Neoplasia Flashcards
What are the relative risks of neoplasia and managemnet suggestions for the following
- Non-proliferative breast changes (fibrocystic changes)
- Proliferatives breast disease without atypia
- Proliferative breast disease with atypia
NON proliferative
- 1.0 x risk
PROLIFERATIVE with NO hyperplasia
- 1.5-2 x risk
- excisional biopsy
PROLIFERATIVE WITH hyperplasia
- 4-5 x risk
- excisional biopsy
What are some examples of non-proliferative breast change? (7)
Duct ectasia Cysts Fibrosis Apocrine change Mild hyperplasia Adenosis Fibroadenoma without complex features
What are some examples of proliferative breast disease without atypia? (5)
Moderate or florid hyperplasia Sclerosing adenosis Papilloma Complex sclerosing lesion (radial scar) Fibroadenoma with complex features
What are some examples of proliferative breast disease with atypia?
Atypical ductal hyperplasia
Atypical lobular hyperplasia
Where are the common sites for metastatic breast carcinoma?
Liver Lungs Bone Brain Meninges Skin Adrenals
What is the function of the BRCA1 and BRCA2 genes and what cancers are they linked to (other than breast)?
Tumour suppressor genes, promote DNA repair
BRCA1: prostate, colon, pancreas
BRCA2: prostate, pancreas, stomach, melanomas
What is the definition of carcinoma in situ?
CIS = neoplastic population of cells limited by the basement membrane
What is the recommended treatment for DCIS?
WLE + RTx
What is the presentation, pathogenesis and management of paget’s disease?
PRESENTATION: unilateral erythematous eruption of scale crust
PATHOGENESIS:
- paget cells extend from DCIS into nipple skin, do not cross basement membrane
MANAGEMENT: as DCIS, WLE and RTx
What are some key morphological differences between benign and malignant histologies?
- pleomorphism: variation in size and shape
- abnormal nuclear morphology: high nuclear:cytoplasm ratio
- mitoses: frequent or bizarre tableaus
- loss of polarity
- ischaemic necrosis when outgrowing vascular supply
- lack of differentiation
Break down the metastatic cascade into its ECM invasion and vascular dissemination phases.
ECM INVASION
- Loosening of tumour cells: e-cadherin lost
- Degradation of the basement membrane and interstitial connective tissue: usually due to MMPs
- Changes in attachment of tumour cells to ECM proteins
- Locomotion/migration using chemoattractants
VASCULAR DISSEMINATION
- adhering to circulating WCCs and platelets
- circulate as single cells
- come to rest in the first capillary bed
- cells secrete cytokines, GFs and proteases that act on the resident stromal cells to make a home for itself
What are the 4 phases of neoplasia?
- Transformation: differentiation and anaplasia
- Growth of the transformed cells
- Invasion locally: involves breaching of ECM
- Metastasis: systemic invasion via blood, lymphatics or body cavities
What are the 7 fundamental changes for carcinogenesis?
- self sufficiency to growth signals(oncogene activation)
- insensitivity to growth inhibiting signals
- evade apoptosis
- defects in DNA repair
- limitless replicative potential (maintenance of telomere length)
- sustained angiogenesis
- ability to invade and metastasise
What is a growth fraction and how does it relate to a tumors susceptibility to chemotherapy?
Growth fraction = proportion of tumour cells that are in the proliferative pool
Low GF = slow growing = not good for chemo
High GF = fast growing = susceptible to chemo
Anti-cancer agents act on cells that are in cycle, hence they are better for those with high GFs
What are proto-oncogenes?
How can they be converted into oncogenes?
Normal cellular genes that affect growth and differentiation -> thus in normal cell, are active and regulate physiological
actions
- transduction into retroviruses (v-onc)
- changes in situ that affect their expression, function, or both
- destruction of adjacent controller genes, which normally suppress their action
- translocation
What are some examples of tumor suppressor genes?
What is their physiological role?
Rb gene, p53, HNPCC, BRCA I & II
Suppress growth
Describe the mechanism of INITIATION of chemical carcinogenesis.
PERMANENT DNA damage
- may be direct or indirect
- highly reactive electrophiles (non-enzymatic)
- carcinogen produes change in DNA and does not always lead to initiation because of repair by cellular enzymes
- carcinogen-altered cell must undergo at least one cycle of proliferation to make the change permanent
Describe the mechanism of PROMOTION in chemical carcinogenesis.
change in DNA due to EXISTING pathways, not new ones
- apply promotors to proliferate initiated cells
- often proliferate pre-neoplastic cells that then convert to malignancy and progress into tumour
What are oncoproteins?
Oncoproteins resemble the normal products of proto-oncogenes but bear mutations that are often inactivate internal regulatory elements
What is the normal function of p53?
- p53 = tumor suppresso gene
- it is a DNA-binding protein localized to the nucleus
- Major function = cell-cyle arrest and initiation of apoptosis in response to DNA damage
- p53-induced cell-cycle arrest occurs late in the G1 phase
o If the DNA is successfully repaired, p53 activates MDM2 whose product binds to and DEGRADES p53
o If DNA damage cannot be repaired, p53 induces the activation of APOPTOSIS-inducing genes eg. BAX
What is the normal function of the Retinoblastoma protein (from the RB gene)
nuclear phosphoprotein that regulates the cell cycle
- In quiescent cells, RB exists in an active hypophosphorylated state
- In G1/S cell cyles, RB exists in an inactive hyperphosphorylated state
If RB is absent, the brakes on the cell cycle are released, and the cell moves into the S-phase
What are 5 key characteristics of hodgkin’s lymphoma that are not present with NON hodgkin’s lymphoma
o Clinically HD may present similar to infection (with fever) B Sx
o Spread is contiguous to adjacent nodes in Hodgkin
o Classification is based on inflammatory response, not on malignant cell
o No leukaemic state
o Extranodal spread uncommon
What are some of the histological features of thyroid papillary carcinoma? What proportion of malignant thyroid tumors do they make up?
- papillary pattern
- occasional psammoma bodies
- clear “Orphan Annie eye” nuclei
- nuclear grooves
80%
What is thrombophlebitis migrans and what cancers are commonly associated?
Migratory thrombophlebitis (Trousseau syndrome) due to hypercoagulability due to the elaboration of platelet-aggregating factors and procoagulants from the tumour or its necrotic products
- adenoCa of the pancreas
- colon
- kidney
- lung
