Chapter 20: Related Neoplasia

Question 1

Which 3 ethnicities are most commonly affected by Wilms Tumor?

Answer 1

Asians > Whites > Blacks

Question 2

How is Wilms tumor most often discovered?

Answer 2

• As large abdominal mass by parent or doc
• May exhibit pain, microscopic hematuria, and HTN

Question 3

Why is the presence of nephrogenic rests in a child a significant finding?

Answer 3

• Putative precursor lesions of Wilms Tumors
• 25-40% of unilateral
• 100% of bilateral arise from nephrogenic rests!

Question 4

Between what ages is peak prevalence for Wilms Tumor?

Answer 4

2-5 yo

Question 5

Which 3 groups of congenital malformation/familial syndromes have associated Wilms Tumor?

Answer 5

1. WAGR –> Wilms tumor + Aniridia + Genital anomalies + Retardation
2. Denys-Drash Syndrome (90% have Wilms)
3. Beckwith-Wiedemann Syndrome

Question 6

What is the most common way that Wilms Tumor is acquired?

Answer 6

90% are SPORADIC arising in previously healthy children w/ no congenital abnormalities

Question 7

Which 2 congenital malformation syndromes associated with Wilms Tumors have a strong association with the WT1 gene?

Answer 7

1. WAGR syndrome
2. Denys-Drash syndrome

Question 8

What is the classic histomorphology/pattern of Wilms Tumor?

Answer 8

• Classic triphasic combination of:
  1) Blastemal cells
  2) Stromal cells
  3) Epithelial cells

*Mimics the germinal development of the normal kindey

Question 9

Anaplasia in the histomorphology of Wilms Tumor tends to be associated with what mutations?

Resistance to?

Answer 9

p53 mutations w/ resistance to chemotherapy

Question 10

What is the most common genitourinary malformation seen in affected males and females with WAGR syndrome?

Answer 10

• Males = undescended testes
• Females = streak gonads or uterine malformations

Question 11

What is the characteristic glomerular lesion seen in patients with Denys-Drash syndrome?

Answer 11

Diffuse mesangial sclerosis

Question 12

In addition to Wilms tumors, patients with Denys-Drash syndrome are at an increased risk for what other tumor?

Answer 12

Gonadoblastoma (germ cell tumor)

Question 13

Beckwith-Wiedemann syndrome is associated with mutations of which chromosomal region and with what associated gene?

Answer 13

WT2 associated w/ IGF2

Question 14

Beckwith-Wiedemann syndrome is characterized by what classic findings?

Answer 14

• Enlargement of body organs (organomegaly)
• Macroglossia
• Hemihypertrophy
• Omphalocele
• Adrenal cytomegaly

Question 15

What is the characteristic gross morphology of Wilms Tumors?

Answer 15

• Well-circumscribed margins
• Tan-to-gray color w/ foci of hemorrhage, cysts, and necrosis
• Large, expansile tumor in lower pole of kidney

Question 16

What is the most common primary renal tumor of childhood?

Answer 16

Wilms Tumor

Question 17

What is the most critical prognostic element (i.e., unfavorable vs. favorable histopathologic features) of Wilms Tumors?

Answer 17

Presence or absence of diffuse anaplasia

Question 18

Genetic mutations in which 2 genes may have a synergistic role in development of Wilms Tumors?

Answer 18

WT1 and β-catenin

Question 19

Why is the histological presence of schwannian stroma in a neuroblastoma important?

Answer 19

Associated w/ favorable prognosis

Question 20

Common sites for metastasis of Neuroblastoma?

Answer 20

• Liver
• Lungs
• Bones and Bone Marrow
• Periorbital region –> proptosis and ecchymosis

Question 21

In neonates, disseminated neuroblastomas may present with multiple cutaneous metastases causing a deep blue discoloration of the skin, known clinically as what?

Answer 21

“Blueberry muffin baby”

Question 22

In children, under 2 years of age, how do neuroblastomas typically present?

Answer 22

• Large abdominal mass
• Fever
• Weight loss

Question 23

Which 4 stages are associated with favorable prognosis of Neuroblastomas?

Answer 23

• Stage 1
• Stage 2A
• Stage 2B
• Stage 4S

Question 24

How is the presence of TRKA expression vs. TRKB expression related to prognosis of Neuroblastomas?

Answer 24

• Presence of TRKA expression = Favorable
• Presence of TRKB expression = Unfavorable

Question 25

Which DNA ploidy of neuroblastomas is favorable and which is unfavorable for prognosis?

Answer 25

• Hyperdiploid (whole chromosomal gains) = favorable
• Near-diploid (segmental chromosomal losses) = unfavorable

Question 26

How is age of diagnosis related to prognosis in neuroblastoma?

Answer 26

• <18 months old = favorable
• >18 months old = unfavorable

Question 27

Amplification of which oncogene in neuroblastomas has possibly the most profound impact on prognosis?

Answer 27

MYCN

Question 28

Hemizygous loss of genetic material on which chromosome may be the most common deletion event in neuroblastomas?

Answer 28

Chromosome 11q