HD2 Revision7 Flashcards
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
Which type of cells does Wilms tumour arise from? [1]
Wilms tumour contains the three cell types are present in the embryonic kidney, what are they? [3]
pluripotent embryonic renal precursors
blastema, epithelia, stroma (the three cell types present in the embryonic kidney)
Explain pathophysiology of retinoblastoma
- Which gene is mutated?
- Which cells are effected?
- Overview of mechanism?
germline mutation of RB1 gene usually present in patients
Occurs in cone precursor cells
Signalling pathways promote cell survival after loss of RB1
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!
What type of genes are WT1, WTX & TP53? [1]
WT1, WTX & TP53 are Tumour Suppressor Genes
How does Rb gene work under normal function? [2]
Explain how mutation to Rb gene causes cancer [1]
Normal:
* Keeps cells at G1 phase: stops cell cycle progession.
- When it becomes phosphorylated, releases E2F (a transcription factor) which induces G1 –> S transition
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
Tx of retinoblastoma:
- Small tumour? [3]
- Advanced tumours [3]
Small tumours: cryotherapy, laser therapy or thermotherapy
More advanced tumours or distant disease: chemotherapy, surgery &/or radiation
Neuroblastoma:
how does it often present at diagnosis? [1]
Metastatic disease in >50% cases at diagnosis; spreads via lymphatics and blood stream
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
How do Pro-B ALL cells appear histologically? [1]
Lots of pre-cursor cells
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
What are the treament phases for ALL? [4]
Induction
Consolidation; CNS-directed treatment
Maintenance
Bone marrow transplantation
What is the causative agent of Strep throat? [1]
How does someone with Strep throat present? [4]
When is it a problem? [1]
group A Streptococcus: Streptococcus pyogenes
Sore throt
Trouble swallowing
Fever
Stomach Pain
Headache
problem when it becomes septic
Name a viral infection that is worse in childhood than in adulthood? [1]
Name a viral infection that is worse in adulthood than in childhood? [1]
Name a viral infection that is worse in childhood than in adulthood? [1]
HSV
Name a viral infection that is worse in adulthood than in childhood? [1]
VZV - leads to shingles
Why are there less treatment options for viruses than bacterial infections?
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
What is the difference between Strep throat and scarlet fever? [1]
Name a symptom of scarlet fever not in strep throat
Both caused by Streptococcus pyogenes / group A Streptococcus
When Group A strep just infects throat: strep throat
* fever and an inflamed, painful throat with swelling of the tonsils.
When Group A strep becomes more systemic: scarlett fever:
* Rash and strawberry tongue presentation
When are the primordial follicles formed during development? [1]
Where are primordial follicles found in ovary? [1]
Describe the cell type the primordial follicles are comprised of [1]
Formed during first 5 months of development
Location: outside of ovary
Cell type: single layer of squamous follicular cells
Follicle development:
Early primary follicle
Describe the structure
What cell structural change occurs after their development from primordial follicle? [1]
Which hormone triggers change from primordial follicle to early primary follicle? [1]
- Central oocyte & single layer of cuboidal cells
- Squamous (primordial) to cuboidal
- Stimulated by FSH
Note the cuboidal cells surrounding the oocyte
Follicle development:
What changes in structure occur from early primary folllicle to a late primary follicle? [2]
- Follicular cells proliferate into stratified epithelium called zona granulosa
- Development of zona pellucida occurs: layer that seperates oocyte from the follicular cells
-
Which two structural layers are created whe the late primary follicle develops? [2]
Zona pellucida
Zona granulosa
Follicle development:
What development occurs from late primary follicle to secondary follicle? [3]
- Follicular antrum within granulosa layer
- Thicker zona pellucida
- Larger zona granulosa
- Larger oocyte
- Thecal cells outside of follicle proliferate
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
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
Describe the cell structure of the oviduct / uterine tube [2]
What are the two types of epithelium found? [2]
Structure:
* wall of smooth muscle
* elaborate mucosa: appears like a labyrinth
Epithelium consists of:
- Ciliated cells (move ovum along)
- Non-ciliated cells: secrete lubricating secretions to nourish & protect ovum
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
What is the epithelial cell structure of the vagina? [1]
Why does the vagina release glycogen into epithelium? [1]
Describe the structure of CT found behind ^ [1]
Stratified squamous epithelium (small degree of keratinisation)
The release of glyocgen feeds commensal bacteria Lactobacillus lactic
Vagina has dense irregular CT
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
Leiomyoma are proliferations of which cell type? [1]
Driven by XS of which hormone? [1]
Which part of the vagina are fibroids found? [1]
- SMC proliferations
- Driven by oestrogen rise
- In myometrium
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
A 4 year old boy is brought to the physician by his mother due to a 5 week history of lethargy, a progressively enlarging left sided neck mass and a 5 day onset of unexplainable bilateral diffuse lower leg petechial hemorrhage. On exam, the left posterior cervical lymph node is enlarged and nontender to palpation. A lymph node biopsy shows a predominance of interfollicular infiltrate containing numerous blast cells and focal necrosis. Immunohistochemistry is positive for PAX5, CD10 and TdT. Upon further workup, which of the following translocations would be associated with a good prognosis?
t(12;21)
t(14;18)
t(8;14)
t(9;22)
A 4 year old boy is brought to the physician by his mother due to a 5 week history of lethargy, a progressively enlarging left sided neck mass and a 5 day onset of unexplainable bilateral diffuse lower leg petechial hemorrhage. On exam, the left posterior cervical lymph node is enlarged and nontender to palpation. A lymph node biopsy shows a predominance of interfollicular infiltrate containing numerous blast cells and focal necrosis. Immunohistochemistry is positive for PAX5, CD10 and TdT. Upon further workup, which of the following translocations would be associated with a good prognosis?
t(12;21)
t(14;18)
t(8;14)
t(9;22)
