1. MALE GENITAL SYSTEM Faculty of Medicine Department of Pathology

2. MALE GENITAL SYSTEM PENIS SCROTUM, TESTIS, & EPIDIDYMIS PROSTATE SEXUALLY TRANSMITTED DISEASES

3. PENIS MALFORMATIONS INFLAMMATORY LESIONS NEOPLASMS

4. MALFORMATIONS OF THE PENIS ABNORMAL LOCATION OF URETHRAL ORIFICE ALONG PENILE SHAFT HYPOSPADIAS (VENTRAL ASPECT) MOST COMMON (1/300 LIVE MALE BIRTHS) EPISPADIAS (DORSAL ASPECT) MAY BE ASSOCIATED WITH OTHER GENITAL ABNORMALITIES INGUINAL HERNIAS UNDESCENDED TESTES CLINICAL CONSEQUENCES CONSTRICTION OF ORIFICE URINARY TRACT OBSTRUCTION URINARY TRACT INFECTION IMPAIRED REPRODUCTIVE FUNCTION

6. INFLAMMATORY LESIONS OF THE PENIS SEXUALLY TRANSMITTED DISEASES BALANITIS (BALANOPOSTHITIS) INFLAMMATION OF THE GLANS (PLUS PREPUCE) ASSOCIATED WITH POOR LOCAL HYGIENE IN UNCIRCUMCISED MEN SMEGMA (accumulation of desquamated epithelial cells, sweat, and debris ). DISTAL PENIS IS RED, SWOLLEN, TENDER +/- PURULENT DISCHARGE

7. PHIMOSIS PREPUCE CANNOT BE EASILY RETRACTED OVER GLANS MAY BE CONGENITAL USUALLY ASSOCIATED WITH BALANOPOSTHITIS AND SCARRING PARAPHIMOSIS (TRAPPED GLANS) URETHRAL CONSTRICTION INFLAMMATORY LESIONS OF THE PENIS

8. FUNGAL INFECTIONS CANDIDIASIS ESPECIALLY IN DIABETICS warm moist conditions and poor local hygiene EROSIVE, PAINFUL, PRURITIC CAN INVOLVE ENTIRE MALE EXTERNAL GENITALIA Scrapings or biopsy:budding yeast and pseudohyphae INFLAMMATORY LESIONS OF THE PENIS

9. Condyloma acuminatum Caused by low risk HPV 6, 11.

10. Condyloma acuminatum

11. Penile Carcinoma in Situ All are strongly associated with HPV infection. 1-Bowen Disease – solitary,plaquelike lesion on the shaft of penis. 2.Erythroplasia of Queyrat – erythematous patch on the glans penis 3. Bowenoid Papulosis – venereally transmitted viral lesion involving the penile shaft.

12. Bowen ’ s Disease ( carcinoma in situ ) Malignant cells within the epidermis with no invasion of the underlying stroma. Can occur in: Penis Vulva Oral mucosa Skin Can transform to invasive carcinoma (~10%). Associated with an increased incidence of visceral malignanccies

13. Bowen Disease (carcinoma in situ )

14. NEOPLASMS OF THE PENIS SQUAMOUS CELL CARCINOMA (SCC) EPIDEMIOLOGY UNCOMMON - ABOUT 1 % OF CA IN US MEN UNCIRCUMCISED MEN BETWEEN 40 AND 70 Glans penis and prepuce affected most PATHOGENESIS POOR HYGIENE, SMEGMA( exposure to potential carcinogens) HUMAN PAPILLOMA VIRUS (16 AND 18) Environmental irritants (Coal tar, soot) CIS FIRST, THEN PROGRESSION TO INVASIVE SQUAMOUS CELL CARCINOMA

15. CLINICAL COURSE USUALLY INDOLENT LOCALLY INVASIVE HAS SPREAD TO INGUINAL LYMPH NODES IN 25% OF CASES AT PRESENTATION DISTANT METS RARE 5 YR SURVIVAL 70% WITHOUT LN METS 27% WITH LN METS SCC OF THE PENIS

16. Carcinoma of Penis

19. SCROTUM, TESTIS, AND EPIDIDYMIS

20. SCROTAL ENLARGEMENT HYDROCELE - MOST COMMON CAUSE ACCUMULATION OF SEROUS FLUID WITHIN TUNICA VAGINALIS INFECTIONS, TUMOR, IDIOPATHIC HEMATOCELE :accumulation of blood due to trauma or bleeding disorders. CHYLOCELE : accumulation of lymphatic fluid FILIARIASIS - ELEPHANTIASIS TESTICULAR DISEASE LESIONS INVOLVING THE SCROTUM

22. Testicular Diseases Congenital Inflammatory Neoplastic Manifestations Infertility Enlargement Atrophy Pain

23. Normal Atrophy

24. Cryptorchidism (Failure of Testicular Descent Into the Scrotum) Testis descends to pelvis at the 3rd gestational month, into the scrotum in the last 2 months of gestation. Incidence: 0.7%-0.8% of the male population. RIGHT > LEFT, 25% BILATERAL Etiology: Hormonal: deficiency of LHRF Mechanical: Short spermatic cordblocked inguinal canal Intrinsic testicular abnormalities. Unknown ( vast majority ) A feature of some congenital syndromes (Prader-willi syndrome)

25. Cryptorchidism Morphology: Smaller than normal testes, the higher the testis the smaller its size. Hypoplastic or atrophic germinal layer of tubules Leydig cell hyperplasia. Thickened basement membrane Intratubular germ cell neoplasia (ITGCN)

26. Cryptorchidism Complications Infertility Four-fold increased risk of testicular malignancy in both testes,even if unilateral cryptorchidism Trauma Management - Orchiopexy ( surgical placement of undescended testis into scrotum before puberty ) - This will decrease atrophy but does not guarantee fertility. Patients remain at same increased risk of testicular cancer. Controversial !!!!.

27. OTHER CAUSES OF TESTICULAR ATROPHY CHRONIC ISCHEMIA INFLAMMATION OR TRAUMA HYPOPITUITARISM EXCESS FEMALE SEX HORMONES THERAPEUTIC ADMINISTRATION CIRRHOSIS MALNUTRITION IRRADIATION CHEMOTHERAPY

28. INFLAMMATORY LESIONS OF THE TESTIS USUALLY INVOLVE THE EPIDIDYMIS FIRST SEXUALLY TRANSMITTED DISEASES NONSPECIFIC EPIDIDYMITIS AND ORCHITIS SECONDARY TO UTI BACTERIAL AND NON-BACTERIAL SWELLING, TENDERNESS ACUTE INFLAMMATORY INFILTRATE

29. MUMPS 20% OF ADULT MALES WITH MUMPS EDEMA AND CONGESTION CHRONIC INFLAMMATORY INFILTRATE MAY CAUSE ATROPHY AND STERILITY TUBERCULOSIS GRANULOMATOUS INFLAMMATION CASEOUS NECROSIS AUTOIMMUNE GRANULOMATOUS ORCHITIS RARE FINDING IN MIDDLE AGED MEN INFLAMMATORY LESIONS OF THE TESTIS

30. Acute epididymitis

31. Torsion of testis

32. Testicular Tumors Firm painless enlargement of testis. Peak incidence age is between 15-34 years 95% are germ cell tumors; almost all are malignant. Non germ cell tumors may synthesize and result in endocrine abnormalities. Risk factors: Cryptorchidism ; four-fold increased risk Testicular feminization syndrome Klinefelter ’ s syndrome Siblings of patients with germ cell tumors Cytogenetic abnormalities; isochromosome i(12p) Unknown

33. TESTICULAR NEOPLASMS EPIDEMIOLOGY MOST IMPORTANT CAUSE OF PAINLESS ENLARGEMENT OF TESTIS 6/100,000 MALES, WHITES > BLACKS (US) INCREASED FREQUENCY IN SIBLINGS PEAK INCIDENCE 15-34 YRS MOST ARE MALIGNANT ASSOCIATED WITH GERM CELL MALDEVELOPMENT CRYPTORCHIDISM TESTICULAR DYSGENESIS(XXY)

34. PATHOGENESIS 95% ARISE FROM GERM CELLS ISOCHROMOSOME 12, i(12p), IS A COMMON FINDING RARELY ARISE FROM SERTOLI CELLS OR LEYDIG CELLS THESE ARE OFTEN BENIGN Lymphoma men > 60 yo TESTICULAR NEOPLASMS

35. WHO CLASSIFICATION OF TESTICULAR TUMORS ONE HISTOLOGIC PATTERN (40%) SEMINOMAS (30%) EMBRYONAL CARCINOMA YOLK SAC TUMOR CHORIOCARCINOMA TERATOMA (mature, immature, with malignancy in somatic elements ) MULTIPLE HISTOLOGIC PATTERNS (60%) EMBRYONAL CA + TERATOMA CHORIOCARCINOMA + OTHER OTHER COMBINATIONS

36. HISTOGENESIS OF TESTICULAR NEOPLASMS (PEAK INCIDENCE) GERM CELL PRECURSOR SEMINOMA (40-50 Y) GONADAL DIFFERENTIATION EMBRYONAL CA (UNDIFFERENTIATED) (20-30 Y) TOTIPOTENTIAL DIFFERENTIATION (NONSEMINOMA) CHORIOCARCINOMA (20-30 Y) hCG + TROPHOBLASTIC DIFFERENTIATION YOLK SAC TUMOR (< 3 Y) AFP + YOLK SAC DIFF TERATOMA (20-30 Y) MATURE IMMATURE MALIGNANT TX SOMATIC DIFFERENTIATION

37. Testicular Germ Cell Tumors Tumor Seminoma Embryonal Ca. Yolk sac tumor Choriocarcinoma Teratoma Mixed tumors Peak age (yr) 40-50 20-30 3 20-30 all ages 15-30 Tumor Markers ~10% have elevated hCG 90% have elevated hCG and/or AFP 100% have elevated AFP 100% have elevated hCG 50% have elevated hCG and/or AFP 90% have elevated hCG and AFP

39. Seminoma 35-50% of all testicular germ cell tumors. Malignant germ cell tumour. Analogous to Dysgerminoma of ovary Large well demarcated soft homogenous white/gray masses without hemorrhage. Cells are large with distinct cell borders, round nuclei and conspicuous nucleoli. Lymphocytic infiltrate and granulomas are common.

40. Seminoma 10-15% have giant cells containing hCG. Metastases are predominantly lymphatic and involve iliac and para-aortic lymph nodes. Very radiosensitive

41. Seminoma

44. Embryonal Carcinoma The second most common germcell tumour (20-30% ) Often presents with pain or metastasis Admixed with other germ cell tumour in most cases.Pure forms comprises 2-3%.

45. Embryonal Carcinoma Invasive hemorrhagic masses with necrosis. Cells are large with indistinct cell borders, basophilic cytoplasm large nuclei and conspicuous nucleoli. Cells form solid nests or gland like structures. Metastases by hematogenous and lymphatic routes are common even in small tumors.

46. Embryonal carcinoma

48. Yolk Sac Tumor Most common testicular tumor below the age of 3 years. Large well demarcated masses. Cuboidal and columnar cells forming sheets, glands, papillae and microcysts. Schiller Duval bodies are common ( resembe primitive glomeruli ). Hyaline globules are also common. Alpha fetoprotein in the serum and in tumor cells can be identified in all cases.

49. Yolk sac tumour

50. Teratoma Firm masses with cystic structures. Mature teratomas contain differentiated tissue from one or more germ cell layers. Immature teratomas contain immature somatic elements. Teratomas with malignant transformation contain malignancy arising in a teratomatous element ( SCC & adenocarcinoma ). Most frequently malignant Prepubertal pure teratoma are benign. Teratomas in adults are malignant and often contain other germ cell elements.

51. Teratoma of Testis

53. Choriocarcinoma Often small non palpable tumor with wide spread metastases. Aggressive malignant germ cell tumor Has the worst prognosis of germ cell tumor Pure forms are rare representing only 1% of GCT. Similar tumors may arise in placenta,ovary,mediastinum, or abdomen.

54. Choriocarcinoma Tumor contains cytotrophoblasts and syncytiotrophoblasts in a hemorrhagic background. hCG can be identified in tumor cells and in the serum.

55. Choriocarcinoma

56. CLINICAL COURSE OF TESTICULAR TUMORS USUALLY PRESENT WITH PAINLESS ENLARGEMENT OF TESTIS MAY PRESENT WITH METASTASES NONSEMINOMAS (MORE COMMON) LYMPH NODES, LIVER AND LUNGS SEMINOMAS USUALLY JUST REGIONAL LYMPH NODES TUMOR MARKERS (hCG AND AFP) TREATMENT SUCCESS DEPENDS ON HISTOLOGY AND STAGE SEMINOMAS VERY SENSITIVE TO BOTH RADIO- AND CHEMOTHERAPY

57. Testicular Stromal/sex Cord Tumors 5% of testicular tumors. Most are benign ; 10 % are invasive or malignant. Leydig cell tumors may produce testosterone leading to precocious puberty. In adults, they may cause feminization.( intracytoplasmic Reinke crystals) Sertoli cell tumors form tubular arrangements.No significant endocrine effects

58. Leydig cell tumor

59. DISEASES OF THE PROSTATE PROSTATITIS NODULAR HYPERPLASIA CANCER

60. Adult Prostate

61. Benign prostate gland

62. PROSTATITIS ACUTE BACTERIAL PROSTATITIS CHRONIC BACTERIAL PROSTATITIS CHRONIC ABACTERIAL PROSTATITIS

63. ACUTE BACTERIAL PROSTATITIS ETIOLOGY SAME ORGANISMS THAT CAUSE UTI E COLI, PROTEUS, OTHER GNR PATHOGENESIS ORGANISMS ASCEND FROM URETHRA AND URINARY BLADDER RARELY, HEMATOGENOUS SPREAD

64. MORPHOLOGY ACUTE INFLAMMATION, ESPECIALLY IN THE GLANDS, WITH MICROABSESSES CONGESTION, EDEMA CLINICAL COURSE DYSURIA, FREQUENCY, LOW BACK PAIN, PELVIC PAIN ENLARGED, EXQUISITELY TENDER +/- FEVER,CHILLS OR LEUKOCYTOSIS USUALLY RESOLVES WITH AB RX ACUTE BACTERIAL PROSTATITIS

65. CHRONIC PROSTATITIS ETIOLOGY MAY FOLLOW ACUTE PROSTATITIS MAY DEVELOP INSIDIOUSLY CULTURE POSITIVE (BACTERIAL) SAME ORGANISMS THAT CAUSE AP CULTURE NEGATIVE (ABACTERIAL) MAY BE RELATED TO CHLAMYDIA TRACHOMATIS UREAPLASMA UREALYTICUM TRICHOMONAS MOST COMMON FORM OF CP

66. MORPHOLOGY LYMPHOCYTIC INFILTRATE NEUTROPHILS AND MACROPHAGES SOME EVIDENCE OF TISSUE DESTRUCTION CLINICAL COURSE SIMILAR TO AP LESS ACUTE SYMPTOMS MORE RESISTANT TO AB RX CBP OFTEN ASSOCIATED WITH RECURRENT UTI CHRONIC PROSTATITIS

67. PROLIFERATIVE LESIONS OF THE PROSTATE URETHRA PERIURETHRAL AND TRANSITIONAL ZONES PERIPHERAL ZONE NORMAL PROSTATE NODULAR HYPERPLASIACARCINOMA

68. NODULAR HYPERPLASIA OTHER TERMS USED GLANDULAR AND STROMAL HYPERPLASIA BENIGN PROSTATIC HYPERTROPHY (HYPERPLASIA) EPIDEMIOLOGY OCCURS IN 20% OF MEN OVER 40 OCCURS IN 70% OF MEN OVER 60 OCCURS IN 90% OF MEN OVER 70

69. PROLIFERATION OF BOTH EPITHELIAL AND STROMAL ELEMENTS BOTH ANDROGENS AND ESTROGENS MAY PLAY A ROLE NOT SEEN IN MALES CASTRATED BEFORE PUBERTY INHIBITORS OF TESTOSTERONE METABOLISM USEFUL IN TREATMENT RELATIVE INCREASE IN ESTROGENS IN OLDER MEN MAY INCREASE DHT RECEPTORS IN PROSTATE PATHOGENESIS OF NODULAR HYPERPLASIA

70. Pathogenesis of prostatic hyperplasia

71. Nodular prostatic hyperplasia Periurethral nodules

72. CLINICAL COURSE OF NODULAR HYPERPLASIA SYMPTOMS OCCUR IN ONLY 10% OF MEN WITH NODULAR HYPERPLASIA( URETHRAL OBSTRUCTION & NARROWING ) HESITANCY URINARY RETENTION URGENCY, FREQUENCY, NOCTURIA, UTI TREATMENT MEDICAL SURGICAL COMMON CAUSE FOR ELEVATED PROSTATE SPECIFIC ANTIGEN (PSA)

73. Association of BPH and Prostate Carcinoma Both are related to advanced age and androgens. Both may respond to androgen deprivation. Carcinoma occurs 10-15 yr after BPH. 10% of BPH cases contain incidental carcinoma. BPH is not a premalignant condition and is not precursor of carcinoma.

74. CARCINOMA OF THE PROSTATE EPIDEMIOLOGY MOST COMMON VISCERAL CANCER IN MALE ABOUT 70/100,000 MEN IN US 200,000 NEW CASES/YR IN US 20% ARE LETHAL SECOND MOST COMMON CAUSE OF CANCER DEATH IN MEN PEAK INCIDENCE OF CLINICAL CANCER IS 65-75 YO

75. CARCINOMA OF THE PROSTATE PEAK INCIDENCE OF CLINICAL CANCER IS 65-75 YO IT IS DISEAE OF ELDERLY MEN 10% at 50 yr of age (autopsy studies ) 80% at 80 yr of age (autopsy studies ) 5 per 100,000 (45-49yr) 500 per 100,000 (70-75yr) LATENT CA IS EVEN MORE PREVALENT >50% IN MEN > 80 YO

76. PATHOGENESIS HORMONAL FACTORS DOES NOT OCCUR IN CASTRATED MEN ORCHIECTOMY AND/OR ESTROGEN TREATMENT INHIBITS GROWTH GENETIC FACTORS INCREASED RISK IN FIRST ORDER RELATIVES BLACKS > WHITES (SYMPTOMATIC CA) ENVIRONMENTAL FACTORS GEOGRAPHIC DIFFERENCES IN INCIDENCE OF CLINICAL CANCER (NOT OF LATENT CA) CHANGE IN INCIDENCE WITH MIGRATION CARCINOMA OF THE PROSTATE

77. Prostatic Carcinoma Clinical features: Often clinically silent. Urinary obstructive symptoms. 75% present in stages C and D. Diagnosis is made in one of the following instances: Routine surveillance in men over 40 yr. Incidental finding in TURP. Adenocarcinoma with unknown primary. Rarely, rectal or perirectal mass.

78. CLINICAL COURSE DIGITAL RECTAL EXAM (DRE) PROSTATE SPECIFIC ANTIGEN (PSA) > 4 ng/ml IN PERIPHERAL BLOOD FREE PSA < 25% TRANSRECTAL ULTRASOUND NEEDLE BIOPSY METASTASES OSTEOBLASTIC TREATMENT- SURGERY, RADIATION, HORMONES, CHEMO CARCINOMA OF THE PROSTATE

79. Prostate Specific Antigen (PSA) Specific for prostate tissue. Not cancer specific. Normal level < 4ng/ml. Elevated in Carcinoma BPH Prostatitis After bx. For screening: PSA should be used in combination with digital or ultrasound exam. PSA can be used for : Monitoring success of prostatectomy. Detecting early relapses Differential diagnosis of other malignancies. PSA velocity & density.

80. Prostatic Carcinoma Pathology Yellow-white hard multifocal foci with predilection for peripheral zones. Haphazard small irregularly shaped invasive glands with abortive lumens. Glands lack basal cell layer. Cells contain prominent nucleoli. Perineural invasion.

81. Prostatic Intraepithelial Neoplasia PIN

82. Adenocarcinoma of prostate

84. Metastatic osteoblastic prostatic carcinoma

87. Prostatic adenocarcinoma

88. Perineural invasion

89. Gleason Scoring Low grade carcinoma

90. Prostate adenocarcinoma