Renal Tumors

Question 1

Renal tumors epidemiology

Answer 1

7% of all childhood cancers
Wilms tumor most common renal Tumor of. Childhood 95%
RCC most common renal tumor in adolescents 15-19 y

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Question 2

Wilm’s tumor epidemiology

Answer 2

7.5 cases per million 
AA the highest- Asians lowest
Median age at dx- 43 months girls 37 months in boys 
More common in girls 
5-10% are bilateral on

Question 3

Overgrowth Syndromes associated with Wilms tumor (7)

Answer 3

• BWS (Loss of 11p15), associated with hemi-hypertrophy, macroglosia, organomegaly…
• Perlman syndrome (DIS3L2 inactivating mutation)
  Fetal gigantism, visceromagaly, unusual face, bilateral renal hamartomas and Wilms tumors
• Sotos syndrome
• NSD1
• Simpson-Golabi-Behmel syndrome
• Gycpican-3- X linked genetic disorder
• 9q22.3 microdel syndrome (PTCH1 deletion), associated with craniofacial abnormalities, craniosynostosis, hydrocephalus, macrosomia,

Question 4

Nonovergrowth syndromes associated with Wilms (6)

Answer 4

WAGR (WT1 gene product gonadal and renal development)
Denys- Drash (WT1 point mutation in 8/9 Econ) - Nephropathy, male pseudohemaphroditism, 90% develop Wilms
Bloom syndrome
Li- Fraumeni syndrome
Fanconi anemia
Trisomy 18

Question 5

Known somatic mutation associated with WT

Answer 5

WT1 mutation
Bilateral Wilms tumors
Unilateral tumors with nephrogenic rest

WTX can be inactivated

Question 6

Pathological subtypes of Wilms tumors

Answer 6

Classic pathology triad

• glomeruli tubular and strongly evidence
• blastema
• stroma

Nephroblastomatosis- nephrogenic rest are an increase risk of recurrence

Anaplasia - Anaplastic nuclear changes, hyperchromatia and increased mitotic rate.
Worse outcome if diffuse anaplasia

Question 7

Clear cell sarcoma histology

Answer 7

Second most common renal tumor.

Cords and nest of pale stained Tumor cells with abundant extacellular matrix

Can metastasize to bone, brain and soft tissue

High recurrence and death rate

Question 8

List 4 benign renal tumors

Answer 8

1) Congenital mesoblastic nephroma
2) Metanephric adenoma
3) Cystic nephroma
4) Cystic partially differentiated nephroblastoma

Question 9

List 7 non-Wilms renal tumors

Answer 9

1) Clear cell sarcoma
2) Synovial sarcoma
3) Renal cell carcinoma
4) PNET
5) Rhabdoid
6) Lymphoma
7) Desmoplastic small round cell tumors

Question 10

Congenital mesoblastic nephroma: higher risk of recurrence?

Answer 10

Age > 3 months, cellular subtype, stage III, incomplete resection

Question 11

Renal cell carcinoma: current approach to treatment

Answer 11

Surgical resection of all sites, including affected LN
Systemic therapy: no standard approach; many agents have been used: IL-2, interferon, doxorubicin/gemcitabin, bevacizumab, sunitinib, …

Question 12

Syndromes predisposing to RCC (6)

Answer 12

1) Von Hippel Lindau
2) Tuberous sclerosis
3) Succinate deshydrogenase deficiency (paraglanglioma/pheochromocytoma)
4) Hereditary leiomyomatosis - fumarate hydratase
5) Birt-Hogg-Dube (FLCN gene)
6) Familiary papillary RCC - MET

Question 13

Renal expression of DICER1 (3)

Answer 13

• Renal cysts
• Cystic nephromas
• Wilms tumor

Question 14

What is CPDN (Cystic partially differenciated nephroblastoma)?

Answer 14

Rare variant of Wilms; 
Entirely cystic; has low malignant potential
100% survival
Stage I: nephrectomy alome
Stage II: VCR/dactino adjuvant

Question 15

Management of recurrent WT?

a) patient treated with VCR/dactino initially
b) patient treated with 3 drugs (VCR-doxo-dactino) or more
c) anaplastic or blastemal predominant WT

Answer 15

a) surgical excision, radiation, alternating course of VCR-Doxo-Cyclo/cyclo-etoposide
b) surgical excision, radiation, alternating courses of cyclo/etop and carbo/etop
c) same as b), but VHR patients

Question 16

Clear cell sarcoma of the kidney:

- Recommended treatment?

Answer 16

Regimen I: VCR-dactino-doxorubicin, with cyclophosphamide/etoposide (based on NWTS-5)
along with radiation and surgery

Question 17

Clear cell sarcoma of the kidney:

- Recommended staging?

Answer 17

Chest CT-scan
Abdominal MRI
Bone scan
Brain MRI
re: far wider distribution of metastases (lung, brain, bone, soft tissue, etc.

Question 18

Clear-cell sarcoma of the kidney

- Prognosis?

Answer 18

75-80% 4 year EFS, as per NWTS-5

Question 19

Typical cytogenetic anomaly in desmoplastic small round cell tumor

Answer 19

T(11;22)(p13;q12) - EWS-WT1

Question 20

Typical cytogenetic anomaly in rhabdoid tumors

Answer 20

22q deletion - SMARCB1 inactivation

Question 21

Clear cell sarcoma of the kidney: what are the associated genetic defects?

Answer 21

• Internal tandem duplication at exon 15 of BCOR gene

- t(10;17), leading to YWHAE-NUT2M

Question 22

Name favorable prognosis factors for relapsed Wilms (6)

Answer 22

• Relapse more than 12 months after diagnosis
• Relapse more than 6 months after nephrectomy
• Primary treatment with 2 drugs only (e.g. dactino-VCR)
• Relapse outside radiation field
• Isolated pulmonary nodule
• Favorable histology