscesses may occur. There is extensive destruction of the parenchyma. Instead, a dense infiltrate of macrophages with granular eosinophilic cytoplasm containing Michaelis-Gutmann bodies stands out. Among the etiological agents, E. coli and a failure in the mechanisms that regulate the lysosomal degradation of the germs are found. The differential diagnosis classically arises with the Leydig cell tumor.
Orchioepididymitis caused by fungi and parasites: Histoplasma capsulatum produces necrosis and abscesses. They are observed with silver-stained tissue spores of 2–4 microns. Blastomyces dermatitidis affect the epididymis in 30% of cases of disseminated blastomycosis. They form abscesses with a cheesy necrosis center. In the giant cells of the periphery, fungi from 8 to 15 microns in diameter with double refringent contours, PAS, and silver metenamine positive are observed. Coccidioides immitis produce necrotizing and nonnecrotizing granulomas. Silver techniques show 100-micron spheres of diameter containing numerous endospores. Cryptococus are easily identified in stains with mucicarmine. The orchioepididymitis caused by Candida albicans are rare and appear after instrumentation of the urinary system.
The parasites that most frequently affect the genital tract are Filaria, Schistosoma, Leishmanias, Echinococcus, and Trichomonas vaginalis. In patients with filarial and schistosoma, worms do not usually reach the testicle although it is injured by vascular compromise. In the case of Filaries, lymphatic obstruction produces elephantiasis of the penis and scrotum (Janssen et al. 2017).
Peritumoral granulomatous orchitis or Granulomatous tubulitis: It is an inflammatory process that develops in the tubular wall outside the seminiferous epithelium with the presence of macrophage, lymphocytes, and giant cells in patients with germ cell tumors. The selective localization of the lesion makes it possible to differentiate it from other granulomatous orchitis, such as idiopathic granulosa orchitis or sarcoidosis.
Primary autoimmune orchitis (focal orchitis): It is characterized by the association of infertility and asymptomatic orchitis with the presence of antisperm-specific antibodies (ASA) directed against the basement membrane of the seminiferous tubules in the absence of systemic disease. Histologically, at the beginning, there is an infiltrate of polynuclear leukocytes that are located between the myoid cells and the basal lamina. As the process progresses, the infiltrate becomes richer in lymphocytes and the seminiferous epithelium is destroyed. The infiltrate is predominantly of type T lymphocytes. These orchitis can pose differential diagnosis with a lymphoma. This form of orchitis has been observed in biopsies of infertile patients, in patients with cryptorchidism, in patients who had undergone inguinal hernia surgery, in patients with recurrent spermatic cord torsion, patients with Crohn’s disease, and patients with testicular piercing.
Lymphocytic orchitis is a term that refers to the presence of a dense infiltrate of inflammatory cells in the interstitium that, at low power magnification, suggests an idiopathic interstitial granulomatous orchitis, but the lymphoid infiltrate often contains lymphoid follicles with marked hyalinization of blood vessels. Another reactive testicular lesion is pseudolymphoma, composed of infiltrates rich in lymphocytes and plasma cells. It must be differentiated from the following processes: lymphoma (monoclonality), syphilitic orchitis (Levaditti stain), granulomatous orchitis, and even seminomas with abundant lymphoid infiltrate.
Xanthogranulomatous orchioepididymitis: It is a destructive lesion that presents a histological picture similar to xanthogranulomatous pyelonephritis. Macroscopically, yellowish areas and abscesses are observed. Histologically, surrounding the abscesses and extending to the neighboring tissues, there are a large number of histiocytes of clear cytoplasm microvacuoled by the high lipid content. The etiology is not known in many cases. Some are caused by Gram negative bacilli and in diabetic patients (Yamashita et al. 2017).
Ischemic granulomatous epididymitis: It is a noninfectious, asymptomatic lesion described in series of autopsies of elderly people. It is characterized by the presence of necrosis of efferent and interstitial ducts, infiltrates of macrophages, granulomatous reaction with giant cells with cholesteric crystals, and signs of regeneration of the most respected ducts. It is associated in the most evolved cases with fibrosis, accumulation of macrophages with lipofuchins, or cystic areas.
References and Further Reading
- Moazenchi, M., Totonchi, M., Salman Yazdi, R., Hratian, K., Mohseni Meybodi, M. A., Ahmadi Panah, M., Chehrazi, M., & Mohseni Meybodi, A. (2018). The impact of chlamydia trachomatis infection on sperm parameters and male fertility: A comprehensive study. International Journal of STD & AIDS, 29, 466–473.CrossRefGoogle Scholar