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Kidney tumor - cysts, children, adult benign

Childhood neoplasms

Wilms’ tumor of children


Reviewers: Mandolin Ziadie, M.D. (see Reviewers page)
Revised: 29 January 2012, last major update January 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

See also Cystic partially differentiated nephroblastoma,  Teratoid Wilms' tumor

General
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● Also known as nephroblastoma, this triphasic renal tumor was first described by Dr. Max Wilms

Epidemiology
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● Most common pediatric renal tumor, affecting 1 per 8-10,000 children (500 new cases/year in US)
● 90% diagnosed prior to age 6 years; rarely congenital; occasionally diagnosed in teenagers / adults; age distribution
● M=F
● Most are sporadic but some are associated with several syndromes as well as with nephroblastomatosis
WAGR syndrome: Wilms’ tumor (1/3), Aniridia, Genitourinary anomalies, mental Retardation; due to 11p13 deletion (WT1); also intralobar nephrogenic rests (OMIM 194072)
Denys-Drash syndrome: gonadal dysgenesis (male pseudohermaphroditism), glomerulosclerosis and Wilms’ tumor; also intralobar nephrogenic rests; most develop Wilms’; have WT1 dominant negative missense mutation, NOT a deletion (Am J Surg Pathol 1983;7:387, Hum Pathol 1987;18:80, eMedicine)
Beckwith-Wiedemann syndrome: exophthalmos, macroglossia and gigantism; also hemihypertrophy, renal medullary cysts, adrenal cytomegaly and hypoglycemia; have 11p15.5 abnormality, may be due to genomic imprinting; higher risk for hepatoblastoma, adrenocortical tumors, rhabdomyosarcoma, pancreatic tumors or perilobar nephrogenic rests (OMIM 130650, eMedicine)

Children’s oncology group staging of pediatric renal neoplasms
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Stage I (43%):
● 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) and no nodal involvement or distant metastases

Stage II (23%):
● Tumor extends beyond kidney but is completely resected
● Regional extension of tumor (vascular invasion outside of renal parenchyma or within the renal sinus, or capsular penetration but with negative surgical margin), no nodal or distant metastases

Stage III (23%):
● Residual tumor or non-hematogenous metastases confined to abdomen
● Metastases may be to regional lymph nodes, peritoneal tumor contamination and/or implants
● Gross or microscopic tumor present postoperatively (i.e. positive resection margins), tumor spill before or during surgery, pre-surgical biopsy (including FNA) and removal of tumor in > 1 piece

Stage IV (10%):
● Hematogenous metastases or spread beyond abdomen

Stage V (5%):
● Bilateral renal involvement (sub-stage each tumor separately according to above criteria)

● Reference: American Cancer Society

Pathophysiology
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● Apparently derives from nephrogenic blastema cells

Clinical features
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● Presents as large abdominal mass; occasionally extrarenal (retroperitoneum, sacrococcygeal region, testis, uterus, inguinal canal and 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 or peritoneum; rarely bone (1%)
● Tissue diagnosis important as clinical diagnosis is wrong in 5%; FNA and frozen section are unreliable
Treatment information from US National Cancer Institute; 80-90% overall are cured; a small percentage develop second neoplasms

Poor prognostic factors:
● Anaplasia in stage II-IV tumors; diffuse anaplasia is worse than focal anaplasia, but even small foci are associated with poor prognosis due to chemotherapy resistance
● High stage (most epithelial-predominant tumors are stage I; most blastema-predominant tumors are stage III/IV)
● Age > 2 years
● Large size

Case reports
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● Infant with coexisting neuroblastoma and Fanconi’s anemia (Hum Pathol 2002;33:1047)
● 7 year old boy with teratoid tumor (Arch Pathol Lab Med 1998;122:925)
● 7 year old girl with sudden death due to tumor emboli (Arch Pathol Lab Med 1990;114:605)
● Immature glomeruli and aberrant glomerulogenesis (Arch Pathol Lab Med 1988;112:536)
● Botyroid tumor of renal pelvis (Arch Pathol Lab Med 1984;108:147)
● With membranoproliferative glomerulonephritis, focal and segmental glomerulosclerosis (Arch Pathol Lab Med 1984;108:141)
● With hemihypertrophy and bilateral, sequential tumors (Arch Pathol Lab Med 1978;102:639)
● Extrarenal tumors thought due to displaced mesonephric / metanephric rests (Hum Pathol 1989;20:691)
● Bilateral cystic nephroblastomas and multiple malformations (Hum Pathol 1985;16:754)

Gross description
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● Large, solitary, well-circumscribed mass (10% bilateral or multicentric), soft, homogenous and tan-gray
● Hemorrhage, necrosis, cysts and lobular pattern are common

Grossing notes:
● Adequate sampling is important and should include at least one block per centimeter of largest dimension
● Also required are sections through the renal pelvis / sinus, sections of the medial sinus margin (medial end of soft tissues surrounding renal artery and vein), section of the junction between normal kidney and tumor, tumor capsule and uninvolved kidney
● Document where sections are taken on a diagram, snap freeze tumor and normal tissue for molecular studies (Arch Pathol Lab Med 2003;127:1280)

Gross images
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Tumor protrudes into the renal pelvis resembling botyroid rhabdomyosarcoma


Metastases to lung


Well circumscribed tumor with hemorrhage and necrosis

Expansively growing tumor,  necrotic kidney tumor and adherent ileum,  gray spherical tumor

Micro description
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Triphasic: undifferentiated blastema (diffuse, nodular, cordlike or basaloid pattern of densely packed primitive small blue cells with scanty cytoplasm, overlapping nuclei with finely dispersed chromatin), fibroblast-like stroma and epithelial elements (abortive tubules, glomeruli with elongate / ovoid nuclei having molded / wedged shapes); may have heterologous epithelial and stromal elements including smooth muscle, cartilage, adipose tissue, squamous or mucinous epithelium, bone and neural tissue; prominent skeletal muscle is associated with bilateral tumors in young children
● Biphasic / monophasic tumors have been described (the dominant component should be documented in the diagnosis)
Anaplasia: marker of unfavorable histology; associated with poor treatment response; defined as hyperchromatic, pleomorphic nuclei that are 3x larger than adjacent cells and have abnormal mitotic figures
     ● Focal anaplasia: all conditions must be met - (a) no anaplasia in tumor within renal vessels or outside kidney; (b) random biopsies are free of anaplasia; (c) anaplasia confined to sharply localized regions within primary intrarenal tumor site and (d) each focus of anaplasia must be surrounded on all sides by non-anaplastic tissue, which does not show severe nuclear unrest (Am J Surg Pathol 1996;20:909)
     ● Diffuse anaplasia: any conditions met - (a) anaplasia in tumor in any extrarenal site, including vessels of renal sinus, extracapsular infiltrates, metastases or intrarenal vessels; (b) anaplasia in random biopsy; or (c) anaplasia unequivocally present in 1 region of tumor with extreme nuclear unrest elsewhere in the lesion
Severe nuclear unrest: nuclear pleomorphism or atypia approaching, but insufficient for anaplasia
Renal sinus vascular invasion: tumor fills lumen or invades vessel wall; also free floating rounded tumor fragments not associated with other displacement artifact
Note: epithelial cell complexes from damaged nephrons, metaplastic calyceal urothelium, mesothelial inclusions and Tamm-Horsfall protein within nodal sinuses may be mistaken for metastases (Hum Pathol 1990;21:1239)

Micro images
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Diagram of renal sinus and tumor invasion


Tumor within vessels and soft tissue of the renal sinus

   

Triphasic tumor,   #3,   #4,   #5


Blastema, primitive glomeruli and tubules


Mature pattern with glomerular, tubular and stromal cells showing little or no proliferative activity

Tumor compresses renal medulla,  blastema with glomeruloid epithelial structure,  blastema, epithelium and mitotic figures,  blastema with cribriform epithelial component

Blastema:
   

Various images

       
Diffuse patterns

           
Various patterns (left to right): serpentine, serpentine and diffuse, nodular, basaloid

Epithelium:

Monophasic epithelial pattern is predominant


Embryonal tubular pattern, with tall columnar cells and small lumina


Tubular structures predominate in this lesion


Mature tubulopapillary pattern with low cell density and no / rare mitotic figures


Tubular and glomerular differentiation


Relatively mature glomeruli


Tubules and rosettes


Rosettes in PNET (for comparison) often lack the nuclear concentration around the center of the rosette


Rosettes in neuroblastoma have nuclear concentration around the center of the rosette


Mucinous epithelium may be prominent


Squamous epithelial focus

Other features:

Skeletal muscle is a common tumor element,   #2


Botyroid protrusions of tumor cells into lumen of the pelvicaliceal system


Adipose differentiation with associated nodule of skeletal muscle


Cartilage formation

Anaplasia:

Anaplasia


Huge, irregular-shaped nuclei are a major criterion for recognition of anaplasia


Sharply demarcated nodular region (left side) was only site of anaplasia


Multipolar mitotic figure


True tripolar mitosis (left edge) has each limb nearly the size of a normal metaphase plate (right lower corner)


X-shaped mitotic figure (left upper corner) is similar size as metaphase plate in right lower corner, may be due to uneven separation of a normal metaphase and is NOT a multipolar mitotic figure

Post-chemotherapy:
   

Total tumor necrosis; persistence of mature skeletal muscle

Stains:

H&E and INI1+

Virtual slides
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Various virtual slides

Videos
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Wilms' tumor

Positive stains
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Blastema: WT1, desmin but not other muscle markers (Mod Pathol 1997;10:895), focal vimentin
Epithelium: WT1, keratin and EMA; tubules are CK57+
Stroma: weak WT1; other stains consistent with morphologic appearance (myogenin if rhabdomyoblastomatous, S100 if neural, etc.)

Negative stains
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● Blastema negative for CK7, CD57 and usually p53
● Epithelium negative for vimentin

Molecular description
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● Abnormal expression of WT1 (11p13, encodes zinc finger transcription factor expressed early in urogenital system development) and WT2 (11p15.5)
● p53 abnormalities in anaplastic foci
● FWT1 (17q12-121) and FWT2 (19q13) mutations described in familial WT
● Inactivating mutations of WTX (Xq11.1)
● No t(12;15) of cellular mesoblastic nephroma
● No t(11;22) of Ewing’s / PNET
● No 22q11.2 abnormalities of rhabdoid tumor
● No N-myc of neuroblastoma

Electron microscopy description
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● Resembles developing metanephros with well developed cell junctions, microvilli and layer of thick flocculent coating around cell surface

Differential diagnosis
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Neuroblastoma: no triphasic patterns; has rosettes with no lumen, > 1 cell layer, no distinct basal lamina; Wilms’ immature tubules have a lumen, a single cell layer, distinct basal lamina and surrounding fibromyxoid stroma
● Perilobar nephrogenic rest: no fibrous capsule
Renal cell carcinoma: may resemble epithelial predominant Wilms’
Other small blue cell tumors: if blastema predominates

Additional references
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Wikipedia, eMedicine


Cystic partially differentiated nephroblastoma

General
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WHO definition: rare multilocular cystic benign neoplasm of very young children believed to be a part of the nephroblastoma spectrum; composed of cystic spaces with delicate septa containing primitive blastema, epithelium and stroma without evidence of anaplasia; usually hyperdiploid with trisomy 12

Case reports
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● Hyperdiploidy and trisomy 12 (Hum Pathol 1996;27:980)

Gross images
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Numerous thin walled cysts

Micro images
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Embryonal elements are present, but conform to the septa between cysts


Cysts with hobnail epithelium

Differential diagnosis
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Cystic nephroma: no primitive elements in septa of cystic neoplasm


Teratoid Wilms’ tumor

General
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● Rare
● Wilms’ tumor that arises within a teratoma
● Has large variety of tissues resembling teratoma
● Usually presents at high stage and has high mortality (
J Pediatr Urol 2007;3:282)

Micro images
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Ciliated epithelium


Cluster of 6 mature ganglion cells is present centrally with other mature tubular and stromal elements


Neuroglial differentiation was confirmed by GFAP staining

End of Kidney tumor - cysts, children, adult benign > Childhood neoplasms > Wilms’ tumor of children


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