Diseases of the Penis Congenital Anomalies EPISPADIAS: Dorsal surface opening HYPOSPADIAS: Ventral surface opening MISCELLANEOUS PHIMOSIS: Small prepuce orifice secondary to repeated infections INFLAMMATIONS: Balanoposthitis, infection of glans and prepuce with smegma. Organisms: candida, anaerobes, pyogenic

CARCINOMA IN SITU: 3 types Tumors of the Penis BENIGN: 1. CONDYLOMA ACCUMINATUM: Human papilloma virus (HPV) Sexual transmission HPV types 6 - 11 associated with carcinoma CARCINOMA IN SITU: 3 types A. BOWEN DISEASE: Limited by basement membrane; mainly in shaft B. ERYTHROPLASIA OF QUEYRAT: Similar to Bowen’s but in glans-prepuce C. BOWENOID PAPULOSIS: Sexually active; pigmented lesions

Tumors of the Penis Malignant SQUAMOUS CELL CARCINOMA HPV INFECTION: type 16 most common, also 18 40 - 70 years of age More common in uncircumcised populations Glans - inner surfer of prepuce Papillary or flat VERRUCOUS CARCINOMA: Giant condyloma (BUSCHKE-LOWENSTEIN TUMOR) Also HPV related types 6, 11 Invasive carcinoma metastasizes to inguinal-iliac LN 66% 5-year survival, if LN involved 27% 5-year survival

SQUAMOUS CELL CARCINOMA

Testis Epididymis Congenital anomalies CRYPTORCHIDISM: Undescended testis Descent in 2 phases: a. Transabdominal, to lower abdomen b. Inguino-scrotal, to scrotum (MOST COMMON DEFECT) Asymptomatic - bilateral 25% Testicular atrophy; prominent Leydig cells Complications: Sterility - cancer

CRYPTORCHID

Diseases of Testis Inflammation TB, GONORRHEA: Epididymis, spreads to testis SYPHILIS: Testis involved first CHLAMYDIA: Epididymitis in sexually active E. COLI PSEUDOMONAS: Epididymitis in older than 35; may cause abscess, sterility MUMPS: Orchitis VASCULAR DISTURBANCES: Torsion due to trauma, incomplete descent, may cause hemorrhage-infarction

GONORRHEA

A. GERM CELL TUMORS B. NONGERMINAL CELL TUMORS (STROMA - SEX CORD) Testicular Tumors A. GERM CELL TUMORS B. NONGERMINAL CELL TUMORS (STROMA - SEX CORD)

Germ Cell Tumors spermatocytic malignant (EMBRYONAL, CHORIOCARCINOMA) A. SEMINOMA: Typical, anaplastic, spermatocytic B. EMBRYONAL CARCINOMA C. YOLK SAC TUMOR D. POLYEMBRYOMA E. CHORIOCARCINOMA F. TERATOMA: Mature, immature, malignant G. MIXED: Teratocarcinoma (EMBRYONAL, CHORIOCARCINOMA)

Testicular Tumors Morphology A. SEMINOMAS 1. TYPICAL: Grossly white-gray homogeneous. Microscopic: large, polyhedral cells with large central nucleus, nucleoli, by IP positive for Placenta like alkaline phosphatase (PLAP) ; lymphocytic reaction, granulomas 2. ANAPLASTIC: Large, irregular cells, frequent mitoses 3. SPERMATOCYTIC: Medium and large cells, giant cells

SEMINOMA

Testicular Tumors Children up to 3 years B. EMBRYONAL CARCINOMA: Hemorrhage - necrosis. Cells are large, hyperchromatic nuclei, nucleoli, arranged in glandular, alveolar or tubular patterns, with papillary convolutions. 20 - 30 years C. YOLK SAC TUMORS (INFANTILE EMBRYONAL OR ENDODERMAL SINUS TUMOR): Children up to 3 years Cuboidal or elongated cells, with papillary formation Endodermal sinus (50%): resemble primitive glomeruli, mesodermal core, central capillary lined by visceral and parietal layers Eosinophilic globules with alpha-fetoprotein

EMBRYONAL CARCINOMA

YOLK SAC TUMORS

Testicular Tumors Aggressive, small tumors, metastasize widely D. CHORIOCARCINOMA Aggressive, small tumors, metastasize widely Hemorrhage - necrosis common Syncytiotrophoblastic - Cytotrophoblastic components; positive for HCG

CHORIOCARCINOMA

Three histologic variants Testicular Tumors E. TERATOMAS Common in child, rare in adults Gross: large (SOLID, CARTILAGINOUS, CYSTIC) Three histologic variants 1. MATURE: nerve, muscle, cartilage, thyroid, bronchial, intestinal, brain in myxoid or fibrous stroma. All well differentiated. 2. IMMATURE: poorly differentiated tissues, but identifiable. Glands, neuroblasts, cartilage 3. MALIGNANT TRANSFORMATION: squamous or adenocarcinoma, sarcoma

Testicular Tumors Mixed 60% e.g. teratomas - embryonal teratoma - yolk sac seminoma - embryonal or teratoma

Mixed: Embryonal and Choriocarcinoma Teratocarcinoma Mixed: Embryonal and Choriocarcinoma HCG

Testicular Tumors Clinical Features CLINICALLY: Classified as seminomatous or nonseminomatous Painless masses LYMPHATIC SPREAD TO LYMPH NODES: Retroperitoneal, paraaortic, mediastinal, supraclavicular HEMATOGENOUS SPREAD: Lung, liver, bones, brain

Testicular Tumors Staging STAGE 1: Confined to testis, epididymis, spermatic cord STAGE II: Retroperitoneal lymph nodes, below the diaphragm STAGE III: Metastases into lymph nodes above the diaphragm STAGE IV: Metastases into other organs: or lung, liver, brain, bones

Testicular Tumors Biologic Markers 1. HUMAN CHORIONIC GONADOTROPHINS (HCG) choriocarcinomas 2. ALPHAFETOPROTEIN (AFP) yolk sac tumors 3. PLACENTA-LIKE ALKALINE PHOSPHATASE (PLAP) seminomas Others include placental lactogen, LDH Helpful in diagnosis, staging, monitoring testicular tumors

Testicular Tumors Sex Cord – Gonadal Stromal Tumors SEX CORD (SERTOLI) Estrogen or androgen producers Gynecomastia, precocious masculinization MORPHOLOGY: gray, white or yellow nodules Entirely Sertoli type or partly granulosa cells Cordlike structures, resembling seminiferous tubules Benign tumors; 10% malignant

SERTOLI TUMOR

Gonadal Stromal Tumors Leydig Cell Tumors May produce androgens, estrogens, corticosteroids Gynecomastia – sexual precocity in children Golden brown, homogeneous nodules Cells are large, round or polygonal Eosinophilic cytoplasm, central, round nucleus Reinke crystalloids in 25% of tumors Benign; 10% invasive

Leydig Cell Tumor

Tunica Vaginalis Hydrocele (FLUID ACCUMULATION) Hematocele (TRAUMA) Chylocele (ELEPHANTIASIS) Spermatocele Varicocele

Prostate Posterior, middle, anterior, 2 laterals EMBRYO: 5 lobes Posterior, middle, anterior, 2 laterals ADULT: 4 lobes Peripheral, central, transitional, periurethral GLANDS: 2 cell layers: basal, columnar

Prostate Inflammation ACUTE BACTERIAL: Gram negative rods, staphylococci CHRONIC BACTERIAL: Same organisms CHRONIC ABACTERIAL: Most common type Sexual activity (CHLAMYDIA, MYCOPLASMA) MORPHOLOGY: Necrosis, later fibrosis, chronic with lymphocytes, neutrophils, lymphs, macrophages

Prostate Inflammation ACUTE

Prostate Glandular - stromal Androgens stimulate growth (DHT) HYPERPLASIA: Glandular - stromal INCIDENCE: 20% over age 40, 70% by age 60, 90% by age 70 ENLARGEMENT: Androgens stimulate growth (DHT) DHT synthesized in prostatic stromal cells DHT inhibitors cause decrease in volume MORPHOLOGY: Cellular nodules in transitional zone; later stromal periurethral nodules; compress urethra and prostate, creating cleavage (NOT CAPSULE). Nodules with squamous metaplasia or infarction.

HYPERPLASIA: Glandular - stromal

Carcinoma of Prostate Most common tumor in males 300,000 new cases / year – 69/100,000 20% 50 – 60 years 70% 70 – 80 years Highest rates in blacks

Carcinoma of Prostate

Carcinoma of Prostate Unknown Age – environmental Role of androgens ETIOLOGY: Unknown RISK FACTORS: Age – environmental Role of androgens Genetics Molecular

Carcinoma of Prostate 70% arise in peripheral zone, posterior aspect Detectable by rectal examination May invade seminal vesicles, base of bladder HEMATOGENOUS METASTASES TO BONES: Lumbar spine, femur, pelvis, ribs (OSTEOBLASTIC) LYMPHATIC SPREAD TO LYMPH NODES: Obturator, perivesical, hypogastric, iliac, paraaortic

Carcinoma of Prostate Morphology MICROSCOPIC: Well-defined small glands Uniform layer cuboidal or low columnar cells Occasionally larger with papillary or cribriform pattern Nuclei large, vacuolated, 1 – 2 nucleoli Mitoses uncommon GROWTH PATTERN: Rounded masses, back to back pattern UNDIFFERENTIATED: Cords, nests, sheets Tendency to invade capsule, lymphatic – vascular channel and nerves PREMALIGNANT LESION: PIN (PROSTATIC INTRAEPITHELIAL NEOPLASIA) DIFFERENCE: Presence of basal layer

Carcinoma of Prostate Clinical Features 70% incidence in men over 80 years, Stage A VISUAL COURSE: Non-progressive Stage A2 progresses (30 – 50%) Over 60% present with local disease Urinary symptoms are late DIAGNOSTIC APPROACH: Rectal exam, serum PSA, biopsy

Carcinoma of Prostate Grading (Gleason System) GRADE 1: Closely packed single or separate uniform glands GRADE 2: Same as 1 with less uniformity, limited infiltration GRADE 3: Separate, irregular glands, cribriform pattern GRADE 4: Fused glands and cords, cribriform pattern GRADE 5: Sheets or cords; few or no glands

GRADE 1: Closely packed single or separate uniform glands

GRADE 3: Separate, irregular glands, cribriform pattern

GRADE 5: Sheets or cords; few or no glands

Carcinoma of Prostate Prostate Specific Antigen (PSA) Serine protease produced by prostatic epithelium SERUM LEVEL: 4 ng/ml upper limit “Organ specific”, not “cancer specific” Elevated in BPH, prostatitis cancer BPH: 30% have elevated PSA CARCINOMA: 80% have elevated PSA, 20 – 40% have less than 4 ng/ml

Prostatic Specific Antigen (PSA) TWO FORMS: a) Free b) Bound to alpha 1 antichymotrypsin Free PSA is lower in cancer than in BPH Specially important in values 4 – 10 ng/ml

Carcinoma of Prostate Treatment SURGERY: Localized disease (Stages A – B) RADIATION: HORMONAL TREATMENT: Metastatic disease (Stages C – D) (ESTROGEN THERAPY – ORCHIECTOMY)