Surgical Kidney Flashcards
Name 5 familial cancer syndromes associated with renal neoplasms
- Von Hippel-Lindau (VHL) - Hereditary papillary renal cell carcinoma syndrome (HRPC) - Birt-Hogg-Dube syndrome - Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) - Tuberous sclerosis
Name 5 familial pediatric renal tumor syndromes
- WAGR (Wilms, aniridia, genitourinary malformations, mental retardation) - Denys-Drash - Beckwith-Wiedemann syndrome - Familial nephroblastoma - Trisomy 18, Perlman Syndrome, Bloom syndrome, Frasier syndrome
Von Hippel Lindau: Gene involved, gene product, pathway, type of renal tumor, other associations
Gene: VHL (3p25) Product: pVHL pathway: Hypoxia-inducible factor (HIF) tumor: Clear cell RCC others: cysts, CNS/retinal hemangioblastoma, pheochromocytoma, pancreatic cysts, pancreatic endrocrine tumor
Hereditary papillary renal cell carcinoma: Gene, gene product, pathway, type of tumor, others
Gene: c-MET (7q31) Product: MET tyrosine kinase Pathway: MET/hepatocyte growth factor Tumor: Papillary renal cell carcinoma, type 1 others: no
Birt-Hogg-Dube: gene, gene product, pathway, type of tumor, others
Gene: BHD (17), product: folliculin pathway: MTOR (mammalian target of rapamycin) tumor: Oncocytic tumors (chromophobe, oncocytoma, hybrid), other RCC Others: cutaneous lesions, lung cysts, pneumothorax, lipomas
Hereditary leiomyomatosis and RCC: gene/gene product, pathway, tumors, others
gene: Fumarate hydratase (1q)/fumarate hydratase gene product pathways involed: HIF tumor: High-grade RCC with papillary, tubular, solid architecture others: leiomyomas of skin/uterus
Tuberous sclerosis: gene/product, pathway, tumors, others
gene: Tuberous sclerosis complex (TSC1, chromosome 9, TSC2, chromosome 16) products: hamartin, tuberin pathway: MTOR tumors: AML, RCC others: lymphangioleioyomatosis of lung, clear cell tumors of lung, pancreas, uterus, pecomas, subependymomas, giant cell astrocytoma
Renal malakoplakia: what are gross features
- Pelvicalyceal system outlined by thick bands of friable/necrotic tissue - Irregular yellow masses centered on renal medulla - Hydronephrosis or pyelonephrosis - Renal calculi (especially staghorn)
Renal malakoplakia/xanthogranulomatous pyelonephritis: What are microscopic features
- Aggregates of histocytes with eosinophilic cytoplasm (von Hansemann histocytes) - Cytoplasm is PAS+ - Some contain concentrically lamellar, basophilic, calcified inclusions (Michaelis-Gutmann) - Mixed inflammatory infiltrate of lymphs/plasma cells/neutrophils - Multinucleated giant cells
Renal malakoplakia: What organisms are involved and what is the pathogenesis:
- Gram negative bacteria (E. coli, proteus, klebsiella, pseudomonas, shigella, enterobacter( - Defective macrophage lysosomal digestion of phagocytosed bacteria, possible due to decreased levels of intacellular cyclic guanosine monophosphate - Inadequate elimination leading to accumulation of partially digested bacteria with deposition of calcium/iron
Renal malakoplakia: What are the ultrastructural features?
- Bacilliform microorganisms, eithe rintact or in different stages of disintegration within phagolysosomes in macrophages
What genetic syndrome is associated with multiple chromophobe renal cell carcinomas?
- Birt-Hogg-Dube syndrome
- Other associations: cutaneous fibrofolliculomas, pulmonary cysts, multifocal renal tumors INCLUDING chromophobe RCC, oncocytoma, clear cell RCC, hybrid tumors
What are the genetic changes associated with chromophobe RCC? What is the prognosis?
- Losses of whole chromosomes, including Y, 1, 2, 6, 10, 13, 17, 21
- Better than clear cell RCC (especiallly at lower stage)
Name 3 histologic features, 5 IHC that can distinguish between chromophobe and clear cell RCC (eos. variant).
- Histo: chromophobe has large, polygonal cells with thick plant-like borders, finely vesicular cytoplasm, with 2nd population of smaller eosinophilic cells with perinuclear clearing; randomly arranged broad fibrous septae with medium-caliber blood vessels (clear cell lacks the thick walls, has small delicate sinusoidal blood vessels)
- IHC: CHROMOPHOBE: RCC neg, CK7+, CD10 neg, vimentin neg, e-cadherin +
- CLEAR CELL RCC: RCC +, CK 7 neg, CD10 +, vimentin +, e-cadherin neg
Compare chromophobe RCC to oncocytoma with regards to nuclear features, histochemistry, EM and IHC.
- chromophobe: wrinkled nuclei with perinucelar halos, binucleation; DIFFUSE staining with colloidal iron, EM: microvesicles, CK7+, BER-EP4 positive, PaX 2 negative, CK20 negative, CD15 negative
- oncotyoma: round nuclei with prominent nucleoli; negative for colloidal iron, EM: dilated mitochondria, CK7 negative, Ber-EP4 negative, PAX2 positive, maybe CK20 positive, CD15 positive
Chromophobe renal cell carcinoma: List 4 histologic features
- cell arranged in solid sheets, may have tubulocystic architecture
- Radomly intersecting fibrous septa with medium sized blood vessels
- Nuclei: irregular and hyperchromatic, wrinkled contours +//- multinucleation
- 2 cell types: chromophobe cell, large polygonal with plant-like cell wall borders, finely vesicular cytoplasm and eosinophilic cell which is smaller, less cytoplasm and has perinuclear halo
What is the cell of origin in angiomyolipoma? What IHC stains are positive (5)?
- Perivascular epithelioid cell
- IHC: vimentin, muscle-specific actin, SMA, HMB45, Melan-A
Name a clinical syndrome associated with angiomyolipoma and 3 histological components.
- Tuberous sclerosis: AD tumor suppression gene syndrome, associated with cerebral cortical tubers, cardiac rhabdomyomas, facial angiofibromas, renal AML, lymphangioleiomyomas
- Smooth muscle cells: colar around blood vessels, may be perpendicular
- adipocytes
- dysmorphic blood vessels (thick-walled artery-like without elastic)
Rhabdoid tumor of kidney: List 3 clinical features, prognosis, 3 histologic features, IHC, EM
Clinical: infants <24 months, hematuria, advanced disease at presenation
Prognosis: Extremely poor, <25% survival at 1 yr
Histologic features: sheets of large cells with vesicular nuclei, eosinophilic cytoplasmic inclusions, infiltrative tumor borders
IHC: vimentin strongly positive, focal EMA and cytokeratin
EM: inclusions formed by whorled intermediate filaments
List 4 entities in the DDx of rhabdoid tumor of kidney
Nephroblastoma, neuroblastoma, mesoblastic nephroma, clear cell sarcoma of kidney
Classify cystic diseases of the kidney
- Multicystic renal dysplasia
- Polycystic kidney disease (AD: adult, AR: children)
- Medullary cystic disease (medullary sponge, nephronopthisis)
- Acquired cystic disease
- Localized renal cysts (simple cysts)
- Renal cysts in hereditary malformation syndromes (TSC)
- Glomerulocystic disease
- Extraparenchymal renal cysts (pyelocalyceal, hilar lymphangitic cysts)
Name 4 common extrarenal manifestations of AD polycystic kidney disease
- Cysts in liver (polycystic liver disease)
- Cysts in spleen, pancreas, lung
- Intracranial berry aneurysms (circle of Willis)
- Mitral valve prolapse
Name the causes and morphology of multicystic renal dysplasia
Cuases: uteropelvic obstruction, ureteral agenesis/atresia, anomalies of lower genitourinary tract
Morphology: gross: enlarged, irregular, multiple cysts of varying sizes
micro: presents of undifferentiated mesenchyme, often with cartilage and immature collecting ducts
RCC: Name 5 risk factor and 5 associated syndromes
Risk factors: smoking, obesity, hypertension, unoposed estrogen, asbestos/petrolium/heavy metals, chronic renal failure, acquired cystic disease
syndromes: TSC, VHL, hereditary clear cell carcinoma, hereditary papillary carcinoma
List 5 paraneoplastic syndromes associated with renal cell carcinoma
- Polycythemia
- Hypercalcemia
- Hypertension
- Hepatic dysfunction
- Virilization
- cushing syndrome
- eosinophilia
- leukemoid reactions
- amyloidosis
Outline the Fuhrman grading system for RCC
- Based on nuclear features with a x10 objective
- Grade according to worst area
- Incorporates nuclear size, nuclear outline, chromatin, nucleolar prominence
- Grade 1: 10 um, round, no nucleoli; Grade 2: 10-15 micron, round, small nucleoli; Grade 3: 14-20 micron, ovan, open chromatin and large nucleoli; Grade 4: >20 micron, pleomorphic, macronucleoli
Describe grossing a kidney and the important sections to take
- Look up history, imaging, orient and weigh specimen
- Measure kidney, fat, tumor, length of ureter
- Margins: renal vein, ureter, renal artery and soft tissue
- Sections: 1/cm of tumor size, with areas of possible sarcomatoid diff.
- Show extent of invasion: large vessels, perinephric fat, renal sinus fat (no capsule here),
- Show normal kidney, adrenal gland if present
What features are necessary to report for RCC?
- histologic type
- invasion into renal vein
- invasion into renal sinus fat/perinephric fat
- Fuhrman nuclear grade
- lymphatic invasion
- Sarcomatoid morphology and quantity
- Geographic necrosis
- Invasion into collecting system/ureter
- Resection margin status
- Assessment of background kidney
Describe the gross features of the main types of RCC
- Clear cell: solitary, well circ., golden-yellow, hemorrhage, necrosis common
- chromophobe: solitary, round, tan-light brown
- papillary: well circumscribed, fibrous pseudocapsule, necrosis/hemorrahge, bilateral/multifocal
- sarcomatoid areas: fish-flesh appearance
What is the most common genetic alteration in clear cell renal cell carcinoma?
Loss of chromosome 3p
Renal papillary adenoma: presentation, histologic features, cut-off for malignancy
Presentation: often incidental, commonly found at autopsy (7-22%)
Gross features: usually less than 0.5 cm, within cortex as pale yellow-gray, well circumscribed nodule
micro: complex, branching papillomatous structures with numerous complex fronds. may form tubules, glands, cords, sheets. Cells are cuboidal/polygonal with regular small nuclei and no atypia
Malignant cut-off: 3 cm, also show same cytogenetic features as papillary rcc (trisomy 7 and 17)
Angiomyolipoma: definition, presentation, pathogenesis
Defn: benign tumor consisting of blood vessels, smooth muscle, fat
Presentation: present in 25-50% of patients with tuberous sclerosis (loss-of-function mutations in TSC1/TSC2 tumor suppressor genes), susceptibilty to spontaenous hemorrhage
Compare the cytogenetics and genetics of sporadic and hereditary clear cell rcc and papillary RCC
- sporadic papillary:
- Cytogenetics: trisomy 7, 16, 17 loss of Y
- Genetics: mutated, activated MET t (X;1) PRCC oncogenes
- Hereditary papillary:
- Cytogenetics: trisomy 7
- Genetics: mutated, activated MET t (X;1)
- Sporadic/hereditary clear cell:
- Cytogenetics: t (3;6) t (3;8) t (3;11)
- Genetics: loss of VHL, inactivated mutated VHL, hypermethylated VHL
List common causes of ureteric obstruction
- Congenital anomalies: posterior urethral valves, urethral strictures, meatal stenosis, bladder neck obstruction, ureteropelvic junction narrowing, severe vesicoureteral reflux
- Urinary calculi
- Benign prostatic hypertrophy
- Tumors (psroste, bladder, retroperitoneal, cervix, uterus)
- inflammation (prostatitis, ureteritis, urethritis, retroperitoneal fibrosis)
- sloughed papillae or blood clots
- pregnancy
- uterine prolapse, cystocele
- functional disorders (neurogenic bladder)
Renal stones: Name 4 main types and their prevalence
- Calcium oxalate and phosphate-70%
- Struvite (magnesium ammonium phosphate) 15-20%
- Uric acid 5-10%
- Cystine 1-2%
Give the general pathogenesis and predisposing conditions for each type of renal stone.
- General pathogenesis: increased urinary concentration of stone’s constituents, such as it exceeds their solubility.
- Predisposing conditions:
- Calcium oxalate: hypercalcemia, hypercalciuria (hyperparathyroidism, diffuse bone disease, sarcoidosis), hyperoxaluria, hyperuricosiura, hypocitraturia, no known
- Struvite: UTI with bacteria that convert urea to ammonia (proteus, some staph)
- Uric acid: hyperuricemia (gout, leukemia), hyperuricosuria, urine pH below 5.5
- cystine: genetic defects in reabsorption of amino acids including cystine
What is the differential diagnosis for spindle-cell tumors of the kidney, and what IHC stains are helpful
- RCC, sarcomatoid component (AE1/AE3+, Cam 5.2+, EMA/MUC1+, desmin -, SMA -, Cd99-, S100-, MelanA-, HMB45-, MiTF neg, CK7-, CAIX-positive
- Mucinous tubular and spindle cell carcinoma (AE1/AE3+, CAM 5.2+, EMA/MUC1+, neg for sarcoma/AML markers, CK7+, CAIX negative
- Sarcoma (focal keratin/ema pos, postitive for desmin/actin in leiyomyosarc, CD99 in synovial sarc, neg. for AML markers, mitF, CK7)
- Angiomyolipoma (cytokeratins negative, positive for esmin, actin, S100, melan A, HMB45, MiTF)
