Cancer as a disease: Cellular Pathoglogy of cancer Flashcards
Define Metaplasia
A reversible change in which one adult cell type (usually epithelial)is replaced by another adult cell type
Adaptive
Describe physiological metaplasia
Cervix during pregnancy – the cervix opens up and the columnar epithelium of the endocervical canal is exposed to the acidic uterine fluids making it squamous
pH of cervix is the key stimulus here
Describe pathological metaplasia
Barrett’s Oesophagus – gastro-oesophageal reflux (regurgitated stomach acid) can change the stratified squamous epithelium of the distal oesophagus to simple columnar
Reversible and adaptive to changes in pH (I.,e if you treat GERD- the epithelium will return to squamous)
Ultimately, what is meant by an adaptive response in metaplasia
ADAPTIVE response where cells sensitive to the stressful stimulus – reflux of acid, cigarette smoke, etc – and are replaced by cells which can withstand the adverse environment e.g. respiratory columnar ciliated epithelium changes to squamous, squamous oesophageal to columnar/ intestinal.
What are the two types of metaplasia that can take place in Barrett’s Oesophagus?
Gastric metaplasia – stratified squamous to simple columnar (but no goblet cells)
Intestinal metaplasia – goblet cells begin to appear (becomes columnar too)
What else can cause metaplasia
Or reprogramming of stem cells (reserve cells) to differentiate along a different pathway in response to signalling by cytokines, growth factors and extracellular matrix components.
Define dysplasia
an abnormal pattern of growth in which some of the cellular and architectural features of malignancy are present
pre-invasive stage with
intact basement membrane - hence non-invasive
What is important to remember about dysplasia
Cells are dysplastic before invasive (so it is the step before cancer). The cells show many of the cytoplasmic, genetic and molecular features of cancer- but the BM is intact and the cells themselves are not invasive yet.
Morphological correlation of molecular changes is seen in dysplasia.
Describe the clinical importance of detecting cells
Easier to treat and treatment will be 100% effective due to the lack of invasion
Therefore it is associated with a better prognosis
Aim of screening programmes.
List the key features of dysplasia
Large nuclei (and hyperchromatic) Increased mitoses Abnormal mitoses Increased nucleo-cytoplasmic ratio Loss of architectural orientation Loss of uniformity of individual cells
Why are the nuclei hyperchromatic in dysplasia
Due to the increased concentration of DNA in the cell
Why does the nuclear: cytoplasmic ratio increase in dyslaisa
Because the nucleus grows without the cell itself growing (hence the percentage of the cell that is nucleus increases).
What is meant by the loss of architectural orientation
Lose the normal differentiation of squamous epithelium.
Should go from basal - mature- keratinised- but this pathway of differentiation is lost in dysplasia.
What is dysplasia common in
CERVIX – HPV infection BRONCHUS – Smoking COLON – Chronic Ulcerative Colitis LARYNX – Smoking STOMACH -Pernicious Anaemia (chronic inflammatory process) OESOPHAGUS-Barret’s metaplasia
Describe the basis of screening for cervical cancer
Previously looking for dysplastic changes
Now moved to looking at genotypes of HPV.
What is important to remember about the relationship between metaplasia and dysplasia
Often occur in the same sites
metaplasia first- then dysplasia
why you can get squamous carcinomas of the lung (first metaplastic change from columnar, then the squamous cells become dysplastic and then cancerous)
Compare low grade dysplasia to high grade dysplasias
Low grade- lower risk of progression and more likely to revert back to normal spontaneously
high grade- darker- due to increased nuclei:cytpolasm ratio.
Define neoplasia, tumour and malignancy
A tumour is an abnormal, autonomous proliferation of cells which are unresponsive to normal control mechanisms governing their growth, and which persists in proliferating even when whatever stimulus started it going has stopped.
What are the characteristics of benign tumours
do not invade do not metastasise encapsulated usually well differentiated slowly growing normal mitosess
first one is absolute- functional classification of benign tumours, the rest are just descriptive and help with the diagnosis.
Describe non-encapsulated tumours that are benign
§ Encapsulated – note NOT always like this – i.e. Leiomyomas are NOT encapsulated but ARE benign
i.e fibroids in the uterus are not encapsulated but are benign.
Describe fibrous adenoma of the breast
Benign
Encapsulated- sharp, well demarcated edge, so can be resected easily
Can move around easily upon palpation- not adherent to skin or pectoral muscle (good thing)- less likely to be invasive
What is meant by well differentiated
Looks like the tissue from which the cancer originated from.
Under what conditions can benign tumours become fatal
In a dangerous place: meninges (tumour blocks flow from lateral ventricles to 3rd ventricle- hydrocephalus raising ICP), pituitary (impinges on optic chiasm)
Secretes something dangerous: insulinoma
Gets infected: bladder
Bleeds: stomach (presses on artery and bleeds into peritoneal cavity))
Ruptures: liver adenoma
Torts (twisted): ovarian cyst (twist artery- leading to ischaemic death- infarction).
Describe the features of malignancy
o Characteristics: § Invade surrounding tissue. § Metastasize. § No capsule (but not always). § Well à poorly differentiated (but tend to be poorly differentiated). § Rapidly growing. § Abnormal mitotic figures.
First 2- functional behaviours
The rest- how we recognise them- descriptive
Describe the basis of screening for malignancy
Pick up malignant tumours early- before they have spread to distant sites- heavily improves diagnosis as in metastasis- local treatment not enough.
Define metastasis
A metastasis is a discontinuous growing colony of tumour cells, at some distance from the primary cancer
What does metastasis depend on
These depend on the lymphatic and vascular drainage of the primary site
Lymph node involvement has a worse prognosis
Lateral breast tumours — axillary nodes
Medial breast tumours — mammillary chain
Testicular cancers- drain to aortic nodes
Describe the staging of colon cancers
Duke’s A (confined to wall of colon)- 90%
Duke’s C (spread to lymph nodes) -30%
What is meant by a pleomorphism
The nuclei look different from one to the other
What does the suffix -oma mean
Benign.
Describe the nomenclature of benign epithelial tumours
Of surface epithelium
= PAPILLOMA
e.g. skin, bladder
Of glandular epithelium = ADENOMA
e.g. stomach, thyroid, colon, kidney, pituitary, pancreas
Define carcinoma
A malignant tumour derived from epithelium
Describe the different types of carcinoma
Basal cell carcinoma
Squamous cell carcinoma
Transitional cell carcinoma (transitional epithelium is found in the bladder and urinary tract)
Adenocarcinoma
State some different types of benign soft tissue tumours
Osteoma – bone
Lipoma - fat
Leiomyoma – smooth muscle (uterus)
Define sarcoma
A malignant tumour derived from connective tissue (mesenchymal) cells
Describe the different types of sarcoma
Fat = LipoSARCOMA Bone = OsteoSARCOMA Cartilage = ChondroSARCOMA
Muscle
striated = RhabdomyoSARCOMA,
smooth = LeiomyoSARCOMA
Nerve sheath = Malignant Peripheral Nerve Sheath Tumour
Define tumours of the blood cells
Tumours of white blood cells:
Leukaemia a malignant tumour of bone marrow derived cells which circulate in the blood
Lymphoma is a malignant tumour of lymphocytes (usually) in lymph nodes
Describe the inter-relationship between lymphomas and leukaemia
Leukaemias can spread to lymph nodes and be recognised as lymphomas
Lymphomas can move to the blood and become leukaemias
Where can lymphomas be found
Any tissue where lymphocytes reside
i.e lymph nodes, spleen ,stomach, tonsils
Define a teratoma
A teratoma is a tumour derived from germ cells, which have the potential to develop into tumours of all three germ cell layers:
ectoderm,
mesoderm,
endoderm
Compare teratomas in males and females
Different developmental pathways:
Gonadal teratomas in males, all malignant
Gonadal teratomas in females, most are benign
What type of cells are found in teratomas and where can they occur
Totipotent stem cells
Can be found in cells where stem cells are present (i.e gonads)
but occur in midline situations outside the gonads (Pituitary, pineal, mediastinum, sacrococcygeal areas)
Describe dermoid cysts
§ E.G. Dermoid cysts – can contain anything such as teeth, bone, eyes, et
Define hamartoma
localised overgrowth of cells and tissues native to the organ.
cells are mature but architecturally abnormal
therefore the cells look the same, but they are arranged abnormally.
Describe some common hamartomas
common in children, and should stop growing when they do,
e.g. bile duct hamartomas, bronchial hamartomas,
Common ones are haemangiomas, bronchial hamartomas, Peutz-Jegher polyps in the gut.
Can have a mass of normal cartilage in the lungs- normal cells- but can incur problems for the diagnosis.
What should you expect to find in a hamartoma
o Cells are mature but architecturally abnormal – expect to find the same types of tissue expected to grow in the organ but not in the right place in the organ.
Describe the criteria for assessing the differentiation of a malignant tumour
Evidence of normal function still present production of: keratin, mucin bile hormones
i.e is it doing what a normal squamous epithelium or glandular epithelium would normally do
look for glands for glandular epithelium
What is important to remember about lymphomas and melanomas
They are malignant
Despite their suffix suggesting that they are benign.
Outline a method for assessing the differentiation of a malignant tumour
- Evidence of normal function is still present – i.e. production of keratin, mucin, etc.
a. E.G. A ectopic squamous cell cancer of the lung produces PTH-rp. - If no evidence of normal function – high-grade or anaplastic carcinoma.
- If no evidence of differentiation – anaplastic carcinoma.
- Presence of abnormal mitoses – some tumours have a mitotic count.
a. I.E. Tumour with 15 mitoses/mm2 behaves worse than one with 5 mitoses/mm2. - Various grading systems – for cancer of breast, prostate & colon.
if the tumour shows no differentiation, what do we call it
no differentiation, ANAPLASTIC carcinoma
What are the different grading systems for breast and prostate cancers
Breast – Nottingham scoring system
Prostate – Gleason classification
What is the difference between grade and stage and describe the relationship between the two
The grade of a tumour describes its degree of differentiation
The stage of a tumour describes how far it has spread
Tumours of higher grade (i.e. more poorly differentiated) tend to be of higher stage (i.e. spread further)
What is more important for determining prognosis
Overall, stage is more important than grade in determining prognosis
Summarise the TNM system
The Tumour, Node, Metastasis (TNM) system can be applied, and individualised, to tumour in all sites
Tumour: TX (not assessed) and then T0-T4 based on invasion
Nodes: NX (not assessed) then N0-N3 based on number/size nodes
Metastasis: M0-1 (not spread | spread)
T can sometimes be size or distance the tumour has spread
