Kidney-tumor

Increased (7-50x) risk of renal cell carcinoma (7% @ 10 years, usually papillary), often multifocal, usually 3 cm or less, tumors usually not as aggressive as classic renal cell carcinoma with only rare metastases; papillary or clear cell tumors may have non-classic molecular mechanisms in these patients (Mod Path 1999;12:301, Archives 1986;110:592); tumors have lower proliferative activity (Mod Path 1998;11:339, Hum Path 2002;33:230)

Cysts may form due to obstruction by oxalate crystals, fibrosis or hyperplasia

Atypical epithelial proliferations are present in 1/3 of cases, and are associated with gains of #7, #12, #17, #20, Y, suggesting they represent early neoplasms (Hum Path 2002;33:761)

Case reports: associated renal cell carcinomas (clear cell and papillary subtypes) with abundant calcium oxalate crystals (Archives 2003;127:E89)

Gross: moderately enlarged bilateral kidneys with cysts up to 2 cm in cortex and medulla containing clear fluid, often with calcium oxalate crystals; papillary hyperplasia common

Gross images: associated with chronic dialysis (cause unknown)

Micro: cysts lined by flattened to hyperplastic cuboidal or columnar epithelium; may have atypical papillary projections

Micro images: figure 1A: high grade papillary renal cell carcinoma with calcifications, arising in acquired cystic disease of kidney; 1B: multiple calcium oxalate crystals in papillary renal cell carcinoma with oncocytic features; 2: atypical papillary hyperplasia arising in acquired cystic disease of kidney; 3A: clear cell carcinoma with cystic tubular formation; 3B: clear cell carcinoma, eosinophilic type with calcium oxalate crystals

Adult polycystic kidney disease

top

Also called autosomal dominant polycystic kidney disease

Autosomal dominant, almost complete penetrance

1-2/1000 live births, no gender preference; causes 10% of chronic renal failure requiring transplantation or dialysis

Multiple expanding cysts of both kidneys destroy renal parenchyma slowly, leading to renal failure in adulthood

Associated with von Meyenburg complexes in liver (97%), hepatic cysts (40-88%), berry aneurysms (10-30%, cause death in 4-10%), mitral valve prolapse (20%), cysts in pancreas, lung, spleen, pineal gland, seminal vesicles; also aortic aneurysms, hepatic fibrosis, intestinal diverticula

Associated with loss of ability to concentrate urine, hypertension by age 20, infection, hematuria, renal stones (20%)

Cysts compress and obstruct only part of normal nephron, so normal renal function until age 30-49 years

25% die from infection, 40% from hypertension and heart disease, 15% from berry aneurysms or stroke

Cause of cysts unknown: may be due to altered cell-cell and cell-matrix interactions

Poor prognostic factors: sickle cell trait (not disease), men, hypertension

Molecular:

PKD1 gene on 16p13.3 (altered in 85-90% of cases) produces polycystin 1; function unknown

PKD2 gene on 4q13-23 (altered in 10% of cases) produces polycystin 2; later onset and development of chronic renal failure than PKD1

PKD3 gene: minority of cases, gene unmapped

10% lack a family history and are considered new mutations

Case reports: with littoral cell angioma of spleen (Archives 2001;125:1505), with polycystic liver disease and hemorrhagic hereditary telangiectasia (AJSP 1998;22:368), 15 year old white girl with no family history but classic findings and oral-facial-digital syndrome type I (Archives 1991;115:519)

Gross: large kidneys (up to 4 kg), always bilateral (although degree of involvement may vary), bosselated outer surface composed of mass of cysts up to 4 cm; cysts contain clear to brown fluid

Gross images: enlarged kidney with variably sized cysts #1; #2; #3 (at autopsy); #4; #5; #6; #7

Micro: cysts are saccular expansions or diverticula of all portions of renal tubule and glomerular capsule that later become disconnected and filled with fluid; cysts are lined by cuboidal or flattened epithelium, may have papillary projections or polyps; functional nephrons exist between cysts; may have foci of interstitial scarring, tubular atrophy and pyelonephritis; 20% have associated renal adenomas

Micro images: large cysts (compare to size of glomeruli; various images

References: AJSP 2002;26:198 (TSC2/PDK1 continuous gene syndrome), Mod Path 1996;9:233 (hepatic cysts)

Childhood polycystic kidney disease

top

Autosomal recessive; bilaterally enlarged kidneys at birth; affects 1 per 6,000-20,000 live births

Mapped to chromosome #6p

Perinatal mortality 30-50%; 5 year survival is 80-95% if survive first month of life

Must remove kidneys so lungs can grow; children have Potter sequence with characteristic facies due to oligohydramnios, pulmonary hypoplasia and joint deformities

Possible pulmonary hypoplasia since kidneys restrict growth of lungs; later develop portal hypertension with splenomegaly; usually no cysts other than kidney and liver

Liver always affected (every portal triad, every case) with herring duct cysts, congenital hepatic fibrosis, variable bile duct ectasia and biliary dysgenesis

Gross: markedly enlarged kidneys with smooth surface; small cysts in cortex and medulla; dilated channels are perpendicular to cortical surface; cysts present in medulla (collecting duct)

Gross images: markedly enlarged kidneys filling abdomen and causing pulmonary hypoplasia; uniform distribution of small cysts

Micro: dilation of all collecting tubules with fluid accumulation; cysts lined by cuboidal or flattened cells from collecting tubules

Micro images: (1) radial arrangement of cysts with only rare glomeruli; (2) associated congenital hepatic fibrosis

Virtual slides: dilated cysts

Cystic renal dysplasia

top

Also called multicystic renal dysplasia

Abnormal metanephric differentiation, occurring by week 20 in utero, results in persistence of abnormal structures

90% are associated with ureteropelvic obstruction, ureteral agenesis, atresia or reflux; 10% have unknown cause

May be due to hyperplastic smooth muscle in ureters

Causes the majority of neonatal abdominal masses; presents as flank mass or pyelonephritis

Also most common form of cystic renal disease in children

If blastema present, patient at risk for Wilms’ tumor

Rarely familial, but is associated with Dandy Walker syndrome

Also associated with cardiac malformations

2/3 unilateral

Segmental dysplasia seen only in children with duplex (duplicated) kidney (incomplete fusion of upper and lower poles)

Case reports: newborn with bilateral renal dysplasia, severe pancreatic fibrosis, intrahepatic biliary dysgenesis, total situs inversus with normal cytogenetics (Hum Path 1988;19:871)

Gross: large, irregular kidney, usually cystic, often multicystic with variably sized cysts, can’t distinguish cortex from medulla; cysts are variably sized

Gross images: multiple cysts of various sizes #1; #2

Micro: lobar disorganization present; cysts of various sizes lined by flattened to cuboidal epithelium, may contain nodular blastema (undifferentiated cells), islands of undifferentiated mesenchyme, cartilage (10-20%), immature collecting ducts with fibromuscular collar, primitive glomerular structures

Micro images: large cysts lined by flattened epithelium with fibrotic and cartilaginous stroma

Glomerulocystic kidney of tuberous sclerosis

top

Case report in newborn (Archives 2000;124:327)

Not a typical finding in tuberous sclerosis

Glomerulocystic kidneys (kidneys with glomerular cysts) also seen in non-tuberous sclerosis patients (maternal phenacetin use during pregnancy, Archives 1977;101:462; no known cause, Archives 1976;100:186)

Case reports: newborn with features of tuberous sclerosis (Path Res Pract 1992;188:367)

Gross: enlarged kidney with cortical cysts

Micro: Bowman’s epithelium and tubular epithelium show hyperplastic changes; cells have abundant granular cytoplasm and may fill tubular lumina; also vascular dysplasia (abnormal smooth muscle hyperplasia), metanephric hamartoma

Micro images: figure 1: gross-spongelike kidney with numerous round, cystic spaces; 2: low magnification EM-cystic spaces are variably sized with glomeruli somewhere along cyst wall (small arrows) and capsule (bottom right); 3: EM-cells covering Bowman’s capsule are tall and columnar (large arrow); hyperplasia is also present (curved arrows); glomerulus (fat arrow) is covered by plump, irregular podocytes; 4: H&E shows Bowman’s capsule lining cells have eosinophilic granularity (big arrows)

Medullary sponge kidney

top

Multiple cystic dilations of collecting ducts in medulla bilaterally with normal cortex

1 per 5000 births; no gender preference; not familial

Normal renal function; does not progress to end stage renal disease

Associated with hemihypertrophy of body (25% of cases), Marfan’s, Caroli’s, Ehlers-Danlos

Signs/symptoms: calcifications on Xray, hematuria, stones, infection at age 30+ years

Treatment: cranberry juice to keep urine acid (don’t remove these kidneys)

Gross: normal sized kidneys with dilated medullary ducts with multiple, small cysts in medullary pyramids and papillae, giving medulla a sponge-like appearance

Micro: medullary cysts lined by cuboidal epithelium or urothelium; may have concretions adherent to cyst wall; often severe inflammation and scarring in interstitium, often with tubular atrophy near papillary tips

Micro images: various images

Mesothelial cysts

top

Also called primary retroperitoneal cysts of mesothelial origin

Somewhat rare

May present as renal masses

Radiologic images: figure 1A: MRI shows cystic mass (arrows) involving upper pole; 1B: cystic mass (arrows) at lower pole

Gross: may be hemorrhagic

Gross images: A/B: hemorrhagic unilocular cysts

Micro: cyst lined by single cell lining of non-pleomorphic cells with abundant eosinophilic cytoplasm, vesicular nuclei and small nucleoli; may have small gland-like spaces

Micro images: (1) cyst lining cells have abundant eosinophilic cytoplasm, vesicular nuclei and small nucleoli; (2) cyst lining cells are A: CEA negative; B: keratin+; C: HBME1+; D: WT1+

Positive stains: keratin, vimentin, hyaluronic acid, HBME-1, WT1, thrombomodulin, calretinin

Negative stains: BerEP4, CEA, B72.3, LeuM1

DD: mucinous cystadenoma (ovarian-like stroma, mucin+, CEA+, negative for hyaluronic acid), lymphangioma (multicystic, has smooth muscle and lymphocytes in cyst wall and lumen, keratin negative), simple hemorrhagic cysts

References: Archives 2000;124:766

Nephronophthisis - uremic medullary cystic disease complex

top

Small medullary cysts at corticomedullary junction with cortical atrophy, interstitial fibrosis

Incidence: 1 per million

Cortical and tubulointerstitial damage initially causes polyuria and polydipsia, progressing to chronic renal failure in 5-10 years

Consider in children/teenagers with unexplained chronic renal failure, family history, chronic tubulointerstitial nephritis on biopsy

Nephronophthisis: autosomal recessive; median onset of end stage renal disease by type is infantile-1-3 years, juvenile-13 years, adolescent-19 years

Infantile/adolescent nephronophthisis: responsible genes are at 9q22-31 and 3q21-22; function unknown

Juvenile nephronophthisis: most common cause of end stage renal disease in children; no gender preference; symptoms at age 4 years with polydipsia, polyuria, enuresis, decrease in urinary concentration, severe anemia, growth retardation; 12% associated with retinitis pigmentosa; rarely associated with hepatic fibrosis, skeletal malformations, CNS defects; affected by NPHP1 gene at 2q13 encoding nephrocystin, function unclear

Medullary cystic kidney disease: autosomal dominant; no associated growth retardation or anemia; is associated with hyperuricemia and gout; median age of onset of end stage renal disease is MCKD1-62 years, MCKD2-32 years; responsible genes are at 1q21 and 16p13

Case reports: 4 year old girl who also had basal ganglia calcification and pancreatic lipomatosis (Archives 1988;112:630)

Gross: bilateral involvement of normal or moderately small kidneys with contracted granular surface, thin-walled medullary cysts up to 2 cm, particularly at corticomedullary junction, which is indistinct

Micro: cysts lined by flattened or cuboidal epithelium; also tubulointerstitial fibrosis and lymphocytic infiltrate, tubular atrophy with thickened tubular basement membrane (highlighted by PAS); glomeruli usually preserved

EM: homogenously thickened tubular basement membrane, split into thin lamellae, reticulated or disintegrated

Simple cysts

top

Not a disease, but an occasional finding that increases with age (0.1% in children, 20% at age 50+ years)

May be confused with cystic renal cell carcinoma, but avascular with smooth contours

Hemorrhage may cause acute pain; may calcify

Gross: up to 10 cm, but translucent, with glistening membrane, filled with clear fluid, usually cortical

Gross images: simple cyst of upper pole, large cyst

Micro: single layer of cuboidal, flattened or atrophic epithelium; may have thickened walls with hemosiderin-laden macrophages and atrophic epithelium

Kidney Neoplasms

Pediatric tumors

Clear cell sarcoma

top

Also called bone metastasizing renal tumor

Mean age 36 months, range 2 months-14 years, peaks at ages 2-3 years; 2/3 male

4% of childhood renal tumors; 20 new cases per year in US; rarely in adults

Frequent relapse, bone and skull metastases common; also metastases to regional lymph nodes (29% at presentation), brain, lung, liver; metastases often 5 years or more after removal of primary tumor

Overall survival 69%, 98% for stage 1

Good prognostic factors are treatment with doxorubicin and low stage; death more common after combination chemotherapy other than doxorubicin

Gross: large (mean 11 cm), well circumscribed, centered in central kidney or medulla; homogenous tan/gray or myxoid appearance; firm with occasional cysts

Micro: classic - nests or cords of small cells with indistinct cell margins; light staining cytoplasm, round nuclei containing fine chromatin and grooves, no nucleoli, rare mitoses; only 20% have clear cells (due to vacuoles); vascularized stroma is alveolar and arborizing, scattered preexisting tubules or glomeruli are trapped in periphery of tumor; vascular invasion common; other patterns are myxoid (50%), sclerosing (35%, includes hyalinizing which has osteoid-like pattern resembling osteosarcoma), cellular (26%), epithelioid (13%, tumor cells align along vessels), palisading (11%), spindle (7%), storiform (4%) and anaplastic (3%)

Micro images: sheets of monotonous cells with indistinct cell margins, pale cytoplasm, round/oval nuclei with fine chromatin #1; #2

Positive stains: vimentin

Negative stains: keratin, CD99, WT1, p53

EM: rare organelles, sparse cytoplasmic filaments, primitive cell junctions, complex cytoplasmic processes

DD: Wilms’ tumor (pushing border, more aggressively invasive, epithelioid areas are keratin+)

References: AJSP 2000;24:4, AJSP 1999;23:1455 (teenager/young adult tumors), Hum Path 1985;16:1219

Congenital mesoblastic nephroma

top

Also called fetal, mesenchymal or leiomyomatous hamartoma

Most common renal tumor of infancy, first described in 1967 (Pediatrics 1967;40:272)

A congenital tumor; age at presentation varies by type (classic: 16 days, cellular: 5 months, mixed: 2 months); may present in utero causing nonimmune fetal hydrops and polyhydramnios

Diagnosis should be questioned if applied to patients over 2 years old

Frequency: classic (24%), cellular (66%), mixed (10%)

5-10% recur or metastasize (usually cellular type), usually by age 1, to lung, brain or rarely bone

Some consider similar tumor in adults to be a mixed epithelial and stromal tumor

Report: involvement or not of medial kidney margin by tumor

Treatment: nephrectomy with wide margins; chemotherapy if resection is incomplete in infants 3 months or older or if tumor ruptures during surgery

Case reports: Case of Week #57, 3 week old infant with flank mass and mixed type (Archives 2004;128:929), tumor in newborn (Archives 2002;126:103)

Gross: classic - variably circumscribed, white/yellow, whorled mass, mean 5 cm, near hilum, involving over half of kidney with indistinct tumor-kidney interface; resembles leiomyoma with whorled cut surface; may be cystic; may involve renal sinus; hemorrhage and necrosis are uncommon

cellular - necrosis, large cystic areas and hemorrhage, mean 9 cm

mixed - mean 10 cm; cysts, hemorrhage and necrosis in cellular areas

Gross images: image

Micro: classic, cellular and mixed types; usually no necrosis or hemorrhage, not well circumscribed

Classic – resembles infantile fibromatosis or leiomyoma with fascicles and whorls of bland spindled myofibroblasts and thin collagen fibers; tumor surrounds tubules and glomeruli, has irregular borders; metaplastic and dysplastic elements common, usually cartilage, also extramedullary hematopoiesis and cuboidal metaplasia; usually few mitotic figures; no desmoplasia

Cellular – resembles infantile fibrosarcoma with densely packed plump atypical spindle cells with abundant cytoplasm, vesicular nuclei and nucleoli; frequent mitotic figures (25-30/10 HPF) and necrosis

Micro images: (1) well circumscribed; (2) medium power; (3) high power; (4) infiltrative margin; (5) glomerular entrapment; (6) angiomatoid area; (7) figure 1: circumscribed, pale-tan tumor; 2: spindle cells surround and entrap normal glomeruli and tubules; 3: rare cartilaginous nodules; (8) figure 1: cellular variant is tan fleshy mass with large areas of hemorrhage, necrosis and cystic degeneration; 2: cellular areas composed of compact spindle cells with fingerlike projections infiltrating into normal kidney; 3: cellular areas have mitotic figures, cysts, hemorrhage and necrosis; (9) left-congenital mesoblastic nephroma; right-consistent with infantile fibrosarcoma; (10) left-congenital mesoblastic nephroma; right-infantile fibrosarcoma; (11) mimics clear cell sarcoma of kidney; A: fascicular pattern of dense spindle cells; B: hypocellular region with sclerosis, myxoid change, small vessels, entrapment of native tubules; (12) mimics rhabdoid tumor - A: fascicles of spindled cells with pale cytoplasm and inconspicuous nucleoli, typical of cellular congenital mesoblastic nephroma; B: invasive edge shows more hyperchromatic, epithelioid-appearing cells with prominent nucleoli; C: resembles rhabdoid tumor, but t(12;15) fusion product was present; (13) mixed type

Positive stains: smooth muscle actin, desmin, vimentin, renin (within tumor vessels or vessels in trapped cortex)

Negative stains: keratin (except for entrapped epithelium), laminin

Molecular: cellular subtype has t(12;15)(p13;q25) translocation, results in ETV6-NTRK3 fusion gene, also present in infantile fibrosarcoma (Mod Path 2000;13:29; Mod Path 2001;14:1246); mixed and classic subtypes lack this translocation (Histopathology 2006;48:748)

Molecular images: ideogram and FISH; gel for fusion transcript

DD: Wilms’ tumor (also has skeletal muscle and blastema, older age and nephrogenic rests; previously treated tumors may have well differentiated spindle cell stroma), clear cell sarcoma (similar age but clear cells and chicken-wire vasculature; fine nuclear chromatin and low mitotic rate; negative smooth muscle markers, tumor cells isolate single nephrons), rhabdoid tumor (more invasive margins, usually epithelioid cells with cytoplasmic inclusions and prominent nucleoli, usually presents with metastases), metanephric stromal tumor (nodular low power pattern, onion-skin cuffing around entrapped renal tubules, heterologous differentiation and vascular changes, CD34+, older patients), adult mixed epithelial and stromal tumor (look and stain similar but mean age in 50’s, usually women, positive for estrogen and progesterone receptors)

References: Hum Path 1989;20:682, Hum Path 1988;19:1347 (renin)

Metanephric stromal tumor

top

Benign abdominal mass in infants (mean age 2 years)

Often misdiagnosed as congenital mesoblastic nephroma

Treatment: excision is curative

Gross: fibrous lesion centered in renal medulla containing smooth walled cysts; mean 5.5 cm

Micro: identical to stromal component of metanephric adenofibroma; unencapsulated bland spindle cells that entrap native kidney; usually undermine calyceal or pelvic urothelium, may entrap nerves, often has scalloped border with renal cortex; nodular appearance of hypo- and hypercellular areas with onion-skin cuffing around entrapped renal tubules; spindle cells have thin, tapered, hyperchromatic nuclei with thin or indistinct cytoplasmic extensions; occasional epithelioid cellular stroma; stroma may show glial, cartilaginous or neuroblastic differentiation, angiodysplasia of entrapped arterioles and juxtaglomerular cell hyperplasia in entrapped glomeruli; no vascular invasion

Positive stains: vimentin, CD34 (often patchy), S100 (variable)

Negative stains: smooth muscle actin, muscle specific actin, desmin, keratin, EMA, CD117/c-kit

DD: congenital mesoblastic nephroma (deeply invasive, sharply defined linear transitions in cellularity, no perivascular or peritubular collarettes, no heterologous differentiation, CD34-, desmin+, older patients), clear cell sarcoma (regular branching capillary vascular pattern, no heterologous differentiation, CD34-), metanephric adenofibroma (neoplastic epithelium, not entrapped tubules)

References: AJSP 2000;24:917

Nephroblastomatosis

top

Congenital, not neoplastic

Single or multiple, unilateral or bilateral

Massive aggregates of primitive metanephric tissue, present in 1% of neonatal kidneys and 30% with Wilms’ tumor

Florid cases are associated with congenital anomalies and hypertension

Case histories: male newborn died at age 1 hour of respiratory failure with bilateral, pancortical nephroblastomatosis (Archives 1989;113:729)

Treatment: conservative

Gross: diffuse involvement of entire subcapsular region

Micro: tightly packed nephrogenic cells with primitive appearance, but not anaplastic; scanty stroma; no cartilage or primitive mesenchyme

References: Adv Anat Path 2001;8:276

Nephrogenic rests

top

Congenital, not neoplastic; may originate from persistent nephrogenic blastema

Single or multiple, unilateral or bilateral; rarely occur in ectopic sites

Considered precursor lesion of Wilms’ tumor, found in 30-44% of kidneys resected for Wilms’ tumor

Intralobar rests (compared to perilobar rests): may progress to Wilms’ tumor at higher rate, more commonly associated with WT1 mutations, Denys-Drash syndrome and WAGR syndrome

Perilobar rests rarely progress to malignancy, may be associated with loss of imprinting at 11p, are associated with idiopathic hemihypertrophy and Beckwith-Wiedemann syndrome

Case reports: midline lumbosacral ectopic nephrogenic rest in healthy newborn male (AJSP 2004;28:1389)

Micro: microscopic aggregates of primitive metanephric tissue, either perilobar or intralobar

Perilobar: peripheral with sharply demarcated margins, composed of blastema and tubules with scanty or sclerotic stroma, often solitary

Intralobar: randomly distributed throughout cortex and medulla with irregular margins, more stroma than blastema or tubules, usually multifocal

DD: Wilms’ tumor (particularly for extrarenal rests)

Neuroblastoma

top

Primary renal tumors or secondary spread from adrenal or other retroperitoneal site

Metastases to bone and orbit

Poor prognosis if N-myc amplification (30%) or 1p-

Laboratory: catecholamines in serum and urine

Micro: small blue cell tumor with Homer-Wright rosettes

Positive stains: catecholamines (90%), NSE, S100

DD: Wilms’ tumor (rosettes resemble Wilms’ tubules)

Oncocytoid renal cell carcinoma after neuroblastoma

top

Mean age 9 years, range 5-13 years; with mean interval between neuroblastoma and carcinoma of 7 years (range 3-12 years)

Micro: expansile masses composed of solid and papillary patterns of large cells with well defined cell membranes, abundant eosinophilic, oncocytic or reticular cytoplasm; enlarged nuclei with mildly irregular contours, distinct nucleoli; occasional lipid-laden histiocytes, psammoma bodies, mitotic figures; often resembles high grade papillary renal cell carcinoma, but predominantly solid and without necrosis

Positive stains: EMA, vimentin; variable CK 20

Negative stains: HMB45, S100, CK 7

Molecular: loss of 20q13; also others not typical for other renal cell carcinomas

EM: microvilli and cell junctions, less mitochondria than oncocytoma; no microvesicles

References: AJSP 1999;23:772

Ossifying renal tumor of infancy

top

Calcified mass in renal pelvis composed of spindle cells in partially calcified osteoid matrix

References: Pediatr Pathol Lab Med 1995;15:745

Renal cell carcinoma in children

top

<1% of all renal cell carcinomas occur in children

22%% are papillary, 15% clear cell, 5% collecting duct, 24% unclassified; ASPL-TFE3 and PRCC-TFE3 carcinomas are common

Usually no loss of heterozygosity for VHL gene, even for clear cell carcinomas

References: AJSP 2004;28:1117; AJSP 1999;23:795

Rhabdoid tumor

top

1-2% of childhood renal tumors

60% are < 1 year old, 30% 1-3 years old, rare > 5 years

Associated with hypercalcemia and calcifications in tubules

Usually stage 2 or higher; 9% are bilateral

Very aggressive; 82% present with metastases; 90% die in 2 years

15% are associated with primary embryonal tumors in the midline posterior fossa, often medulloblastoma

Case reports: tumor in 38 year old woman (Archives 2003;127:e371); 10 year old girl with extrarenal pelvic rhabdoid tumor (Archives 2003;127:633), presentation as skin metastasis (Archives 1998;122:1099)

Gross: solid, soft, well circumscribed, involves medullary region

Micro: diffuse, trabecular or alveolar patterns of large monomorphic cells with well defined cell borders; cells have pink cytoplasm; cleared chromatin, macronucleoli and eccentric nuclei due to large eosinophilic hyaline globule (perinuclear inclusions); tumor has aggressive invasive pattern; occasionally cells are spindled; variable necrosis and mitoses

Fine needle aspirates: usually single cells

Micro images: high grade round cell tumor with abundant cytoplasm and prominent nucleoli

Micro images - adult tumor - figure 1: tumor grossly replaces much of kidney, arrow points to hilar lymph node; 2A: sheets of discohesive round cells separated by delicate fibrovascular stroma; 2B: cells are uniform with pink cytoplasm, eccentric nuclei and macronucleoli; 3A: vimentin+; 3B: EMA+ (focally); 4: EM shows large swirls of intermediate filaments

Positive stains: keratin (particularly CK8), vimentin, EMA

Negative stains: muscle markers, neural markers, WT1

EM: hyaline globules composed of tangled intermediate filaments

Molecular: deletions or mutations of hSNF5/INI1 gene at 22q11.2 (use FISH)

DD (rhabdoid features): Wilms’ tumor with myogenic cells (usually foci of typical Wilms’ blastema or definitive nephrogenic differentiation is present), congenital mesoblastic nephroma, renal cell carcinoma, urothelial carcinoma, PNET/Ewing’s, collecting duct carcinoma

References: AJSP 1989;13:439

Wilms’ tumor of children

top

Also called nephroblastoma

Most common kidney tumor of childhood, affecting 1 per 8-10,000 children, no gender preference

90% occur before age 6 years, only rarely a congenital lesion; occasionally in teenagers or adults

Presents as large abdominal mass felt by mother holding child; occasionally extrarenal (retroperitoneum, sacrococcygeal region, testis, uterus, inguinal canal, mediastinum); may present with lung metastases or traumatic rupture

Spreads into perirenal soft tissue; may invade renal vein; metastasizes to regional lymph nodes (15%), lung, liver, peritoneum; rarely bone (1%)

Apparently derives from nephrogenic blastema cells

Bilateral tumor or tumor early in life is associated with urogenital congenital abnormalities

Tissue diagnosis important as clinical diagnosis is wrong in 5%; FNA and frozen section are unreliable

90% long term survival

Risk factors: WAGR syndrome, Denys-Drash and Beckwith-Wiedemann syndromes (although most are sporadic); nephroblastomatosis

WAGR syndrome (OMIM #194072): Wilms’ tumor (1/3), Aniridia, Genitourinary anomalies, mental Retardation; due to 11p13 deletion (WT-1); also intralobar nephrogenic rests

Denys-Drash syndrome: gonadal dysgenesis (male pseudohermaphroditism), glomerulosclerosis and Wilms’ tumor; also intralobar nephrogenic rests; most develop Wilms’; have WT-1 dominant negative missense mutation, NOT a deletion (AJSP 1983;7:387, Hum Path 1987;18:80)

Beckwith-Wiedemann syndrome (OMIM #130650): exophthalmos, macroglossia, and gigantism; also hemihypertrophy, renal medullary cysts, adrenal cytomegaly, hypoglycemia; have WT-2 (11p15.5) abnormality, may be due to genomic imprinting; higher risk for hepatoblastoma, adrenocortical tumors, rhabdomyosarcomas, pancreatic tumors, perilobar nephrogenic rests

Nephroblastomatosis: premalignant lesion; immature nephrogenic elements within otherwise normal kidney; called nephrogenic rests when microscopic in size; found in 1% of neonatal kidneys vs. 30% of kidneys with Wilms’ tumor; more diffuse than Wilms’, no anaplasia, have only scanty stroma; treat conservatively

Anaplasia: hyperchromatic, pleomorphic nuclei that are 3x larger than adjacent cells plus abnormal (polypoid) mitotic figures; seen in 5%

Focal anaplasia: tumors with anaplasia confined to one or a few discrete loci within primary tumor, with no anaplasia or marked nuclear atypia elsewhere

Case reports: 7 year old boy with teratoid tumor arising within supernumerary ectopic ureteropelvic structure (Archives 1998;122:925), presentation as sudden death due to tumor emboli (Archives 1990;114:605), immature glomeruli and aberrant glomerulogenesis (Archives 1988;112:536), botyroid tumor of renal pelvis (Archives 1984;108:147), associated with membranoproliferative glomerulonephritis and focal and segmental glomerulosclerosis (Archives 1984;108:141), hemihypertrophy and bilateral, sequential tumors (Archives 1978;102:639), infant also with neuroblastoma and Fanconi’s anemia (Hum Path 2002;33:1047), extrarenal tumors thought due to displaced mesonephric / metanephric rests (Hum Path 1989;20:691), bilateral cystic nephroblastomas, Dandy-Walker syndrome, microcephaly, cataracts, cerebellar heterotopia; also in sister, both with trisomy 8 mosaicism (Hum Path 1985;16:754)

Poor prognostic factors:

(a) anaplasia in stage II-IV tumors only; diffuse anaplasia worse than focal anaplasia but even small foci are associated with poor prognosis due to chemotherapy resistance

(b) high stage (most epithelial-predominant tumors are stage I; most blastema-predominant tumors are stage III/IV)

(c) in tumors with rhabdomyomatous features, serum creatine kinase and CK-MB levels may reflect clinical course (AJCP 2001;116:354)

(d) age >2 years

(e) P-glycoprotein expression in endothelial cells (AJCP 2002;117:484)

(f) inflammatory pseudocapsule, invasion of renal sinus, tumor invasion of intrarenal vessels

(g) large size

Staging (National Wilms Tumor Study Group)

top

Stage I: tumor limited to kidney and completely resected, renal capsule intact, tumor not ruptured or biopsied prior to removal, no residual tumor beyond margins of resection, no tumor within renal vein (tumor within intrarenal vessels is OK), no nodal involvement or distant metastases