tumour pathology Flashcards
whats a tumour
abnormal growing mass of tissue
what are the two groups of tumours
benign and malignant (cancer)
whats cancer
ability to invade into adjacent tissue and to metastasise (spread) and grow at other sites within the body”
what is the benign form of glandular
adenoma
what is the benign form of squamous
squamous papilloma
what is the malignant form of glandular
Adeno- Carcinoma
what is the malignant form of squamous
squamous carcinoma
what are the benign and malignant forms of bone
B- osteoma
M- osteo-sarcoma
what are the benign and malignant forms of fat
lipoma
lipo-sarcoma
what are the benign and malignant forms of fibrous
fibroma
fibro-sarcoma
what are the malignant forms of lymphoid tissue
lymphoma
what are the benign and malignant forms of melanocyte
naevus
melanoma
whats the tumours in central nervous system
Astrocytoma
whats the tumours in peripheral nervous system
Schwannoma
are Ovarian teratomas usually benign or malignant
benign
are Testicular teratomas usually benign or malignant
malignant
what are fetures of benign and malignant tumours 1
Growth pattern
Presence of capsule
Invasion
Presence of metastases
what are fetures of benign and malignant tumours 2
Differentiation
Appearance of tumour cells
Function
Behaviour
Features Of
Benign Tumours 1
Non-invasive growth pattern
Usually encapsulated
No evidence of invasion
No metastases
Features Of
Benign Tumours 2
Cells similar to normal
Benign tumours are “well-differentiated”
Function similar to normal tissue
Rarely cause death
Features Of
Malignant Tumours 1
Invasive growth pattern
No capsule or capsule breached by tumour cells
Features Of
Malignant Tumours 2
Cells abnormal Cancers often “poorly differentiated” Loss of normal function Often evidence of spread of cancer Frequently cause death
what are the Properties Of Cancer Cells 1
Loss of tumour suppressor genes
Adenomatous polyposis (APC)
Retinoblastoma (Rb)
BRCA1
Gain of function of oncogenes B-raf Cyclin D1 ErbB2 c-Myc K-ras, N-ras
what are the Properties Of Cancer Cells 2
Altered cellular function Abnormal morphology Cells capable of independent growth But no single feature is unique to cancer cells Tumour biomarkers
Tumour Angiogenesis
New blood vessel formation by tumours
Required to sustain tumour growth
But provides route for release of tumour cells into circulation
More blood vessels in a tumour equals poorer prognosis
Invasion And Metastasis
Multi-step process
Increased matrix degradation by proteolytic enzymes
Altered cell-to-cell and cell-to- matrix adhesion
Modes Of Spread Of Cancer
Local spread
Lymphatic spread
Blood spread
Trans-coelomic spread
what is Trans-coelomic Spread
Special form of local spread
Spread of tumour cells across body cavities e.g. pleural or peritoneal cavities
Tumours of lung, stomach, colon and ovary show trans-coelomic spread
what are common sites of metastasis
Liver Lung Brain Bone Axial skeleton Adrenal gland Omentum/ peritoneum
what are Uncommon Sites
Of Metastasis
Spleen
Kidney
Skeletal muscle
Heart
Local Effects Of
Benign Tumours
Pressure
Obstruction
Local Effects Of
Malignant Tumours 1
Pressure Obstruction Tissue destruction Ulceration/infection Bleeding Anaemia Haemorrhage
Local Effects Of Malignant Tumours 2
Pain Pressure on nerves Perineural infiltration Bone pain from pathological fractures Effects of treatment
Systemic Effects Of Malignant Tumours
Weight loss-cancer cachexia Secretion of hormones “Normal” “Abnormal”/inappropriate Paraneoplastic syndromes Effects of treatment
Hormone Production
By Tumours 1
“Normal” - produced by tumours of endocrine organ
But abnormal control of hormone production/secretion
Hormone Production
By Tumours 2
“Abnormal”/inappropriate
Produced by tumour from an organ that does not normally produce hormone
what does the hormone ACTH link to what specific tumour
lung cancer
what does the hormone ADH link to what specific tumour
lung cancer
Dysplasia 1
Pre-malignant change
Earliest change in the process of malignancy that can be visualised
Dysplasia 2
Identified in epithelium
No invasion
But can progress to cancer
Features Of Dysplasia
Disorganisation of cells Increased nuclear size Increased mitotic activity Abnormal mitoses Grading of dysplasia High grade Low grade No invasion
Early Detection Of Cancer
Requires effective test
Sensitive/specific
Acceptable
Cervical cancer screening
what are external factors of cell cycle control
Hormones, growth factors, cytokines, stroma
what are intrinsic factors of cell cycle control
critical checkpoints
prior to restriction point progress through G1 depends on external stimuli
after restriction point progression becomes autonomous
what checkpoint is for cell size inadequate
G1 or G2 arrest
what checkpoint is for nutrient supply inadequate
G1 arrest
what checkpoint is for Essential external stimulus lacking
G1 arrest
what checkpoint is for the DNA is not replicated
S arrest
what checkpoint is for DNA damage is detected
G1 or G2 arrest
what checkpoint is for Chromosome mis-alignment
M-phase arrest
what are catalytic subunits called
cyclin-dependent kinases (CDKs
regulatory sub-units are called …
cyclins
what do Active CDK/cyclin complexes do
phosphorylate target proteins
what does Phosphorylation results in
activation/inactivation of that substrate
are cyclins destroyed aas the cycle progresses?
yes
what is the function of CDK inhibitors (CKIs)
regulate cell cycle
what bind to CDK4 and 6 and prevent association of these CDKs with their cyclin regulatory proteins
INK4A family
what does The Retinoblastoma gene encode
110 kDa phosphoprotein (pRb)
what is pRb
hypophosphorylated
what is the most important target
E2F transcription factor
how is E2F inactivated
Hypophosphorylated/active Rb
whats the affinity between Phosphorylated/inactive pRb and E2F
low
what causes a brake to the cell cycle
Active pRb
how is carcinogenesis caused?
by mutation of genetic material that upsets the normal balance between proliferation and apoptosis (cell death)
purine and pyrimidine bases in DNA are critically damaged by what
various oxidizing and alkylating agents
what is produced from Chemical carcinogens or their active metabolites react with DNA
forming covalently bound products (DNA adducts)
Adduct formation at particular chromosome sites causes what
cancer
the primary defect in cancer is
Uncontrolled cell proliferation via
cell cycle dysregulation
whats the importance of cyclins/CDK/CDKIs
Many genes mutated in cancer regulate the cell cycle
Two regulatory pathways frequently disrupted -
The cyclin D-pRb-E2F pathway
- p53 pathway
what happens when pRb is abscent or inactive
releases the cell cycle brake
whats the function of p53
Maintains genomic integrity p53 levels increase in damaged cells induces cell cycle arrest at G1 facilitates DNA repair severe damage: p53-induced apoptosis (programmed cell death)
what happens when p53 is mutated
can not repair dan and prliferates malignant cells
