Flashcards in Kidney Deck (379):
Infantile polycystic kidney disease: Inheritance.
Infantile polycystic kidney disease:
A. Gene and its location.
B. Encoded protein.
A. PKHD1 on chromosome 6p21-23.
B. Polyductin / fibrocystin.
Infantile polycystic kidney disease: Presentation (2).
Stillbirth or early neonatal death in most cases.
Infantile polycystic kidney disease: Associated abnormalities (2).
Congenital hepatic fibrosis.
Infantile polycystic kidney disease: Gross pathology.
Massive enlarged kidneys with smooth surface.
Infantile polycystic kidney disease:
A. Location and arrangement of cysts.
B. Calyceal system.
A. Cortex and medulla; oriented perpendicular to the renal capsule.
Infantile polycystic kidney disease: Histopathology (2).
Dilated collecting ducts lined by bland cuboidal cells.
Nephrons appear normal.
Medullary cystic disease: Presentation.
Renal dysfunction in childhood:
− Polyuria and polydipsia.
− Growth retardation.
Medullary cystic disease: Gross pathology.
Kidneys are small; both are affected.
Medullary cystic disease: Number, size, and location of cysts.
Up to 2 cm in diameter.
Medullary sponge kidney: Presentation.
Found in children or adolescents.
Medullary sponge kidney: Gross pathology.
Kidneys are typically of normal size.
Medullary sponge kidney: Size and location of cysts.
Less than 0.5 cm.
Medullary pyramids, renal papillae; communication with collecting ducts.
Medullary sponge kidney: Prognosis.
Renal function is usually normal.
Progression to end-stage renal disease occurs rarely.
Renal dysplasia: Clinical significance (2).
Dysplastic kidneys usually do not function.
Nearly always accompanied by other abnormalities of the urinary tract.
Renal dysplasia: Presentation (2).
If large: Palpable mass.
If small: May remain asymptomatic for many years.
Renal dysplasia: Possible outcomes in utero (2).
Oligohydramnios with Potter's sequence.
Death from pulmonary hypoplasia.
Renal dysplasia: Gross pathology.
Distorted kidneys with variable of cysts.
Renal dysplasia: Histopathology (3).
Disorganized renal parenchyma containing cartilage.
Dysplastic ducts lined by columnar epithelium and surrounded by spindle cells.
Cystic spaces lined by flat epithelium.
Adult polycystic kidney disease: Type of inheritance.
Adult polycystic kidney disease: Genes, locations, proteins (2).
PKD1, chromosome 16, polycystin 1.
PKD2, chromosome 4, polycystin 2.
Presentation of adult polycystic kidney disease:
A. Age of patient.
B. Laboratory abnormalities (2).
A. Fourth or fifth decade.
B. Hematuria or proteinuria.
Adult polycystic kidney disease: Extrarenal manifestations (4).
Cysts in pancreas, liver.
Cardiac valvular abnormalities.
Adult polycystic kidney disease: Gross pathology (2).
Early: Normal-sized kidneys with a few cysts.
Later: Markedly enlarged kidneys with irregular contour due to cysts.
Adult polycystic kidney disease: Size and location of cysts.
From a few millimeters to several centimeters in diameter.
Cortical and medullary.
Adult polycystic kidney disease: Histopathology (2).
Cysts: Flat or cuboidal epithelial lining.
Parenchyma: Fibrosis, atrophy.
Adult polycystic kidney disease: Complications (2).
End-stage renal disease.
Acquired cystic disease: Presentation (2).
Cysts develop in the setting of chronic renal failure, usually dialysis dependent.
Acquired cystic disease:
B. Extrarenal manifestations.
Acquired cystic disease:
A. Gross pathology.
B. Size and location of cysts.
A. Kidneys are moderately enlarged at the most.
B. Variable as in ADPKD; cortical.
Acquired cystic disease: Parenchymal changes.
Acquired cystic disease: Complication.
Renal-cell carcinoma (can arise in a cyst or in the parenchyma).
Xanthogranulomatous pyelonephritis: Clinical significance.
Can form mass(es) and mimic renal neoplasia.
Xanthogranulomatous pyelonephritis: Most common agents (2).
Xanthogranulomatous pyelonephritis: Associated renal disease.
Xanthogranulomatous pyelonephritis: Progression.
Begins in renal pyramids and spreads to renal pelvis and then to capsule and to perinephric fat.
Xanthogranulomatous pyelonephritis: Gross-pathologic types (2).
Diffuse: More common.
Segmental: Polar; occurs in children.
Xanthogranulomatous pyelonephritis: Histopathologic zones of a nodule.
Inner: Necroinflammatory debris that is rich in neutrophils.
Outer: Lipid-laden macrophages.
Outermost (sometimes): Multinucleate giant cells, spindled fibroblasts.
Xanthogranulomatous pyelonephritis: Histopathologic pitfalls (2).
Lipid-laden macrophages may be confused with RCC.
Multinucleate giant cells and spindled fibroblasts may be confused with sarcomatoid carcinoma.
Most tumors are sporadic.
Angiomyolipoma: Relation to tuberous sclerosis (2).
20% of tumors as associated with TS.
Most patients with TS develop an angiomyolipoma.
Angiomyolipoma: Relation of inheritance to gross pathology (2).
Sporadic: Large, single, unilateral.
TS: Smaller, multiple, bilateral.
Thick-walled hyalinized blood cells.
Angiomyolipoma: Possible atypical gross findings (2).
Presence of tumor in renal vein or in regional lymph nodes.
Angiomyolipoma: Possible atypical histopathologic features (3).
Epithelioid smooth-muscle cells.
Angiomyolipoma: Immunohistochemistry (2,1).
Positive: Melanocytic markers, smooth-muscle markers.
Negative: Epithelial markers.
Angiomyolipoma: Importance of careful sampling.
To exclude a coexisting renal-cell carcinoma.
A. Potentially malignant but unlikely to metastasize.
B. Flank pain or no symptoms.
Epithelioid angiomyolipoma: Radiography.
Lack of fat imparts resemblance to RCC.
Epithelioid angiomyolipoma: Association.
Epithelioid angiomyolipoma: Gross pathology (3).
Solid, hemorrhagic cut surface.
More likely than conventional angiomyolipoma to be necrotic.
Epithelioid angiomyolipoma: Cellular components (3).
Short spindle cells.
Large epithelioid cells.
Pleomorphic cells that resemble ganglion cells or multinucleate giant cells.
Epithelioid angiomyolipoma: Immunohistochemistry.
Similar to that of conventional angiomyolipoma.
Epithelioid angiomyolipoma: Significance of invasion of renal vein.
Observed more frequently in clinically malignant cases.
Epithelioid angiomyolipoma: Sites of metastasis (4).
A. Age group.
B. Possible "paraneoplastic" finding.
A. Most common in the fifth decade.
Metanephric adenoma: Cytology.
Small, bland cells with dark nuclei and scant cytoplasm.
Metanephric adenoma: Histologic architecture (3).
Small, tightly packed acini in an acellular stroma.
− Papillary foci.
− Solid (blastema-like) foci.
Metanephric adenoma: Immunohistochemistry (3,2).
Positive: Pancytokeratin, CD57, WT-1.
Negative: CK7, AMACR, CD56.
Metanephric adenoma: Electron microscopy (2).
Basal lamina, microvilli.
Metanephric adenoma: Mutation.
V600E in BRAF.
Metanephric adenoma: Behavior.
The nuclear grading system of Fuhrman.
1: 20 μm, pleomorphic, open or dark chromatin, macronucleolus.
Papillary adenoma: Associations (3).
von Hippel−Lindau syndrome.
B. Histologic architectural patterns (3).
A. Less than 5 mm.
B. Tubular, papillary, or both.
Papillary adenoma: Cytology (2).
Bland cuboidal cells.
Nuclei correspond with Fuhrman grades 1 and 2.
Papillary adenoma: Other histologic features (2).
Papillary adenoma: Disqualifying cytologic feature.
Papillary adenoma: Immunohistochemistry (2,1).
Positive: CK7, AMACR.
Papillary adenoma: Mutations (3).
+7, +17, -Y.
Renal oncocytoma: Radiography.
Central scar ("spoke-wheel" appearance).
Renal oncocytoma: Histologic patterns (3).
Classic: Well-defined nests of oncocytes.
Tubulocystic: Tubules and cysts contain eosinophilic secretions.
Mixed: Nests and tubules.
Renal oncocytoma: "Tolerable" histopathologic anomalies (3).
Occasional smudged nuclei.
Occasional clear cells.
Focal extension into perinephric fat.
Renal oncocytoma: Features that are incompatible with the diagnosis (4).
Gross extension into the perinephric fat.
Sarcomatoid or spindle-cell areas.
Atypical mitotic figures.
Renal oncocytoma: Immunohistochemistry (4,1),
Positive: CK7, S100, E-cadherin, claudin 8 (cytoplasmic).
Renal oncocytoma: Special stain.
Negative: Hale's colloidal iron.
Renal oncocytoma: Mutation.
t(5;11) in some cases.
Renal oncocytoma vs. clear-cell RCC with eosinophilic cytoplasm: Immunohistochemistry (3).
Clear-cell RCC expresses vimentin but neither CK7 nor E-cadherin.
Renal oncocytosis: Causes (2).
Chronic renal failure.
Renal oncocytoma: Putative origin.
Intercalated cells of the collecting ducts.
Birt-Hogg-Dubé syndrome: Renal tumor.
Combines features of renal oncocytoma and chromophobe RCC.
Renal-cell carcinoma, clear-cell type: Classic presentation.
Pain, flank mass, hematuria: Reported in only 10% of patients.
Renal-cell carcinoma, clear-cell type: Genes (4).
Renal-cell carcinoma, clear-cell type vs. clear-cell papillary renal-cell carcinoma: Immunohistochemistry.
Clear-cell papillary renal-cell carcinoma . . .
− Positive: CK7 and keratin 34βE12.
− Negative: CD10, AMACR.
Both tumors express CA9.
Renal-cell carcinoma, clear-cell type vs. adrenocortical carcinoma: Immunohistochemistry (2).
Adrenocortical carcinoma . . .
− Positive: Inhibin, calretinin.
− Negative: EMA, cytokeratins.
Clear-cell papillary renal-cell carcinoma: Cytology (2).
Clear cells with low-grade nuclei.
Nuclei are oriented away from the basement membrane and toward the lumen.
Renal-cell carcinoma, papillary type: Syndrome, gene, location.
Hereditary papillary RCC syndrome: c-met on chromosome 7q31.
Renal-cell carcinoma, papillary type: Gross pathology (2).
May be multifocal or bilateral.
Renal-cell carcinoma, papillary type, type I: Histopathology.
Papillae are lined by a single layer of cells with low-grade nuclear features and scant cytoplasm.
Renal-cell carcinoma, papillary type, type II: Histopathology.
Papillae are lined by pseudostratified cells of higher nuclear grade and much cytoplasm.
Renal-cell carcinoma, papillary type: Cytokeratins.
CK7 is expressed by 80% of tumors of type I and by 20% of tumors of type II.
Renal-cell carcinoma, papillary type: Additional immunohistochemical stains (3).
Positive: RCC antigen, CD10, PAX8.
Renal-cell carcinoma, papillary type: Mutations (3).
+7, +17, -Y.
No mutation of VHL.
Renal-cell carcinoma, chromophobe type: Syndrome.
Renal-cell carcinoma, chromophobe type: Histopathology.
Thick cell membranes resembling walls of plant cells.
Koilocyte-like wrinkled nuclei with halo.
Thick-walled, hyalinized blood vessels.
Renal-cell carcinoma, chromophobe type: Histopathologic types.
Classic: Pale cytoplasm.
Eosinophilic: Intensely eosinophilic cytoplasm.
Renal-cell carcinoma, chromophobe type: Electron microscopy (2),
Classic: Many microvesicles.
Eosinophilic: Many mitochondria.
Renal-cell carcinoma, chromophobe type vs. oncocytoma: Stains (3).
Renal-cell carcinoma, chromophobe type . . .
− CK7, Hale's colloidal iron: Diffusely positive.
− S100A1: Not expressed.
Renal-cell carcinoma, chromophobe type: Prognosis.
Significantly better than that of clear-cell RCC.
Multilocular cystic renal-cell carcinoma: Gross pathology.
Concysts entirely of sists filled with serous or hemorrhagic fluid.
Multilocular cystic renal-cell carcinoma: Histopathology.
Cysts are lined by one layer of epithelium.
Fibrous septa contain small clusters of clear cells.
Multilocular cystic renal-cell carcinoma vs. renal-cell carcinoma with cystic change.
The former contains no solid, expansile tumor nodules of any size.
Multilocular cystic renal-cell carcinoma: Prognosis.
Carcinoma of the collecting ducts: Location.
Carcinoma of the collecting ducts: Histopathologic architecture (2).
Tubular or tubulopapillary structures with tapered ends.
Inflamed desmoplastic stroma.
Carcinoma of the collecting ducts: Cytology (4).
Hobnail appearance of cells that line glands.
Many mitotic figures.
Cytoplasm may contain mucin.
Carcinoma of the collecting ducts: Adjacent renal tissue.
Shows epithelial dysplasia.
Carcinoma of the collecting ducts: Immunohistochemistry (5,1).
Positive: HMWCK, CK7, CEA, peanut agglutinin, Ulex europaeus agglutinin.
Carcinoma of the collecting ducts vs. papillary renal-cell carcinoma: Immunohistochemistry.
Papillary renal-cell carcinoma does not express HWMCK or Ulex europaeus agglutinin.
Carcinoma of the collecting ducts vs. urothelial carcinoma with glandular differentiation.
Urothelial carcinoma with glandular differentiation is more likely if the tumor arises in the calyces or the renal pelvis.
Carcinoma of the collecting ducts: Prognosis.
Poor; one third of patients present with metastases.
Renal medullary carcinoma: Epidemiology.
Near all patients have sickle-cell trait or the disease.
Patients are typically under 40 years old.
Renal medullary carcinoma: Gross pathology.
Arises in the medulla but tends to extend into the calyces and often into the perinephric fat.
Renal medullary carcinoma: Histopathologic patterns (3).
Areas that resemble yolk-sac tumor at low power.
Areas that resemble adenoid-cystic carcinoma.
Renal medullary carcinoma: Cytology.
Poorly differentiated cells with vesicular nuclei and a large nucleolus.
Renal medullary carcinoma: Stroma.
Desmoplastic and inflamed and may contain mucin or edema.
Renal medullary carcinoma: Blood vessels.
Contain sickle cells.
Usually invaded by the tumor.
Renal medullary carcinoma: Immunohistochemistry (1,2).
Negative: HMWCK, INI-1.
Renal medullary carcinoma: Prognosis.
Most patients are dead within 1 year.
Mucinous tubular and spindle-cell carcinoma:
A. Usually asymptomatic.
B. Low-grade carcinoma with a good prognosis.
Mucinous tubular and spindle-cell carcinoma: Histopathologic components (3).
Elongated and compressed tubules.
Spindle-shaped epithelial cells.
Extracellular mucinous Krappe.
Mucinous tubular and spindle-cell carcinoma: Cytology.
Bland cells with inconspicuous nucleoli.
Mucinous tubular and spindle-cell carcinoma: Immunohistochemistry (2,2).
Positive: Cytokeratins, AMACR.
Negative: CD10, villin (markers of proximal tubules).
Renal-cell carcinoma with translocations involving TFE3: Epidemiology.
Affects mainly children and young adults.
Renal-cell carcinoma with translocations involving TFE3: Location of TFE3 gene.
Renal-cell carcinoma with translocations involving TFE3: Most common translocation partners of TFE3 (2).
ASPL (17q25): Advanced stage at presentation.
Renal-cell carcinoma with translocations involving TFE3: Histopathologic patterns (2).
Papillary and nested.
Renal-cell carcinoma with translocations involving TFE3: Cytology (4).
Clear or pink cytoplasm.
Discrete cell borders.
Renal-cell carcinoma with translocations involving TFE3: Extracellular features (2).
Renal-cell carcinoma with translocations involving TFE3: Effect of translocation partner on histopathology (2).
ASPL: Cells have more cytoplasm; more psammoma bodies, more hyaline nodules.
PRCC: Less of all three.
Renal-cell carcinoma with translocations involving TFE3: Immunohistochemistry (4).
Positive: TFE3, cathepsin K, CD10, RCC.
Renal-cell carcinoma with t(6;11):
A. Affects mainly children and young adults.
B. Similar to that of conventional RCC.
Renal-cell carcinoma with t(6;11): Gene.
TFEB on chromosome 6p21.
Renal-cell carcinoma with t(6;11): Cellular components (2).
Polygonal epithelioid cells with discrete borders.
Smaller cells with dark nuclei, forming clusters around hyaline matter.
Mitotic figures are rare.
Renal-cell carcinoma with t(6;11): Architecture.
Renal-cell carcinoma with t(6;11): Immunohistochemistry (2,2).
Positive: TFEB, melanoma markers.
Negative: TFE, epithelial markers.
Renal-cell carcinoma associated with neuroblastoma: Timing.
Diagnosed around 10 years after the original diagnosis of neuroblastoma.
Sarcomatoid differentiation in renal-cell carcinoma:
A. Can occur in any type of renal-cell carcinoma.
B. Imparts poor prognosis.
Sarcomatoid differentiation in renal-cell carcinoma: Histopathology (3).
Nondescript spindle cells.
May resemble MFH.
May resemble leiomyosarcoma or other differentiated sarcoma.
Sarcomatoid differentiation in renal-cell carcinoma: Immunohistochemistry.
May express epithelial markers and PAX8.
May not express other markers that are expressed in the better-differentiated parts of the tumor.
Renal tumors that contain spindle cells (4).
Any carcinoma with sarcomatoid differentiation.
Any carcinoma (esp. conventional) containing a scar.
Mucinous tubular and spindle-cell carcinoma.
Primary renal sarcoma.
Renal-cell carcinoma, unclassified: Examples of histopathology (3).
A tumor combining features of recognized renal tumors.
A tumor showing sarcomatoid differentiation only.
A high-grade tumor.
Cystic nephroma: Typical patient.
Cystic nephroma: Presentation and behavior.
Asymptomatic and benign.
Cystic nephroma: Gross pathology.
Consists of many cystic spaces that do not communicate with the renal pelvis.
Cystic nephroma: Histopathology (2).
Cysts lined by bland cells.
Ovarian-type or hyalinized stroma.
Cystic nephroma: Disqualifying histopathologic feature.
Nephronic elements in the stroma.
Cystic nephroma: Immunohistochemistry.
Ovarian-type stroma expresses ER and PR.
Cystic nephroma: Significance of pediatric type.
Considered a variant of nephroblastoma.
Cystic nephroma vs. nephrogenic adenoma vs. metanephric adenoma.
Cystic nephroma: Bland cysts and ovarian-type stroma.
Nephrogenic adenoma: Renal-tubular-like proliferation outside the kidneys.
Metanephric adenoma: Small acini consisting of small, dark cells.
Mixed epithelial and stromal tumor: Epidemiology and putative etiology.
Mostly in females; estrogen imbalance.
Mixed epithelial and stromal tumor: Gross pathology (2).
Central location in the kidney.
Contains cystic (epithelial) and solid (stromal) areas.
Mixed epithelial and stromal tumor vs. cystic nephroma.
− Epithelial component: Tubules as well as cells.
− Stromal component: Grossly evident; histologically more variable (e.g. fat, smooth muscle).
Both tumors are considered part of the same spectrum.
Tubulocystic carcinoma: Typical patient.
Tubulocystic carcinoma: Gross pathology (3).
Entirely cystic, resembling bubble wrap.
Well circumscribed but has no capsule.
Tubulocystic carcinoma: Histopathology.
Closely packed cysts separated by delicate septa or a fibrotic stroma.
No tumor cells in those septa.
Tubulocystic carcinoma: Cytology.
Cells resemble hobnails and contain large nucleoli.
Tubulocystic carcinoma: Immunohistochemistry (2,1).
Positive: CD10, AMACR.
Tubulocystic carcinoma vs. multilocular cystic renal-cell carcinoma.
Multilocular cystic renal-cell carcinoma: Nests of clear cells in the septa.
Clear-cell tubulopapillary renal-cell carcinoma: Behavior.
Low grade, low stage.
Clear-cell tubulopapillary renal-cell carcinoma: Gross pathology.
Cystic; fibrous capsule.
Clear-cell tubulopapillary renal-cell carcinoma: Architecture (3).
Papillae, tubules, cysts.
Clear-cell tubulopapillary renal-cell carcinoma: Cytology.
Bland nuclei (Fuhrman grade 1 or 2).
Nuclei are oriented toward the lumens and away from the basement membranes.
Clear-cell tubulopapillary renal-cell carcinoma: Cytogenetics.
No +7, +17, -Y.
Clear-cell tubulopapillary renal-cell carcinoma: Immunohistochemistry (2,2).
Positive: CK7 (membranous), CA9.
Negative: AMACR, CD10.
B. Tumors (3).
A. Autosomal dominant.
B. Leiomyomas, uterine leiomyosarcoma, renal-cell carcinoma.
Hereditary leiomyomatosis: Gene and its location.
Fumarate hydratase on 1q42.
Renal-cell carcinoma of hereditary leiomyomatosis: Architecture.
Similar to that of papillary RCC, type II.
Renal-cell carcinoma of hereditary leiomyomatosis: Cytology.
Large nucleus contains a very large, red nucleolus with a clear halo.
Renal-cell carcinoma of hereditary leiomyomatosis: Immunohistochemistry.
Positive: 2SC (2-succinylcysteine).
Renal-cell carcinoma of hereditary leiomyomatosis: Prognosis.
Birt-Hogg-Dubé syndrome: Skin tumors (3).
Birt-Hogg-Dubé syndrome: Gene, location, product.
BHD, 17p11.2, folliculin.
Renal-cell carcinoma associated with Birt-Hogg-Dubé syndrome: Histopathology (3).
Oncocytoma + chromophobe RCC.
Oncocytosis outside the tumor.
Clear cells without wrinkled nuclei.
Renal-cell carcinoma associated with Birt-Hogg-Dubé syndrome: Immunohistochemistry (3).
Positive: CK7, CD117, parvalbumin.
Renal-cell carcinoma associated with Birt-Hogg-Dubé syndrome: Prognosis.
Excellent; no aggressive behavior reported.
SDH syndrome: Tumors (3).
Paraganglioma / pheochromocytoma.
Gastrointestinal stromal tumor.
SDH syndrome: Genes.
SDHB, SDHC, SDHD: Subunits of succinate dehydrogenase in Krebs' cycle.
Renal-cell carcinoma of SDH syndrome: Mean age at presentation.
Renal-cell carcinoma of SDH syndrome: Histopathology (2).
Mutation in SDHB: Consists of oncocytes containing large vacuoles and bland nuclei.
Mutation in SDHC or SDHD: Resembles clear-cell RCC.
Renal-cell carcinoma of SDH syndrome: Prognosis.
May be aggressive, especially in younger patients.
Renal-cell carcinoma associated with acquired cystic disease: Risk factors (2).
Renal-cell carcinoma associated with acquired cystic disease: Architecture.
Mixture of sheets, nests, tubulopapillary areas, and cystic areas.
Renal-cell carcinoma associated with acquired cystic disease: Cytology (2).
Nuclei of Fuhrman grade 3.
Renal-cell carcinoma associated with acquired cystic disease: Intracellular features (2).
Renal-cell carcinoma associated with acquired cystic disease: Extracellular feature.
Renal-cell carcinoma associated with acquired cystic disease: Immunohistochemistry (2,3).
Positive: AMACR, CD10.
Negative: CA9, PAX8, CK7.
Renal medullary interstitial-cell tumor / medullary fibroma: Presentation.
Asymptomatic; found incidentally.
Renal medullary interstitial-cell tumor / medullary fibroma: Histopathology.
Medullary tubules entrapped in a paucicellular matrix that is collagenous or myxoid.
Renal medullary interstitial-cell tumor / medullary fibroma: Cell of origin.
Renal medullary interstitial cell, which helps to control the blood pressure.
Juxtaglomerular-cell tumor: Presentation.
Juxtaglomerular-cell tumor: Laboratory findings (3).
Elevated plasma renin.
Juxtaglomerular-cell tumor: Location.
Juxtaglomerular-cell tumor: Architecture (3).
Trabeculae or glomeruloid formations.
Myxoid stroma containing lymphocytes.
Juxtaglomerular-cell tumor: Cytology (3).
Polygonal or spindle shape.
Moderate or abundant pink, granular cytoplasm.
Juxtaglomerular-cell tumor: Immunohistochemistry (2,3).
Positive: CD31, actins.
Negative: Cytokeratins, desmin, melanoma markers.
Juxtaglomerular-cell tumor: Electron microscopy.
Rhomboid crystals of renin.
Juxtaglomerular-cell tumor: Prognosis.
Never reported to recur or metastasize.
Nephroblastoma: Age group.
Children below the age of 6.
Nephroblastoma: Syndromes (4).
A. Wilms' tumor, aniridia, genital anomalies, mental retardation.
B. del(11p13), including WT1.
Denys-Drash syndrome: Mutation.
Point mutation in WT1.
WT2 on 11p15.
Nephroblastoma: Typical presentation.
Abdominal mass or tenderness.
A. Histological components (3).
A. Blastemal, stromal, epithelial.
B. Only two or only one component may be represented.
Consists of small, round, blue cells with coarse chromatin.
Nephroblastoma: Stroma (2).
Myxoid or fibromyxoid.
May show differentiation toward skeletal muscle, cartilage, etc.
Nephroblastoma: Epithelial component (2).
Poorly or well-formed tubules and papillae.
Squamous or mucinous foci may be seen.
Nephroblastoma: Definition of nuclear anaplasia (3).
− or −
Multipolar mitotic figures
− or −
Greater-than-threefold variation in nuclear size.
Nephroblastoma: Significance of nuclear anaplasia.
Predicts responsiveness to chemotherapy.
Nephroblastoma: Immunohistochemistry for WT1.
Blastema and undifferentiated epithelium: Diffuse expression.
Stroma: Little or no expression.
Differentiated epithelium: Variable.
Nephroblastoma: Distinction from other tumors of small, round, blue cells (2).
IHC: Expression of WT-1 by nephroblastoma.
EM: Variety of organelles in blastemal cells of nephroblastoma.
Nephroblastoma: Sites of metastasis (3).
Lymph nodes, liver, lung.
Nephroblastoma: Prognosis (2).
About 90% of cases get cured.
Younger patients do better.
B. State of multiplicity.
A. Increased likelihood of contralateral nephroblastoma.
Nephroblastoma: Histopathology (2).
Perilobar type: Mainly blastema and tubules; very little stroma.
Intralobar type: Rich in stroma.
Cystic partially differentiated nephroblastoma: Histopathology (3).
Epithelial-lined cysts or unlined cyst-like structures.
Septa may contain nephroblastomatous epithelium.
No expansile solid component.
Cystic partially differentiated nephroblastoma: Variant.
Pediatric cystic nephroma contains no nephroblastomatous elements.
Cystic partially differentiated nephroblastoma vs. Cystic nephroblastoma.
The latter has an expansile solid component.
Mesoblastic nephroma: Epidemiology (2).
Patients are usually no more than 3 months old.
Most frequent congenital renal neoplasm.
Mesoblastic nephroma: Presentation.
Mesoblastic nephroma: Behavior (2).
Excellent if completely resected.
Mesoblastic nephroma: Location.
Mesoblastic nephroma: Gross pathology (2).
Classic: Small; firm; resembles leiomyoma.
Cellular: Large; soft; cystic; focally hemorrhagic and necrotic.
Mesoblastic nephroma: Histopathology of classic type.
Resembles benign fibromatosis.
Mesoblastic nephroma: Histopathology of cellular type.
Sheets or vague fascicles of densely packed, plump, mitotically active cells.
Same as infantile fibrosarcoma.
Mesoblastic nephroma: Immunohistochemistry (2).
Positive: SMA, vimentin.
Mesoblastic nephroma: Electron microscopy.
Much endoplasmic reticulum.
Mesoblastic nephroma: Translocation.
Mesoblastic nephroma vs. cystic nephroma.
Mesoblastic nephroma: Spindle-cell mesenchymal tumor in infants.
Cystic nephroma: Bland cysts and ovarian-type stroma; occurs mainly in women.
Mesoblastic nephroma vs. metanephric adenoma.
Mesoblastic nephroma: Spindle-cell mesenchymal tumor in infants.
Metanephric adenoma: Small acini consisting of small, dark cells; occurs in adults.
Clear-cell sarcoma: Age group.
Between 6 months and 5 years.
Clear-cell sarcoma: Cytology of classic type (3).
Clear-cell sarcoma: Histopathology of classic type (2).
Cells form cords that are separated by regularly spaced fibrovascular arcades.
Normal renal structures are entrapped at the periphery of the tumor.
Clear-cell sarcoma: Variants (3).
Myxoid, sclerosing, epithelioid, many others.
Clear-cell sarcoma: Immunohistochemistry (2,3).
Positive: Vimentin, nerve-growth-factor receptor.
Negative: Cytokeratins, neural markers, WT1.
Clear-cell sarcoma: Prognosis.
Rhabdoid tumor: Age at presentation.
Usually less than 2 years.
A. Laboratory findings.
B. Associated tumor.
A. Hypercalcemia, hematuria.
B. PNET of the posterior fossa.
Rhabdoid tumor: Cytology.
Cytoplasm: Abundant, pink; often contains large eosinophilic globular inclusions.
Nucleus: Vesicular; thick membrane.
Rhabdoid tumor: Immunohistochemistry (1,1).
Positive: Epithelial markers.
Rhabdoid tumor: Electron microscopy.
Intermediate filaments make up the cytoplasmic inclusions.
Rhabdoid tumor: Mutation.
Inactivation of INI-1 (hSNF5) on chromosome 22.
Rhabdoid tumor: Prognosis.
Bad enough in older children; dismal in infants.
Metastasis to the kidney: Leading primary sites (5).
Metastasis to the kidney: Location.
Cortex or medulla (or both).
Diseases of podocytes: Laboratory finding.
Minimal-change disease: Epidemiology (2).
Most patients are young children.
Adults can be affected, particularly secondary to nephrotoxins.
Minimal-change disease: Histopathology.
Normal by H&E and by special stains.
Minimal-change disease: Electron microscopy (4).
Loss of foot processes.
Extensive microvillous transformation.
Generally normal glomerular basement membrane.
Focal-segmental glomerulosclerosis: Laboratory findings (2).
Focal-segmental glomerulosclerosis: Etiologies (5).
Focal-segmental glomerulosclerosis: Electron microscopy (4).
Loss of foot processes.
Wrinkled glomerular basement membranes.
HIV-associated FSGS: Tubuloreticular inclusions may be seen.
Renal diseases of collagen: Affected parts of the nephron.
Glomerular basement membrane and/or mesangium.
Disorders of collagen, type IV (3).
Benign familial hematuria: Hematuria only; no progression.
Thin-basement-membrane disease: Hematuria; usually no progression.
Alport's syndrome: Hematuria and proteinuria.
Alport's syndrome: Additional manifestations (2).
X-linked type: Ocular abnormalities, sensorineural deafness.
Alport's syndrome: Electron-microscopic changes in the glomerular basement membrane (3).
Variations in thickness, sometimes with breaks.
"Basket-weave" alternation of dense and lucent areas.
Multilamellation and scalloping.
Alport's syndrome: Prognosis.
X-linked Alport's syndrome: End-stage renal disease in 90% of patients by age 40.
Alport's syndrome: Mutations (2).
Most cases of X-linked disease: COL4A5.
Some cases of AR or AD disease: COL4A3 or COL4A4.
Alport's syndrome: Histopathology of early lesion.
Alport's syndrome: Histopathology of the glomerulus in a late lesion.
Irregular thickness of glomerular basement membrane.
Segmental solidification of the glomerular tuft (as in FSGS).
Alport's syndrome: Histopathology of the renal interstitium in a late lesion.
Fibrosis with tubular atrophy.
Sclerosis and hyalinosis of arterioles.
Glomerular basement membrane: Normal thickness.
At least 200 nm.
Thrombotic microangiopathies: Components (2).
Thrombotic microangiopathies: Examples (6).
Renal crisis of scleroderma.
Iatrogenic thrombotic microangiopathy.
Thrombotic microangiopathies: Histopathology of acute glomerular disease (2).
Thickened walls of capillaries.
Thrombotic microangiopathies: Histopathology of chronic glomerular disease (2).
Membranoproliferative features with double contours ("tram-track" appearance).
Mesangial and global sclerosis.
Thrombotic microangiopathies: Histopathology of chronic interstitial disease (2).
Thrombotic microangiopathies: Histopathology of malignant hypertension (2).
"Onion-skin" appearance of blood vessels.
Extreme duplication of elastic lamina.
ANCA-mediated vasculitis of small vessels: Presentation (3).
Hematuria, proteinuria, rapid progression to renal failure.
Signs of systemic vasculitis.
ANCA-mediated vasculitis of small vessels: Types of ANCA.
c-ANCA: Proteinase 3.
ANCA-mediated vasculitis of small vessels: Pathogenesis.
The ANCAs activate neutrophils, which injure the endothelium.
ANCA associated with
A. Wegener's granulomatosis.
B. Microscopic polyangiitis.
C. Churg-Strauss syndrome.
D. Renal-limited glomerulonephritis.
ANCA-mediated vasculitis of small vessels: Glomerular changes (2).
Cellular crescents progress to segmental glomerular scars.
Bowman's capsule may be occluded or disrupted.
ANCA-mediated vasculitis of small vessels:
A. Contents of cellular crescents (4).
B. Contents of glomerular scars.
A. Parietal epithelial cells, podocytes, inflammatory cells, fibrinoid necrotic débris.
B. More fibroblasts and fibrin.
ANCA-mediated vasculitis of small vessels: Extraglomerular vascular changes (2).
Transmural arteritis with fibrinoid necrosis.
ANCA-mediated vasculitis of small vessels: Other changes (3).
Interstitial granulomas in Wegener's granulomatosis.
Acute tubular injury in aggressive forms.
Anti-glomerular-basement-membrane disease: Epidemiology (2).
Anti-glomerular-basement-membrane disease: Presentation (2).
Acute renal failure with hematuria and proteinuria.
Anti-glomerular-basement-membrane disease: Pathogenesis.
Antibodies against the noncollagenous-1 domain of the α₃ chain of collagen, type IV.
Anti-glomerular-basement-membrane disease: Relevance to HLA type.
Strongly associated with HLA-DR and HLA-DQ.
Anti-glomerular-basement-membrane disease: Histopathology (4).
Cellular crescents involving all glomeruli.
Progression of crescents to segmental glomerular scars.
Acute tubular injury in aggressive forms.
Anti-glomerular-basement-membrane disease: Serologic diagnosis (3).
DIF: Linear pattern of IgG on the GBM.
IIF: Anti-GBM antibodies in patient's serum react with normal kidney.
Immune-complex-mediated glomerular diseases: Types (3).
Infection-mediated glomerular diseases.
IgA-mediated glomerular diseases.
Membranous glomerulopathy: Presentation.
Nephrotic syndrome progressing to ESRD in 30% of cases.
Membranous glomerulopathy: Etiologies (5).
Primary: Idiopathic, congenital.
Secondary: HCV, HBV, syphilis.
Membranous glomerulopathy: Pathogenesis of idiopathic form.
Antibodies to phospholipase-A2 receptors in podocytes.
Membranous glomerulopathy: Histopathology (3).
Thickening of the GBM.
Mesangial expansion and proliferation.
Glomerulitis in cases associated with malignancy.
Membranous glomerulopathy: Special stain.
Silver stain: Spikes and/or gaps in the GBM.
Membranous glomerulopathy: Direct immunofluorescence (2).
GBM: IgG, C3, kappa, lambda in granular pattern.
Tubular basement membrane: Deposits seen in secondary forms.
Membranous glomerulopathy: Type of IgG (2).
Primary: Mainly IgG4.
Neoplastic: IgG1, IgG2.
Membranous glomerulopathy: Electron microscopy
Extensive effacement of foot processes.
Subepithelial electron-dense deposits.
Secondary forms: Deposits in mesangium, tubular basement membrane.
Infection-mediated glomerular disease: Laboratory findings (3).
Infection-mediated glomerular disease: Presentation.
Infection-mediated glomerular disease: Etiologies (6).
Viruses, rickettsiae, fungi, parasites.
Infection-mediated glomerular disease: Special stain.
Trichrome stain may show subepithelial humps.
Infection-mediated glomerular disease: Electron microscopy (2).
Subepithelial humps with effacement of overlying foot processes.
Subendothelial, intramembranous, and mesengial electron-dense deposits.
Infection-mediated glomerular disease: Direct immunofluorescence (2).
Granular pattern in basement membrane and mesangium
− Most cases: IgG and C3.
− MRSA-related: IgA and C3.
IgA-related nephropathies: Epidemiology.
Common in Asians; rare in blacks.
IgA-related nephropathies: Clinical presentations (2).
Asymptomatic: Occult hematuria and proteinuria.
Symptomatic: Nephritic syndrome.
A. Laboratory finding.
A. Normal serum complement levels.
B. Recurs in 30% of transplants.
IgA-related nephropathies: Pathophysiology (2).
Abnormal glycosylation of IgA1.
Increased production of IgA.
IgA-related nephropathies: Relevance to HLA type.
Associated with HLA-DQ.
IgA-related nephropathies: Histopathology (2).
Variable; may resemble other glomerular diseases.
Diagnosis requires immunofluorescence.
IgA-related nephropathies: Direct immunofluorescence.
IgA, kappa, lambda, C3, generally in a mesangial pattern.
IgA-related nephropathies: Electron microscopy (3).
Basement membrane: Variable thinning; deposits in some cases.
Foot processes: Variable effacement.
IgA-related nephropathy vs. ANCA-associated vasculitis.
Significant mesangial proliferation favors an IgA-related nephropathy.
IgA-related nephropathy vs. FSGS.
Demonstration of mesangial deposits (by DIF or EM) favors an IgA-related nephropathy.
Membranoproliferative glomerulonephritis: Classification.
Types I and III: Mediated by immune complexes.
Type II: Mediated by complement; now known as dense-deposit disease.
Immune-complex-mediated membranoproliferative glomerulonephritis:
A. Children and young adults.
B. Both nephrotic syndrome and nephritic syndrome.
Immune-complex-mediated membranoproliferative glomerulonephritis:
A. Laboratory finding.
B. Etiologies (2).
A. Decreased serum complement.
B. HCV; idiopathic.
Immune-complex-mediated membranoproliferative glomerulonephritis, type I: Constant histopathologic feature.
Double contours formed by interposition of mesangial cytoplasm and deposits.
Immune-complex-mediated membranoproliferative glomerulonephritis, type III of Burkholder: Histopathology.
Features of MPGN I + mesangial proliferation and diffuse thickening of capillary walls.
Immune-complex-mediated membranoproliferative glomerulonephritis, type III of Anders and Strife: Histopathology (2).
Features of MPGN I + irregular thickening of capillary walls.
Less mesangial proliferation than in type III of Burkholder.
Immune-complex-mediated membranoproliferative glomerulonephritis, type III of Anders and Strife: Special stain.
Silver stain shows non-staining ("moth-eaten") areas of basement membrane.
Immune-complex-mediated membranoproliferative glomerulonephritis: Direct immunofluorescence.
"Lumpy-bumpy" deposits of IgG and C3 in mesangium and capillary walls.
Electron microscopy of immune-complex-mediated membranoproliferative glomerulonephritis:
A. Type I.
B. Type III of Burkholder.
C. Type III of Anders and Strife.
A. Double contours.
B. Double contours and numerous subepithelial deposits.
C. Double contours and deposits all throughout the basement membrane.
A. Age group.
A. Children and young adults.
B. Both nephrotic and nephritic syndromes.
C3 glomerulopathies: Pathogenesis.
Dysfunction of the alternative pathway of complement.
C3 glomerulopathies: Type (2).
C3 glomerulonephritis: Similar to MPGN I and III, but without immune complexes.
C3 glomerulopathies: Histopathology (2).
C3 glomerulonephritis: Variable.
DDD: Irregular thickening of basement membrane; mild mesangial proliferation.
C3 glomerulopathies: Special stains (2).
Silver stain and PAS
− C3 glomerulonephritis: Double contours.
− DDD: "Moth-eaten" GBM.
C3 glomerulopathies: Direct immunofluorescence (2).
C3 glomerulonephritis: Granular deposition of C3.
DDD: "Garland" pattern of C3.
C3 glomerulopathies: Predictors of poor prognosis (3).
Older age at presentation.
Higher creatinine at presentation.
Lupus nephritis: Frequency (2).
Occurs in 80% of patients with lupus.
Presenting manifestation in 20% of lupus patients.
Lupus nephritis: Class I (2).
Normal glomeruli by histology.
Mesangial deposits by IF or EM.
Lupus nephritis: Class II (2).
Mesangial expansion and proliferation by histology.
Mesangial deposits by IF or EM.
Lupus nephritis: Class III (2).
Segmental or global focal endocapillary proliferation involving less than half of glomeruli.
Mesangial and subendothelial deposits by EM.
Lupus nephritis: Class IV (2).
Segmental or global diffuse endocapillary proliferation involving at least half of glomeruli.
Mesangial and subendothelial deposits by EM.
Lupus nephritis: Class V (2).
Thickened GBM by histology.
Subepithelial deposits by EM.
Lupus nephritis: Class VI.
Global sclerosis involving more than half of glomeruli.
Lupus nephritis: Definition of endocapillary proliferation (3).
Proliferation of mesangial and endothelial cells.
Inflammatory cells may be marginated.
Glomerulus appears lobulated and hypercellular.
Lupus nephritis: "Wire loops".
Large subendothelial deposits.
Best seen with trichrome stain.
Lupus nephritis: Definition of extracapillary proliferation.
Lupus nephritis: Interstitial changes (2).
Acute: Plasmacytic inflammation and edema.
Chronic: Fibrosis and tubular atrophy.
Lupus nephritis: Vascular changes.
Lupus nephritis: Silver stain (2).
Classes III and IV: Double contours.
Class V: Spikes and holes in the GBM.
Lupus nephritis: Direct immunofluorescence (2).
Granular distribution of all immunoglobulins and complement.
C1q is always present.
Electron microscopy of lupus nephritis:
A. Appearance of deposits.
B. Another abnormal structure.
A. May resemble fingerprints.
B. Tubuloreticular inclusions in endothelial cells.
Diabetic nephropathy: Early sign.
Microalbuminuria: Occurs more than 5 years before onset of diabetes.
Diabetic nephropathy: Stage 1 (2).
Light microscopy: Normal glomeruli.
Em: Thickened GBM.
Diabetic nephropathy: Stage 2 (2).
LM: Diffuse mesangial expansion.
EM: Thickened GBM; increased collagen in mesangium.
Diabetic nephropathy: Stage 3 (2).
LM: Diffuse nodular glomerulosclerosis (Kimmelstiel-Wilson lesion); abundant hyalinosis.
Diabetic nephropathy: Stage 4.
More than half of glomeruli are sclerotic.
Diabetic nephropathy: Types of hyaline lesion (3).
Fibrin caps (hyalinosis of capillaries).
Diabetic nephropathy: Interstitial changes (2).
Fibrosis and tubular atrophy.
Diabetic nephropathy: Vascular change.
Arteriolar hyalinosis involving afferent and efferent arterioles.
Diabetic nephropathy: Special stain.
Silver stain emphasizes sclerotic nodules.
Diabetic nephropathy: Direct immunofluorescence (2).
GBM, tubular BM: Linear IgG and albumin.
Areas of glomerular and vascular hyalinosis: C3 and IgM.
Electron microscopy of diabetic nephropathy:
A. Glomerular basement membrane.
A. Diffuse and sometimes massive thickening.
B. Sclerosis; collagen fibrils.
Diabetic nephropathy vs. anti-GBM disease (2).
− Usually has no crescents.
− Linear deposition of albumin.
Fabry's disease: Affected organs (4).
B. Gene and its product.
B. AGAL; α-galactosidase A.
C. Accumulation of lipids in cells.
B. Special stain.
A. Lipid vacuoles in podocytes, tubular epithelial cells, and endothelial cells.
B. Toluidine blue reveals the inclusions.
Fabry's disease: Electron microscopy.
Lipids have lamellated appearance (zebra bodies).
Fabry's disease: Drug that can cause similar inclusions.
Renal amyloidosis: Presentation.
Renal amyloidosis: Immunoglobulin-derived amyloid (2).
AL, especially λ light chain.
A. Most common genetic form.
B. Associated with chronic inflammation.
C. Associated with dialysis.
B. AA (serum amyloid A).
Renal amyloidosis: Other forms of amyloid (2).
Leukocyte chemotactic factor 2.
Renal amyloidosis: Histopathology (4).
Glomeruli: Thickening of basement membranes; mesangial nodules.
Tubules: Thickening of basement membranes.
Arterioles: Intimal nodules.
Renal amyloidosis: Electron microscopy.
Non-branching, randomly organized fibrils, 9-11 nm in diameter.
Renal amyloidosis vs. light-chain-deposition disease.
In the latter, there are finely granular, electron-dense deposits.
Acute tubular injury:
B. Laboratory finding.
A. Acute renal failure with oliguria or anuria.
B. Granular casts.
Acute tubular injury: Causes.
Acute tubular injury: Most vulnerable part of nephron.
The distal part.
Acute tubular injury: Histopathology (4).
Tubular epithelial cells:
− Loss of brush border.
− Necrosis in a minority of tubules.
− Regenerative changes.
Glomeruli and blood vessels: No change.
Acute tubular injury: Special stain.
PAS reveals loss of brush borders.
Drug-induced interstitial nephritis: Classic triad.
Drug-induced interstitial nephritis: Laboratory findings (3).
Drug-induced interstitial nephritis: Causes (4).
Drug-induced interstitial nephritis: Electron microscopy.
NSAIDs: Diffuse injury to podocytes, with a effacement of foot processes.
Acute obstructive nephropathy: Causes (3).
Myeloma cast nephropathy: Histopathology (3).
Fractured or crystalline-appearing casts surrounded by giant cells.
Reactive epithelial cells in the affected tubules.
Interstitial fibrosis and lymphocytic inflammation.
Myeloma cast nephropathy: Special stain.
Negative for PAS (Tamm-Horsfall casts are positive).
Hypertensive nephropathy: Other histologic changes (3).
Glomeruli: Global sclerosis.
Hypertensive nephropathy: Histologic changes in arteries (3).
Intimal fibrosis, medial hypertrophy, duplication of the elastic lamina.
Hypertensive nephropathy: Histologic change in arterioles.