Overview

Question 1

What is the estimated annual incidence of Wilms tumor (WT) in the United States?

Answer 1

∼500 cases/yr of WT are diagnosed in the United States.

Question 2

What is the median age at Dx?

Answer 2

Median age at Dx is 3–4 yrs (95% <10 yrs) for WT.

Question 3

Is there a sex predilection?

Answer 3

Yes. Females are more commonly affected than males.

Question 4

How does the age of presentation differ with Wilms when compared to neuroblastoma (NB)?

Answer 4

NB often presents at <2 yrs. Unilat WT presents at 3.5–4 yrs.

Question 5

What is the age of presentation for hereditary/bilat tumors?

Answer 5

Hereditary/bilat tumors often present at 2.5 yrs (younger than sporadic cases).

Question 6

Name 3 genetic syndromes associated with Wilms

Answer 6

1. WAGR
2. Denys–Drash
3. Beckwith–Wiedemann

Question 7

What is WAGR syndrome, and what is the associated genetic change?

Answer 7

Mnemonic: WAGR:

Wilms

Aniridia

GU anomalies

Mental Retardation

Associated genetic change: del 11q13 (WT1 deletion)

Question 8

What is Denys–Drash syndrome, and what is the associated genetic change?

Answer 8

Denys–Drash: Wilms, renal Dz (proteinuria during infancy, nephritic syndrome, progressive renal failure), male pseudohermaphroditism

Associated genetic change: point mutation of WT1 gene

Question 9

What is Beckwith–Wiedemann syndrome, and what is the associated genetic change?

Answer 9

Beckwith–Wiedemann: macrosomia, macroglossia, omphalocele, hemihypertrophy

Associated genetic change: 11p15.5, duplication of WT2 locus

Question 10

What transcription factor is important for normal kidney/gonadal development and is associated with Wilms?

Answer 10

WT1 (a zinc finger protein) is associated with Wilms and is important for normal kidney/gonadal development.

Question 11

What is the function of WT2?

Answer 11

Function of WT2 is unknown. It affects IGF2, the H19 tumor suppressor, and p57 cell cycle protein.

Question 12

What are the other genetic defects seen in Wilms?

Answer 12

LOH 1p16q, FWT1 (17q), and FWT2 (19q)

Question 13

Name 1 paternal and 1 maternal environmental risk factor for WT.

Answer 13

Fathers who are welders/machinists (RR 5.3); mothers who use hair dyes (RR 3.6)

Question 14

What are some poor prognostic factors seen in Wilms?

Answer 14

Unfavorable histology (UH), advanced tumor stage, molecular (+telomerase) and genetic (LOH 1p16q) markers, age >24 mos

Question 15

What histology has the worst outcome in Wilms?

Answer 15

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)

Question 16

What study demonstrated the prognostic importance of LOH 1p16q for Wilms?

Answer 16

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.

Question 17

What are the UH subtypes in Wilms?

Answer 17

Anaplastic: focal or diffuse

Question 18

How is focal anaplasia (FA) defined?

Answer 18

FA is sharply localized within the primary tumor, without atypia in the rest of the tumor.

Question 19

What renal tumors are not WT but are treated similarly to WTs?

Answer 19

Malignant rhabdoid tumor and clear cell sarcoma of the kidney

Question 20

What are the 4 sets of criteria used to define DA?

Answer 20

Criteria to define DA:

1. Nonlocalized
2. Localized with severe nuclear unrest elsewhere in the tumor
3. Anaplasia outside the tumor capsule or mets
4. Anaplasia revealed by random Bx

Question 21

What is the stage-by-stage 4-yr OS for anaplastic/UH WT?

Answer 21

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)

Question 22

How does the 4-yr OS compare b/t focal and diffuse anaplasia?

Answer 22

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%

Question 23

What are the typical presenting Sx in Wilms? How does this compare to NB?

Answer 23

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)

Question 24

What genetic syndromes are associated with Wilms tumors?

Answer 24

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).