Other: liver tumors, retinoblastoma, GCT, etc.

Question 1

Pathology of hepatoblastoma: what is the most frequent subtype?

Answer 1

Mixed fetal-embryonal

Question 2

Pathology of hepatoblastoma: frequency and prognostic significance SCU?

Answer 2

Small cell undifferenciated: 5%, poor prognosis; overlap with low AFP

Question 3

Pathology of hepatoblastoma: frequency and prognostic significance of pure fetal histology?

Answer 3

7%; very good prognostic factor

Question 4

What is the most significant toxicity of SUPER-PLADO (Cisplatin/carboplatin-doxorubicin) acute? chronic?

Answer 4

• Hematological toxicity (G-CSF needed)

- Ototoxicity (up to 50% with dose-dense regimen)

Question 5

What is characteristic of fibrolamellar histology in HCC?

Answer 5

Surrounded by normal liver, rather than cirrhotic liver; increases chance of resectability

Question 6

Name 5 prognostic factors of hepatoblastoma?

Answer 6

1. Resectability/staging
2. Histology
3. AFP < 100
4. Multifocality
5. Age > 5 years old

Question 7

What is the main difference between SIOP and COG approaches? Name 1 advantage for each.

Answer 7

SIOP: neoadjuvant for all cases; increase resectability and give more time for surgical planning
COG: upfront resection whenever possible; early identification of histology and potential reduction of therapy in pure fetal histology; no evidence of increased surgical morbidity

Question 8

What is the outcome of hepatoblastoma:

• Localized?
• Metastatic?

Answer 8

Localized: 90%
Metastatic: 40-60%

Question 9

What is the outcome of HCC?

What is the main prognostic factor?

Answer 9

5 year OS: 28%; 5 year: 17-19%

Resectability

Question 10

Name 5 genetic syndromes associated with hepatoblastoma.

Answer 10

• Beckwitt-Wiedemann
• Hemihypertrophy, overgrowth syndromes
• Gardner syndrome
• Familial polyposis
• Glycogen storage disorders

Question 11

Name 3 environnemental causes associated with hepatoblastoma.

Answer 11

• VLBW
• Prematurity
• Parental exposure to R-OH (controversial)

Question 12

Name genetic causes of HCC.

Answer 12

• Glycogen storage disorder
• A1-antitrypsine deficiency
• Tyrosinemia
• Hemochromatosis

Question 13

Name acquired/environnemental causes of HCC.

Answer 13

• Biliary cirrhosis
• Viral hepatitis
• Alcool
• Anabolic steroids
• Aflatoxins, environmental carcinogens

Question 14

PRE-TEXT staging: name the other “high-risk” features

Answer 14

\+V: invasion of IVC and all hepatic veins
\+P: invasion of portal system
\+E: biopsy-proven extrahepatic disease
\+M: distant metastasis
\+H (controversial): hemorrhage/rupture

Question 15

Describe SIOPEL risk stratification of HB

Answer 15

Standard risk: PRETEXT 1-2-3, no high risk features

High risk: PRE-TEXT 4, or high risk features; AFP<100, hemorrhage/rupture (controversial)

Question 16

Describe COG risk stratification of HB

Answer 16

VLR: Pure fetal histology, stage I
LR: Stage I or II, non-SCU histology
IR: Stage I or II, SCU histology; 
     Stage III
HR: Stage IV; AFP <100

Question 17

Describe COG staging of HB

Answer 17

(Post-surgical)
I: fully resected
II: residual microscopic disease
III: gross residual disease
IV: metastatic disease

Question 18

Retinoblastoma: what is the “pathognomical” sign of histology?

Answer 18

Flexner-Wintersteiner rosettes (70%)

Rarely, fleurettes can be seen as well; show more photoreceptor differenciation

Question 19

Which immunostaining of small, round blue cell tumor would identify RB?

Answer 19

CRX (cone-rod homeobox)

Question 20

How many cases of RB are related to a germline mutation? How much of them are de novo?

Answer 20

25% germ line (multifocal or bilateral)

25% of them are inherited and 75% are de novo

Question 21

What is associated with a 13q14 deletion?

Answer 21

Syndrome including:

• Heredity retinoblastoma
• Dysmorphisms
• Mental retardation
• Subtle skeletal abnormalities
• Motor impairment

Question 22

What is trilateral RB?

Answer 22

Association of bilateral RB and asynchronous midline intracranial tumor, generally a PNET (such as pineoblastoma)

Question 23

Retinoblastoma:

1) What is the metastatic work up?
2) In which patients can the work up be omitted?

Answer 23

1) Bone scintigraphy; BMA/Bx; LP
(Also, ocular US and brain MRI should be done as part of the diagnostic work up, prior to staging)
2) Patients w/o HR features undergoing enucleation; patients with intra-ocular disease undergoing ocular salvage therapy

Question 24

Describe grossly the International Classification for Intraocular RB?

Answer 24

Group A: small tumors, away from foveola and disk
Group B: all remaining tumors confined to the retina
Group C: local subretinal fluid or seeding
Group D: diffuse subretinal fluid or seeding
Group E: presence of HR features (invasion of anterior segment, ciliary body, > 2/3 of globe, etc.)

Question 25

Retinoblastoma: which chemotherapy agents are active?

Answer 25

- Microtubules inhibitors: VCR, paclitaxel - Platinum compounds (cisplatin, carboplatin) - Alkylating agents: cyclophosphamide, ifos - Anthracyclins: doxorubicin, idarubicin - Topoisomerase I inhibitor: topotecan - Topoisomerase II inhibitors: etoposide, teniposide

Question 26

Retinoblastoma: high risk features (5)

Answer 26

High risk pathology: - Massive choroidal involvement - Scleral invasion - Invasion of optic nerve past the lamina cribosa Transcleral involvement Extension of disease to cut end of optic nerve

Question 27

Describe the surgical approach to ovarian GCT

Answer 27

- En bloc resection of affected ovary and Fallopian tube - Resection of enlarged/suspicious LN - Peritoneal cytology necessary (collection of ascites or peritoneal washings) Not necessary: random omental or LN sampling, biopsy of contralateral ovary if appears normal

Question 28

Describe the surgical approach to testicular GCT

Answer 28

- Inguinal approach: orchiectomy or testis-sparing enucleation (if focal lesion in pre-pubertal male) - If equivocal LN (2-4cm): LN biopsy (pre-pubertal) or RPLND (post-pubertal)

Question 29

Describe the surgical approach to sacrococcygeal GCT

Answer 29

- En bloc resection of the tumor with coccygectomy | Consider biopsy followed by delayed resection (might increase survival by increasing rates of complete resection)

Question 30

Infantile choriocarcinoma

Answer 30

- Very rare entity - Thought to be placental metastasis of maternal choriocarcinoma - Median age: 1 month old - Typical: FTT, anemia, hepatomegaly, seizures with very elevated b-HCG - Tx: multi-agent chemo (cisplatin, etposide +/- MTX) followed by delayed surgical resection - Screen mother after the diagnosis

Question 31

Terminology: what is the difference between germinoma, seminoma and dysgerminoma?

Answer 31

It is the location: Germinoma: CNS Seminoma: testicular Dysgerminoma: ovary Seminoma/dysgerminomas: usually occur in young adults, rare in children and teenagers Very sensitive to radiation, but chemotherapy 1st line treatment to decrease long term morbidity Surveillance only acceptable for stage I disease

Question 32

What pre-treatment tests are necessary in a patient with stage III gonadal tumor?

Answer 32

- GFR - PFT, with DLCO measurements - Audiology testing - Fertility preservation: sperm banking, oocyte cryopreservation

Question 33

Cytogenetics in gonadal GCT

Answer 33

Pre-pubertal: del 6q, del 1p Post-pubertal: i(12p), loss of 13, +21

Question 34

Growing teratoma syndrome

Answer 34

Situation when tumor enlarge during or after chemotherapy; repeat biopsy shows exclusively mature teratoma Hypothesis: chemotherapy-induced differenciation of tumors Treatment: surgery, when feasible; surveillance

Question 35

What proportion of patients with unilateral RB carry a germline mutation?

Answer 35

15%

Question 36

Which techniques are used to detect RB1 mutations? | What is the overall sensitivity?

Answer 36

``` Multiples techniques (no hot spot, many point mutations): FISH, PCR, MLPA, sequencing, methylation SE: 90-95% ``` **therefore, offsprings and sibling of survivors should be screened even if RB1 (-)ve re: possibility of false (-)ve

Question 37

Which second malignancies are commonly seen in retinoblastoma survivors?

Answer 37

- Osteosarcomas (25-40%) - Soft tissue sarcomas (10-15%) - Melanomas and other skin cancers (15-20%) - Lung cancer and other common cancer of adulthood

Question 38

Cumulative incidence of malignancies in survivors of retinoblastoma: - treated with radiation? - not treated with radiation?

Answer 38

a) 35-40% | b) 20%