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

Author: Mandolin Ziadie, M.D. (see Authors page)

Revised: 13 January 2017, last major update January 2012

Copyright: (c) 2003-2007, PathologyOutlines.com, Inc.

PubMed search: Wilms tumor [title] children kidney

Related topics: Cystic partially differentiated nephroblastoma, Teratoid Wilms tumor
Cite this page: Wilms tumor of children. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/kidneytumorwilmkids.html. Accessed January 24th, 2017.
Definition / General
  • Also known as nephroblastoma, this triphasic renal tumor was first described by Dr. Max Wilms
Epidemiology
  • Most common pediatric renal tumor, affecting 1 per 8 - 10,000 children (500 new cases per 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)
Childrens oncology group staging of pediatric renal neoplasms
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 nonhematogenous 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, presurgical 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 (substage each tumor separately according to above criteria)

Pathophysiology
  • Apparently derives from nephrogenic blastema cells
Clinical Features
  • 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
Gross Description
  • 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

Images hosted on PathOut server:

Tumor protrudes
into the renal pelvis
resembling botryoid
rhabdomyosarcoma

Metastases to lung



Images hosted on other servers:

Well circum-
scribed tumor
with hemorrhage
and necrosis

Expansively growing tumor

Necrotic kidney tumor and adherent ileum

Gray spherical tumor


Triphasic tumor

Blastema

Tubules and rosettes

Anaplasia

Micro Description
  • 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 3× 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 nonanaplastic 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
Scroll to see all images:

Images hosted on PathOut server:

Tumor within vessels and soft tissue of the renal sinus

Triphasic tumor

Mature pattern



Blastema:

Diffuse patterns


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



Epithelium:

Monophasic epithelial pattern is predominant

Embryonal tubular pattern

Tubular structures predominate in this lesion

Mature tubulopapillary pattern

Tubular and glomerular differentiation


Relatively mature glomeruli

Rosettes in PNET often lack concentration around their center

Mucinous epithelium may be prominent

Squamous epithelial focus



Other features:

Skeletal muscle is a common tumor element,

Botryoid protrusions of tumor cells into lumen

Adipose
differentiation with
associated skeletal
muscle nodule

Cartilage formation

Huge, irregular shaped nuclei


Sharply demar-
cated nodular
region was only
anaplasia site

Multipolar mitotic figure

True tripolar mitosis
has each limb nearly
the size of a normal
metaphase plate

Nephroblastoma



Post chemotherapy:

Total tumor necrosis; persistence of mature skeletal muscle



Images hosted on other servers:

Diagram of renal sinus and tumor invasion

Triphasic tumor

Blastema, primitive glomeruli and tubules


Tumor compresses renal medulla

Blastema with glomeruloid epithelial structure

Blastema, epithelium and mitotic figures

Blastema with cribriform epithelial component



Stains:

H&E and INI1+

Virtual Slides

Images hosted on other servers:

Various virtual slides

Videos


Wilms tumor
Positive Stains
Negative Stains
  • Blastema negative for CK7, CD57 and usually p53
  • Epithelium negative for vimentin
Molecular / Cytogenetics Description
  • 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 Ewings / PNET
  • No 22q11.2 abnormalities of rhabdoid tumor
  • No N-myc of neuroblastoma
Electron Microscopy Description
  • Resembles developing metanephros with well developed cell junctions, microvilli and layer of thick flocculent coating around cell surface
Differential Diagnosis
  • 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