Male Genital system Dr.Mahmood Nazar M.B.Ch.B,MSc Path Big Robbins: 1034-1047, Little Robbins: 657-664

Hypospadias and Epispadias Malformation of the urethral groove and urethral canal on the ventral (hypospadias) or dorsal (epispadias) surface May be associated with other GU malformations May result in stricture and resulting ascending infection When the orifice is located towards the base of the penis, may cause sterility

Phimosis The orifice of the prepuce (foreskin) is too small to permit normal retraction May be congenital, but more commonly due to repeated infection and scarring

Paraphimosis When a phimotic prepuce (foreskin) is forcibly retracted over the glans penis, marked constriction and swelling may block replacement

Penis: Inflammation Infections Risk Syphilis Gonorrhea Chancroid Granuloma inguinale Herpes Risk Number of sexual partners Hygiene

penis Neoplasms in situ carcinoma - Bowen disease squamous call carcinoma ulcerative and hemorrhagic the prognosis related to the extent of tumor growth

Testis: Congenital Anomalies Cryptorchidism Risk of sterility and carcinoma development The majority of inguinal cryptorchid testes descend spontaneously during the first year of life (if not, surgically corrected) Undescended or “hidden” testicle One or both testes fail to descend through inguinal canal into the scrotal sac Inguinal hernias are commonly associated with this Most infants with cryptorchidism will have spontaneous descent of their testes during the first year of life; Surgical intervention after that

Testis: Congenital Anomalies Cryptorchidism Undecended testicle Unilateral 75% At about 2 years of age, a malpositioned testicle starts to undergo histologic changes Atrophy Fetal development: testes descend from the abdomen during 7th – 9th month gestation Failure to descend unknown abnormality of testis itself insufficient hormonal stimulation for the normal descent process

Testis: Regressive Changes Atrophy Regressive testicular change characterized by loss of spermatogenesis and gradual fibrosis, Leydig cells appear prominent Atherosclerosis Inflammatory orchitis Crytorchidism Hypopituitarism Malnutrition Irradiation Prolonged female sex hormone exposure (iatrogenic) High FSH levels

Testis and Epididymis: Inflammation Non-Specific Epididymitis and Orchitis Children Uncommon, but usually related to GU abnormality with secondary infection by Gram negative rods Sexually active men less than 35 Chlamydia Neisseria Men older than 35 Urinary tract pathogens such as E. coli and Pseudomonas The chlamydia & Neisseria point is common on boards.

Testis and Epididymis: Inflammation Granulomatous (Autoimmune) Orchitis Rare cause of testicular enlargement in middle-aged men Characterized by granulomas confined within the seminiferous tubules An autoimmune etiology is suspected

Testis and Epididymis: Inflammation Granulomatous (Autoimmune) Orchitis “Wouldn’t expect you to recognize this, but each of these was a tubule.”

Testis and Epididymis: Inflammation Specific Inflammations Gonorrhea Mumps Tuberculosis Syphilis

Testis and Epididymis: Inflammation Gonorrhea Late course of a neglected infection Extension from urethra, prostate, seminal vesicle, to epididymis Frank abscess Can progress to involve the testicle

Testis and Epididymis: Inflammation Mumps Systemic viral disease of school aged children When it affects post-pubertal males, 20-30% develop acute interstitial orchitis 1 week after the onset of parotid swelling In school aged children this doesn’t really give testicular problems, but with older ages, there can be severe swelling.

Testis and Epididymis: Inflammation Tuberculosis Almost invariably begins in the epididymis, but may spread to the testis Usually secondary spread from prostate and seminal vesicles Caseating granulomas Central necrosis with histiocytes.

Epididymal Tuberculosis Caseating granuloma - Central necrosis with histiocytes. Different from autoimmune (within seminiferous tubules – sheets of cells without central necrosis).

Testis and Epididymis: Inflammation Syphilis Almost invariably, the testis is involved before the epididymis Lymphocytes and plasma cells Obliterative endarteritis Unique b/c testis is involved first – typical pimp question.

Syphilis Lymphocytes & plasma cells actually damaging vessel wall – wouldn’t have to ID, but vessel damage is characteristic.

BRUCELLOSIS Complications: osteoarticular complications (up to 60% of cases) genitourinary (up to 20% of cases): most commonly orchitis and epididymitis

Testis: Vascular Disturbance Twist of blood supply.

Testis: Vascular Disturbance Torsion Twisting of the spermatic cord, obstructing venous drainage and arterial supply Medical emergency Manually untwist within 6 hours After 6 hours, testicle dies Neonatal and adult forms Adult form due to anatomic defect allowing increased mobility After 6 hours, testicle dies. Neonatal form is more due to “bad luck”; adult form is usually b/c of anatomic defect.

Intrascrotal Cysts Tunica Vaginalis Epididymis Veins Testis Hydrocele Hematocele Chyloclele Epididymis Spermatocele Veins Varicocele Testis Can basically be from 3 sources. Tunica vaginalis creates a potential space.

Markedly dilated tubule on right – can see all the sperm on left. Spermatocele Markedly dilated tubule on right – can see all the sperm on left. Not a lot of non-neoplastic to talk about b/c prostate has its own lecture. Markedly dilated tubule on right – can see all the sperm on left.

Testicular Tumours Most common malignancy in men 20-34 yrs old Few symptoms (self-exam) 1st sign painless testicle mass or harder consistency of testes Pain or increase in size usually due to bleeding

WHO classification of testicular tumours A. Germ cell tumours B. Sex cord / gonadal stromal Seminoma 1. Leydig cell tumour Spermatocytic seminoma 2. Sertoli cell tumour Teratoma differntiated 3. Granulosa cell tumour Embryonal carcinoma 4. Tumours of thecoma / fibroma group Yolk sac tumour 5. Mixed tumours Choriocarcinoma C. Miscellaneous - lymphoma, metastases, rete tumours, paratesticular tumours, mesenchymal (sarcomatous) tumours

seminoma Most common type of germ cell tumors(30%) Never occur in infants, peak in fourth decade. Grossly solid, homogenous and grey-white. Microscopically large and round cells, with large clear cytoplasm, multiple nucleoli & stromal lymphocytic infiltration. Spermatocytic variant: well differentiated, old age groups and slow growing.

classic seminoma - Gross, cut surface The specimen has been bisected classic seminoma - Gross, cut surface  The specimen has been bisected. Note the bulging, nodular, tan tumor replacing most of the gonad. The tumor has a fairly uniform appearance and lacks cysts, necrosis, or obvious hemorrhage.

sheets of uniform polygonal cells with clear cytoplasm, round nuclei, and prominent nucleoli. Typically, the cells are divided into ill-defined nodules by fibrous trabeculae containing lymphocytes.

The clear cytoplasm, round nucleus, and prominent nucleoli of the seminoma cells are best seen at high power. Note the fibrous trabeculae infiltrated with lymphocytes

Teratoma Various cellular and organoid components reminiscent of normal derivatives from more than one germ cell layer. Any age from infancy to adult life. Combined with other tumors. Mature, immature and teratoma with malignant transformation.

Embryonal carcinoma In 20-30 years mostly, more aggressive. Cells grow in glandular, alveolar, or tubular patterns. Yolk sac tumor Occur in infants and children. With good prognosis. Cuboidal cells in papillary structures with solid cords. Choriocarcinoma Highly malignant, with hemorrhage, necrosis, and malignant syncytiotrophoblasts.

embryonal carcinoma - Low power  Compared with classic seminoma, embryonal carcinoma is composed of more pleomorphic cells, which often are arranged into trabeculae or gland-like formations.

embryonal carcinoma with syncytiotrophoblasts

Staging Stage I: tumor confined to testis. Stage II: distant spread confined to retroperitoneal lymph nodes below diaphragm. Stage III: metastasis outside the retroperitoneal nodes or above the diaphragm.

Diagnostic importance of biologic markers HCG, AFP, placental alkaline phosphatase, placental lactogen and lactic acid dehydrogenase. 80 % of NSGCT show elevated levels. Value in: 1- evaluation of testicular masses. 2- staging of testicular GCT (elevated levels after orchiectomy indicates stage II). 3- monitoring the response to therapy.

Tumors of sex cord gonadal stroma Leydig cell tumor: occur at any age, secretes androgens, microscopically large cells with eosinophilic cytoplasm and rounded nuclei. Sertoli cell tumors: formed of granulosa cells also secrets hormones. Testicular lymphoma: 5% of T tumor, but it is the most common from of testicular caner in men over age of 60.

Acute bacterial prostatitis Diffuse suppuration. Gram negative bacilli from intraprostatic reflux of urine, follow surgical manipulation, catheterization, cystoscopy, urethral dilatation, or prostatic resection. PR tender and boggy.

Chronic bacterial prostatitis Difficult to diagnose, low back pain, dysuria, and perineal and suprapubic pain. History of recurrent UTI. Diagnosis by presence of WBC in prostatic secretions and isolation of micro.o. by culture. Caused mostly by chlamydia.

Nodular hyperplasia (Benign prostatic hyperplasia) Large nodule in periurethral prostatic tissue (middle and lateral lobes) (urine drainage obstruction) common after age of 50. Unknown cause, but doubt about effects of androgens. High levels of dihydrotestosterone in it (from testosterone by effect of alpha reductase) Microscopy show hyperplastic changes.

well circumscribed, white-tan, rubbery hyperplastic nodules on either side of the compressed urethra

nodule composed of crowded, hyperplastic glands nodule composed of crowded, hyperplastic glands. Note the well-circumscribed margin of the process in the upper right hand corner. Also note the two-cell-layer epithelium characteristic of benign prostatic glands.

Prostatic carcinoma Affect posterior lobe and peripheral tissues palpable by rectal examination. Direct invasion to seminal vesicle and the base of the urinary bladder. Blood stream to bones, particularly the axial skeleton, osteolytic or osteoblastic (lumbar spine, proximal femur, pelvis, thoracic spine, and ribs). Visceral dissemination. Lymphatic spread to obturator nodes followed by perivesical, hypogastric, iliac, presacral, and paraaortic.

histology Adenocarcinoma (single layer of cuboidal cells or low columnar). Occasionally glands larger with cribriform or irregular sheets of cells, and sometimes poorly differentiated. Perineurial invasion. Prostatic intraepithelial neoplasia.

Prostate gland, adenocarcinoma - Gross, cut surface  This is a cross section of a formalin-fixed prostate gland containing both adenocarcinoma and hyperplasia. Note the contrast in location between the two.

Prostatic adenocarcinoma can display several architectural arrangements, including back-to-back small neoplastic glands and coalesced, or fused, glands forming cribriform patterns

Malignant prostatic glands are lined by a single layer of cells that typically display large nucleoli (as opposed to a two-cell layer without large nucleoli in benign glands)

Grading and Staging Gleason grading system: based on degree of glandular differentiation and growth pattern of tumor in relation to the stroma. Prognostic importance. Staging according to microscopic, macroscopic mass or extra-capsular invasion or pelvic or distant metastasis.

Clinical features Can be asymptomatic in microscopic lesions. In stage B nodule on rectal examination. 75% of cases present in stage C and D with urinary symptoms and pain due to perineurial invasion or back pain due to bone metastasis. Dx by trans-rectal US, biopsy, CT scan, MRI. Biochemical markers: prostate specific antigen (PSA) elevations may indicate the presence of prostate disease, more specific PSA density. Serum acid phosphatase elevated in metastatic disease.

spine shows multiple firm white nodules representing metastatic prostate cancer. Bony metastases of prostatic adenocarcinomas are typically (but not always) osteoblastic.