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Tumors of kidney & urinary tract 2012
 

Tumors of kidney & urinary tract 2012

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    Tumors of kidney & urinary tract 2012 Tumors of kidney & urinary tract 2012 Presentation Transcript

    • To discussCystic Lesions of KidneyCommon Tumors of kidney and Urinary bladder
    • Learning OutcomesClassify cystic diseases of kidneyExplain pathogenesis of adult &childhood polycystic kidney diseasesDescribe Morphology of adult &childhood polycystic kidney diseases
    • Learning Outcomes Classify tumors of kidney and bladder Compare and discussage and sex prdeominance & incidence, genetic, clinical presentation & clinical course, morphology, prognosis of Renal cell carcinoma Wilms Tumor Transitional cell carcinoma
    • Cystic Diseases of the KidneyCystic diseases of the kidney areheterogeneous, comprisingHereditaryDevelopmentalacquired disorders
    • Classification of renal cysts1. Multicystic renal dysplasia2. Polycystic kidney diseasea. Autosomal-dominant (adult) polycystic diseaseb. Autosomal-recessive (childhood) polycystic disease
    • Classification of renal cysts3. Medullary cystic disease a.Medullary sponge kidney b. Nephronophthisis4. Acquired (dialysis-associated) cysticdisease5. Localized (simple) renal cysts
    • Classification of renal cysts6. Renal cysts in hereditary malformation syndromes (e.g., tuberous sclerosis)7. Glomerulocystic disease8. Extraparenchymal renal cysts (pyelocalyceal cysts, hilar lymphangitic cysts)
    • Adult polycystic kidney diseaseInheritanceAutosomal dominantPathologic Features Large multicystic kidneys, liver cysts,berry aneurysms
    • Adult polycystic kidney diseaseClinical Features or ComplicationsHematuria, flank pain, urinary tractinfection, renal stones, hypertensionChronic renal failure beginning at age 40–60 years
    • Adult polycystic kidney diseaseA hereditary disorder characterized bymultiple expanding cysts of bothkidneys that ultimately destroy therenal parenchyma and cause renalfailure
    • Adult polycystic kidney diseaseDespite the autosomal dominantinheritancethe manifestation of the disease requiresmutation of both alleles of either PKD genemutations in genes located on chromosome16p13.3 (PKD1) & 4q21 (PKD2)
    • Adult polycystic kidney diseaseGenetics and PathogenesisThe PKD1 gene encodesa large integral membrane protein namedpolycystin-1 which hasa large extracellular region, multipletransmembrane domains, and a short cytoplasmictail
    • Adult polycystic kidney diseaseGenetics and PathogenesisThe PKD2 gene product polycystin-2 is an integral membrane proteinIt has been localized to all segments of the renal tubules and is also expressed in many extrarenal tissuesPolycystin-2 functions as a Ca2+-permeable cation channel, and a basic defect in ADPKD is a disruption in the regulation of intracellular Ca2+ levels
    • Adult polycystic kidney diseaseGenetics and PathogenesisThe epithelial cells of the kidney each contain a single nonmotile primary cilium, a 2–3 μm long hairlike organelle that projects into the tubular lumen from the apical surface of tubular cellsFunction of cilium in tubular cells-sense mechanical signals (mechanosensor)to monitor changes in fluid flow and shear stress
    • Adult polycystic kidney diseaseGenetics and PathogenesisIn response to external signals, these sensors regulate ion flux (cilia can induce Ca2+ flux in cultured kidney epithelial cells) and cellular behavior, including cell polarity and proliferationThe hypothesis that defects in mechanosensing, Ca2+ flux, and signal transduction underlie cyst formation
    • Adult polycystic kidney diseaseGenetics and PathogenesisBoth polycystin-1 and polycystin-2 are localized to the primary ciliumPolycystin-1 and polycystin-2 may form a protein complex that acts to regulate intracellular Ca2+ in response to fluid flow, perhaps because fluid moving through the kidney tubules causes ciliary bending that opens Ca2+ channels   
    • Adult polycystic kidney diseaseGenetics and PathogenesisMutation of either of the PKD genes lead toloss of the polycystin complex or the formation of an aberrant complexchanges in intracellular Ca2+ level
    • Adult polycystic kidney diseaseGenetics and Pathogenesisecond-messenger effects of Ca2+ lead tochanges in cellular proliferationbasal levels of apoptosisinteractions with the ECMsecretory function of the epitheliathat together result in the characteristic feature of ADPKD
    • Adult polycystic kidney disease
    • Adult polycystic kidney diseaseGenetics and PathogenesisProgressive enlargement of cyst result from increase in the number of cells caused by abnormal proliferation expanding volume of intraluminal fluid caused by abnormal secretion from epithelial cells lining the cysts mediators in cyst fluids enhance fluid secretion and induce inflammationThese abnormalities contribute to further enlargement of cysts and the interstitial fibrosis characteristic of progressive polycystic kidney disease.
    • Adult polycystic kidney diseaseMorphology (Gross)kidneys are usually bilaterally enlargedexternal surface appears to be composed solely of a mass of cysts, up to 3 to 4 cm in diameter, with no intervening parenchyma
    • Adult polycystic kidney diseaseMorphology (Gross)
    • Adult polycystic kidney diseaseMicroscopic examination revealsfunctioning nephrons dispersed between the cystsThe cysts may be filled with a clear, serous fluid or, more usually, with turbid, red to brown, sometimes hemorrhagic fluidThe cysts arise from the tubules throughout the nephron and therefore have variable lining epitheliaOn occasion, papillary epithelial formations and polyps project into the lumenBowman capsules are occasionally involved in cyst formation, and glomerular tufts may be seen within the cystic spaceAs these cysts enlarge, they may encroach on the calyces and pelvis to produce pressure defects
    • Childhood polycystic kidneydiseaseInheritanceAutosomal recessivePathologic Features Enlarged, cystic kidneys at birth
    • Chidhood polycystic kidneydiseaseClinical Features or ComplicationsHepatic fibrosisVariable, death in infancy or childhood
    • Chidhood polycystic kidneydiseaseSubcategoriesdepending on the time of presentation and presence of associated hepatic lesions1. Perinatal2. Neonatal3. Infantile4. juvenile
    • Chidhood polycystic kidneydiseaseGenetic and PathogenesisMutations of the PKHD1 gene, which maps to chromosome region 6p21–p23PKHD1 gene encodes a large novel protein, fibrocystinFibrocystin is an integral membrane protein with a large extracellular region, a single transmembrane component, and a short cytoplasmic tail
    • Chidhood polycystic kidney diseaseGenetic and PathogenesisFibrocystin also has been localized to the primary cilium of tubular cellsThe function of fibrocystin is unknownits putative conformational structure indicates it may be a cell surface receptor with a role in collecting-duct and biliary differentiation
    • Chidhood polycystic kidneydiseaseMorphologyThe kidneys are enlarged and have a smooth external appearanceOn cut section, numerous small cysts in the cortex and medulla give the kidney a spongelike appearanceDilated elongated channels are present at right angles to the cortical surface, completely replacing the medulla and cortex
    • Chidhood polycystic kidney disease Morphology
    • Chidhood polycystic kidneydiseaseMorphologyOn microscopic examination, there is cylindrical or, less commonly, saccular dilation of all collecting tubulesThe cysts have a uniform lining of cuboidal cells, reflecting their origin from the collecting ducts.
    • TUMORSBENIGN Papillary Adenoma Fibroma/Hamartoma Angiomyolipoma Oncocytoma Juxtaglomerular apparatus tumorMALIGNANT Renal cell CA(Adenoca.) Wilm’s tumor T.C.C. Primary sarcomas
    • RENAL CELL CARCINOMA (RCC)1-3% of all visceral cancers, 85% of all renal cancerMost common 60-70 years ; M:F = 2:1Risk factors  Smoking, obesity, hypertension  Unopposed estrogen Rx  Asbestos, petroleum products & heavy metals  CRF & acquired cystic disease (30 folds )  Familial (4%) Von Hippel-Lindau (VHL) syndrome Hereditary clear cell carcinoma Hereditary papillary carcinoma
    • RENAL CELL CARCINOMA (RCC)Grossly: Mainly polar, spherical yellow variegated tumor with hemorrhagic, necrotic & cystic areas. May extend into renal v.Microscopically: Clear cell carcinoma: (70-80%) Papillary carcinoma: (10-15%) Chromophobe renal carcinoma (5%) Sarcomatoid carcinoma
    • Clear cell carcinomaMost common ,70-80% of renal cancerClear cells with clear or granular cytoplasmMajority are sporadicFamilial forms : von Hippel-Lindau
    • RENAL CELL CARCINOMA (RCC) Site - any portion of the kidney, but more commonly affects the poles solitary unilateral lesions, spherical masses composed of bright yellow-gray- white tissue that distorts the renal outline large areas of ischemic, opaque, gray- white necrosis, and foci of hemorrhagic discoloration The margins are usually sharply defined and confined within the renal capsule
    • RENAL CELL CARCINOMA (RCC)Clear cell carcinoma solid to trabecular or tubular growth pattern rounded or polygonal shape and abundant clear or granular cytoplasm, which contains glycogen and lipids
    • Papillary RCC10-15% of all renal cancerPapillary growth patternFrequently multifocal &bilateralAppear as early stage tumormost common cytogenetic abnormalities are trisomies 7, 16, and 17
    • Papillary RCCarise from distal convoluted tubulesmultifocal and bilateraltypically hemorrhagic and cystic especially when largemost common type of renal cancer in patients who develop dialysis-associated cystic disease
    • Papillary RCC
    • RENAL CELL CARCINOMA (RCC)
    • Chromophobe renal carcinoma5% of all RCCArise from cortical collecting ducts or their intercalated cellscomposed of cells with prominent cell membranes and pale eosinophilic cytoplasm, usually with a halo around the nucleus
    • Chromophobe renal carcinoma
    • Clinical features of RCCThree classic diagnostic features of renal cellcarcinomaHematuria (50%), costovertebral pain, massAsymptomatic/incidental findingConstitutional symptoms (fever, malaise,weakness, and weight loss)Present with metastasis (lungs and bones )Paraneoplastic syndromes
    • Clinical features of RCCParaneoplastic syndromes Polycythemia 5-10% Hypercalcemia Cushing’s syndrome Hypertension Feminization or masculinization Eosinophilia, leukemoid reactions, and amyloidosis
    • Clinical features of RCCCommon characteristics of this tumor is its tendency to metastasize widely before giving rise to any local symptoms or signslocations of metastasis are the lungs (more than 50%) and bones (33%), followed in frequency by the regional lymph nodes, liver, adrenal, and brain.
    • Renal cell CarcinomaPrognosis: 5 yr survival is around 70% in the absence of distant metastasesWith renal vein invasion or extension into the perinephric fat, the figure is reduced to approximately 15% to 20%
    • Clear Cell Renal Cell Carcinoma Total nephrectomy (gross)(Most common renal tumor in adults)
    • Renal cell carcinoma
    • Renal cell carcinoma
    • Renal Cell Carcinoma, Clear Cell, Type (microscopic)
    • Wilms Tumor1 in every 10,000 children in the United Statesmost common primary renal tumor of childhoodpeak incidence for Wilms tumor is between 2 and 5 years of age5% to 10% of Wilms tumors involve both kidneys
    • Wilms TumorCongenital anomalies related:WAGR syndrome: WT1 (11p13)DENYS-DRASH syndrome: similar path.BECKWITH-WIEDEMANN syndrome: WT2WT3
    • Wilms TumorClinical• Good outcome with early diagnosis.Tumor has tendency to easily metastasizemajor complaint is associated with largesize of the tumor - readily palpable mass•
    • Wilms Tumor• less common complaints include  a) fever  b) abdominal pain  c) hematuria  d) intestinal obstruction (uncommon)
    • NEPHROBLASTOMA (WILM’STUMOR)Grossly: Large well-circumbscribed soft tan-gray homogenous tumorMICRO: Blastemal, stromal and epithelial elementsPrognosis: Currently 90% long term survival
    • MICRO: Blastemal, stromal and epithelial elements
    • MICRO: Blastemal, stromal and epithelial elements
    • Renal pelvis carcinomaTransitional & squamous carcinomas of renal pelvis5-10% of renal neoplasmsOften small and present early with Painless Hematuria Pain or mass due to hydronephrosisMay be multifocal
    • Renal pelvis carcinomaPrognosis:variable, depend on stage & gradeDespite removal by nephrectomy :50% 5YSR
    • Transitional Cell Carcinoma Gross
    • Urinary bladder tumorsExophytic papillomaInverted papillomaPapillary urothelial neoplasms of low malignant potentialLow grade and high grade papillary urothelial cancersCarcinoma in situ (CIS, or flat non-invasive urothelial carcinoma)Mixed carcinomaAdenocarcinomaSmall-cell carcinomaSarcomas
    • Bladder Carcinoma Things you must knowDerived from transitional epitheliumPresent with painless hematuriaPrognosis depends on grade and depth of invasionOverall 5y survival = 50%
    • Bladder CarcinomaMorphologyThe gross patterns of urothelial tumors vary from purely papillary to nodular or flatPapillary lesions appear as red, elevated excrescences varying in size from less than 1 cm in diameter to large masses up to 5 cm in diameterMulticentric origins
    • Urinary bladder tumorslarge papillary tumor multifocal smaller papillary neoplasms
    • Bladder CarcinomaGrading of Urothelial (Transitional Cell Ca)WHO/ISUP Grades  Urothelial pappiloma  Urothelial neoplasm of low malignant potential  Papillary urothelial carcinoma low gradePapillary urothelial carcinoma, high grade
    • Low-grade papillary urothelial carcinoma with an overallorderly appearance, with a thicker lining than papillomaand scattered hyperchromatic nuclei and mitotic figures(arrows)
    • High-grade papillary urothelial carcinoma withmarked cytologic atypia
    • Flat carcinoma in situ