Diseases of the Penis Congenital Anomalies

EPISPADIAS: Dorsal surface opening

HYPOSPADIAS: Ventral surface opening

MISCELLANEOUSPHIMOSIS: Small prepuce orifice secondary to repeated infections

INFLAMMATIONS: Balanoposthitis, infection of glans and prepuce with smegma.

Organisms: candida, anaerobes, pyogenic

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 CARCINOMAHPV 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 Leydigcells

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

Testicular Tumors

A. GERM CELL TUMORS

B. NONGERMINAL CELL TUMORS (STROMA - SEX CORD)

Germ Cell Tumors

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

A. SEMINOMAS

Morphology1. 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

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

D. CHORIOCARCINOMA Aggressive, small tumors, metastasize widely

Hemorrhage - necrosis common

Syncytiotrophoblastic - Cytotrophoblastic components; positive for HCG

CHORIOCARCINOMA

Testicular TumorsE. 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

TeratocarcinomaMixed: 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 thediaphragm

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, monitoringtesticular 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 seminiferoustubules

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

EMBRYO: 5 lobes Posterior, middle, anterior, 2 laterals

ADULT: 4 lobes

Peripheral, central, transitional, periurethral

GLANDS: 2 cell layers: basal, columnar

ProstateInflammation

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

InflammationACUTE

ProstateHYPERPLASIA: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

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 ProstateClinical 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 ProstateProstate 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 ProstateTreatment

SURGERY:Localized disease (Stages A – B)

RADIATION:Localized disease (Stages A – B)

HORMONAL TREATMENT:Metastatic disease (Stages C – D)(ESTROGEN THERAPY – ORCHIECTOMY)