HD EOYS5 Flashcards
How does Wilms tumour present histologically? [1]
tumor shows attempts to form primitive glomerular and tubular structures. Pediatric neoplasms are often composed of cells that resemble primitive embryonic counterparts: -blasts. In this case the cells are reminiscent of developing nephroblasts.
Which is the main gene involved in high risk patients of neuroblastoma?
MYCN
WT1
ALK
PHOX2B
Which is the main gene involved in high risk patients of neuroblastoma?
MYCN
WT1
ALK
PHOX2B
Which is the main gene involved in hereditary patients of neuroblastoma?
MYCN
WT1
ALK
PHOX2B
Which is the main gene involved in hereditary patients of neuroblastoma?
MYCN
WT1
ALK
PHOX2B
Endometrial cancer is caused by an excess of which hormone?
progesterone
oestrogen
LH
FSH
Endometrial cancer is caused by an excess of which hormone?
progesterone
oestrogen
LH
FSH
What are oncogenes activated by? [4]
Activated by gain of function mutations:
- mutation
- chromosome translocation
- gene amplification
- retroviral insertion
What are tumour suppressor genes inactivated by? [3]
Inactivated by:
* mutations
* deletions
* DNA methylation (epigenetic)
How does Wilm tumour present? [3]
- Tumour of the kidney (aka nephroblastoma)
- Mostly children under 5
- asymptomatic abdominal mass without metastasis
- Often bilateral
Describe the molecular pathology of Wilms tumour
Which genes are affected if somatic gene alterations occur [3]
Which genes are affected if germline alterations occur? [2]
Somatic gene alterations:
* In WT1, WTX and TP53 genes
* Inactivated CTNNB1 (beta catenin gene
* Epigenetic changes at IGF2/H19 locus
Germline alterations:
* In WT1 genes
* Inactivated CTNNB1 (beta catenin gene
What is the key role of WT1 gene? [1]
Ureteric branching - has key role in the epithelial induct of the metanephric mesenchyme
WT1 is critical in the key pathways for the developing kidney!
How does Rb gene work under normal function? [2]
Explain how mutation to Rb gene causes cancer [1]
Normal:
* pRb restricts the cell’s ability to replicate DNA by preventing its progression from the G1 (first gap phase) to S (synthesis phase) phase of the cell division cycle
- pRb binds and inhibits E2 promoter-binding–protein-dimerization partner (E2F-DP) dimers, which are transcription factors of the E2F family that push the cell into S phase.
- By keeping E2F-DP inactivated, RB1 maintains the cell in the G1 phase, preventing progression through the cell cycle and acting as a growth suppressor.
Pathology:
* Mutation causes no Rb1 hyperphosphorylation due to lack of binding to E2F
Which other genes are implicated in retinoblastoma? [4]
MYCN activation
MDM2 or MDM4 over-expression or amplification - leads to inactivation of TP53
Neuroblastoma is a tumour of which body system? [1]
Which organs does it usually occur in? [2]
Tumour of the sympathetic nervous system, usually arising in the adrenal gland or sympathetic ganglia
Which oncogenes are involved with neuroblastoma? [3]
MYCN amplification, ALK & PHOX2B
What is the difference betwen molecular pathology of neuroblastoma between high risk, low risk and hereditary patients? [3]
High risk patients
* Have high MYCN amplification; ATRX & ALK mutations
* Near-diploid/near-tetraploid karyotype, complex chromosome aberrations
* Deletions in 1p and 11q
Low risk:
* Numerical chromosome gains (e.g. spontaneous chromosomes)
Hereditary
* Germline ALK mutations
How do patients with Acute Lymphoblastic Leukaemia (ALL) present [3]
Where does infiltration of ALL usually occur? [4]
- bruising or bleeding due to thrombocytopaenia
- pallor and fatigue due to anaemia
- infection due to neutropenia
- Infiltratration to the liver, spleen, lymph nodes and mediastinum common at diagnosis
In children, what are the three major types of ALL? [3]
In children ~80% are CD19+, CD10+ “B-cell precursor ALL”
Which comes first Pro-B or Pre-B? [1]
What are Pro-B and Pre-B cells characterised by on their cell surfaces? [3]
Pro-B then Pre-B
ProB cells are characterized by cell surface marker CD19+
PreB cells are characterized by cell surface markers CD19+ and CD10+
What are the distinctive cell abnormalites that often occur in Pro-B cells and Pre-B cells? [2]
There are distinctive cell abnormalities:
Pro-B (CD19+, CD10-) always have translocation of MLL gene translocated
Pre-B always have translocation of chromosomes 12 & 22
Explain the two step model that causes ALL
Step 1: developmental error in utero
Step 2: Dysregulated immune response to infection (This occurs in patients who
carry a covert pre- leukaemic clone and have a deficit of infectious exposures in infancy; children who are born by C-section may not be exposed to microbes during the birth canal)
What is the prognosis for patients with:
Pro-B ALL? [1]
Pre-B ALL [1]
Pro-B ALL / MLL translocation: unfavourable for children
Pre-B ALL: ETV6-RUNX1 translocation: more favourable
Which vaccines are given in the 6 in 1 vaccine? [6]
At what ages is it given to children? [3]
Describe the vaccination plan so that th full course is given [:)]
Diptheria, tetanus, pertusis, polio, Haemophilus influezae type B (Hib) and hep B
All given at: 8 weeks; 12 weeks; 16 weeks
Diphtheria, tetanus, pertussis and polio given again at 3 years 4 months
Tetanus, diphtheria and polio at 14 years
When is rotavirus vaccine given? [2]
8 weeks
12 weeks
The HPV vaccine protects agaisnt which strains? [4]
Which strains cause HPV? [2]
Which strains cause genital warts? [2]
Protects agaisnt: 6, 11, 16, 18, 31, 33, 45, 52, and 58
Human papillomavirus (HPV) types 16 and 18
Genital warts: caused by type 6 and 11
At which stage is first meiotic division complete by
- Primordial follicle
- Early Primary Follicle
- Late Primary Follicle
- Secondary Follicle
- Tertiary / Graffian Follicle
- Corpus luteum
- Corpus albican
At which stage is first meiotic division complete by
- Primordial follicle
- Early Primary Follicle
- Late Primary Follicle
- Secondary Follicle
- Terteriay / Graffian Follicle
- Corpus luteum
- Corpus albican
What level of development are primordial follicles in? [1]
When do they develop further? [1]
They remain in the first meiotic division
At puberty they begin to develop further
Which two structural layers are created whe the late primary follicle develops? [2]
Zona pellucida
Zona granulosa
Describe how the formation of oestrogen occurs in oocyte
- Cholesterol from blood stream goes to thecal cells (both located on outside of follicle)
- Theca cells catalyse cholesterol into androgens, but lack aromatase to finalise conversion into oestrogen
- Androgens move to granulosa cells, which have aromatose; granulosa cells are stimulated by FSH to make oestrogen
Follicle development
Which structural changes occur when the oocyte develops into a tertiary oocyte?
- Large follicular antrum makes up most of follicle
-
Corona radiata develops: layer of cells that surrounds the zona pellucida
Corona radiatia
Corpus luteum:
Which hormone do granulosa cells make before ovulation? [1]
Which hormone do granulosa cells make after ovulation? [1]
granulosa cells: switch from making oestrogen to making progesterone
How long does the corpus luteum stay active before turning into a corpus albicans if oocyte is not fertilised? [1]
What happens to the corpus albican when it degenerates? [1]
The decrease of which hormone causes this to happen? [1]
14 days
Secretory cells degenerate and are phagocytosed by macrophages and replaced by fibrous material
Due to drop in LH
Describe what atretic follicles are and why they are formed [2]
Which hormone decreasing creates atretic follicles? [1]
Atretic follicles:
- Several primordial follicles are stimulated to develop - but only one completes the development to become the ovum
- The rest undergo a process called atresia which can occur at any stage – become scar tissue and break down: look like little corpus albucans
- Triggered by decrease if FSH
Name the three stages in the uterine cycle and which hormones drive each phase [6]
Proliferative phase: driven by oestrogen
Secretory phase: Driven by progesterone
Menstrual phase: driven by progesterone levels falling
Describe each stage of the uterine cycle [3]
Proliferative stage:
* Robust growth of epithelial cells in stratum functionalis
* Formation of coiled and densely packed glands
Secretory phase:
* Glands become more complexly coiled & filled with secretions (appears pink) rich in glycogen and glycoproteins
* Endometrium is maximum thickness
Menstrual phase:
* If fertilisation occurs - nohCG and corpus luteum degenerates
* Spiral arteries in endometrium constrict and tissue becomes ischemic
* Cells die and this causes sloughing of stratum functionalis
* Forms the menstrual flow
How does endometrial cancer appear histologically? [1]
They can grow as polypoid masses that project into endometrial cavity:
- Irregular crowded glands lined by columnar epithelium with pseudostratified nuclei and mild atypical cytologic
Which cell types are the predominate type that cause ovarian cancer? [1]
Serous ovarian cancer:
2/3rds of cases epithelial ovarian cancer (outer coating of ovary and peritoneum – CT around the ovary, not the cyst itself)
Ovarian cancer - describe the histopathology of serous cystadenoma [2]
Multi-cystic with fine papillary projections from cyst wall
Thin walled cysts lined with ciliated pseudostratified cuboidal pr columnar epithelium
Why does taking oral contraceptive pills cause a protective effect for ovarian cancer? [1]
Suppresses ovulation
