ࡱ> PRO7 q7bjbjUU "X7|7|q3lRRRRRRRfdf2giiiiii$ :"RRRRRgg*/RR{x r'fG{0O,""{ffRRRRLower Urinary and Male Genital Tract Lower Urinary Vesico-ureteral reflux: incompetent valve w/ regurgitation of urine into the distal ureter during micturition (bladder pressure () Etiology congenitally short intra-vesical portion of ureter (changes angle) or acquired abnml patence of valve due to bladder enlargement either from atony or outlet obstruction Outcome infxn, hydronephrosis ( CRF (reflux nephropathy) Cystitis (cysto-urethritis): acute and/ir chonic inflamm. of the urinary bladder due to infxn or injury Clinical features Triad = ( freq, lower abd. pain, dysuria (hematuria, urgency) Infectious cystitis common in young females, elderly males, those w/ UT abnormalites (ex: stones), diabetics; organisms coliforms and TB, candida, shistosoma, adenovirus, chlamydia, mycoplasma Non-infectious direct toxic mucosal damage or ischemia; ex: cytotoxic chemo(cyclophosph.), radiation, can be idiopathic Pathology inflamm. w/ edema, hyperemia, hem. poss.; inflamm. cells center on mucosa w/in the lamina propria; if chronic there is fibrosis (w/ plasma cells); fungal and TB = granulomatous; Hemorrhagic cystitis w/ sloughing of mucosa is seen w/ severe acute bact. infection, chemo., and adenovirus Complications pyelonephritis, VUR, stones, CRF, fistula formation Calculi (stones): common malady (1/2 mill. in US/yr); also known as nephrolithiasis Etiology stasis, infxn (urea-splitters = proteus), foreign body, metabolic disease (hyperuricemia, hypercalcemia) Complications stones may lodge at sites of narrowing such as urethral-vesical jxn, etc. and cause obstruction; this may in turn lead to infxn, hydronephrosis, CRF, and more stones Urothelial Carcinoma: arises in urothelial (transitional) epithelial lining of the bladder Incidence increasing but mortality decreasing; M>F; age = 50-80 yo Risk Factors smoking; industrial expos. to arylamine & analine dyes; long term analgesic use (phenacetin); cytotoxic chemo.; shistosoma haematobium infxn = endemic in Nile river area, assoc. w/ squamous cell CA Location bladder > renal pelvis > ureter > urethra Histologic types all urothelial in origin w/ transitional cell predominating (may be mixed); squamous possible: assoc. w/ chronic irritation (catheter, etc. ); adeno. possible: assoc. w/ glandular metaplasia and urachal remnants Transitional (95%) > Squamous (4%) > Adeno (1%) Pathology G: can be papillary, nodular, sessile, or mixed; papillary less aggressive than sessile Histopathologic findings look at pg. 5 Grading and Staging the same pg.; for staging invasion of the muscularis propria is a critical indicator of prognosis w/ a fall in survival by 50% - indicates cystectomy for tx Presentation painless hematuria Therapy low stage (CIS and T1) can be treated w/ chemo or immunotherapy; higher stage = surgery; radiation is of limited effectiveness; metastasis in to LN first then pelvis, lungs, liver Clinical challenge is early diagnosis and therapy Male GU Prostatitis: acute or chronic inflamm. of the prostate (composed of tubulo-alveolar glands and ducts surrounded by fibromuscular stroma; this is divided into 4 main zones of stroma: anterior, central , transitional, and peripheral); ususally seen in mid-aged males Bacterial Acute: diffuse suppurative inflamm. due to pyogenic bacteria; prediposed by reflux of infected urine, instrumentation, hematogenous spread; presents w/ fever, chills, dysuria Chronic: indolent infxn; fairly common; pediposed by incomplete recovery from acute infxn (prostate poorly penetrated by abos; presents w/ recurrent UTI w/ same organism, dysuria, perineal/low back pain Chronic non-bacterial etiology unknown (chlamydia/ mycoplasma?); indistiguishable from above except no UTI and cultures are negative Diagnosis differentiation is based on quantitative bacterial cultures and microscopic exam of secretions; pyuria, leukocyte count, and culture all factor in Pathology Acute = necrotizing inflamm. w/ neutrophils, may have microabscesses, in glands and ducts Chronic = lympho-plasmacytic infiltrate in stroma w/ macros (aging also causes some Lyc in stroma) Granulomatous = uncommon; induration of the prostate simulating cancer; usually non-infectious  Nodular Hyperplasia (BPH): multinodular proliferation of both stroma and glands in the mid-prostate (transitional zone); can cause obstructive UT disease; no malignant potential Incidence elderly men; 25% by age 50, 50% by 70; Blacks > Whites Etiology mediated by DHT (converted from T by 5(-reductase in stroma); DHT stims. growth thru nuclear growth factors; estradiol may increase its effects Pathology histological evidence more common than symptoms Gross: nodular appearance in transitional and periurethral zones; predominantly glandular prolif. = soft and yellow-pink w/ milky exudate; stromal nodules appear later and are more firm Micro: stroma-rich nodules have hypo-cellular concentric fibromuscular tissue; epithelial nodules have dilation, infolding; they lack prominent nucleoli and have the usual double layered lining (inner secretory and outer basal cell) Clinical features symptoms are due to compression of the urethra = difficulty voiding, hesitance, nocturia, frequency Complications bladder distention, retained urine leading to infxn, overflow incontinence, VUR, hydronephrosis (late) Therapy 5(-reductase inhibitors and surgery Prostatic Adenocarcinoma: most common cancer in males and the second most common cause of cancer death in males; 90% of cases are low stage/grade at dx and have a good px Incidence 99% diagnosed over 50yo and 70% over 70yo; Blacks > Whites and Americans > Asians Etiology exact etiology is unknown; Risk factors = age, race, FamHx, hormonal (androgens are permissive), and diet ((fat) Clinical features 90% are assymp. at diagnosis; obstructive urinary symps. are late if at all; distant mets such as vertebral may show up as back pain and are more common if less that 60 yo Diagnosis detection is based on a multi-modal approach w/ biopsy being performed for abnormality identified on DRA, Trans-rectal US, or PSA in serum; diagnosis is confirmed by microscopic examination of the specimen PSA this is an organ specific (not cancer specific) protease; production is normal and it can be elevated in non-neoplastic conditions such as BPH, infxn, etc.; some organ-confined prostate CA has a normal PSA level; Percent free PSA is used when serum PSA is questionable Pathology the adenocarcinoma arises from the glandular epith. (secretory); - Location: Peripheral >> Central > Transitional ; multifocality is common - Gross: yellow, rubbery, indurated nodules (if present) - Micro: well formed glands lacking the basal layer and with prominent nucleoli; peripheral invasion is frequent; - Prostatic Intra-epithelial Neoplasia (PIN): precursor lesion to prostatic CA; characterized by intra-glandular malignant secretory cells w/ intact basal layer; ( risk if found on biopsy - Grading (adeno): Gleason system is used and is based on architecture; this is particularly important in these tumors since there is good correlation between prognosis and degree of differentiation; based on a low power exam of the tumor, two #s are assigned to the two most predominant patterns when are then summed for a total score; the first number indicates the most predominate pattern so that a 4+3=7 is actually worse than a 3+4=7; the higher the sum total, the worse the grade of the tumor Staging this is important to select therapy and help determine prognosis Therapy ablative for localized disease w/ radiotherapy or excision for organ confined disease; endocrinologic (LH-RH agonists, orchietomy) for advanced/metastatic disease (bone lesions are osteoblastic) Testis and Epididymis: non-neoplastic pathology Development testes are derived from the urogenital ridge and descend early in 3rd trimester Cryptorchidism undescended testicles; found in 1% of 1yo males; predisposes to infertility and testicular tumors Testicular atrophy regressive change; numerous etiological factors; bilaterallity leads to sterility Inflammation of Epididymis and/or testis more common in the epididymis; usually secondary to UTI or STD (gon. or chlam.); Gon. and TB tend to involve the epid. first whereas syph. likes the balls; predisposing factors include congenital defects, obstruction, and promiscuity Pathology: of bacterial infxn acute interstitial inflamm. of epid. 1st w/ secondary involvement of the testis; with chronic infection there can be scarring and infertility Vascular disturbances Torsion = twisting of the spermatic cord; prediposed by trauma; vascular engorgement may occur Testicular Tumors: including tumors of germ cell origin (95%), sex-cord stromal differentiation tumors, or adventitial tumors; incidence of GCTs is mostly in 15-34 yo men; Whites > Blacks (5:1) Clinical features presents w/ either no symps., painless enlargement of testis, or swelling w/ diffuse testicular pain; any testicular mass is presumed neoplastic until proven otherwise Classification usually catagorized as either GCTs or non-GCTs; GCTs are then subdivided based on propensity for diff. Histogenesis most GCTs are thought to arise from tubular germ cells (ITGCN) exhibiting differentiation along the gonadal lines (seminoma), or embryonic lines (embryonal carcinoma) ( these may be further subdivided into along placental lines (choriocarcinoma), allantoic lines (yolk sac tumor), or somatic lines (teratoma); Note if ITGCN is found on biopsy = 90% chance of becoming invasive in 7 yrs Pathology and Correlates tumors are designated as either pure or mixed GCTs, w/ a listing of components a %s Types: Seminoma primitive germ cells w/ stromal Lyc; most common pure GCT; older pts (30 yo); Best prognosis; may see HCG Spermatocytic seminoma oldest pts (65 yo); benign unless rarely assoc. w/ sarcoma Choriocarcinoma prolif. of primitive placental cells w/ hemorrhage/necrosis; most aggressive GCT; rarely pure; (( HCG Embryonal Carcinoma anaplastic cohesive nest of cells, some w/ abortive gland formation; freq. component of mixed Yolk Sac Tumor (endodermal sinus tumor) cohesive tumor often w/ a lace-like micro pattern; pure yst is m/c testicular tumor in infants up to 3yo (good prognosis); in adults the pure form is rare; ( AFP seen Teratoma heterogeneous bulky tumor w/ cystic and sclerotic foci; has components of all 3 germ layers; pure versions are common and mostly benign in children but rare and malignant behaving in adults - Staging as usual Tumor markers used to help evaluate testicular masses, for staging, assessment of tumor burden (LDH), and response to Tx; AFP, HCG, LDH not always specific for any particular tumor Clinical outcome overall cure rate = 90%; radiation and chemo used; Px is better for pure seminoma than for a non- seminomatous (mixed) GCT Lesions of the Tunica Vaginalis and Spermatic Cord Hydrocele accumulation of clear or serous fluid w/in the tunica vaginalis; etiology = infxn, tumor, unknown Hematocele blood w/in the tunica vaginalis; etiology = direct trauma, torsion, or bleeding d/o Varicocele dilated veins w/in the spermatic cord Spermatocele cystic accumulation of semen w/in the spermatic cord Penile Disease Congenital anomalies - Hypospadias and Epispadias malformation of the urethral groove leading to abnormal opening of the urethra on either the ventral or dorsal side respectively; may result in urination, ejaculation, etc. problems - Phimosis the prepucial orifice is too small to allow for normal retraction; can lead to infxn, constriction, CA, etc. Infections most problems w/ the penis have an infectios etiology (ex: balanoposthitis = inflamm. of the shaft and foreskin); specific infections include HSV, syph, gon, lymphogranuloma venereum,etc. Tumors - Condyloma accuminatum benign growth assoc. w/ HPV; usually squamous w/ hyperkeratosis; cells show perinuclear vacuolization (koilocytotic changes) and raisinoid nuclei - Penile Carcinoma - CIS: squamous malignancy confined to epith. (includes Bowens, Erythroplasia of Queyrat, and Bowenoid papulosis); Bowens and Eryth. can progress to invasive CA; assoc. w/ HPV - Invasive Squamous CA: 40-70 yo; related to poor hygiene, lack of circumcision, HPV, smoking; slow progression w/ local mets to inguinal nodes; complications of bleeding and infxn are freq. 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