Signalment (JPC #1454646): Dog

HISTORY: None

HISTOPATHOLOGIC DESCRIPTION: Testis and epididymis: Expanding the connective tissue of the epididymis are multiple granulomas, up to 3x6 mm, centered on foci of numerous degenerate spermatozoa and inflammatory cells, clear acicular clefts (cholesterol), and abundant eosinophilic cellular and karyorrhectic debris (necrosis). These areas are rimmed by a zone of lymphocytes, plasma cells, epithelioid macrophages, and rare multinucleated giant cells and are further surrounded by thin bands of fibrous connective tissue. Multifocally within the surrounding connective tissue, there are few lymphocytes, plasma cells, and occasional macrophages, some of which contain granular, golden-brown pigment (hemosiderin). Within the epididymis there is diffuse aspermia. Within the testis, seminiferous tubules are degenerate with an undulant basement membrane, vacuolated Sertoli cells, and decreased amounts of mature sperm. Multifocally in the testis, low numbers of similar inflammatory cells infiltrate and surround seminiferous tubules and there are rare multinucleated spermatids.

MORPHOLOGIC DIAGNOSIS:

Epididymis: Sperm granulomas, multiple, breed not specified, canine.
Testis, seminiferous tubules: Degeneration, chronic, diffuse, moderate with hypospermatogenesis.

SYNONYMS: Spermatic granulomas

GENERAL DISCUSSION:

Sperm granulomas may occur within the testes, efferent ductules, epididymis, and ductus deferens
Predisposing factors include trauma, inflammation, congenital ductular abnormalities (e.g., forming blind-ended efferent ductules such as segmental aplasia of the mesonephric ducts [absence of the tail of the epididymis]), or surgical manipulation
1. Reported in cervids secondary to Brucella ovis infection
2. Reported in mice secondary to experimental Trypanosoma equiperdum infection (Tanaka, J Comp Pathol. 2023)
Effects on fertility depend on the location and severity of the lesion

PATHOGENESIS:

Can form due to any defect resulting in disruption of a seminiferous tubule or rupture of a duct
1. Sperm granulomas are often preceded by spermiostasis (abnormal stasis and accumulation of spermatozoa within tubules or ducts of the epididymis and deferent duct) and spermatocele (a cavity filled with spermatozoa)
Spermatozoa are “foreign” to the body
1. Innate and acquired immune function is actively suppressed in testicular parenchyma
2. Any injury exposing spermatozoa to the immune system leads to severe, predominately granulomatous, inflammation
  - Sperm releases into extratubular space > recruitment of CD4+ and CD8+ lymphocytes > upregulation of MHC II molecules on epithelial cells > inflammation exacerbated
3. Inflammation -> fibrosis -> further obstruction of tubules, ductules, and ducts -> more inflammation (self-perpetuating)
Spermatic granuloma of the epididymal head: A specific disorder of sexual development (DSD) in which efferent ductule(s) are blind ended due to failure to join with the epididymal duct during development; these blind-ended ductules fill with spermatozoa -> rupture -> spermatic granuloma

TYPICAL CLINICAL FINDINGS:

Chronic epididymitis: Fibrosis can cause hard nodules and testicular atrophy
Semen analysis: Abnormalities may be observed

TYPICAL GROSS FINDINGS:

Irregularity of epididymal size and shape in comparison to contralateral side
Usually a single, hard epididymal nodule, although can be multiple
Fibrinous or fibrous adhesions between epididymis and tunics

TYPICAL LIGHT MICROSCOPIC FINDINGS:

Accumulations of spermatozoa and macrophages within tubules or adjacent interstitium of efferent ductules or epididymis
Ducts contain fibrin, neutrophils, disintegrating spermatozoa, damaged epithelium, macrophages (especially epithelioid macrophages), multinucleate giant cells with engulfed spermatozoa
Macrophages form a distinct layer in the granuloma wall, external to the mass of extravasated spermatozoa
Foreign body and Langhans type multinucleate giant cell macrophages

ADDITIONAL DIAGNOSTICTESTS

    Cytology: Numerous spermatozoa admixed with marked inflammatory response, predominantly macrophages and lymphocytes

DIFFERENTIAL DIAGNOSIS:

Epididymitis due to Brucella ovis, Histophilus ovis, or Actinobacillus seminis in rams
Neoplasia

COMPARATIVE PATHOLOGY:

    Reported in many species, both mammalian and avian

REFERENCES:

Barnes HJ, Fletcher OJ, Abdul-Aziz T. Chapter 13: Reproductive System. In: Abdul-Aziz T, Fletcher OJ, Barns HJ, eds. Avian Histopathology. 4th ed. Madison, WI: Omnipress; 2016: 582.
Clark SD, Nabity MB. Male Reproductive Tract: Prostate, Testes, Penis, and Semen. In: Valenciano AC, Cowell RL, eds. Diagnostic Cytology and Hematology of the Dog and Cat. 5th ed. St. Louis, MO: Elsevier Mosby; 2014:417.
Howerth EW, Nemeth NM, Ryser-Degiorgis MP. Cervidae. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. London, UK: Academic Press; 2018:164.
Foster RA, Premanandan C. Male Reproductive System. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:1310-1311,1317, 1323.
Foster RA. Male genital system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 3. 6th ed. Philadelphia, PA: Saunders Elsevier; 2016: 467-468, 480-481, 497.
Schmidt R, Reavill DR, Phalen DN. Reproductive System. In: Pathology of Pet and Aviary Birds. 2nd ed. Ames, IA: John Wiley & Sons, Inc.; 2015:146.
Tanaka Y, Suganuma K, Watanabe K, Kobayashi Y. Epididymitis in mice experimentally infected with Trypanosoma equiperdum: a histopathological and immunohistochemical study. J Comp Pathol. 2023;201:1-9.