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1. Male Genital System Dr-Ahmad Itmezeh

2. PENIS – Malformations Abnormal location of the distal urethral orifice  among the most common malformations of the penis. Hpospadias : + The most common one ( 1 in 300 live male births) + opening is found on the ventral aspect of the penis anywhere along the shaft  sometimes constricted  urinary tract obstruction & ↑ risk for UTIs. + may be associated with other congenital anomalies, such as inguinal hernia and undescended testis. 2

3. PENIS - Malformations Epispadias + less common. + the abnormal urethral orifice is on the dorsal aspect of the penis. 3

4. PENIS - Inflammatory Lesions Balanitis : local inflammation of the glans penis Posthitis : local inflammation of the overlying prepuce. Most common agents are Candida albicans , anaerobic bacteria, Gardnerella , and pyogenic bacteria. PATHOGENESIS : Mostly as a consequence of poor hygiene in uncircumcised males  accumulation of desquamated epithelial cells, sweat, and debris (termed smegma ) which acts as a local irritant. 4

5. PENIS - Inflammatory Lesions Phimosis is a condition in which the prepuce cannot be retracted easily over the glans penis. Phimosis may be a congenital anomaly, but most cases stem from scarring of the prepuce caused by balanoposthitis . 5

6. PENIS - Neoplasms More than 95% of penile neoplasms arise on squamous epithelium  SCC. Most cases occur in uncircumcised patients older than 40 years of age. Pathogenesis: poor hygiene (potential carcinogens in smegma ), smoking, & infection with human papillomavirus ( HPV )  specifically types 16 and 18 . Bowen disease: Squamous cell carcinoma in situ of the penis  grossly as a solitary plaque on the shaft of the penis. 6

7. PENIS - Bowen disease histologically  dysplastic cells throughout the epidermis with no invasion of the underlying stroma It gives rise to invasive squamous cell carcinoma in ~10% of patients. 7

8. PENIS - SCC Invasive squamous cell carcinoma of the penis most commonly on the glans penis or prepuce. 8

9. PENIS - SCC Histologically , the tumor is most often a typical keratinizing squamous cell carcinoma. The prognosis is related to the stage of the tumor. 9

10. TESTIS- Cryptorchidism It is a failure of testicular descent into the scrotum. Normally, the testes descend from the abdominal cavity into the pelvis (3rd month of gestation)  then through the inguinal canals into the scrotum (last 2 months of intrauterine life). Diagnosis: only established with certainty after 1 year of age, particularly in premature infants, because testicular descent into the scrotum is not always complete at birth. 10

11. TESTIS- Cryptorchidism Cryptorchidism affects 1% of the male population. Mostly the cause is unknown. Bilateral in ~ 10% of affected patients Undescended testes may become atrophic  if bilateral  sterility. Ass with a 3-5 fold increased risk for testicular cancer  in both testes, (including normally descended testis) suggesting that some intrinsic abnormality) 11

12. TESTIS- Vascular Disturbances Torsion or twisting of the spermatic cord  results in obstruction of testicular venous drainage ( thick-walled & more resilient arteries are left patent) Leads to intense vascular engorgement & infarction if not relieved. Two types: + Neonatal torsion occurs in utero or shortly after birth. No ass anatomic defect. + Adult torsion. 12

13. TESTIS- Adult Torsion Adult Torsion + typically in adolescence. + Symptoms: sudden testicular pain (awaken the patient). + In contrast with neonatal torsion, it results from a bilateral congenital anomaly; testis is abnormally anchored in the scrotal sac  ↑ mobility ( bell clapper abnormality ). +Often occurs W/o any inciting injury. 13

14. TESTIS- Adult Torsion One of the few urologic emergencies. If explored surgically & the cord is manually untwisted within ~ 6 hours, the testis will likely remain viable. To prevent the catastrophic occurrence of another torsion in contralateral testis  unaffected testis is surgically fixed within the scrotum ( orchiopexy ). 14

15. TESTIS- Neoplasms In the 15-34-year-old age group, they are the most common tumors in men (peak in incidence). Heterogeneous groups include: + Germ cell tumors: 95%, all are malignant. + Sex cord–stromal tumors: uncommon, usually benign, & derived from Sertoli or Leydig cells. The cause of testicular neoplasms is poorly understood. 15

16. Testicular Neoplasms – Risk factors Whites Whites >> blacks Cryptorchidism 3-5-fold increase in the risk for cancer in both testis. Intersex syndromes e.g.; Androgen insensitivity syndrome & gonadal dysgenesis 16 Family history brothers of males with germ cell tumors have an 8-10-fold increased risk. C ancer in one testis ass with increased risk for neoplasia in the contralateral testis. isochromosome 12 i(12p) Extra copies of the short arm of chromosome 12, found in virtually all germ cell tumors .

17. Testicular Neoplasms - GCNIS Most testicular tumors in postpubertal males arise from germ cell neoplasia in situ (GCNIS). A precursor lesion is present in conditions associated with a high risk for developing germ cell tumors (e.g., cryptorchidism, dysgenetic gonads). 17

18. Testicular germ cell tumors Subclassified into: (1) seminomas. (2) nonseminomatous germ cell tumors. Seminomas are most common, 50%. Histologically the may be: Pure (i.e., composed of a single histologic type)  60% 2. Mixed  40% of cases 18

19. Seminoma- germ cell tumors Third decade of life – never in infants. Histologically identical tumors called dysgerminomas  in the ovary, and germinomas  CNS & other extragonadal sites. Presentation : progressive painless enlargement of the testis. Morphology - Gross : soft, well-demarcated gray-white, usually w/o hemorrhage. 19

20. Seminoma 20

21. GCTs - Seminoma Morphology - histopathology : +Large, uniform cells with clear, glycogen-rich cytoplasm, round nuclei, and conspicuous nucleoli. + Intervening fibrous septa with dense lymphocytic infiltrate. +Granulomatous reaction & syncytiotrophoblasts (15%). 21

22. GCTs - Embryonal carcinoma Morphology - Gross: ill-defined, invasive masses containing foci of hemorrhage and necrosis. Morphology - histopathology large cells with basophilic cytoplasm, they are undifferentiated & may form primitive glandular. 22

23. GCTs – Yolk sac tumor The most common primary testicular neoplasm in children younger than 3 years old. In this age group, it has a very good prognosis. In adults, yolk sac tumors most often are seen admixed with embryonal carcinoma (incidence of yolk sac elements is 80% in mixed). 23

24. GCTs – Yolk sac tumor Morphology – histopathology: tumor composed of low cuboidal to columnar epithelial cells that form microcysts , lacelike (reticular) patterns. A distinctive feature is the presence of structures resembling primitive glomeruli, the so-called Schiller-Duval bodies. Tumors have eosinophilic globules containing α1- anti-trypsin and alpha fetoprotein (AFP – can be detected in the serum) 24

25. GCTs – Yolk sac tumor Blue arrows: Schiller-Duval bodies 25

26. GCTs – Choriocarcinoma In this tumor the pluripotent neoplastic germ cells differentiate into cells resembling placental trophoblasts Morphology - Gross: + may be small lesions, even those with extensive systemic metastases + May show total necrosis & extensive hemorrhage 26

27. GCTs – Choriocarcinoma Morphology - histopathology : (1) Cytotrophoblast : Sheets of small cuboidal cells, irregularly intermingled with (2) Syncytiotrophoblast : large, eosinophilic cells with multiple dark, pleomorphic nuclei. HCG can be identified in serum. 27

28. GCTs – Teratoma Neoplastic germ cells differentiate along multiple somatic cell lineages. Pure forms of teratoma are common in infants and children , 2 nd in frequency only to yolk sac tumors. In adults it is seen in combination with other histologic types ( mixed ), pure forms are rare. 28

29. GCTs – Teratoma Morphology - microscopically : Elements may be: mature (resembling various tissues within the adult) immature (sharing features with fetal or embryonal tissues). In prepubertal males, teratomas are benign. The majority of teratomas in postpubertal males are malignant whether they have mature or immature elements. 29

30. GCTs – Teratoma 30

31. GCTs – Clinical features Presentation: mostly as a painless testicular mass. Biopsy of a testicular neoplasm is associated with a risk of tumor spillage (contraindicated). Standard management of a solid testicular mass is radical orchiectomy, based on the presumption of malignancy. 31

32. GCTs – Clinical features Seminomas and nonseminomatous tumors differ in their behavior & clinical course: Seminomas : remain confined to the testis for long periods & Metastases most commonly to iliac & paraaortic lymph nodes, Nonseminomatous tumors : metastasize earlier, by lymphatic & hematogenous routes. (mostly to liver & lungs). 32

33. GCTs – tumor markers Serum tumor markers secreted by germ cell tumors is important in two ways; diagnostically & in following the response to therapy after the diagnosis: Human chorionic gonadotropin  ( hCG ): always elevated in choriocarcinoma Alpha fetoprotein (AFP) : when elevated in testicular neoplasm  indicates a yolk sac tumor component. Lactate dehydrogenase (LDH): correlate with the tumor burden. 33

34. Seminoma: extremely radiosensitive and has the best prognosis. > 95% with early-stage disease cured. Nonseminomatous germ cell tumors: as a group, 90% of patients achieve complete remission with aggressive chemotherapy, and most are cured. Pure choriocarcinoma : ass with a poorer prognosis. With all testicular tumors, recurrences, typically as distant metastases, usually occur within the first 2 years after treatment. 34

35. PROSTATE can be divided into biologically distinct regions, the most important of which are the peripheral and transition zones. 35

36. Prostate – main pathology: Hyperplastic lesions Most arise in inner transition zone. Causes urinary obstruction. Carcinomas 70%–80% arise in peripheral zones. Often detected by rectal examination. 36

37. Prostate – Histology Normal prostate contains glands with two cell layers, a flat basal cell layer & an overlying columnar secretory cell layer . Surrounding prostatic stroma contains a mixture of smooth muscle and fibrous tissue. 37

38. Prostate - Benign Prostatic Hyperplasia (BPH) An extremely common cause of prostatic enlargement by the age of 40 years & the frequency ↑ with age. An important cause of urinary obstruction. Although the cause of BPH is incompletely understood, excessive androgen-dependent growth of stromal & glandular elements has a central role. Does not occur in males castrated before the onset of puberty. 38

39. BPH - Pathogenesis Dihydrotestosterone (DHT): the main androgen in the prostate  mediator of prostatic growth. Synthesized in the prostate from circulating testosterone by the action of the enzyme 5α- reductase , type 2. Although the ultimate cause of BPH is unknown, it is believed that DHT-induced growth factors act by increasing the proliferation of stromal cells & decreasing the death of epithelial cells. 39

40. BPH - Clinical Features Symptoms: \ + occur in only 10% of cases. + symptoms of lower urinary tract obstruction (LUTO); hesitancy, urgency, frequency, and nocturia . + ↑ risk of urinary tract infections. Tx : + Initial pharmacologic ; agents inhibit formation of DHT. + Surgical treatment for severely symptomatic cases &/or resistant to medical ( Transurethral resection of the prostate (TURP) ). 40

41. Carcinoma of the Prostate Adenocarcinoma of prostate is the most common form of cancer in men. Age: older than 50 years. Significant drop in prostate cancer mortality  increase detection of disease through screening. 41

42. Prostatic adenoCa . - Pathogenesis Androgens: are of central importance; evident by Cancer of the prostate doen’t develop in males castrated before puberty. Cancers often regress for a time in response to surgical or chemical castration. Heredity: also contributes, as there is an increased risk among first-degree relatives of patients with prostate cancer. 42

43. Prostatic adenoCa . - Pathogenesis Environment: geographical variations that may be due to dietary variations. Acquired somatic mutations : + The most common gene rearrangements create fusion genes consisting of the androgen regulated promoter of the TMPRSS2 gene & the coding sequence of ETS family transcription factors. + TMPRSS2-ETS fusion genes are found in ~ 50% of cases. 43

44. Prostatic adenoCa . - Morphology GROSS : firm, gray-white lesions with ill-defined margins. Note the solid whiter tissue of cancer (Lt), in contrast with the spongy appearance of the benign peripheral zone on the contralateral side ( Rt ) 44

45. Prostatic adenoCa . - Morphology Microscopically : AdenoCa . produce well-defined glands, typically smaller than benign glands and are lined by a single uniform layer of cuboidal epithelium, lacking basal cell layer seen in benign glands. 45

46. Prostatic adenoCa . - Clinical Features Serum screening tests: elevated prostate-specific antigen ( PSA ) level. If elevated it is followed by needle biopsy. 70-80% of arise in outer ( peripheral ) zone  palpable as irregular hard nodules on digital rectal examination ( DRE ). Bone metastases, particularly to the axial skeleton, are frequent late in the disease and typically cause osteoblastic (bone-producing) lesions. 46

47. Prostatic adenoCa . - Clinical Features The most common treatments for clinically localized prostate cancer are radical prostatectomy and radiotherapy. The prognosis after radical prostatectomy is based on: the pathologic stage . the margins of the resected specimens are free of tumor or not. Gleason grade (grading system on the basis of glandular patterns of differentiation) 47

48. 48 THANKS! Any questions?