Introduction to Tumour Biology Flashcards
Differentiation in the Embryo
Early cells identical
Cells become different from one another
-ectoderm, mesoderm, endoderm
Cells also differentiate within each layer
Post embryonic Differentiation
Occurs at the level of cells rather than whole tissues
Maturation of Differentiated cells from (basal) Proliferating cells
-mitotic activity gradually migrating to surface, differentiating as they move up producing keratin, forming flakey layer and terminating proliferation genes
Differentiation involves:
Inactivation fo Proliferation genes
-Activation of specific Function genes
De-differentiation involves:
Involves reversion to Primitive, embryonic, proliferative phenotype as occurs in neoplasia
-when things go wrong
-not the mature cells,
-is more the proliferating cells, instead of maturating, continue proliferating and forming abnormal tissues that are incompletely differentiated and have excess proliferative activity
-“neoplasia” = new growth
“tumour”= swelling
Disorders of Growth
Disorders in the regulation of cell proliferation or differentiation
- Embryo - malformation
- Post-natal
- Abnormalities of Tissue function
- Abnormalities of Tissue Mass
Malformations
Caused by abnormality in growth and development in utero
- Haematoma= malformation of mature tissue
- e.g. “haematoma” in brain - arterial venous malformation –> can lead to hemoorahge/rupture
- Disorders in the regulation of cell proliferation or differentiation in the Embryo
Clinical Implications of disorders of Growth
- Not all are “disorders” - some normal (physiological) (callus thickening of skin in epidermis on hands with manual labour/hyperplasia)
- some have clinical consequences (ventricular hypertrophy –increased risk of myocardial infarct, decompensation and heart failure)
- some are reversible (cell enviro- hormones, irritation) (if stimulus removed tissue will return to normal state)
- others are irreversible (dysplasia, neoplasia- DNA change) (if cell divides changes are inherited by daughter cells)
Reduction in tissue mass
Agenesis/Aplasia: total absence
-e.g. one kidney doesnt develop
Hypoplasia: Congenital Reduction in size
-one kidney smaller than normal due to small number of callusies
Atrophy: Acquired reduction in size
-kidney w. poor blood supply due to atheromic plaque in renal artery –> shrinked/hypoplastic kidney (normal number of calluses)
-muscle in cast, less use, leads to atrophy
Change in Myocardium
all same magnification as nucleus size is the same
Atrophy: elderly or malnourished people. brown pigmenting
Hypertrophy: increased size of heart due to increase in size of heart muscle fibres. due to increased strain. e.g. due to increased systemic BP (hypertension)/ malfunctioning of valves in heart –> increased tendency to myocardial infarct –> dilation and failure
-Left Ventricular Hypertrophy
–> dilation
–> failure
Hypertrophy and Hyperplasia
Not neoplasia Hypertrophy=increased growth -organ and cells -e.g. only one kidney so enlarged -no relationship to cancer Hyperplasia= increased number of cells -relationship to cancer
Hyperplasia
Some examples are Premalignant (statistical/hyperplasia of uterus endometrium, rate of carcinoma of endometrium, discover risk)
Causes:
-“Functional” (Physiological) (thickening of epidremis in hands)
-Endocrine Stimulation (ovarian tumour produce estrogen causing hyperplasia (premalignant))
-Chronic Stimulation (ulcers thickening on edge)
Effects:
-Increased function (endocrine) (thyroid)
-Risk of Malignancy (some types)
Prostatic hyperplasia/Hypertrophy
Hyperplasia + Atrophy
Small Transition state of Prostate enlargens considerably
-hypertrophic/hyperplastic prostate
-hyperplasia increase in cell number occurs only in that cell
–not assoc. w increased carcinoma rate
–common but cancer risk is no larger compared to those with normal prostate
-simultaneously outer zone undergoes atrophy (thin epithelium lining glands)
Hyperplasia- Thyroid
Grave’s Disease= abnormal antibody
=autoimmune disease
TSH receptor= self
Hyperplastic
-stimulation of TSH receptor by autoantibody
-would do same if had tumour of pituitary to produce TSH
-same in Adrenal gland ACh inappropriately secreted –> hyperplasia of adrenal cortex
-histology: proliferation, cells chew up colloid , making into thyroid hormone –> hyperthyroidism
- density increases + gland expands
-gland becomes a visible palpable mass in the neck
= doesn’t predispose to malignancy
Which Hypertrophy/Hyperplasias result in predisposition of Malignancy?
Breast Hyperplastic changes
-accompanied by cystic change
-Endometrial changes in Uterus
=increased chance of cancer of those organs
Metaplasia
Some examples PRe Malignant
Change from one mature tissue type to another
Bronchus: normally only squamous as far as larynx, then respiratory epithelium in trachea/bronchus (which contain cilia)
-Smokers= irritation changes epithelium to squamous epithelium of throat/larynx
=premalignant change
=has to undergo additional change to undergo dysplasia - manifestation of premalignant features
Cervical metaplasia
Squamous metaplasia is normal
Endocervix (canal)= columnar epithelium
Squamous metaplasia
Ectocervix (vaginal) squamous epithelium
-occurs in every girl
-maturing to menarche, uterus grows and cervix changes in shape
-exposes thin glandular layer, upon exposure to different vaginal environment (from canal) changes to squamous epithelium
-can all look like vaginal ectocervical squamous epithelium - non keratinising squamous epithelium
-occurring in response to a stimulus
Metaplasia
Some types Premalignant
Cause: due to change of environment or irritation
-noxious change cigarette smoke in trachea/bronchi
May be normal (cervix)
-reflux in oesophagus (becomes gastric epithelium) Barrets oesophagus= premalignant = consistently cheked for dysplasia or malignancy devel.
Most common in epithelial tissues
Usually change to that of adjacent tissue type (protection for dif. stimulus/enviro)
-CT metaplasia - fribrous –> cartilagneous/boney (usually due to irritation/abnormality)
Some types are premalignant
-cancer type is same/ that of metaplastic epithelium
-squamous cell carcinoma in lung (from smoking)
metaplasia –> dysplasia –> carcinoma
Dysplasia
ALL examples premlaignant (By definition)- increased chance of becoming cancer (not inevitable)
Histological Abnormality
Partial Malignant Transformation (histologically and genetically)
-nuclei enlarged and irregular
-structure disorganised
-less severe than cancer. and NOT invasive
-remains confined by epithelium and bound by BM of epithelium
May be macroscopically Evident (colon adenoma)
Various grades -mild. -moderate -severe (carcinoma in situ= “in place” in normal posiion not invaded)
Remains same mass/ Flat= cervix (smears)
-becomes more vascular
Adenoma of Colon= benign tumour = dysplastic increased mass
Dysplasia and Cacner
Dysplastic cells are clonal (in fact, neoplastic)
-every cell has orginiated form one cell (esp. when becomes higher grade. Monoclonal/single clonal)
Alternative terminology -INTRAEPITHELIAL Neoplasia (IEN))
So for cervix:
-CIN1 (cervical intraepithelial neoplasia 1)
-CIN2
-CIN3 (carcinoma in situ)
Opportunity to remove tissues, prevent invasive cancer
Clinical importance of Dysplasia
Can follow it and interrupt it
-not all will devleop to cancer (immune system defeats)
Opportunity to remove tissues, prevent invasive cancer
-cervical surgery w/o damaging uterus or compromising pregnancy , to prevent invasive cancer occuring
Dysplasia Solar Keratosis
Solar Keratosis
- Precursor of squamous cell carcinoma of skin
- light skinned people from sun burn
- proliferation, increased keratin produced, irregularity of cells
Reactive Atypia
NOT malignant
Looks atypical like dysplasia, but is “Reacting to inflammatory or ulcerative stimulus”
Similar to dysplastic progression, even though may not be any genetic abnormality
-bladder uretherial cells enlarged, irregular, some inflammatory cells
-increased genetic activity, makes them show morphological (not genetic) features of dysplasia
-try and distinguish between dysplasia and reactive atypia
-if worried, do 2nd biopsy after inflammation has settled
Injury –> cell Loss –> Regeneration
a) If chronic –> Suspicious Microscopic Nuclear Changes
b) Proliferation “ Promotor effect” –> Real increased risk of cancer
-Inflammation can lead to increased chance of cancer developing (Ulcerative colitis). promotor effect. increased inflammation and proliferation.
If mutation or genetic abnormality occurs, since cells are rapidly turning over, cell division can fix abnormality before repair happens, upon accumulation of these cells, tumour can develop
Dysplastic Mass
Adenoma of Large Intestine
-dysplasia + benign neoplasm
Not Pre-Malignany
Adenoma of Parathyroid Lypoma in skin -still monoclonal proliferations and genetic abnormalities -but limited ability to cause disease -Benign Neoplasm
