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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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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
● 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
● Hyperdiploidy and trisomy 12 (Hum Pathol 1996;27:980) Gross images
Micro images
Differential diagnosis
● Cystic nephroma: no primitive elements in septa of cystic neoplasm Teratoid Wilms’ tumor General
● Rare Micro images
End of Kidney tumor - cysts, children, adult benign > Childhood neoplasms > Wilms’ tumor of children
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Numerous thin walled cysts
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Embryonal elements are present, but conform to the septa between cysts
Cysts with hobnail epithelium
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● 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)
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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
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