j0305257 Kidney and urinary tract pathology Systematic pathology j0305257 Kidney diseases j0305257 Congenital diseases û Renal agenesis (bilateral) ð incompatible with life û û Renal dysplasia (uni-, bilateral) ð developmental disorder due to abnormal morphogenesis and differentiation. Parenchyma with foci of immature renal tissue. ð ðClinically: diff.dg. x renal tumors of childhood û j0305257 Congenital diseases û Horseshoe kidney (ren arcuatus) ð both kidneys fused by their lower poles û û Cysts and cystosis 2 main forms : ð autosomal recessive polycystic kidney disease • Infantile, microcystic • death commonly soon after birth, kidneys completely replaced by multiple cysts < 2mm û û j0305257 Congenital diseases ð Adult polycystic kidney disease • common congenital disease, ↓of renal function in the 3.- 4. dec., autosomal dominant - gen usually on the short arm of chromosome 16 • • gross: symmetrical kidney enlargement – lenght to 30 cm, multiple cysts 0,5-50mm » » j0305257 Congenital diseases ð Solitary kidney cysts • accidental finding . Important diff. dg x cystic renal carcinoma j0305257 Polycystic kidney j0305257 Vascular kidney disorders û Renal artery stenosis ð renovascular hypertension (Goldblatt‘s) ð pressure ↓ in afferent arterioles ð↓ of filtration pressure in the glomerulus ð juxtaglomerular apparatus hyperplasia + renin overproduction ð blood pressure ↑ - by longer duration - vascular atrophy. j0305257 Vascular kidney disorders û Benign nephrosclerosis ð by benign (compensated) hypertension • gross : symmetrical decrease in size, fine granulated surface • micro : hyalinne insudates in arteriolar walls, median hypertrophy + intimal sclerosis, ischemic changes +/- glomerular loss, vascular atrophy of the tubules, adjacent interstitial fibrosis. û j0305257 Benign nephrosclerosis ischermické změny glomerulů.jpg ûIschemic glomerular chamges, „wrinkling“ of the GBM j0305257 Benign nephrosclerosis û benigní nefroskleroza.jpg j0305257 Vascular kidney disorders û Malignant nephrosclerosis ð due to accelerated arterial hypertension (diastole >130mmHg), endothelial damage •gross : renal oedema, infarctions possible •micro: oedema, intimal mucoid seepage in arteries, fibrinoid necrosis of the arteriolar wall, possible trombi û j0305257 ûSingificant arteriolar luminal narrowing, endothelial oedema Malignant nephrosclerosis j0305257 Malignant hypertension Fibrinoidní nekroza arterioly.jpg ûFibrinoid necrosis of the hilar arteriole j0305257 Malignant nephrosclerosis û Oedema, mucoid intimal seepage, luminal narrowing in a muscular artery û j0305257 Vascular kidney disorders û Thrombotic microangiopathy (HUS, TTP) ð endothelial damage + platelet trombi formation in the systemic microcirculation ð platelets consumption •gross: renal oedema, infarctions possible •micro: intimal oedema, endothelial distention, platelet trombi, infarctions û û û j0305257 Thrombotic microangiopathy ûLuminal thrombi in glomerular capillaries û HE 200x 3 j0305257 Vascular kidney disorders û renal infarction ð ischemic coagulative necrosis due to blockage of peripherale branches of the renal artery •gross: yellowish conical necrosis •micro: necrosis with haemorragic rim û j0305257 Renal infarction Renal infarkt j0305257 Renal infarction ûcoagulativeí necrosis přehled 20x j0305257 Glomerular diseases û Glomeral damage caused by various factors ð vascular changes ð metabolic diseases ð familiar diseases ð immune-mediated disorders ð ð ð ð ð û j0305257 Normal glomerulus AtlasOfRenalPathology 003_1 j0305257 Mechanism of the glomerular damage û Immune-mediated damage ð circulating immune complexes ð in situ immune complexes ð anti-GBM antibodies ð antineutrophilic antibodies ð ð ð ð ð ð ð û j0305257 Mechanism of the glomerular damage û Non-immunological damage ð haemodynamic factors ð hypertension ð ischemia ð ð ð ð ð ð ð ð ð j0305257 Glomerular reaction to the damage û proliferation: ðhyperplasia of mesangial, endothelial, epithelial cells – hypercellularity. Epithelial cells (podocytes) may be a part of crescents filling the Bowman‘s capsule. ð û exudation: ðleukocytes + fibrin û û thickening of the glomerular capillary wall ðusually due to deposition of immune complexes and/or GBM reaction j0305257 Glomerular reaction to the damage û sclerosis: ð eosinophilic material consisting of the mixture of collapsed membranes, mesangial matrix and plasmatic proteins. PAS + silver impregnation highly positive ð û hyalinosis: ð foci of refractive amorphous material comprising insudated plasmatic proteins and lipoproteins (PAS intensive positivity, silver impregnation negative) û ð û j0305257 Clinical presentation of the glomerular disorders ð According to the number of affected glomeruli • diffuse changes (> 50% of gl.) • focal changes • – ðAccording to the extent of glomerular lesion • global changes (the whole gl.) • segmental changes – ð ð j0305257 Clinical presentation of the glomerular disorders û nephritic syndrome: ð acute gl. damage, hematuria, proteinuria, oligouria, oedema, hypertension û ð û nephrotic syndrome: ð severe proteinuria with protein loss> 3,5g/24h, hypoalbuminemia, decrease of production of concentrated urine, oligouria → anuria, ↑ azotemia û j0305257 Clinical presentation of the glomerular disorders û acute renal failure: ð sudden decrease of production of concentrated urine, oligouria → anuria, ↑ azotemia ð û chronic renal failure: ð gradual loss of renal functions j0305257 Glomerular diseases classification û Mostly according to the clinical signs û ð Glomerulopathy with proteinuria or nephrotic syndrome ð ð Glomerulopathy with isolated or predominant hematuria ð • a. j0305257 Glomerular diseases classification ð ð ð Glomerulopathy with acute nephritic syndrome ð ð Glomerular/kidney involvment by SLE ð ð Chronic glomerulonephritis ð j0305257 Glomerular diseases classification û primary x secondary GN ð primary GN – disorder limited to the kidney, without systemic disease ð secondary GN – part of other disease ( SLE, hepatitis C, neoplasia, … ) j0305257 Glomerulopathies manifestated by proteinuria/nephrotic sy Proteinuria with nephrotic syndrome Minimal change disease Focal segmental glomerulosclerosis Membranous glomerulopathy Amyloidosis Diabetic nephropathy j0305257 Glomerulopathies with proteinuria/nephrotic sy û Minimal glomerular change disease û ð mostly in children‘s age ð heavy selective proteinuria (albuminuria) ð nefrotic syndrome responsive to steroid therapy ð normal renal functions ð • LM: normal glomerular morphology • IMF: negative, without immunodeposits • EM: diffuse fusion of podocytes‘ foot processes û j0305257 Minimal glomerular change disease PAS1.jpg ûNormal glomerular morphology j0305257 ûdiffuse fusion of podocytes‘ foot processes Minimal glomerular change disease (EM) j0305257 Glomerulopathies with proteinuria/nephrotic sy û Focal segmental glomerulosclerosis (FSGS) ð children, adults (↑ incidence) ð non-selective proteinuria up to nephrotic type ð nephrotic syndrome, steroid-resistant ð gradual progression to the renal failure • LM: Focal segmental sclerotic and hyalinne gl. changes due to capillary loops collapse and mesangial expansion • IMF: negative, without immune deposits • EM: fusion of podocytes‘ foot processes and podocytes‘ detachment from the GBM – j0305257 FSGS ûSegmental sclerosis of the capillary tuft j0305257 Glomerulopathies with proteinuria/nephrotic sy û Membranous glomerulopathy ð immune complex-mediated glomerulopathy, mostly in adults. ð proteinuria of nephrotic type, hematuria. • LM: diffuse and global gl. involvment, normocellular. Deposition of immune complexeson the outer aspect of the glomerular basal membrane (GBM), thickened in futher stages. • IMF: granular deposits along GBM (IgG, C3) • EM: subepithelial electron-dense immune deposits • j0305257 Membranous glomerulopathy ûDiffuse GBM thickening ûGlomerulus without inflammation or proliferation j0305257 Membranous glomerulopathy (IMF) ûGranular deposits along the GBM in IgG j0305257 Membranous glomerulopathy (EM) ûDiffuse subepithelial (outer aspect of the GBM) immune deposits j0305257 Glomerulopathies with proteinuria/nephrotic sy û Amyloidosis û ð extracellular deposition of pathological fibrilary protein with typical staining features ð systemic amyloidoses most clinically important ð 4 main groups: • AA amyloidosis (SAA protein precursor) in chronic diseases (RA, IBD, …) • – j0305257 Amyloidosis • AL amyloidosis (precursor - plasma cell product) in monoclonal plasma cell disorders • • hereditary amyloidosis: genetically determinated protein defect ( transthyretin) • • amyloidosis associated with haemodialysis • • j0305257 Amyloidosis ð proteinuria with nephrotic syndrome • LM: structure-less eosinophilic masses in the glomeruli, tubules, intersticium and vessels • Positive Congo red staining, green dichroism in polarisation • IMF: positivity of AA amyloid, light chains • EM: non-branching, randomly orientated fibrils, size of 6-13nm û j0305257 Amyloidosis ûAmyloid deposition in the glomerulus j0305257 Amyloidosis ûCongo red-positive amyloid deposition in the glomerulus j0305257 Glomerulopathies with proteinuria/nephrotic sy û Diabetic glomerulopathy û ð renal involvment by diabetic microangiopathy ð proteinuria of nephrotic type • LM: thickening of GBM, mesangial expansion by PAS positive mesangial matrix, mildly increased cellularity, glomerular enlargement – diffuse diabetic glomerulosclerosis • û – ð j0305257 Diabetic glomerulopathy û • later homogennous eosinophilic nodular formations, mesangial cells pushed to the periphery – nodular diabetic glomerulosclerosis . • Hyalinne insudations in arterioles •IMF: without immune deposits •EM: thickening of GBM û j0305257 Diabetic glomerulopathy ûMesangial nodules j0305257 Glomerulopathies with haematuria Glomerulopathies with isolated or prevalent haematuria IgA nephropathy (Berger‘s disease) Henoch-Schönlein purpura Alport syndrome / thin basement membranes sy j0305257 Glomerulopathies with haematuria û IgA nephropathy (Berger´s disease) û ð immune complex-mediated disorder with raised levels of circulating IgA ð IgA mesangial deposits by chronic GIT, respiratory tract mucosal inflammations, liver cirrhosis ð episodic macroscopic haematuria in coincidence with respiratory infection j0305257 Glomerulopathies with haematuria û • LM: mesangial proliferation • IMF: mesangial IgA granules • EM: Mesangial and paramesangial ID û Henoch-Schönlein purpura ð extensor skin vasculitis with purpuric rash, GIT manifestations, arthralgia ð renal involvment - IgA nephropathy ð ð ð û ð j0305257 IgA nephropathy IMF Image001.tif ûMesangial IgA immune deposits j0305257 Glomerulopathies with haematuria û Alport syndrome/ thin basement membrane lesion û ð mutation in genes for collagen IV, part of basement membranes, (mostly gene COL4A5 encodedon the X. chromosome). ð ð gradual progression of renal failure ð in the fully evolved Alport sy – bilateral hearing disorders, ocular abnormities ð û j0305257 Alport syndrome/ thin basement membrane lesion û thin basement membrane lesion û ð without progression into renal failure, mild clinical signs (benign familiar haematuria) ð typical morphology possible in female carriers of X-linked Alport syndrome • – j0305257 Alport syndrome/ thin basement membrane lesion ELMI ûCharacteristic picture of lamellar glomerular basement membrane in hereditary nephropathy. hereditální nefropatie.jpg j0305257 Glomerulopathies with acute nephritic syndrome Glomerulopathies with acute nephritic syndrome Acute diffuse proliferative GN Membrano-proliferative GN Rapidly progressive glomerulonephritis (RPGN) j0305257 Glomerulopathies with acute nephritic syndrome ð usually proliferative glomerulonephritis with increased mesangial and endocapillary cellularity, commonly with crescent formation. ð û Acute diffuse endocapillary proliferative GN ð syn. acute post-infective, acute proliferative, exudative GN ð immune complex-mediated disorder ð ð ð û j0305257 Acute diffuse endocapillary proliferative GN ð usually post-infective glomerulonephritis ( beta-hemolytic streptococcus, staph., G-bacteria, viruses, parasites ) û ð systemic disorders (SLE, infective endocarditis, nectorising arteritis) may be accompanied by this GN ð ð most commonly children , 1-4 wks. after streptococcal infection ð û ð ð û j0305257 Acute post-infective GN ð ð haematuria, proteinuria , hypertension, oedemas, renal failure ð ð possible asymptomatic course ð ð raised ASLO titre and drop of C3 ,C4 complement in serum ð j0305257 Acute post-infective GN ð benign course in children ð ð protracted course in adults, with hypertension,variable grade of renal failure ð •LM : ↑ endocapillary and mesangial cellularity, capillary lumen compression – ð ð ð • ð j0305257 Acute post-infective GN ð •IMF: diffuse segmental IgG and C3 granules in capillary loops, in mesangium • •EM: humphs – electron-dense subepithelial immune deposits ð ð û j0305257 Acute post-infective GN ûhypercellularity, neutrophils j0305257 Acute post-infective GN (IMF) ûGranular IgG deposits on GBM and in mesangium AtlasOfRenalPathology 019_4 j0305257 Acute post-infective GN (EM) ûGranular subepithelial deposits AtlasOfRenalPathology 020_4 j0305257 Glomerulopathies with acute nephritic syndrome ð Membrano-proliferative GN (mesangio-capillary) ð Type I.-III. according morphology, ðcommonly C3 glomerulopathy (problem in complement C3 activation control), activation of mesangial + endothelial cells • • Type I. – immune complex-mediated, cryoglobulinemia (esp. hepatitis C), other causes - more common in children, teens • ↓ serum complement, nephritic syndrome, nephrotic sy possible. –LM: diffuse glomerulopathy, endocapillary and mesangial hypercellularity, accentuation of capillary tuft lobular architecture, – GBM duplication („tram track“) in PAS, silver impregnation. – – ð – » û j0305257 Membrano-proliferative GN •EM: subendothelial immune deposits + mesangial interposition (inclusion of mesangium + new layer of BM inbetween the immune deposits and original BM – duplication, „splitting“), subendothelial + mesangial ID. û ð Type II. – dense deposit disease ð > 60% of patients with antibody C3nephritic factor (NeFa) binding to C3 convertase → stabilisation (no enzymatic degradation), → permanent C3 activation of alternative pathway of complement cascade – • j0305257 Membrano-proliferative GN •EM: dense-deposit disease (DDD). Ribbon-like immune deposits in the GBM and mesangium, ð Typ III. rare • LM: same findings as in the type I. • EM: + subepithelial ID. » » » j0305257 Membrano-proliferative GN ûLobulisation of the capillary tuft, hypercellularity in mesangium + endocapillary j0305257 Membrano-proliferative GN (EM) û1.Subendothelial immune deposits 2. podocyte foot processes fusion û3. mesangial interposition j0305257 Glomerulopathies with acute nephritic syndrome û Rapidly progressive GN (RPGN), crescentic ð Hematuria, proteinuria ð Rapid loss of renal functions ð Extensive crescentic formation ð û û ð • j0305257 RPGN ðVariable group of diseases: ðpauci-immune GN (part of systemic vasculitis, sm. ANCA+) ðAnti-GBM disease ðimmune-complex mediated GN • complication of other GN (IgA, post-infectious GN, SLE) ð ð ð ð ð ð ð * ð j0305257 RPGN ûCellular crescents within the Bowman capsule j0305257 RPGN û1. Fibrin in the crescent û2. Cellular crescent (incipient) j0305257 RPGN Fibrinoidní kapilární nekroza.jpg ûFibrinoid necrosis of capillaries j0305257 Vascular kidney/glomerular diseases anti-GBM vasculitis Systemic vasculitis immune-complex mediated vasculitis ANCA-associated vasculitis Hypertensive kidney disorders Thrombotic microangiopathy Others renal infarction renal artery stenosis j0305257 Vascular kidney/glomerular diseases û Systemic vasculitis û Anti-GBM glomerulonephritis ð antibodies against Goodpasture antigen (part of noncollagenous portion of the GBM) j0305257 Vascular kidney/glomerular diseases ð ð binding of anti-GBM antibody→ complement + proteases activation k aktivaci → GBM destruction ðLM: RPGN appearance •IMF: diffuse linear IgG deposits positivity of GBM • •Immune complex-mediated vasculitis ð Henoch-Schönlein purpura •IgA nephropathy morphology • – ð ð ð û û ð ð j0305257 Vascular kidney/glomerular diseases û ANCA-associated vasculitis (antineutrophil cytoplasmic antibodies) û ð Granulomatosis with polyangiitis (Wegener granulomatosis) ð Microscopic polyangiitis •RPGN morphology • j0305257 Anti - GBM û1. Cellular compressive crescent û2. Collapsing capillary tuft j0305257 Anti-GBM (IMF) antiGBM4Nik_4x 3.jpg ûLinear peripheral IgG positivity ( on the GBM) j0305257 Vascular kidney/glomerular diseases ûThrombotic microangiopathy ð Haemolytic uremic syndrome, Thrombotic thrombocytopenic purpura – formation of platelet thrombi in small vessels of systemic circulation, platelets consumption, endothelial damage and haemolysis ð Intimal and endothelial oedema, fibrinoid necrosis of the arteriolar wall, fibrin thrombi in capillaries ðtypes: •epidemic (E.coli – shiga-like toxin) •other – drugs, irradiation, infection •TTP – hereditary/acquired excessive activation of platelets j0305257 Chronic glomerulonephritis û gl. disease in the end-stage (significant renal lesion) û •gross: kidney contracted, granulated • micro: high percentage of globally obliterated glomeruli, interstitial fibrosis, tubular atrophy, vascular changes. û û j0305257 Chronic glomerulonephritis chronická GN1.jpg û1. Obliterated glomeruli û2. Vascular changes j0305257 Tubulo-interstitial disorders ð both parts (tubules + interstitium) affected û Two main categories: ð Ischemic and toxic lesion (acute tubular necrosis ATN) ð ð Inflammatory (tubulointerstitial nephritis TIN) ð • û û j0305257 Tubulo-interstitial disorders ûAcute tubular necrosis ð etiology: ischemic , toxic ð acute renal failure with oligouria/anuria, hemodialysis necessary •gross: kidney edema, markedly pale cortex •micro: variable grade of tubular cells injury, from loss of brush border to necrosis. ðIschemic – segmental lesions along the whole tubular lenght ðtoxic – proximal tubules ð û ð • j0305257 Acute tubular necrosis ûTubular dilatation, simple flat epithelium j0305257 Acute tubular necrosis û C:\My Documents\praktika\specka 4.prakt\Image029.jpg j0305257 Tubulo-interstitial disorders û Acute tubulo-interstitial nephritis ð Etiology: infectious bacterial (acute pyelonephritis) ð toxic drug-induced ( post ATB) ð metabolic (diseases with crystal formation) ð viral (hantaviruses) •micro: interstitial inflammatory infiltrate, variable grade of tubular epithelium injury • j0305257 Tubulo-interstitial disorders û Acute pyelonephritis ð acute pelvis + kidney inflammation - mostly ascennding - bacterial infection – i.e. E. coli ð descending - in sepsis ð febrile ilness, lumbal pain, dysuria + urging, pyuria with numerous neutrophils • – j0305257 Tubulo-interstitial disorders •gross : swollen kidney, yellow subcapsular abscesses. •edematous, hyperemic pelvis, sm. with pus, progression of purulent inflammation to the adjacent tissues - paranephritic abscess •micro: interstitial + tubular neutrophils • • û j0305257 Acute pyelonephritis pyelonefritis 200x j0305257 Tubulo-interstitial disorders û Chronic pyelonephritis ð one of the most common causes of renal failure û ð possible insidious start, manifestation due to hypertension, commonly after multiple attacks of acute pyelonephritis. j0305257 Tubulo-interstitial disorders û gross: irregular shrunken kidney, flat scars, commonly + nephrolithiasis, progressive atrophy - end-stage kidney û micro: interstitial fibrosis, tubular atrophy, dilatation + casts (follicular colloid-like), glomerular hyalinisation j0305257 Tubulo-interstitial disorders û Drug-induced TIN ð Antibiotics, NSAIDs • micro: interstitial oedema, mixed interstitial inflammatory infiltrate with eosinophils j0305257 TIN ûEosinophils in inflammatory infiltrate j0305257 Oxalate nephropaty ûOxalate crystals/deposits in tubules û j0305257 Tubulo-interstitial disorders û Myeloma nephropathy ð renal damage due to myeloma ð excretion of light chains (BJ protein) into primary urine, toxic to epithelia ð + casts formation→ nephrohydrosis, blockage of urine outflow within renal parenchyme. ð tubular epithelial damage, multinucleated macrophages ð j0305257 Myeloma nephropathy û1. Protein casts û2. Giant multinucleated macrophages j0305257 Renal tumors û Benign x malignant û Benign ð angiomyolipoma • Mesenchymal (perivascular epithelioid cell – PEComa) more common in patients with tuberous sclerosis ð cortical adenoma •micro: papillary structure •gross: ochre colour, size< 5mm • accidental finding • û j0305257 Benign tumors ð renal oncocytoma •gross: demarcated tumor of red-brown colour, variable size central scar •micro: eosinophilic, granular cytoplasm, cells in acinar, tubular, solid nests; central hyalinne scar j0305257 Renal oncocytoma onkocytom.jpg j0305257 Renal cell carcinoma (RCC) û More common in males; middle-older age û Smoking as major risk factor û mostly sporadic tumors, 4% part of hereditary syndromes j0305257 Clear cell RCC ð 70-80% of all RCC •gross : demarcated tumor, yellowish colour commonly with haemorrhagic, necrotic, fibrotic foci • • angioinvasive tendency – direct grow into renal vein, vena cava; • invasion into pelvis - haematuria j0305257 Clear cell RCC •Metastases via blood mostly (lungs, bones, brain) û •micro : large cells with clear granular cytoplasm (glycogen + lipids) û û j0305257 Clear cell RCC j0305257 Clear cell RCC ð clinical : local symptoms late, haematuria. Fever, paraneoplastic syndromes ð prognosis according to the tumor size/stage ð ca< 3 cm quite good j0305257 Papillary RCC ð 15% of all RCC •gross: well-demarcated, regressive changes, commonly multifocal and bilateral •micro: malignant epithelial cells covering stromal papillae, with stromal foam macrophages – j0305257 Papillary RCC û û j0305257 Chromophobe RCC ð 5% of RCC. •gross: well demarcated, partial lobulisation, brown colour •micro: eosinophilic granular cytoplasm, distinctive cell membranes, shrunken („raisin“) nucleus • û j0305257 Chromophobe RCC j0305257 Nephroblastoma ð ð 3rd most common malignant pediatric tumor ð Diagnosed mostly in the 3rd-4th year of age ð Sporadic, or part of some syndromes ð •gross: large, well demarcated tumor, greyish colour, regressive changes j0305257 Nephroblastoma •micro: structures attempting to recapitulate variable stages of nephrogenesis • –Triphasic combination of blastemal, stromal and epithelial cell types in variable percentage – Highly cellular foci resembling embryonal blastema divided by strands of immature mesenchyme j0305257 Nephroblastoma ð clinical: large tumor, palpable, complications due to compression of adjacent organs, hematuria ð ð prognosis: good, CHT (RT carefully, second malignancies possible) j0305257 Nephroblastoma RENAL057 j0305257 Nephroblastoma 40x j0305257 Nephroblastoma 200x j0305257 Urinary tract disorders j0305257 Urinary tract û ð Calices ð Pelvis ð Ureters ð Urinary bladder ð Urethra û û j0305257 Inflammations ð Mostly ascending infection ð urethritis ð urocystitis ð possible progression into kidney ð ð etiology: E.coli, Proteus, Klebsiella, Enterococcus,Neisseria gonorrhoeae, etc. ðCandida, Schistosoma, û û û j0305257 Inflammations ð dysuria, polakisuria (urging), raised temperature •gross: haematuria, pyuria – Hypeaemic mucosa, possible pseudomembrane, ulceration – ð complications : progression of inflammation into adjacent structures: glands, interstitium – phlegmona, periurethral abscess » û j0305257 Inflammations • micro: – acute inflammation with prevalence of neutrophils, regressive changes of transitional cell epithelium – – chronic inflammations - reactive changes of transitional cell epithelium, squamous/glandular metaplasia. Brunn nests – cystitis cystica – ð urethra – caruncula urethrae – pseudotumorous hyperplastic polyp in the region of urethral orifice. û j0305257 Hydronephrosis ð ûPathological dilatation of the renal pelvis and calyces • Causes: – Impacted stone, … –Tumors –External compression (pregnancy, prostatic hyperplasia, …) j0305257 Tumors û benign x low malignant potential x frankly malignant û flat x papillary lesions ð Mostly urothelial û Precursor lesions: ð Urothelial dysplasia ð risk factors: • M:F 3:1 • smoking • professional exposure (aromatic amines, etc.) • long-term use of phenacetin, irradiation, … j0305257 Urothelial dysplasia •Micro: flat lesion, cytologic atypia with loss of cell polarity, ↑ mitotic activity in upper layers of urothelium, ↑ N/C ratio, coarse chromatin û ûLG (low grade) IUN (intraurothelial neoplasia) x HG IUN (CIS) j0305257 Urothelial ca in situ j0305257 Papillary urothelial neoplasm û urothelial papilloma •Solitary papillary lesion covered by normal urothelium without cytological or architectonic atypias. û j0305257 Papillary urothelial neoplasm ð papillary urothelial neoplasm of low malignant potential (PUNLMP) • recurrent tumor • papillae covered by hyperplastic urothelium with preserved stratification, minimal cytonuclear atypia, sporadic mitoses. j0305257 Papillary urothelial neoplasm ð non-invasive papillary urothelial carcinoma • low grade • high grade ð Papillary neoplasia without signs of invasion into stroma (suburothelial mesenchymal tissue) ð LG ð altered papillary architectonics, ð mild cytonuclear atypia ð basal layer mitoses j0305257 Low grade non-invasive papillary urothelial carcinoma j0305257 Non-invasive papillary urothelial carcinoma ð HG ð papillary fusion, solid foci ð loss of cell polarity ð moderate – high grade of anisocytosis and anisokaryosis ð atypical mitoses in upper layers of neoplastic epithelium j0305257 High grade urothelial carcinoma j0305257 Bladder carcinoma BLAD060 j0305257 Invasive (infiltrating) urothelial carcinoma ð ca invasion into sub-urothelial fibrotic tissue or deeper (muscle, …) • j0305257 Invasive urothelial carcinoma invazivní uroteliální karcinom 1.jpg j0305257 Bladder carcinoma û Less common carcinomas ð squamous cell carcinoma (schistosomiasis) ð adenocarcinoma ð neuroendocrine carcinoma û j0305257 Mucinous adenocarcinoma he 100x.jpg