2. PATHOLOGIES OF THE TESTIS & EPIDIDYMIS.pptx

MALE REPRODUCTIVE SYSTEM PATHOLOGY

1. SYSTEMIC PATHOLOGY MALE REPRODUCTIVE SYSTEM: TESTIS AND EPIDYDIMIS SAMOEI – EGERTON UNIVERSITY, MBChB

2. MALE REPRODUCTIVE PATHOLOGY TESTIS AND EPIDIDYMIS TESTICULAR NEOPLASMS PENIS TUMORS OF PENIS PROSTRATE CARCINOMA OF PROSTRATE

3. TABLE OF CONTENTS TESTIS AND EPIDYDIMIS Normal structure Developmental disorders Male infertility Inflammations Miscellaneous lesions Testicular tumors PENIS PROSTRATE

4. TESTIS AND EPIDIDYMIS NORMAL STRUCTURE Contents of the scrotal sac: Testicle and epididymis L ower end of the spermatic cord Tunica vaginalis. The epididymis is attached to body of the testis posteriorly, thus, may be regarded as one organ. Structurally, the main components of the testicle are seminiferous tubules which when uncoiled are of considerable length. HISTOLOGICALLY, The seminiferous tubules are formed of a lamellar connective tissue membrane and contain several layers of cells. In the adult, the cells lining the seminiferous tubules are of 2 types: 1. Spermatogonia or germ cells which produce spermatocytes (primary and secondary), spermatids and mature spermatozoa. 2. Sertoli cells which are larger and act as supportive cells to germ cells , produce mainly androgen (testosterone) and little estrogen .

5. Cont… The seminiferous tubules drain into collecting ducts which form the rete testis from where the secretions pass into the vasa efferentia. Vasa efferentia opens at the upper end of the epididymis. The lower end of the epididymis is prolonged into a thick muscular tube, the vas/ductus deferens, that transports the secretions into prostatic urethra . The fibrovascular stroma present between the seminiferous tubules contains varying number of interstitial cells of Leydig. Leydig cells have abundant cytoplasm containing lipid granules and elongated Reinke’s crystals. These cells are the main source of testosterone and other androgenic hormones in males. Thus, Sertoli and Leydig cells are hormone-producing cells homologous to their ovarian counterparts (granulosa-theca cells) and are termed specialised stromal cells of the gonads. Thus, the main functions of the testis are to produce sperms and testosterone.

6. Cont… Coverings of testis ( From superficial to deep) Tunica vaginalis . (Parietal & visceral layers) Tunica albuginea. Tunica vasculosa . Layers of scrotum (SDESCIS) Skin Dartos muscle External spermatic fascia Cremasteric muscle and fascia Internal spermatic fascia

7. BLOOD, NERVE SUPPLY & LYMPHATIC DRAINAGE ARTERIAL SUPPLY Testicular artery , a branch of abdominal aorta. The artery to vas deferens from the superior or inferior vesical artery C remasteric artery from the inferior epigastric artery . VENOUS DRAINAGE Many small testicular veins emerge from the testis to form the pampiniform plexus , which forms the main bulk of the spermatic cord. At the deep inguinal ring the plexus is replaced by testicular vein which drains into the left renal vein (left side) and IVC (right side) LYMPHATIC DRAINAGE D rained by lymphatics to Pre-aortic and para-aortic or lateral aortic lymph nodes on the posterior abdominal wall . E nlargement of these lymph nodes may be the only sign of carcinoma NERVE SUPPLY S ympathetic efferent nerve supply through celiac and testicular plexuses from T10 to T12 segments of spinal cord. Sympathetic afferent nerve supply travel in sympathetic nerves in celiac and testicular plexuses to the lesser and least splanchnic nerves, which carry them to T10 to T12 segments of spinal cord. Testicular pain is referred to the middle and lower abdominal wall.

8. Cont… ARTERIAL SUPPLY OF TESTIS AND EPIDYDIMIS

9. DEVELOPMENTAL DISORDERS Cryptorchidism Male infertility CRYPTORCHIDISM Incomplete or failure of testis to descend into the scrotum (undescended testis) Incidence 1 % in adult male population. Bilateral in 10% of cases Location In 70% of cases , the undescended testis lies in the inguinal ring I n 25% in the abdomen In the remaining 5%, in other sites along its descent from intra-abdominal location to the scrotal sac. Etiology Unknown in most cases, but has been attributed to; Mechanical factors e.g. short spermatic cord, narrow inguinal canal, adhesions to the peritoneum. Genetic factors e.g. trisomy 13, maldevelopment of the scrotum or cremaster muscles. Hormonal factors e.g. deficient androgenic secretions . N/B Because undescended testes become atrophic, bilateral cryptorchidism results in sterility. For some unclear reasons, even unilateral cryptorchidism may be associated with atrophy of the contralateral descended gonad . But generally, unilateral cryptorchidism leads to infertility whereas bilateral cryptorchidism leads to sterility

10. Cont… Morphologic features Unilateral in 80% cases and bilateral in the rest. Grossly , The cryptorchid testis is small in size, firm and fibrotic. Histologically , Changes of atrophy begin to appear by about 2 year of age as under: Seminiferous tubules: Loss of germ cell elements. The tubular basement membrane is thickened. Hyalinised tubules. Few Sertoli cells surrounded by prominent basement membrane. Interstitial stroma: Increase in the interstitial fibrovascular stroma. Conspicuous presence of Leydig cells, seen singly or in small clusters. CLINICAL FEATURES Asymptomatic and is discovered only on physical examination. However, if orchiopexy is not undertaken by about 2 years of age, significant adverse clinical outcome may result: Sterility-infertility Testicular atrophy Inguinal hernia Malignancy Cryptorchid testis is at 30-50 times increased risk of developing testicular malignancy R isk of malignancy is greater in intra abdominal testis than in testis in the inguinal canal (Easy and early detection) Treatment Surgical placement of the undescended testis into the scrotum (orchiopexy ) by 2 years of age to decrease the likelihood of testicular atrophy, infertility, and testicular cancer .

11. INFERTILITY Causes of male infertility Pre-testicular Testicular Post testicular Can be congenital or acquired Pre-testicular causes Hypopituitarism Estrogen excess Glucocorticoid excess Other endocrine disorders; DM & hypothyroidism (both associates with Hypospermatogenesis) Testicular causes Agonadism Cryptorchidism Maturation arrest Hypospermatogenesis Sertoli cell-only syndrome Klinefelter’s syndrome Mumps orchitis Irradiation damage Post-Testicular Causes Congenital block Acquired block Impaired sperm motility LH & FSH are essential for spermatogenesis -ve feedback effects on both GnRH & LH

12. INFLAMMATIONS Inflammation of the testis is termed as orchitis and of epididymis is called as epididymitis Epididymitis is more common . A combination epididymo-orchiti s may also occur. I mportant types: Non-specific epididymitis and orchitis Granulomatous (autoimmune) orchitis Tuberculous epididymo-orchitis Spermatic granuloma Elephantiasis

13. Non-specific epididymitis & orchitis Non-specific epididymitis and orchitis, or their combination, may be acute or chronic. Refers to inflammation of testis and epididymis when spread of infection are via the vas deferens, or via lymphatic and hematogenous routes. Most frequently, the infection is caused by urethritis, cystitis, prostatitis and seminal vesiculitis. Other causes are mumps, smallpox, dengue fever, influenza, pneumonia and filariasis . The common infecting organisms in sexually-active men under 35 years of age are Neisseria gonorrhoeae and Chlamydia trachomatis. In older individuals the common organisms are urinary tract pathogens like Escherichia coli and Pseudomonas. MORPHOLOGIC FEATURES Grossly , T esticle is firm, tense, swollen and congested. M ultiple abscesses, especially in gonorrheal infection. Variable degree of atrophy F ibrosis . Histologically, C ongestion Edema D iffuse infiltration by inflammatory cells (neutrophils , lymphocytes, plasma cells and macrophages) F ormation of neutrophilic abscesses. F ocal or diffuse chronic inflammation Disappearance of seminiferous tubules F ibrous scarring D estruction of interstitial Leydig cells. P ermanent sterility

14. Granulomatous (Autoimmune) orchitis Non-tuberculous granulomatous orchitis is a peculiar type of unilateral, painless testicular enlargement in middle-aged men that may resemble a testicular tumour clinically. The exact etiology and pathogenesis of the condition are not known though an autoimmune basis is suspected. Morphologic features Grossly, A ffected testis is enlarged T hickened tunica. Cut section of the testicle is greyish-white to tan-brown. Histologically, C ircumscribed noncaseating granulomas lying within the seminiferous tubules. These granulomas are composed of epithelioid cells, lymphocytes, plasma cells, some neutrophils and multinucleate giant cells . The origin of the epithelioid cells is from Sertoli cells lining the tubules. The tubules show peritubular fibrosis which merges into the interstitial tissue that is infiltrated by lymphocytes and plasma cells.

15. Tuberculous epididymo-orchitis Tuberculosis invariably begins in the epididymis and spreads to involve the testis. T uberculous epididymo-orchitis is generally secondary tuberculosis from elsewhere in the body. It may occur either by direct spread from genitourinary tuberculosis such as tuberculous seminal vesiculitis, prostatitis and renal tuberculosis, or may reach here by hematogenous spread of infection such as from tuberculosis of the lungs. Primary genital tuberculosis may occur rarely . Morphologic features Grossly , Discrete, yellowish, caseous necrotic areas are seen. Microscopically , N umerous tubercles which may coalesce to form large caseous mass are seen. Characteristics of typical tubercles such as epithelioid cells, peripheral mantle of lymphocytes, occasional multinucleate giant cells and central areas of caseation necrosis are seen. Numerous acid-fast bacilli can be demonstrated by Ziehl-Neelsen staining. The lesions produce extensive destruction of the epididymis and may form chronic discharging sinuses on the scrotal skin. Healing by fibrosis C alcification .

16. Spermatic granuloma Is the development of inflammation due to invasion of spermatozoa into the stroma. M ay develop due to trauma, inflammation and loss of ligature following vasectomy. Morphologic features Grossly , T he sperm granuloma is a small nodule, firm, white to yellowish-brown. Histologically, G ranuloma composed of histiocytes, epithelioid cells, lymphocytes and some neutrophils . Centre of spermatic granuloma contains spermatozoa and necrotic debris. Fibrosis and hyalinization.

17. Elephantiasis I s enormous thickening of the scrotal skin resulting in enlargement of the scrotum. The condition results from filariasis in which the adult worm lives in the lymphatics, while the larvae travel in the blood. The most important variety of filaria is Wuchereria bancrofti . The condition is common in all tropical countries. The vector is generally the Culex mosquito. The patients may remain asymptomatic or may manifest with fever, local pain, swelling, rash , tender lymphadenopathy and blood eosinophilia. An asthma-like respiratory complaint may develop in some cases. Morphologic features Grossly , A ffected leg and scrotum are enormously thickened E nlargement of regional lymph nodes. D ilated dermal lymphatics and varicosities in affected area of skin. Histologically , Lymphatic obstruction by the adult worms . The worm in alive, dead or calcified form may be found in the dilated lymphatics or in the lymph nodes. Dead or calcified worm in lymphatics is usually followed by lymphangitis with intense infiltration by eosinophils. Sometimes, granulomatous reaction may be evident C hronic lymphedema S ubcutaneous fibrosis E pidermal hyperkeratosis (termed elephantiasis).

18. MISCELANEOUS LESIONS Testicular torsion Varicocele Hydrocele Hematocele TESTICULAR TORSION M ay occur either in a fully-descended testis or in an undescended testis (more common and more severe). Refers to sudden cessation of venous drainage and arterial supply to the testis , following sudden muscular effort or physical trauma. C ommon in boys and young men . Morphologic features The pathologic changes vary depending upon duration and severity of vascular occlusion . C oagulative necrosis of the testis and epididymis Hemorrhagic infarction. I nflammatory reaction generally not so pronounced. VARICOCELE I s the abnormal dilatation , elongation and tortuosity of the veins of the pampiniform plexus in the spermatic cord. 2 types : primary (idiopathic) and secondary. Primary or idiopathic form M ore frequent M ore common in young unmarried men. N early always on the left side as the loaded rectum presses the left testicular vein . Besides , the left testicular vein enters the renal vein at right angles while the right spermatic vein enters the vena cava obliquely . Secondary form O ccurs due to pressure on the testicular vein by enlarged liver, spleen or kidney. It is commoner in middle-aged people.

19. Cont… HYDROCELE I s abnormal collection of serous fluid in the tunica vaginalis . It may be acute or chronic, congenital or acquired. The usual causes are trauma, systemic edema such as in cardiac failure and renal disease, and as a complication of gonorrhea , syphilis and tuberculosis. The hydrocele fluid is generally clear and straw-colored but may be slightly turbid or hemorrhagic . The hydrocele sac may have single loculus or multiple loculi . The wall of the hydrocele sac is composed of fibrous tissue infiltrated with lymphocytes and plasma cells. HEMATOCELE I s hemorrhage into the sac of the tunica vaginalis . It may result from direct trauma, from injury to a vein by the needle, or from hemorrhagic diseases. In recent hematocele , the blood coagulates and the wall is coated with ragged deposits of fibrin. In long-standing cases , the tunica vaginalis is thickened with dense fibrous tissue coated with brownish material due to old organised hemorrhage and occasionally may get partly calcified.

20. Review CONTENTS OF SPERMATIC CORD Composed of the following six groups of structures Ductus deferens, in the posterior part. Three arteries: (a) Testicular artery, from abdominal aorta . (b) Cremasteric artery, from inferior epigastric artery . (c) Artery to ductus deferens, from inferior vesical artery . Veins , the pampiniform venous plexus. Lymphatics , especially from testis draining into pre- and para-aortic nodes, and some from the coverings draining into external iliac nodes . Nerves , genital branch of genitofemoral nerve and sympathetic fibres which accompany the arteries. Remains of processus vaginalis.

21. Longitudinal section of the testis and epididymis showing their structures.