Pathology Tumor Flashcards
Normal cell growth requires
Genetic material, aka DNA and RNA
Signals from one cell to another
Growth inhibiting or growth promoting substances
Once a cell stops growing it needs to differentiate - to become specialized - by activating some genes, and suppressing other genes
Tumour cells do not achieve the same level of differentiation as normal cells
Neoplasia
Neoplasm - new growth
Uncontrolled cell growth whose proliferation can not be adequately controlled by normal regulatory mechanisms
Neoplastic cell proliferation is:
Autonomous - independent of normal growth factors and inhibitors
Excessive - doesn’t respond to normal regulators
Disorganized - compared to the formation of normal tissues
Classification of tumour
Benign - limited growth potential and good outcome
Malignant - grow uncontrollably with poor outcome
Histologic classification
Based on how cells look under the microscope
Benign Tumours Microscopic Features
Sharply demarcated
Often encapsulated (CT tissue)
Can have expansive growth which compresses adjacent tissue leading to atrophy and fibrosis
Can be easily removed by surgery
No hemorrhage or necrosis
Resemble the original tissue from which they have arisen
Show high level of differentiation (it might show nucleus, mitochondria)
Benign tumours cellular features
Uniform cell populations (homogenous)
Regularly shaped/same sized nuclei
Well developed cytoplasm (sign that specialized)
Nucleus occupies a small portion of the cell
Nucleus has even distribution of chromatin
Nucleoli are not overprominent
Benign tumors chromosomal features
has normal number of chromosomes
Benign Tumor biological features
Retain normal complex functions
Malignant tumors macroscopic
no clear margins from normal tissue No encapsulation can have INVASIVE growth can not be removed easily by surgery Hemorrhage and necrosis present
Malignant Tumours microscopic
Differ considerably from original tissues
Show anaplasia (cells take on new characteristics)
Undifferentiated
Still can tell where the tissue originally came from (ex. breast tissue in the liver)
What is anaplasia
cells take on new characteristics
Malignant Tumors cellular features
Don’t have uniform cell populations (heterogenous)
Cells vary in size and shape
Nuclei vary in shape and size
Variable amounts of cytoplasm
Nucleus is larger
Hyperchromatic (more chromatin, unevenly distributed, nucleoli prominent, multiple)
Malignant tumours chromosome features
Aneuploid (abnormal number of chromosomes)
Malignant tumours Biological features
No specialization or differentiation
Metabolism is geared toward supporting growth and replication
what is Metastases
A proces by which cells move from one site to another in the body
What is pleomorphism
nucleus or cells in various sizes and shapes
Metastasis of Malignant tumor 3 pathways
Involves a spread of tumor cells from a primary location to another site in the body spread can occur through 3 main pathways 1. Lymphatics 2. Blood (hematogenous spread) 3. Body cavities
Metastastic cascade
Not all malignant cells are capable of metastasis
Cells must acquire the capacity to metastasize
Cells then expand clonally
clone expands, cells reach lymphatics or blood vessels or body cavity
Fluid carries the cells from the primary site to distant locations where cells attach and begin forming a new tumour mass
Metastatic cells must escape immune cells including macrophages, T cells, NK cells
Malignant tumour must form new blood vessels (angiogenesis)
Benign tumours of mesenchymal cells
end in “-oma”
Benign tumor from fibroblast
Fibroma
Benign tumor from Cartilage
Chondroma
Benign tumor From adipose
Lipoma
Benign tumor From smooth muscles cells
Leiomyoma
Benign tumor From bone
Osteoma
Benign tumors of striated muscle cells
Rhabdomyoma
Benign tumors of Epithelial cells
Adenoma -composed of glands or ducts
Benign tumors of Epithelial cells in the GI tract
Tubular or villous adenomas (aka polyps)
Protuberant (round or ropy thing sticking out) tumors of the skin, urinary bladder, mouth, larynx
Papillomas (squamous cell)
Cystic tumors composed of hallow spaces line by neoplastic epithelium
Cystadenomas
Malignant tumours of fibroblast
Fibrosarcoma
Malignant tumors from cartilage
Chondrosarcoma
Malignant tumor from fat
Liposarcoma
Malignant tumors from bone
Osteosarcoma
Malignant tumor of epithelial cells
Carcinomas (e.g. squamous cell carcinoma)
Malignant tumors from glands and ducts
Adenocarcinomas
malignant tumors of lymphoid cells
Lymphoma
malignant tumors from glial cells
Glioma
malignant tumors of testicles
Seminomas
malignant tumors composed of embryonic cells orginating from embryonic primordia (earliest recognizable stage of the embrionic development)
Blastoma Retinoblastoma: eye Neuroblastoma: adrenal medulla or immature neural cells Hepatoblastoma: liver Nephroblastoma: kidney
Tumors derived from germ cells (eggs and sperm) are called
Benign: teratomas (contain tissue formed from all three germ layers Ectoderm, mesoderm and endoderm)
Malignant: teratocarcinoma
Eponymous (named after somebody) tumors examples
Hodgkin’s lymphoma
Ewing’s sarcoma (rare cancer of the bone and soft tissue)
Kaposi’s sacorma (abnormal growth under skin, etc)
Tumor staging
done to clinically assess the extent of tumor spread
based on clinical exam,xray, biopsy, surgery
TNM system of staging takes into account size of tumor (T), presence of lymph node metastases (N), distant metastases (M)
Expressed on a scale from I through IV or A to D
TNM system of staging assigns a number to: tumor size, lymph node involvement and distant metastasis E.g. T1, N1, M0
Grading of tumor
Grade I - well differentiated
Grade II - moderately well differentiated
Grade III - undifferentiated
*staging has more predictive value
Biochemistry of cancer cells
Metabolism of cancer cells is simpler
Require less oxygen
Better adapted for survival
fewer mitochondria
Fewer enzymes
Rough Endoplasmic Reticulum is simpler and less abundant
Simplified metabolism leads to loss of functional capacity
Anaplasia
cells can acquire new characteristics
Anaplastic cells are larger and often show nuclear irregularity. Tumor cells may regress and assume fetal features. EX. Liver cancer cells secrete alpha-feto protein (AFP) a major secretory product of fetal liver cells that is not synthesized by normal adult cells. Intestinal carcinoma cells produce carcinoembryonic antigen (CEA)
Growth properties of Tumor
Lack contact inhibition - tend to pile up forming aggregates and nodules
Do not require firm support for growth
Autonomous - do not depend on growth stimuli
Excessive and unregulated - do not respond to normal inhibitory influences
causes of cancer
Carcinogen
Exogenous carcinogens: Chemicals, physical agents, viruses
Endogenous carcinogens: genetic, oncogene - human cancer gene: can be identical to exogenous viral gene
identification of carcinogens
Clinical studies (case studies)
Epidemiologic studies
Experimental studies performed on animals and in labs (in vitro)
Action of carcinogens
- Locally at the site of contact (e.g. skin and lungs)
- At the site of digestion
- At the site of metabolic activation in the liver
- At the site of excretion in the urine
carcinogenesis
- ingestion of procarcinogen (potentially harmful substance) activated metabolically in the liver
- Starts initiation - induction of genetic changes in the exposed cells
- Promotion - initiated cells are stimulated to proliferate
- Conversion - convert to new cell type and reproduction
- Clonal expansion - expansion of cell clones
Some will be dormant in new location, some will metastasize - Selection - the most adaptable and vital clones will survive
Physical carcinogens
Radiation UV light X-rays Radioactive isotopes Atomic bombs
Biological carcinogens
Aflatoxin (fungi) on peanuts causes liver cancer especially in Africa and Asia
Parasites in Egypt causes bladder cancer
Viral Carcinogen classification
DNA virus (Human Papilloma viruses -HPV, Epstein-Barr Virus -EBV, Hepititis B Virus - HBV)
RNA virus
Retrovirus (such as HIV, Human T-cell Lymphoma/Leukemia virus 1 - HTLV-1)
Etc.
Human PapillomaViruses (HPV)
Human DNA virus
over 70 subtypes linked to human lesions such as warts
Can cause benign or malignant tumors
Some strains of HPV cause genital warts which is linked to invasive cervical carcinoma
Epstein-Barr Virus (EBV)
Human DNA viruse
Human herpes virus with a predilection for B cells
Extremely prevalent
Can be asymptomatic or can produce infectious mononucleosis (IM)
Related to Burkitt’s lymphoma (B cell cancer) and nasopharyngeal carcinoma (nasal, pharyngeal)
Hepatitis B Virus (HBV)
Human DNA virus
transmitted by blood
Associated with liver cancer
Human T-cell lympoma/Leukemia virus 1 (HTLV - 1)
RNA retrovirus
Causes a rare form of adult T cell leukemia
Oncogenes
Normal cellular genes, called “proto oncogenes” encode for proteins important for basic cell functions
Proto oncogenes are transformed into oncogenes (muted normal cellular genes) by four mechanisms
Oncogene 4 mechanisms
- Point mutation
single base substitution in the DNA chain - Gene amplification
increased number of copies of the proto oncogenes - Chromosomal rearrangement
translocations of on e chromosomal fragment onto another or delation of a fragment or insertion of a fragment - Insertion of viral genome
Tumour suppressor genes
Cells have regulatory genetic mechanisms to protect against activated or newly acquired oncogenes
If a tumour cell is fused with a normal cell, the hybrid cell will be benign because the tumor suppressor genes of the normal cell will suppress the oncogenes of the malignant cell
Hereditary cancer
Certain cancers occurs more often in families
Each of these disease has been linked to an absence of a specific tumour suppressor gene
Examples of Hereditary Cancer
Neurofibromatosis type I
common autosomal dominant disease in humans
Numerous subcutaneous neural sheath tumours
also with pigmented lesions of the skin (Cafe’ au lait spots)
Immune response to tumors
- Malignant tumours differ from their normal ancestors
Malignancy may alter tumor cells so mach that they become “foreign” to the body’s immune system - Tumour antigens will induce antibody production and cell-mediated immune response (T suppressor/cytotoxic cells)
Innate immunity - NK Kills, macrophages - Ultimately immune response can limit growth of tumor. Many small tumors are maybe eliminated by immune system. Best clinical example is AIDS. Immunotherapy treatment can be successful in eliminating tumors
Clinical manifestation of neoplasia (7)
High variable Warning signs include 1. Change in bowel/bladder habits 2. A sore that won't heal 3. Unusual bleeding or discharge 4. Thickening or lump in breast or elsewhere 5. Indigestion or difficulty in swallowing 6. Obvious change in wart or mole 7. Nagging cough or hoarseness
Clinical features of a tumor depending on (6)
- Type of tumor
- Location of tumor
- Histological grade of tumor
- Clinical stage of tumor
- Immune status of person
- Sensitivity of tumor to therapy
Local symptoms
Due to tumor growth compressing adjacent structures
Compression of brain causes epileptic seizures
Compression of lung causes coughing
Can cause atrophy
Can cause hemorrhage
Can cause obstruction
Systemic symptoms of tumor
Cachexia -wasting Anorexia - loss of appetite Weight loss Thrombosis Paraneoplastic syndromes
Paraneoplastic syndromes
a consequence of the presence of cancer in the body, but not due to the local presence of cancer cells; can be caused by substances secreted by cancer cells
Paraneoplastic syndrome examples
Cushing’s syndrome : small cell carcinoma of the lung, increase secretion of adrenal gland
Hypercalcemia: squamous cell carcinoma of the lung, trigger thyroid
Polycythemia: renal cell carcinoma, trigger erythropoisis, increased blood cells
Venous Thrombosis: pancreatic carcinoma
Myasthenia gravis: thymoma, secret antibody.
Epidemiology of tumor
Incidence - number of new cases in a specific time period in a given population
Prevalence - the number of all cases within a given population at a given time
Mortality- the number of deaths attributed to a specific population during a specific period
