Other: liver tumors, retinoblastoma, GCT, etc. Flashcards
Pathology of hepatoblastoma: what is the most frequent subtype?
Mixed fetal-embryonal
Pathology of hepatoblastoma: frequency and prognostic significance SCU?
Small cell undifferenciated: 5%, poor prognosis; overlap with low AFP
Pathology of hepatoblastoma: frequency and prognostic significance of pure fetal histology?
7%; very good prognostic factor
What is the most significant toxicity of SUPER-PLADO (Cisplatin/carboplatin-doxorubicin) acute? chronic?
- Hematological toxicity (G-CSF needed)
- Ototoxicity (up to 50% with dose-dense regimen)
What is characteristic of fibrolamellar histology in HCC?
Surrounded by normal liver, rather than cirrhotic liver; increases chance of resectability
Name 5 prognostic factors of hepatoblastoma?
- Resectability/staging
- Histology
- AFP < 100
- Multifocality
- Age > 5 years old
What is the main difference between SIOP and COG approaches? Name 1 advantage for each.
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
What is the outcome of hepatoblastoma:
- Localized?
- Metastatic?
Localized: 90%
Metastatic: 40-60%
What is the outcome of HCC?
What is the main prognostic factor?
5 year OS: 28%; 5 year: 17-19%
Resectability
Name 5 genetic syndromes associated with hepatoblastoma.
- Beckwitt-Wiedemann
- Hemihypertrophy, overgrowth syndromes
- Gardner syndrome
- Familial polyposis
- Glycogen storage disorders
Name 3 environnemental causes associated with hepatoblastoma.
- VLBW
- Prematurity
- Parental exposure to R-OH (controversial)
Name genetic causes of HCC.
- Glycogen storage disorder
- A1-antitrypsine deficiency
- Tyrosinemia
- Hemochromatosis
Name acquired/environnemental causes of HCC.
- Biliary cirrhosis
- Viral hepatitis
- Alcool
- Anabolic steroids
- Aflatoxins, environmental carcinogens
PRE-TEXT staging: name the other “high-risk” features
\+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
Describe SIOPEL risk stratification of HB
Standard risk: PRETEXT 1-2-3, no high risk features
High risk: PRE-TEXT 4, or high risk features; AFP<100, hemorrhage/rupture (controversial)
Describe COG risk stratification of HB
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 <100Describe COG staging of HB
(Post-surgical) I: fully resected II: residual microscopic disease III: gross residual disease IV: metastatic disease
Retinoblastoma: what is the “pathognomical” sign of histology?
Flexner-Wintersteiner rosettes (70%)
Rarely, fleurettes can be seen as well; show more photoreceptor differenciation
Which immunostaining of small, round blue cell tumor would identify RB?
CRX (cone-rod homeobox)
How many cases of RB are related to a germline mutation? How much of them are de novo?
25% germ line (multifocal or bilateral)
25% of them are inherited and 75% are de novo
What is associated with a 13q14 deletion?
Syndrome including:
- Heredity retinoblastoma
- Dysmorphisms
- Mental retardation
- Subtle skeletal abnormalities
- Motor impairment
What is trilateral RB?
Association of bilateral RB and asynchronous midline intracranial tumor, generally a PNET (such as pineoblastoma)
Retinoblastoma:
1) What is the metastatic work up?
2) In which patients can the work up be omitted?
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
Describe grossly the International Classification for Intraocular RB?
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.)
Retinoblastoma: which chemotherapy agents are active?
- Microtubules inhibitors: VCR, paclitaxel
- Platinum compounds (cisplatin, carboplatin)
- Alkylating agents: cyclophosphamide, ifos
- Anthracyclins: doxorubicin, idarubicin
- Topoisomerase I inhibitor: topotecan
- Topoisomerase II inhibitors: etoposide, teniposide
Retinoblastoma: high risk features (5)
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
Describe the surgical approach to ovarian GCT
- 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
Describe the surgical approach to testicular GCT
- 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)
Describe the surgical approach to sacrococcygeal GCT
- En bloc resection of the tumor with coccygectomy
Consider biopsy followed by delayed resection (might increase survival by increasing rates of complete resection)
Infantile choriocarcinoma
- 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
Terminology: what is the difference between germinoma, seminoma and dysgerminoma?
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
What pre-treatment tests are necessary in a patient with stage III gonadal tumor?
- GFR
- PFT, with DLCO measurements
- Audiology testing
- Fertility preservation: sperm banking, oocyte cryopreservation
Cytogenetics in gonadal GCT
Pre-pubertal: del 6q, del 1p
Post-pubertal: i(12p), loss of 13, +21
Growing teratoma syndrome
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
What proportion of patients with unilateral RB carry a germline mutation?
15%
Which techniques are used to detect RB1 mutations?
What is the overall sensitivity?
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
Which second malignancies are commonly seen in retinoblastoma survivors?
- Osteosarcomas (25-40%)
- Soft tissue sarcomas (10-15%)
- Melanomas and other skin cancers (15-20%)
- Lung cancer and other common cancer of adulthood
Cumulative incidence of malignancies in survivors of retinoblastoma:
- treated with radiation?
- not treated with radiation?
a) 35-40%
b) 20%
