WILM’S TUMOUR

Question 1

Nephroblastoma

(Benign or Malignant?) __________ tumour

Occurs in (children or adults?)

Answer 1

Malignant

embryonal

children

Question 2

Nephroblastoma

Does not occur in adults

T/F

Answer 2

F

Occurs in children, though rare forms in adult

Question 3

Nephroblastoma

Origin : __________ __________ tissue (blastema)
Resembles histology of __________________

Answer 3

Nephrogenic embryonal

developing kidney

Question 4

Nephroblastoma

Triphasic tumour:
___________
___________ (undifferentiated)
___________ components

Answer 4

Epithelial
Blastemal (undifferentiated)
Stromal components

Question 5

Nephroblastoma: Epidemiology

Peak age: _____years

95% before ____years

Answer 5

2-5years

10years

Question 6

Nephroblastoma: Epidemiology

Most common in _________
Least common in _____________
Slight female preponderance

Answer 6

Africans

East Asians

Question 7

Nephroblastoma: Epidemiology

5 to 10% involve (one or both?) kidney(s)

Bilateral tumours associated with _________ mutations

10- 15% associated with syndromes and congenital anomalies

_____% are familial

Answer 7

both kidneys

germline

1-2%

Question 8

Nephrblastoma: AETIOLOGY

Thought to develop from _______ tissue/ ___________

Answer 8

metanephric

nephrogenic rests

Question 9

nephrogenic rests are ????

Answer 9

persistent clusters/groups of embryonal cell’s

Question 10

Nephroblastoma: AETIOLOGY

Genetic alterations affecting embryonal development of genitourinary tract

_______ gene ___________

_______ gene

Answer 10

WT1

inactivation

WT2

Question 11

_____ gene is required for normal gonadal and renal development

Answer 11

WT-1

Question 12

Nephroblastoma: AETIOLOGY

Usually __________

1-2% _________

10-15% associated with syndromes: ______, __________ syndrome, Beckwith Wiedemann

Answer 12

sporadic

familial

WAGR; Denys-Drash

Question 13

WAGR syndrome:

Full meaning ?

Answer 13

Wilm’s tumour, aniridia, genitourinary abnormalities, mental disability (retardation)

Question 14

WAGR Syndrome

Lifetime risk of developing Wilm’s tumour is ______% , due to _______________ of _______ (WT-1gene)

Answer 14

33

Germline deletion

11p13

Question 15

WT-1 gene = ____(p or q?) ——

Answer 15

11

p

13

Question 16

Denys Drash Syndrome:

Characterized by ______________ and ______________ leading to renal failure

Answer 16

Male pseudohermaphroditism

Early-onset nephropathy

Question 17

Denys Drash Syndrome: ____% risk of Wilm’s tumor

Due to ___________ mutation in WT-1gene

Answer 17

90

Missense

Question 18

Nephroblastoma: AETIOLOGY

Beckwith Weidermann Syndrome (BWS):
Enlargement of body organs (organomegaly), __________ , __________,___________ , and abnormal _____ cells in the ___________ ( _______________)

Answer 18

macroglossia

hemihypertrophy

omphalocele

large; adrenal cortex; adrenal cytomegalovirus

Question 19

Nephroblastoma: AETIOLOGY

WT-2 locus (11p15.5)
Abnormality results from genomic imprinting (___________________ of one of the parental alleles (paternal or maternal?) )

Answer 19

transcriptional silencing

maternal

Question 20

Nephroblastoma: AETIOLOGY

Molecular changes associated with sporadic tumours still under investigation.

Genes implicated include ______,_______,_________

Tumours with ______ mutation have a poor prognosis

Answer 20

DICER1, DROSHA, DGCR8

TP53

Question 21

Nephroblastoma Tumours with TP53 mutation have a (poor or good?) prognosis

Answer 21

Poor

Question 22

Pathogenesis of Nephroblastoma???

Answer 22

Not clear how nephrogenic rests progress to tumour

Question 23

Wilm’s Tumor: Morphology- Gross

(Small or Large?)

(solitary or clustered ?)

(well or poorly?) -circumscribed mass

Answer 23

Large

Solitary

Well

Question 24

Wilm’s Tumor: Morphology- Gross

10% are ___lateral or ________ at the time of diagnosis

Answer 24

bi

multicentric

Question 25

Wilm’s Tumor: Morphology- Gross (Soft or Hard?) , ______ to ________ color with foci of ____ formation, __________ and __________

Answer 25

Soft grey to light brown cystic; Haemorrhage; necrosis

Question 26

Wilm’s Tumor: Morphology- Microscopy _______,__________, and __________ component in varying proportions About 5% show __________ - presence of cells with large, hyperchromatic, pleomorphic nuclei and abnormal mitoses

Answer 26

Stromal, epithelial and blastemal anaplasia

Question 27

Wilm’s Tumor: Morphology- Microscopy Attempts to recapitulate different stages of nephrogenesis Blastemal- sheets of _______ cells Epithelial- ————-,__________ Stromal- ________,_________

Answer 27

small blue abortive tubules, glomeruli fibroblastic, myxoid

Question 28

Wilm’s tumor : Morphology- Microscopy ______________ are putative precursor lesions of Wilms tumors and are seen in the renal parenchyma adjacent to approximately 25% to 40% of _______ tumors Nearly 100% in _______ Wilms tumors

Answer 28

Nephrogenic rests unilateral bilateral

Question 29

Wilm’s tumor : Morphology- Microscopy It is important to document the presence of nephrogenic rests in the resected specimen T/F With reason

Answer 29

T These patients are at an increased risk of developing Wilms tumors in the contralateral kidney

Question 30

Staging and Grading of Wilm’s tumors ________ or ________

Answer 30

SIOP or COG

Question 31

CLINICAL FEATURES: Wilm’s tumors (Small or Large?) _______ mass that may be unilateral or, when very large, extend across the ——— and down into the ______. ___________, ______ in the abdomen after a traumatic incident, __________ and _________ are other patterns of presentation.

Answer 31

Large ; abdominal midline; pelvis; Hematuria Pain; intestinal obstruction, and hypertension

Question 32

CLINICAL FEATURES: Wilm’s tumors In a significant number of these patients, _________ metastases are present at the time of primary diagnosis.

Answer 32

pulmonary

Question 33

Wilm’s Tumor: TREATMENT ________,__________,___________

Answer 33

Nephrectomy Chemotherapy Radiotherapy

Question 34

Wilm’s Tumor: PROGNOSIS ________________ is perhaps the most important determinant of adverse prognosis as it confers increased risk of recurrence and death Need for accurate identification of this histologic feature.

Answer 34

Anaplastic histology

Question 35

Wilm’s Tumor: Prognosis The presence of anaplasia correlates with the presence of _______ mutations and the emergence of _______________________

Answer 35

TP53 resistance to chemotherapy.

Question 36

Wilm’s Tumor: Prognosis P53 elicits —————- signals in response to DNA damage The loss of p53 function might explain the relative ____________________________ to cytotoxic chemotherapy

Answer 36

pro-apoptotic unresponsiveness of anaplastic cells

Question 37

Wilm’s Tumor: Prognosis Individuals with Wilms tumor have an increased risk of developing second primary tumours, including ________ and soft tissue ________ , ________ and ________, and ________ cancers. Although some of these neoplasms result from the presence of a germline mutation in a cancer predisposition gene, others are a consequence of therapy, most commonly radiation administered to the cancer field

Answer 37

bone and soft tissue sarcomas, leukemia and lymphomas, and breast cancers.