Overview Flashcards
What is the estimated annual incidence of Wilms tumor (WT) in the United States?
∼500 cases/yr of WT are diagnosed in the United States.
What is the median age at Dx?
Median age at Dx is 3–4 yrs (95% <10 yrs) for WT.
Is there a sex predilection?
Yes. Females are more commonly affected than males.
How does the age of presentation differ with Wilms when compared to neuroblastoma (NB)?
NB often presents at <2 yrs. Unilat WT presents at 3.5–4 yrs.
What is the age of presentation for hereditary/bilat tumors?
Hereditary/bilat tumors often present at 2.5 yrs (younger than sporadic cases).
Name 3 genetic syndromes associated with Wilms
- WAGR
- Denys–Drash
- Beckwith–Wiedemann
What is WAGR syndrome, and what is the associated genetic change?
Mnemonic: WAGR:
Wilms
Aniridia
GU anomalies
Mental Retardation
Associated genetic change: del 11q13 (WT1 deletion)
What is Denys–Drash syndrome, and what is the associated genetic change?
Denys–Drash: Wilms, renal Dz (proteinuria during infancy, nephritic syndrome, progressive renal failure), male pseudohermaphroditism
Associated genetic change: point mutation of WT1 gene
What is Beckwith–Wiedemann syndrome, and what is the associated genetic change?
Beckwith–Wiedemann: macrosomia, macroglossia, omphalocele, hemihypertrophy
Associated genetic change: 11p15.5, duplication of WT2 locus
What transcription factor is important for normal kidney/gonadal development and is associated with Wilms?
WT1 (a zinc finger protein) is associated with Wilms and is important for normal kidney/gonadal development.
What is the function of WT2?
Function of WT2 is unknown. It affects IGF2, the H19 tumor suppressor, and p57 cell cycle protein.
What are the other genetic defects seen in Wilms?
LOH 1p16q, FWT1 (17q), and FWT2 (19q)
Name 1 paternal and 1 maternal environmental risk factor for WT.
Fathers who are welders/machinists (RR 5.3); mothers who use hair dyes (RR 3.6)
What are some poor prognostic factors seen in Wilms?
Unfavorable histology (UH), advanced tumor stage, molecular (+telomerase) and genetic (LOH 1p16q) markers, age >24 mos
What histology has the worst outcome in Wilms?
Diffuse anaplasia (DA), f/b rhabdoid and clear cell sarcoma. A review of NWTS-1 and -2 studies involving ∼1,200 children, DA had the shortest survival time compared to nonanaplastic histologies. (Bonadio F et al., JCO 1985) In another study, DA was seen in 10% of cases, but accounted for 60% of the deaths. (Faria P et al., Am J Surg Pathol 1996)
What study demonstrated the prognostic importance of LOH 1p16q for Wilms?
NWTS-5 analysis. (Grundy PE et al., JCO 2005) For FH, LOH 1p or 16q is associated with ↑ (RR) of relapse. LOH of both ↑ RR of relapse + death.
What are the UH subtypes in Wilms?
Anaplastic: focal or diffuse
How is focal anaplasia (FA) defined?
FA is sharply localized within the primary tumor, without atypia in the rest of the tumor.
What renal tumors are not WT but are treated similarly to WTs?
Malignant rhabdoid tumor and clear cell sarcoma of the kidney
What are the 4 sets of criteria used to define DA?
Criteria to define DA:
- Nonlocalized
- Localized with severe nuclear unrest elsewhere in the tumor
- Anaplasia outside the tumor capsule or mets
- Anaplasia revealed by random Bx
What is the stage-by-stage 4-yr OS for anaplastic/UH WT?
4-yr OS for anaplastic/UH Wilms:
Stage I: 83%
Stage II: 81%
Stage III: 65%
Stage IV: 38% (immediate nephrectomy) vs. 56% (preop chemo)
Stage V: 55%
(Dome JS et al., JCO 2006)
How does the 4-yr OS compare b/t focal and diffuse anaplasia?
Overall: 82% vs. 60%
Stage I: 89% vs. 79%
Stage II: 80% vs. 82%
Stage III: 71% (FA: preop chemo) vs. 67% (DA: nephrectomy) vs. 53% (DA: preop chemo)
Stage IV: 72% (FA: preop chemo) vs. 33% (DA: nephrectomy) vs. 44% (DA: preop chemo)
Stage V: 88% vs. 42%
What are the typical presenting Sx in Wilms? How does this compare to NB?
Asymptomatic abdominal mass (83%) → abdominal pain (37%), HTN (25%, d/t ↑ renin), hematuria (25%), fever, anemia (d/t ↓ Epo)
NB most commonly presents with systemic Sx.
(Mnemonic: WWNN—Wilms are Well, Neuroblastomas are Not well)
What genetic syndromes are associated with Wilms tumors?
WAGR syndrome (Wilms tumor with aniridia, genitourinary malformations, and mental retardation) is associated with a deletion of 11p13.
Beckwith–Wiedemann syndrome (Wilms tumor with macrosomia or hemihypertrophy, macroglossia, omphalocele, abdominal organomegaly, and ear pits is associated with deletion of 11p15).
Denys–Drash syndrome (Wilms tumor with pseudohermaphroditism associated with mutation of WT1).
