Chronic Epididymo-Orchitis: Histopathology

General Histopathological Features (Non-specific Chronic Inflammation)

• Mixed chronic inflammatory infiltrate - predominantly lymphocytes, plasma cells, and macrophages in the interstitium and around tubules; neutrophils may be seen if there is superimposed acute activity
• Periductal and interstitial fibrosis - progressive replacement of normal stroma by fibrous tissue; this is the hallmark of chronicity
• Seminiferous tubular atrophy - tubules become shrunken with thickened basement membranes, loss of spermatogenic cells, and eventual hyalinization (tubular "ghost" outlines)
• Tubular destruction - in severe cases, native architecture is destroyed with abscess formation and replacement by fibroinflammatory tissue
• Epididymal duct changes - periductal fibrosis, luminal narrowing/obstruction, and epithelial flattening or loss
• Vascular changes - endovasculitis and obliterative changes, particularly in syphilitic cases
• Sperm granulomas - may form in areas of ductal rupture, with histiocytes and giant cells engulfing extravasated spermatozoa

Cause-Specific Histopathological Features

1. Tuberculous (Mycobacterial) Epididymo-orchitis

• Multiple confluent granulomas with central caseating necrosis - the hallmark finding
• Destruction of the epididymis, seminiferous tubules, and interstitium by caseating or non-caseating granulomatous inflammation
• Aggregates of epithelioid histiocytes with a peripheral rim of lymphocytes (classic "tuberculoid" granuloma)
• Langhans giant cells (horseshoe arrangement of nuclei at the periphery of giant cells) are frequently present
• Late stages show a fibroblastic response with dense scar formation and dystrophic calcification
• The epididymis is almost always the primary site; secondary spread to the testis occurs later
• Gross: irregular mass with foci of caseating necrosis; late stages show extensive cystic change
• ZN (Ziehl-Neelsen) stain for acid-fast bacilli confirms mycobacterial infection
• Bailey and Love's Short Practice of Surgery, p. [block13]

2. Bacterial (Non-tuberculous) Chronic Epididymo-orchitis

• Variable mixed acute, chronic, and granulomatous inflammation
• Abscess formation with seminiferous tubule necrosis
• Chlamydia trachomatis: drives a predominantly fibrotic response leading to epididymal obstruction; persistent intracellular infection
• E. coli (older men): direct epithelial damage + endotoxin-mediated cytokine release and oxidative injury
• Neisseria gonorrhoeae: rapid scarring, particularly in the distal epididymis

3. Mumps Orchitis (Viral)

• Lymphocytic infiltration of the interstitium (not granulomatous)
• Direct viral invasion of testicular parenchyma
• Resultant irreversible seminiferous tubular atrophy - the key long-term finding
• Leydig cells are relatively spared initially
• Late: testicular atrophy with complete loss of spermatogenic elements, leading to infertility if bilateral
• Bailey and Love's Short Practice of Surgery

4. Syphilitic Orchitis

1. Bilateral interstitial orchitis - dense interstitial fibrosis with destruction of seminiferous tubules (bilateral, symptomatic only as infertility)
2. Interstitial fibrosis - gradual destruction of tubules; testes not enlarged
3. Gumma (most common) - central coagulative necrosis surrounded by granulomatous inflammation; abundant plasma cells are characteristic; obliterative endarteritis and periarteritis of the small vessels is pathognomonic

• Confirmatory stains: Warthin-Starry or anti-Treponema pallidum immunostain
• S Das Manual on Clinical Surgery; URochester Pathology case

5. Nonspecific Granulomatous Orchitis

• Diffuse stromal replacement by epithelioid histiocytes, lymphocytes, and plasma cells
• Interstitial fibrosis with hyalinized, atrophic seminiferous tubules (especially subcapsular)
• No caseation (unlike TB)
• Immunohistochemistry: CD68+, S100 focally positive, keratin negative, inhibin negative
• Must exclude seminoma with granulomatous reaction (check for IGCNU in residual tubules)

6. Filarial (Subacute/Chronic) Epididymo-orchitis

• Predominantly affects the globus major (head) of the epididymis
• Eosinophilic infiltration around dying microfilariae
• Granuloma formation around adult worms or larval remnants
• Progressive lymphedema and interstitial fibrosis
• S Das Manual on Clinical Surgery

7. Malakoplakia (Rare)

• Dense infiltrate of large von Hansemann histiocytes
• Pathognomonic Michaelis-Gutmann bodies - spherical, concentrically laminated intracytoplasmic inclusions containing calcium and iron (highlighted by von Kossa and Perl's stains)
• Destruction of seminiferous tubules

8. Sarcoidosis

• Well-formed non-caseating granulomas - distinguishable from TB by absence of caseation and negative AFB stain
• Diagnosis of exclusion; look for systemic disease involvement

Summary Table

Common End-Stage Features (Any Cause)

1. Extensive interstitial fibrosis
2. Complete seminiferous tubular hyalinization and atrophy
3. Loss of spermatogenesis (azoospermia/infertility)
4. Leydig cell hyperplasia (relative, as tubules disappear)
5. Epididymal ductal obstruction