Flashcards in Neoplasia Deck (168):
Describe a neoplastic tumour.
A focal, purposeless overgrowth of one cellular component.
Some tumours are driven by normal genes which are expressed inappropriately. What are they?
(proto-oncogenes in a normal cell)
Some tumours are triggered by the loss of normal genes. What are they?
Tumour suppressor genes
What is dysplasia?
Disordered tissue organisation which can be pre-neoplastic.
Change is reversible, cells have altered differentiation.
What is neoplasia?
A new growth which persists after the initial stimulus is removed.
What is a carcinoma?
A malignant epithelial tumour
What is carcinogenesis?
Production of cancer
What is a blastoma?
Poorly differentiated cell of embryonic type, tend to be very aggressive.
Mainly seen in children.
What is a benign tumour that arises from a gland called?
What is a benign tumour which arises from a gland and contains cavities?
What is a club-shaped tumour dangling from a surface?
What is a sessile polyp?
A polyp which lacks a stalk
What is an adenomatous polyp?
A polyp which contains glandular growth.
What is a papilloma?
An outgrowth from an epithelial surface with long, thin branches.
What is a malignant tumour that arises from a gland?
What is a benign tumour arising from fibroblasts?
What is a benign tumour arising from bone?
What is a benign tumour arising from fat cells?
What is a benign tumour arising from cartilage?
What is a benign tumour arising from blood vessels?
What is a benign tumour arising from lymphatic vessels?
What is a malignant tumour arising from bone marrow?
Are lymphomas benign or malignant?
What is a benign tumour arising from smooth muscle?
What is a malignant tumour arising from smooth muscle?
What is a malignant tumour arising from striated muscle?
What is a benign tumour arising from striated muscle?
What is a tumour of neurons?
What is a malignant glial tumour?
What is a pleomorphic adenoma of salivary glands?
Benign tumour in the salivary glands which contains mixtures of epithelium, connective tissue and cartilage.
What is a fibroadenoma of the breast?
A benign tumour in the breast which contains glands and connective tissue
Why can teratomas contain material that is found anywhere in the body?
They are derived from cells which are so primitive (germ line cells) that they can produce all three embryonic leaflets.
What is a hamartoma?
A lump of tissue belonging to the organ in which it is found but has been wrongly assembled in the course of development.
Are present at birth and grow with the person.
What is a choristoma?
Lumps of normal tissue which doesn't belong in the organ where the lump is found.
What properties do tumour cells share with embryonic and foetal cells?
They tend to grow quickly and are immature
What is anaplasia?
Cells which don't have the morphological characteristics of a normal cell.
What is tumour progression?
Tumours becoming gradually more poorly differentiated in their life.
What are the features of a rapidly dividing cell seen microscopically?
More cytoplasmic basophilia due to increased RNA
Nucleoli increased in size and number
Mitoses increased and mitotic figures may be abnormal
How can mitotic figures be a measure of malignancy?
The number is proportional to the rate of growth and therefore aggressiveness of the tumour.
What is atypia?
Structural abnormality. Tends to parallel the degree of aggressiveness.
Size and shape of the cell is abnormal, nucleus is large and the secretions become irregular.
What are the behavioural changes in malignant cells?
Loss of anchorage dependency
Loss of contact inhibition
Decreased requirement for growth factors as they supply their own
What are the functional changes in malignant cells?
Mobility - allows invasion and gives them the potential to move to another site.
Decreased adhesion between cells which plays a role in invasion
Tendency to shed surface molecules.
- Collagenase helps the cells invade through the ECM
- Tissue factor may lead to exaggerated clotting.
How can surface-related changes to malignant cells assist in diagnosis or treatment of a cancer?
Some of the surface molecules which are shed can be found in the blood and are known as tumour markers.
They are useful for diagnosing a particular malignancy or monitoring response to a treatment.
How and where do ulcerated tumours tend to develop?
Tend to arise from a bacterially contaminated surface such as the skin.
In the gut this is thought to be secondary to bacterial infection and digestive enzymes. The surface of the tumour is eroded by friction, then colonised by bacteria which causes a non-healing ulcer.
An ulcer with a raised edge strongly suggests an ulcerated tumour rather than a non-neoplastic ulcer.
What is scirrhous carcinomas?
A tumour with lots of connective tissue stroma. They are firm or hard.
Describe the cut surface of most tumours.
Most are white
Foci of necrosis common in malignant tumours
Large spaces filled with cysts suggest the tumour is epithelial.
What do you look at to find where a tumour has arisen from?
Identifying features for a specific cell type
If the tumour has lost all differentiation they can still be recognised by a specific antibodies.
What do you look at to determine how aggressive a tumour is?
Cellular abnormalities - lack of differentiation, cytologic atypia, pleomorphism
Architectural atypia - abnormal cellular pattern, infiltration
What are the secondary changes that can be seen in a tumour?
Necrosis (seen in the centre of tumours, more common in malignancy)
Calcification (seen in dead cells/necrotic masses)
Tortion (seen in pedunculated tumours, results in red infarct)
Give an example of a cell other than a tumour cell which is able to invade tissues.
Trophoblasts - invade the uterine wall
Leukocytes - invade tissues in inflammation
What is a metastasis?
A secondary tumour which has arisen from detached, transported cells.
Through what channels are metastases able to travel to a new site?
Fluid in tissue spaces
Are metastases able to metastasise?
Why are metastases the most lethal expression of malignancies?
Greatly increase the disease burden
What are microscopic metastases and which cancers are most likely to produce them before excision?
Non-clinical, dormant metastases.
Breast cancer/malignant melanoma
Which vessels do metastases most commonly permeate?
Capillaries or veins (have very thin walls)
Which cancer is most likely to invade a large vein and grow through it?
Renal cell carcinoma
Where do tumours in organs which are drained by the portal system metastasise to?
What is the seed and soil model for tumours which metastasise?
The 'seed' is the tumour type, and the 'soil' is the tissue in which it embeds. Certain types of tumour have a preferential 'soil', yet the reason for this is yet unknown.
Where do breast carcinomas tend to metastasise to?
Where do bronchial carcinomas tend to metastasise to?
What are Kruckenburg tumours?
Bilateral mesenteric tumours of the ovaries
Why are the lungs a common site for the metastases of many tumours?
They are the first large capillary bed after entry into the veins.
What is a common location for carcinomas to metastasise to, but is very rare for sarcomas?
Describe peau d'orange and why it occurs.
Carcinomas of the breast permeate the lymphatics of the overylying skin, causing the skin to become oedematous and puckered.
If lymph nodes near a tumour are swollen, what could be the cause if it has not metastasised?
Secondary to antigens and irritants which leach out of a tumour (especially if necrotic, ulcerated or infected).
Draining lymph nodes can then undergo hyperplasia.
How can seeding of a metastasis into the peritoneum cause ascites?
Fluid accumulation secondary to factors produced by tumours which cause leaking of fluid from the peritoneal membrane
Secondary to fluid leaking from the surface of the tumour
Why is implantation of metastases onto epithelial surfaces rare?
They are inhospitable surfaces - covered with mucus, cornified cells and bacteria.
How does basal cell carcinoma present?
Small, crusty lesions which don't heal and appear on areas frequently exposed to the sun.
How does basal cell carcinoma most commonly cause death?
By extensive invasion of the surrounding tissue
(does not tend to metastasise)
Why do tumours of the CNS rarely metastasise to the body?
In an enclosed space and often kill before visceral metastases are found.
Give the steps required for a cell to produce haematogenous metastases?
Separate itself from tumour mass and move in the right direction
Digest through intercellular matrix and vascular basement membrane to enter the lumen of a vessel
Escape defensive systems in the blood
Survive impact and mechanical squeeze in small vessels
Penetrate the endothelium and basement membrane, escape further dangerous cells
Multiply, induce angiogenesis and establish a tumour.
State 2 things in the blood which are part of the body's defense against tumours.
Natural killer cells
Toxic concentrations of oxygen
What connects malignant cells to each other?
What connects malignant cells to stromal proteins in the basement membrane?
Give an example of an enzyme produced by malignant cells to help them digest through connective tissue.
Matrix metalloproteinases (MMP)
Are tumour cells more likely to penetrate vessels of the tumour itself or preformed vessels?
The tumours own vessels because they are defective (may lack a basement membrane or endothelial lining).
What connects malignant cells to the basement membrane in blood vessels?
Give an example of how a tumour causing compression can be hazardous or cause problems even if it is not cancerous.
Bulky lesions in the brain cause damage structures and cause ischaemia
They can also cause herniation of the brain into foramen magnum, causing compression of vital structures and potentially death.
Compression of the optic nerve can cause blindness
Compression of the great veins can cause the face to swell.
What problems can be caused by ulceration on the surface of a tumour?
Bleeding and/or infection
What is paraneoplastic syndrome?
Symptom complexes which accompany tumours and concern distant targets whether the mechanisms be hormonal, toxic, immunologic or unknown.
Give something which can cause paraneoplastic hypercalcaemia/
Extensive metastatic bone destruction (seen in multiple myeloma)
Parathyroid hormone-like peptide production
Squamous cell carcinoma producing PTC
What are the symptoms of carcinoid syndrome?
Flushed, sweating, diarrhoea, tachycardia, anxiety
What are the most common substances for carcinoid tumours to secrete?
5-HT and kalikrein
What hormone do renal cell carcinomas commonly produce and what problems does this cause?
Causes high haematocrit causing symptoms related to high blood viscosity
(e.g. spontaneous bleeding from mucous membranes,retinopathy, neurological symptoms)
Describe why tumours can induce a hypercoagulative state.
Platelets can be activated by tumour products e.g. ADP
Tumours secrete procoagulants e.g. tissue factor/mucins
Describe migratory thrombophlebitis (Trousseau's syndrome)
Bouts of inflammation or swelling of the leg veins caused by blood clots, found in multiple locations without an apparent predisposing factor.
Often due to underlying cancer.
Frequently seen in pancreatic, lung or stomach cancer.
Describe acanthosis nigricans
Symmetric, brown, warty hyperpigmentation with hyperkeratosis of the axilla and other flexural areas.
Majority occur in association with an internal malignancy, especially carcinoma of the gastrointestinal tract.
Give two consequences of metastasis which are miscellaneous
Neuropathy (cerebellar degeneration/glove and stocking neuropathy)
What is cachexia?
Wasting of the whole body
What is cachexia thought to be caused by when associated with cancer?
Induction of macrophages to produce TNF which causes wasting
Loss of appetite and changes in sense of taste
Host metabolism is increased
What is tumour lysis syndrome?
Extensive acute necrosis of a tumour which is very sensitive to x-rays or chemotherapy.
Can be life threatening by releasing toxic amounts of potassium and uric acid
What tumour commonly causes tumour lysis syndrome?
Give two methods with which a cancer can cause death.
Infection (cancer and its treatments are anti-inflammatory)
Haemorrhage and thromboembolic phenomena
What is an astrocytoma?
A primary CNS tumour which is mainly found in the cerebellum in children and the cerebral hemispheres in adults.
What is a melanoma?
A (usually) malignant tumour of melanocytic origin, mostly found in the skin but primary lesions can also be seen in the CNS, GI, GU tract, inner ear
Is curable if excised before it begins to invade the dermis.
What is a carcinoid tumour?
An endocrine tumour of the gut and respiratory tract which doesn't produce a known peptide hormone or produces a mixture of peptide hormones.
Often metastasises to the lymph nodes.
What is the most common carcinoma of the exocrine pancreas?
What are the symptoms of pancreatic carcinoma?
Flitting venous thrombosis (Trousseau's sign)
Explain why lung carcinomas tend to have a poor overall prognosis.
Comorbidities are common
Late presentation with advanced dissemination at the time of diagnosis
What is squamous cell carcinoma of the skin?
Malignant skin neoplasm associated with chronic sun exposure and is locally invasive. Metastasises late.
What is basal cell carcinoma?
A very common skin malignancy related to chronic sun exposure which occurs most commonly on the face. Is locally very invasive but metastases are rare.
Are ulcerated irregular lesions with a raised pearly border, often with tiny blood vessels visible on the border
What is gastric carcinoma?
Majority are adenocarcinomas, many arise from a background of chronic gastritis and intestinal metaplasia. Generally present when clinically advanced.
Early cases have a good prognosis.
What is the difference between intrinsic and extrinsic factors in neoplasia pathogenesis?
Intrinsic - genes/hormones. Things which are in the body from birth or as a result of body processes.
Extrinsic - chemicals/radiation. Things which our bodies are exposed to that increase the risk of neoplasia.
What did studies into 2-napthylamine as a carcinogen show about the relationship between exposure and malignancy?
Long delay between carcinogen exposure and onset of malignancy.
Risk depends on total dosage
Sometimes has organ specificity.
Describe the feature of carcinogenic molecules which allows them to cause damage.
Are electrophilic reactants.
Have a relatively electron-deficient site which makes them seek nucleophilic sites. They then form covalent bonds.
Nucleophilic groups are relatively abundant as DNA, RNA and proteins.
Give an example of a mutagenic chemical carcinogen.
Polycyclic aromatic hydrocarbon
Diverse natural products e.g. aflatoxin
What are procarcinogens?
Inactive carcinogens which need to be converted to carcinogens, e.g. by the cytochrome P450 enzymes in the liver.
How do immigrant studies give evidence for diet having a role in carcinogenesis?
People who emigrate and change their diet will change their risk of certain cancers depending on the country that they move to.
Give a piece of evidence for diet having a role in carcinogenesis which is unrelated to immigration.
Incidence of cancer along the colon and rectum increases in the direction of faecal progress, which suggests a role for contact time between mucosa and faeces.
Nitrosamine is a dietary carcinogen. What cancer is it specifically linked to and where can it be found?
Present in tobacco smoke and food additives.
What produces aflatoxin B1, and what cancer is it associated with?
What agents present in the diet can inhibit mutations and tumour formation?
What tumour locations correlate with hormonal levels?
How can obesity be linked to endometrial cancer?
Adipose tissue converts androgens to oestrogens which increases the risk of endometrial cancer.
Give an example of an occupational carcinogen and the problems that it can cause.
Inhaled fibres causes fibrosis and malignant tumours of mesothelium of the pleura, pericardium and peritoneum.
Give an example of a therapeutic carcinogen.
Radiotherapy (targets DNA, but not specific to tumour cells)
Diethylstilboesterol (stops bleeding in pregnancy, causes adenocarcinoma of the vagina in female daughters of the treated woman)
Describe how UV light can be a carcinogen, and indicate a cancer that it is related to.
Behaves as a complete carcinogen, completed exposures are needed. Damage DNA strands by forming dimers and cross-links.
Basal cell carcinoma/squamous cell carcinoma/malignant melanoma
Describe how ionising radiation can be a carcinogen and give an area which is especially sensitive to it.
Single exposure is enough.
Strips electrons from atoms, causing damage directly or causing free radicals. Injury can shorten cell survival.
Bone marrow/intestinal epithelia because they have high mitotic rates.
What are the gene products of proto-oncogenes?
Growth factor receptors
Links an intracellular network so external stimuli induce cell proliferation
What are the two ways that a protooncogene can be converted to an oncogene.
Encode a hyperactive protein
Encode too much protein
Give an example of a DNA oncogenic virus and a neoplasm that it causes.
Hepatitis B - hepatocellular carcinoma
Human papilloma virus - papilloma/cervical carcinoma
Epstein Barr virus - Burkitt's lymphoma/nasopharygeal carcinoma
Molluscum contagiosum - benign molluscum bodies
Give an example of an RNA oncogenic virus and describe how it increases the risk of cancer.
Human T-cell lymphotrophic virus-1 - Relative of HIV which affects helper T-lymphocytes
Humman immunodeficiency virus - tumours are related to immunosuppression e.g. Kaposi's sarcoma.
State a parasite which can cause cancer and give an example of this.
Heliobacter pylori - strong association with stomach cancer
Schistosoma haematobium - associated with squamous cell carcinoma of the bladder
What is the function of RAS in normal cells, and how is it changed in neoplasms?
Encodes a small G-protein which relays signals into the cell to push past the cell cycle restriction point.
It is overactive or overproduced in neoplasms.
What is the function of RB in normal cells, and how is it changed in neoplasms?
Restrains cell proliferation by inhibiting passage through a restriction point.
Both copies are 'knocked out' in affected neoplasms.
Describe xeroderma pigmentosum.
Autosomal recessive, due to XP mutation.
Codes for a protein which is involved in DNA nucleotide excision repair.
The patients are therefore very sensitive to UV damage and develop skin cancer at a young age.
Describe hereditary non-polyposis colon cancer syndrome.
Associated with colon carcinoma
Germline mutation which affects DNA mismatch repair genes.
Describe familial breast cancer
Assocated with BRCA1/2 genes which are important for repairing double strand DNA breaks
What is genomic instability in malignant neoplasms?
Alteration to the cell such as DNA mutations and abnormal chromosome segregation which accellerates the rate of mutation.
What are caretaker genes?
Genes which maintain genomic instability and are a class of tumour suppressor genes.
What is tumour progression?
The steady accumulation of multiple mutations
What are the six hallmarks of cancer?
Self-sufficiency in growth signals
Resistance to growth stop signals
Resistant to apoptosis
Ability to invade and produce metastasis.
What is Burkitt's lymphoma?
A lymphoma of B lymphocytes in germinal centres of the lymph nodes.
The B cells will all have identical IgH genes due to their clonal origin.
Characterised by disruption of the c-myc gene which has a role in cell cycle progression, apoptosis and cellular regeneration.
What is familial adenomatous polyposis (FAP)
Autosomal dominant mutation to APC which is a tumour suppressor gene.
Causes numerous benign colorectal polyps with an increased risk of colorectal carcinoma.
Adenocarcinoma likely to occur by 35 years old.
What is retinoblastoma?
Deletion of RB, a tumour suppressor gene. Seen in both familial and sporadic retinoblastoma.
Presents with visual loss, squint or enlargement of the eye.
Good prognosis as metastases are rare.
What is xeroderma pigmentosum?
Congenital deficiency of DNA repair enzymes.
Children exposed to sunlight will develop skin atrophy and tumours which are more characteristic of elderly people with long term sun exposure.
What is hereditary non-polyposis colorectal cancer?
Autosomal dominant mutations in MLH1 or MSH2 which are involved in DNA mismatch repair, significantly increasing risk of colorectal cancer without forming polyps.
What are the risk factors for bladder cancer?
Exposure to other specific chemicals
What are the risk factors for hepatocellular carcinoma and describe the progression.
Hepatitis B, aflatoxins, underlying cirrhosis
Progression through pre-malignant lesions of dysplastic nodules.
What is malignant mesothelioma?
Primary is strongly associated with occupational exposure to asbestos and other fibrous material.
Begins as nodules in the pleura which extends to surround the lungs and causes fissures.
The chest wall is often invaded, causing severe and intractable pain.
What are the three anti-tumour defences?
Genes which act as guardians of the genome
Non specific responses e.g. Inflammation
What are the normal activities of p53?
Prolongs the G1 phase of the cell cycle to allow extra time for correcting DNA defects
Triggers apoptosis and eliminates the faulty cell
Stimulates transcription of genes involved in differentiation so the cell is set on a path opposite to carcinogenesis
What condition can turn on p53?
What can cause leukocytes to congregate in a tumour?
Chemotaxins secreted by tumour cells
Chemotaxins secreted by inflammatory cells
Chemotaxins secreted by necrotic tumour cells
Bacterial chemotaxins in ulcerated and infected tumours
Adhesion molecules expressed by the endothelium of tumour's vessels
Give a tumour which can spontaneously regress
What are the most common childhood tumours?
What cancer is related to aflatoxin?
What cancers is tobacco associated with?
What cancers can obesity predispose women to?
What are some risk factors for breast cancer to do with sexual development?
Delayed first pregnancy
What cancer the Bence-Jones protein used to indicate when present in the urine?
What causes an increase in prostate specific antigen in the blood?
Massage the prostate
Benign prostatic hypertrophy
What is carcinoembryonic antigen?
Give a cancer that it cause it to be raised.
An oncofoetal protein which isn't significantly expressed in adults.
Colon carcinoma, pancreas, lung, rectal.
What carcinomas can cause a raise in alpha-fetoprotein?
What normally produces alpha-fetoprotein?
Give some examples of chemotherapy agents?
Platinum based agents
Plant derived drugs
How do antimetabolites work in treating cancer?
Mimic normal substrates but can't be utilised.
Describe how alkylating and platinum based agents can be used in chemotherapy.
Cause x-linking of the DNA helix
Describe how plant derived drugs work as chemotherapy agents.
Inhibit microtubule assembly and interfere with mitotic spindle formation.
Describe how Gleevec works as a chemotherapy agent, with the cancer that it's used to treat.
Inhibits the overactive BCR-ABL protein produced in chronic myelogenous leukaemia due to the Philadelphia chromosome
Describe how herceptin works as a chemotherapy agent.
It inhibits HER2 receptors in breast adenocarcinomas which overexpress them.
What is important when predicting the outcome of a tumour?
Tumour site, type, grade, stage
Availability of effective treatments
What is looked at to determine the extent of breast cancer using the Bloom Richardson system?
What is the difference between an adjuvant and a neo-adjuvant in cancer treatment?
Adjuvant - after tumour excised to eliminate subclinical disease. Limits the possibility of a relapse.
Neo-adjuvant - tumour too large for surgery so need to shrink it first.
Why is chemotherapy administered in a number of small doses rather than one large dose?.
Normal cells recover faster so it reduces bystander damage
What can tamoxifen be used to treat in chemotherapy and how does it work?
Selective oestrogen receptor antagonist
Treats breast cancer which is positive for the receptor.