Urinary tract diseases Male genital system V. Žampachová I. ÚP Congenital anomalies •Extrophy of the bladder – non-closure of anterior wall (bladder +/- abdominal, symphysis pubis; infections incl. pyelonephritis; ↑ risk of ca •Congenital stenosis – ureteropelvic junction, double/bifid ureter → hydronephrosis •vesicoureteral / ureteropelvic reflux Urinary tract obstruction •increased susceptibility to urolithiasis •increased susceptibility to infection •risk of hydronephrosis • •Combination of inborn + acquired risk factors • Vesico-ureteric reflux •Incompetence of the vesico-ureteral valve •Combination of congenital defect (short intravesical part of ureter, 1-2% of children) •↓ ureteral contractility in infection •acquired in bladder atonia (spinal cord injury) Vesico-ureteric reflux • refluxrtg reflux cystoureterogram Vesicoureteric junction Intrarenal reflux •Upper and/or lower renal papillae •Progression of infection into the kidney tissue • •No reflux – usually no ascending infection Obstruction causes •Intrinsic – luminal obstruction (stone, blood clot, necrotic papilla, tumor or its part) •Wall stenosis or dysfunction (inborn, inflammation, postinflammatory, tumor, …) •Extrinsic – external compression, some causes common for both sexes, some different Obstruction causes •In males: prostatic hyperplasia, prostatic ca, urethral stenosis, phimosis + complications •In females: pregnancy, cervical ca (+ therapy), uterine myoma, ovarian tumor, uterine prolapse •in both: chronic inflammation/fibrosis (retroperitoneal fibrosis), tumor (colorectal ca, LN,...), aortic aneurysm Massive hematuria from renal calculi, tumors, or papillary necrosis Urinary calculi •Usually of renal origin •Stones > 5 mm cannot pass into ureter •Renal colic – pain + spasms during the passage of a stone along the ureter •Chronic dull pain lumbal – lower pelvic region •↑ risk of obstruction •Repeated infection •Epithelial transformation: squamous metaplasia Urinary calculi •Calcium containing stones: commonest, laid down in an acid urine. •Complex triple phosphate stones: often associated with urinary infection, in an alkaline urine. •Mixture of uric acid and urate-uric acid stones, 20% of patients with gout, in an acid urine. Pure uric acid stones radiolucent. •Cystine stones: in primary cystinuria, important in childhood. Nephrolithiasis Image014 Pyelolithiasis in situ Image041 Urocystolithiasis Urate nephropathy •Hyperuricemic disorders (urate crystals formation) may lead to 3 forms of injury: •Acute urate nephropathy in patients with haematologic malignancies, commonly during chemotherapy (extensive cell breakdown – release of nucleic acids – urate crystals in tubules – acute renal failure •Chronic urate nephropathy – in gout. Urate crystals surrounded by foreign body giant cells, tubulo-interstitial nephritis •Urate stones Urate crystals Urate crystals - polarization Acute pyelonephritis •Common purulent renal inflammation, bacterial infection by Escherichia coli, Proteus, Klebsiella, Enterobakter •Ascending infection by urine reflux in urinary tract inflammation •Descending (haematogenous) infection in septicaemia, rare Acute pyelonephritis schemapyelonefritidy Acute pyelonephritis •Facilitated by DM, gout, all causes of obstructive uropathy (e.g. nephrolithiasis, tumors, urinary tract anomalies incl. vesicoureteric and intrarenal reflux) •Instrumental interventions (cathetrization, cystoscopy) •GROSS: enlarged kidney, cortical and medullary abscessses •MICRO: purulent neutrophilic exudate in tubules and interstitium, oedema Acute pyelonephritis (4) pyelonefritida pyelonephr2 pyememboli Pyelonefritisasvrstela • pyelonphr Acute pyelonephritis Acute pyelonephritis • •Pyonephros •Papillary necrosis in diabetics •Peri- and paranephritic abscess nekrpapil Papillary necrosis Chronic pyelonephritis •Uni- or bilateral chron. tubulo- interstitial renal inflammation with scarring •10-20% end-stage kidney •Obstructive PN - repeated infections •Reflux nephropathy –vesicoureteric and/or pelveorenal reflux (from lower and upper pole calyces into renal parenchyme) chgronpyel2 reflux2 reflux3 Chronic pyelonephritis Reflux Chronic pyelonephritis chronpyel Obstructive Chronic pyelonephritis Image017 Chronic pyelitis Xanthogranulomatous pyelonephritis •Uncommon form of chronic pyelonephritis with accumulation of foamy macrophages in interstitium •Yellowish focal lesions in macroscopy, diff. dg. x renal carcinoma xantoranulomatosnípyelonefritis Hydronephrosis, hydroureter Renal tissue atrophy, renal insufficiency Tumors of the renal pelvis Primary: transitional cell neoplasia, mostly papillary transitional cell carcinoma (invasive, non-invasive) Rarely other types of carcinoma (squamous cell, neuroendocrine, adenocarcinoma) Other types (mesenchymal, melanoma, …) Secondary: local progression from the kidney metastasis Transitional cell ca •in pelvis or ureter less common than bladder •possible multiple dysplastic foci •histopathology similar to bladder ca •possible porogenous seeding •invasion into kidney and surrounding tissues •diff. dg. x renal cell ca • Invasive urothelial carcinoma – renal pelvis Transitional cell ca of the renal pelvis • capanvicky Transitional cell ca of the renal pelvis • capanvicky2 capanvicky3 Concurrent urothelial ca of pelvis + bladder possible Ureter •congenital anomalies (double/bifid ureter, obstruction of the ureteropelvic junction, lesion of the vesicoureteric junction, diverticula •obstruction •inflammation (acute, chronic incl. ureteritis cystica - preneoplastic) •neoplasia and pseudotumorous lesions (transitional cell tu, squamous cell ca, fibroepithelial polyp, etc.) • Ureteritis cystica • •Special form of chronic ureteritis •Numerous cysts in the ureteral mucosa, solid or cystic nests of transitional or metaplastic glandular epithelium. •Terminal stage of chronic inflammations •↑ risk of ca Chronic ureteritis cystica Cystic ureteritis Cystic ureteritis Tumors, tumor-like lesions •Fibroepithelial polyp: small, loose stroma + epithelium •Benign: rare, mesenchymal tumors •Malignant: transitionall cell carcinoma • progression of malignancy from surrounding tissues Image048 Transitional cell carcinoma of the ureter Urinary bladder •congenital anomalies (exstrophy, diverticula, persistent urachus •cystitis (acute, chronic, special forms – malakoplakia, tbc, schistosomiasis,etc.) •metaplasia – usually in cystitis (c. cystica, c. glandularis), squamous m.- leukoplakia •tumors and pseudotumorous lesions •miscellaneous (calculi, fistulae, prolapse) Exstrophy •nonclosure of anterior bladder + abdominal wall incl. missing layers •bladder may be opened to the outside •ascending renal infection •epithelial metaplasia, ↑ risk of ca •commonly in combination with other congenital anomalies Diverticula •Congenital: uncommon, solitary. Wall defect; intrauterine urinary obstruction •Acquired: multiple. Most common in prostatic hyperplasia, concurrent with cystitis •↑ risk of infection, stones, perforation • Image041 Urocystolithiasis + chronic cystitis + diverticula Acute cystitis •highly common in females (short urethra, perineal connection with anus) •mostly fecal bacteria, mixed flora •risk factors – urine pH, hormonal status, iatrogenic •usually purulent (leucocytes, blood in urine), urging, pain; may have systemic signs •complications – ureteral spread, ulcers, rare phlegmona, pseudomembranous infl. Haemorrhagic cystitis Ulcerative cystitis Chronic cystitis •epithelial transformations – polyps, epithelial hyperplasia (Brunn‘s nests, reactive atypia – x neoplastic), metaplasia (squamous - leukoplakia, glandular) •neoformation of lymphatic follicles in stroma •in obstruction + muscular hyperplasia, diverticuli •acute exacerbations, stone formation •may be risk factor for neoplasia •diff. dg. x neoplasia Leukoplakia Chronic cystitis with squamous metaplasia Chronic cystitis with squamous metaplasia Glandular cystitis Granulomatous cystitis •specific –parasites –TB, incl. BCG vaccine as treatment for bladder ca –other •nonspecific –foreign body reaction, incl. post-treatment (endoresection) > Granulomatous cystitis • Schistosomiasis •chronic parasitic inflammation •endemic in Africa, Middle East •possible traveller infection, worm lives for up to 20 years •granulomatous reaction to eggs + fibrosis •strictures, squamous metaplasia •↑ ↑ risk of squamous ca > sch-přehled Schistosomiasis Schistosomiasis schisto 013 Transitional cell (urothelial) tumors •exophytic: •papilloma (benign), inverted papilloma •papillary urothelial neoplasm of low malignant potential (PUNLMP) • non-invasive papillary urothelial carcinoma – low grade, high grade •invasive urothelial carcinoma – low grade, high grade • Transitional cell (urothelial) tumors •Flat lesions •Intraepithelial neoplasia • dysplasia – low grade intraurothelial neoplasia (LG IUN) • high grade (HG IUN) - carcinoma in situ (CIS) • • •Invasive carcinoma Bladder epithelial tumors - other •squamous cell carcinoma •adenocarcinoma •small cell carcinoma (neuroendocrine ca) •mixed ca •secondary tumors – prostatic ca, cervical ca, rectal ca Bladder non-epithelial tumors •Melanocytic •Mesenchymal (benign, malignant sarcomas) •Other from Robbins‘ Pathology of Diseases Transitional ca in situ Urothelial papilloma •Rare •Solitary •Exophytic / endophytic (inverted) •Normal urothelium – no atypia, usual number of layers, superficial differentiation od umbrella cells Papillary urothelial neoplasm of low malignant potential •Slight increase in the number of cell layers, normal stratification, minimal increase in nuclear size and density •Basal sporadic mitotic activity •Risk of recurrence, possible progression into ca • Papillary urothelial neoplasm of low malignant potential Image046 Image045 Non-invasive papillary urothelial carcinoma •low grade •high grade •cytonuclear atypias of a carcinoma •no stromal invasion •histological code of a ca in situ (8130/2) for low grade ca •High grade ca – code for carcinoma (8130/3) • Non-invasive papillary urothelial carcinoma, low grade Non-invasive papillary urothelial carcinoma, high grade Non-invasive papillary urothelial carcinoma, high grade Invasive urothelial carcinoma •ex flat urothelial ca in situ •ex non-invasive papillary urothelial ca (papillary component commonly present) •variable grade •invasion into deep bladder structures (muscle layer), adjacent tissues/organs (fat, ureters, prostate gland, …) Invasive urothelial carcinoma •90% ca in the bladder (rare squamous cell ca or adenocarcinomas), mostly in 50 – 80 yrs old •etiology: smokers, professional (anilin dyes, plastics industry), analgesic abuse, irradiation. Sq. cell ca in chronic inflammation (schistosomiasis) •Differentiation grade G1 – G3 •asymptomatic, possible haematuria • Invasive urothelial carcinoma - staging Image050 Bladder carcinoma Bladder carcinoma BLAD060 Invasive urothelial carcinoma invazivní uroteliální karcinom 1.jpg Carcinoma with glandular transformation Mucinous adenocarcinoma he 100x.jpg Squamous cell carcinoma Malignant melanoma in the bladder MALE GENITAL SYSTEM • Penis, scrotum • Congenital lesions •Epispadia: less common, incomplete fusion of urethra, dorsal opening, may be a part of bladder exstrophy •Hypospadia: more common, opening on inferior part of penis (glans, shaft, perineum) •Phimosis: diminished size of prepuce opening, rare inborn, more common acquired – inflammation, scarring, ! ca • Circulatory disorders –Edema –corpora cavernosa thrombosis, – gangrene (uncommon) – • Balanoposthitis •Glans + prepuce •Sexually transmitted diseases – STD: syphilis, gonorrhea, chancroid, herpes •Non-specific infection: candida, pyogenic bacteria, anaerobic bacteria •Poor hygiene – repeated infection •Phimosis, chronic irritation • Viral infections •inflammation +/- pseudotumorous lesion (molluscum contagiosum) •benign tumors: condyloma accuminatum – HPV 6, 11) squamous cell papilloma •preneoplastic lesion/intraepithelial neoplasia: dysplasia mild – moderate – severe – carcinoma in situ •HPV risk factor Penile condyloma condyloma accuminatum - HPV Molluscum contagiosum Balanitis xerotica obliterans •chronic inflammatory disorder (= lichen sclerosus) •epithelial hyperkeratosis, atrophy, inflammatory infiltrate •possible risky terrain for ca Lichen sclerosus Tumorous lesions •Pseudotumors – fibromatosis (Peyronie‘s disease) – deformation possible •Fibroepithelial polyp •Benign tumors – HPV papilloma, adenoma Malignant tumors •Skin tumors (squamous cell carcinoma, melanoma) •Mucosa tumors (various types of squamous cell carcinoma incl. exophytic verrucous ca) •Urethral tumors •Other primary tumors •Seondary tumors Squamous cell ca in situ –Bowen‘s disease / erythroplasia of Queyrat on the glans: white / red focus on the mucosa –bowenoid papulosis (multiple, HPV 16, non-progressive) • Invasive squamous cell ca – –geography (Latin America, East Asia) –circumcision - protective factor (↓HPV, carcinogenes in smegma) –risk factor – smoking, occupational (mineral oil, tar) –gross – ulcer, non-healing lesion –micro – sq. ca of variable type/grade • Carcinoma of the penis Carcinoma of the penis Squamous cell carcinoma of the penis Prostate gland •infarction (usually in hyperplastic prostate, repair with sq. cell metaplasia may mimic ca) •inflammation (acute/chronic, a/bacterial, granulomatous •benign nodular hyperplasia (adenomyomatous) + related lesions •precancerous lesions, tumors (PIN, adenocarcinoma, other) Inflammation •Acute bacterial: ~ UTI, intraprostatic reflux of urine, iatrogenic – catheterization, cystoscopy, surgery. Pain, dysuria, fever. •Chronic bacterial: repeated UTI, non-specific symptoms. Difficult to treat. •Chronic abacterial: most common, no UTI, negative bacterial culture, reactive (+ prostatolithiasis), Chlamydia, ureaplasma •Granulomatous: specific: Tb, BCG used for bladder ca; reactive Prostatolithiasis Chronic prostatitis www.nature.com Zonal predisposition of prostate diseases prostata schéma.jpg Benign prostatic hyperplasia •Common in older men, high incidence > 60 yrs •Adenomyomatous hyperplasia – stromal (smooth muscle, fibrotic tissue) + glandular, alternating with atrophy, cystic and regressive changes. Two cellular layers – outer myoepithelial, inner secretory •Gross: enlarged, nodular, tougher. •Main changes in central (periurethral) region Benign prostatic hyperplasia • •Outcome: partial → complete urethra obstruction, urinary residuum, risk of infection (+ ascending – pyelonephritis), bladder trabecular hypertrophy, hydronephrosis. •Benign, but setting for possible preneoplastic changes •Th: surgery, drugs Benign prostatic hyperplasia Benign prostatic hyperplasia - complications Benign prostatic hyperplasia Benign prostatic hyperplasia Benign prostatic hyperplasia Image054 Benign prostatic hyperplasia Parabasal hyperplasia Prostate – squamous cell metaplasia Pseudotumors, tumors: –Benign prostatic hyperplasia –Carcinoma •Acinar •Ductal •Squamous cell •Adenosquamous •Transitional cell •Neuroendocrine –Secondary tumors •local ca infiltration from adjacent organs (bladder, rectum) •haematogennous metastases (lung ca, malignant melanoma, ..) • • • Prostatic carcinoma •Adenocarcinoma: usually acinar, less common other types – ductal •most common male ca (~1:6) •late middle age – older males •Highly variable course from clinically latent to extremely aggressive •Recent studies: screening (PSA) generally not beneficial Prostatic carcinoma •Important factors: race, family history, age, hormone level (androgenes), environment •Peripheral part (dorsal) – per rectum •PIN: prostatic intraepithelial neoplasia – precursor lesion. High grade PIN important + included into pathological report •Distinctive nucleoli, architectural changes, in PIN myoepithelial layer still present Prostatic carcinoma + hyperplasia Prostatic carcinoma Prostatic carcinoma Prostatic carcinoma Acinar prostatic adenocarcinoma •Gleason histologic grading (WHO modification): – • grade of glandular differentiation, growth pattern • combined score - dominant + secondary pattern in 5-grade system • grade 1 similar to normal prostatic tissue (uncommon in ca) • grade 5 with solid, dissociated pattern • final combined score, commonly Gleason score 7 (4+3) Prostatic carcinoma •Local spread – into urinary bladder; diff. dg x high grade transitional cell ca, may be concurrent •Metastatic spread: regional lymph nodes, hematogenous typical into bones – osteoplastic meta •Symptoms – urinary commonly late, more due to prostatic hyperplasia; local spread; meta • Prostatic carcinoma Prostatic carcinoma - spine metastases Prostatic carcinoma - spine metastases, X-ray Prostatic ca metastasis in bone Testis, epididymis, cord •congenital (cryptorchidism – atrophy, risk of neoplasia) •regressive changes (atrophy, torsion) •inflammation (orchitis – nonspecific acute/chronic, STD (gonorrhea, syphilis, chlamydia), mumps, tbc, idiophatic granulomatous •tumors • Cryptorchidism •Undescended testis •1 in 10 newborn males, usually descends during 1st year of life •remains in inguinal canal or abdominal avity – surgery necessary before puberty •atrophy – infertility, germ-cell tumors • Cryptorchidism Partial testicular atrophy Testicular atrophy + Leydig cell hypertrophy Intrascrotal swelling •Commonly pathology of epididymis, tunica vaginalis •Hydrocele – serous fluid in tunica vaginalis •Haematocele – haemorrhage into tunica vaginalis •Varicocele – dilated veins •Spermatocele – epididymitis + cystic dilatation of ducts • Intrascrotal swelling Intrascrotal swelling - hydrocele Intrascrotal swelling - varicocele Testicular torsion •Spermatic cord turns around its own axis •Haemorrhagic necrosis •Acute pain, swelling •More common in young •Immediate surgery necessary Torsion Testicular infarction Testis, epididymis inflammations •epididymis >>> testis • •usually ascending from urinary tract and/or prostate • •caused by –gramnegative bacteria (children) –chlamydias, gonococcus (STI, adults) –E. coli (older adults) Testis, epididymis inflammations •Bacterial –purulent→ abscess, non-specific orchitis/epididymitis • •Interstitial non-purulent orchitis –mumps in adults –interstitial oedema + lymphocytes, plasma cells, macrophages • •Granulomatous orchitis –may be posttraumatic, v.s. autoimmune inflammation –non-caseating tuberculoid granulomas centered on tubules –firmer testicular mass (diff. dg. x tumor) – •Spermatocytic granuloma –in the head of epididymis due to rupture of tubules –reactive tuberculoid granulomas around spermatozoa Granulomatous orchitis Tuberculoid granulomas. Testicular tumors WHO pathologic classification of testicular tumors • •GERM CELL TUMORS •Derived from germ cell neoplasia in situ •Tumors of one histologic pattern •Seminoma •Embryonal carcinoma •Yolk sac tumor (embryonal carcinoma, infantile type) •Polyembryoma •Choriocarcinoma GERM CELL TUMORS (cont.) •Teratomas •Mature •Immature •With malignant transformation • •Tumors showing more that one histologic pattern •Embryonal carcinoma + teratoma (teratocarcinoma) •Choriocarcinoma + any other types •Other combinations Germ cell tumors •Unrelated to germ cell neoplasia in situ • •Spermatocytic tumor (formerly spermatocytic seminoma) •Teratoma, prepubertal type •Yolk sac tumor, prepubertal type • Germ cell tumors histogenesis Original primitive germ cell Undifferentiated cell Embryonal carcinoma Totipotent cell Differentiation along gonadal line (gonocyte, spermatogonia) without further differentiation potential. Seminoma Extraembryonal differentiation Yolk sac tumor Choriocarcinoma Intraembryonal differentiation Teratoma (mature, immature, with malignisation of somatic elements) Polyembryoma •SEX CORD-STROMAL TUMORS •Well-differentiated forms •Mixed forms •Leydig cell tumor •Sertoli cell tumor •Granulosa cell tumor •Incompletely differentiated forms Testicular tumors •Other types • Neuroendocrine tumors • Haematopoietic neoplasms • Tumors of collecting ducts and rete testis • (adenoma, carcinoma) • Tumors of paratesticular structures (mesothelial tumors, tumors of the epididymis, …) Testicular tumors •Clinical features •painless unilateral enlargement of testis •secondary hydrocele •symptoms from metastases •retroperitoneal mass •gynaecomastia Testicular tumors : histopatological report •gross picture (incl. size) • •histological type • •presence of vascular / lymphatic propagation • •tumor staging (TNM classification) •presence of intratubular germ cell neoplasia (ITGCN - in situ germ cell lesion) Age structure of testicular tumors patients ITGN Germ cell neoplasia in situ Germ cell neoplasia in situ - IHC Seminoma •most common •peak in 4th decade, not in infants •gross: homogenous, greyish •micro: large cells, clear cytoplasm, hyperchromatic nucleus •stroma with lymphocytic reaction, granulomas possible •good prognosis usual Seminoma Seminoma Seminoma Seminoma Seminoma Embryonal carcinoma •mostly 20-30 yrs •gross: variable, haemorrhage, necrosis •micro: organoid glandular, trabecular formations •large anaplastic cells • Embryonal carcinoma embrca-mi Embryonal carcinoma Embryonal carcinoma Embryonal carcinoma Choriocarcinoma •similar to gestational chca •pure very rare, common admixture •HCG production (! disperse trofoblastic cells possible in seminoma) •extensive haemorrhage •cyto- + syncytiotrophoblast Choriocarcinoma Choriocarcinoma Yolk sac tumor •Pure: most common testicular tu in children < 3 yrs •Common part of mixed germ cell tumors •AFP production •variable histology – microcystic, reticular, papillary formation, variable patterns –glomeruloid structures (Schiller-Duval bodies) •stalk with capillary lined on the surface by layer of tumor cells • Yolk sac tumor Yolk sac tumor – AFP IHC Teratoma •variable components: ecto-, meso- endoderm (intraembryonal) •commonly glandular + squamous epithelium •mesenchymal tissues incl. cartilage •in males usually immature, component of mixed germinal tu (x females) Teratoma •histologic classification –differentiated mature t. •completely maturated tissues with organoid structure •commonly cystic, containing serous fluid, mucus, keratin –differentiated immature t. •immature tissues of embryonal/fetal appearance (neuroectoderm, mesenchyme) –t. with somatic type malignancy •sarcoma, carcinoma, PNET • Teratoma Teratoma + embryonal ca Teratoma + choriocarcinoma Teratoma Germ cell tumors •lymphatic spread common (paraaortic LN) •hematogenous possible, esp. in non-seminomatous (lungs, bones, liver, brain) •different histology in metastasis possible •scarrring of the primary tumor possible (burn-out tumor) – diff. dg. x other primary localization • Spermatocytic tumor •unrelated to germ cell neoplasia in situ •usual age > 65 yrs •slow growth, rare metastasis •more pleiomorphic cells – variable stages of differentiation •no stromal reaction Spermatocytic tumor Mixture of polymorphic tumor cells (~ early stages of spermatogenesis): large cells with lacy chromatin, middle-sized cells with round nuclei, small lymphocyte-like cells. Fibrotic septa without lymphocytic infiltrate Sex cord-stromal tumors •less common than germ cell tu •Leydig cell tumor –any age, peak middle age –androgen secreting cells – clinical signs incl. precocious puberty –benign or malignant, similar histology •Sertoli cell tumors –very uncommon, mostly benign Other testicular tumors •primary malignant lymphoma –older males, in this age ML more common than germ cell tu –commonly DLBCL –may be already systemic Testicular DLBCL Testicular DLBCL – Ki-67 proliferation rate Testicular DLBCL – CD20+ B-cell type Epididymis •nonspecific epididymitis most common •usually connected to UTI, bacterial •purulent, abscess formation, necrosis •progression to orchitis •healing by repair, fibrosis + cysts possible •diff. dg. x tumors Sperm granuloma •pathological situation of sperm in direct contact with stroma •chronic granulomatous inflammation •diff. dg. –macro x tumor –micro x other causes of granuloma incl. TB • Tumors •most commonly extension from testicular tumors •primary tumors rare –adenomatoid tumor: benign, phenotype mesothelial, possibly from remnants of Müllerian tract Adenomatoid tumor Adenomatoid tumor