1. Cellular pathology Flashcards
Metaplasia
alice lee
Metaplasia -‐ a reversible change in which one adult cell type (usually epithelial) is replaced by another adult cell type
- This is usually adaptive
- Example: Barrett’s Oesophagus -‐ gastro-‐oesophageal reflux causes the oesophageal epithelium to change from squamous to columnar (NOTE: this is pathological metaplasia)
- You can get physiological metaplasia e.g. in pregnancy the cervix opens up and the columnar epithelium of the endocervical canal is exposed to the acidic uterine fluids making it become squamous
- When the cervix closes up again, the cell type changes back to normal (hence why metaplasia is a REVERSIBLE change)
Histology Image:
- On the left hand side you can see the normal stratified squamous epithelium of the oesophagus
- On the right hand side you can see that it has become simple columnar epithelium
- There are also some goblet cells on the right
There are a few types of metaplasia:
- Gastric Metaplasia -‐ stratified squamous to simple columnar
- Intestinal Metaplasia -‐ goblet cell appear
Endoscopy Image:
- This bits that are white/pink are stratified squamous epithelium
- The red bits are simple columnar epithelium
Dysplasia
Dysplasia -‐ an abnormal pattern of growth in which some of the cellular and architectural features of malignancy are present
- Cancer is a multi-‐step process so there must be some steps in between normal and cancer
- The cells in dysplasia are on the road to cancer but haven’t reached it yet
- Dysplasia is a pre-‐invasive stage with an intact basement membrane
Features of cancer include:
- Large nuclei
- Increased mitoses
- Abnormal mitoses
- Increased nucleo-‐cytoplasmic ratio
- Dysplasia can be used to screen for cancer, to pick up high risk individuals before they get full-‐blown cancer
- There is a loss of architectural orientation
- There is a loss of uniformity of individual cells
- Nuclei are hyperchromatic and enlarged
- Mitotic figures are abundant, abnormal and in places where they aren’t usually found
- Everything becomes more variable
Dysplasia is common in:
- Cervix -‐ HPV infection
- Bronchus -‐ smoking
- Colon -‐ ulcerative collitis
- Larynx -‐ smoking
- Stomach -‐ pernicious anaemia
- Oesophagus -‐ acid reflux
This is a cervical biopsy (image)
- On the left you can see that the cells are very compact at the bottom then become more and more spaced out towards the lumen -‐ normal cellular maturation
- On the right hand side of this image, the cells are NOT undergoing normal maturation
- There are compact cells with dark, dense nuclei on the surface -‐ these cells are normally seen further down
Low Grade and High Grade Dysplasia
Low Grade -‐ low risk of progression to cancer
High Grade -‐ high risk of progression to cancer
- Difference between low grade and high grade: both show changes of dysplasia, but the changes are more severe in high grade dysplasia
- The nuclei are bigger and the nucleo-‐cytoplasmic ratio is higher in high grade dysplasia
Signs:
- Loss of orientation
- Loss of uniformity
- Hyperchromatic and enlardged nuclei
- Mitotic figures in abundance but abnormal places
Neoplasia, tumour, malignancy
Neoplasia = any new growth, benign or malignant
Tumour = swelling (e.g. nasal polyps are also considered tumours)
Malignancy = an abnormal, autonomous proliferation of cells, unresponsive to normal growth control mechanisms
Example: in the oestrogenic phase of the menstrual cycle, the endometrial epithelium proliferates. When the oestrogen levels drop, the proliferation should stop. But in cancer, the controls have become autonomous and can’t easily be switched off.
List four features which distinguish benign from malignant tumours and explain how they are of use in making that distinction
Benign Tumours
- Slowly growing
- Normal mitoses
- REMEMBER: main definition is that benign tumours DO NOT INVADE and DO NOT METASTASISE
- Encapsulated -‐ they have a compressed capsule around them
- Exception: fibroids (leiomyoma) in the uterus does NOT have a capsule
- ‘Well differentiated’ = they look like the tissues that they come from
- Above is a fibroadenoma of the breast tissue -‐ it is sharply demarcated and is well differentiated
Benign tumours do NOT tend to be fatal unless they:
o Are in a dangerous location
E.g. meninges, pituitary
o Secrete something dangerous
E.g. insulinoma
o Gets infected
E.g. bladder (whenever you block anything that drains fluid, you will create the conditions for infection)
o Bleeds
E.g. stomach
o Ruptures
E.g. liver adenoma (can cause massive haemoperitoneum)
o Torts (twisted)
E.g. ovarian cyst
Malignant Tumours
- INVADE SURROUNDING TISSUES
- SPREAD TO DISTANT SITES
- No capsule
- Well to poorly differentiated
- Rapidly growing
- Abnormal mitoses
- Metastasis -‐ a discontinuous growing colony of tumour cells, at some distance from the primary cancer
- The prognosis of a cancer is very much dependent on whether it has spread
- The sites of metastasis depends on the lymphatic and vascular drainage of the primary site
- Example: the pancreas is drained by the splenic vein, which then goes via the hepatic portal vein to the liver so pancreatic carcinomas tend to present with liver metastases
- Lymph node involvement has a worse prognosis
Example: Colon cancer (uses Dukes staging system)
Dukes A -‐ 90% survival (confined to bowel wall)
Dukes C -‐ 30% survival (lymph node involvement)
BEning vs Malignant
Bening:
- well differentiated
- encapsulated
- slow growing
- normal mitoses
- does not evase
- does not metastasize
Malignant:
- no capsule
- poorly differentiated
- fast growing
- abnormal mitoses
- evades
- and metastazised
Explain the principles underlying the nomenclature of tumours
Nomenclature of Tumours
Benign epithelial tumours
- Carcinoma
- Benign soft tissue tumours
- Sarcoma
- Leukaemia & Lymphoma
- Teratoma
- Hamartoma
Benign Epithelial Tumours
Of SURFACE epithelium = PAPILLOMA
E.g. skin, bladder
Of GLANDULAR epithelium = ADENOMA
E.g. stomach, thyroid, colon, kidney, pituitary, pancreas
Carcinoma
means bad
A malignant tumour derived from epithelium
- Adenomas could become adenocarcinomas
- Types of carcinoma:
- Squamous cell carcinoma
- Adenocarcinoma
- Transitional cell carcinoma (transitional epithelium is found in the bladder)
- Basal cell carcinoma
- So we classify tumours based on the tissues that they come from
Benign Soft Tissue Tumours
- Bone -‐ osteoma
- Fat -‐ lipoma
- Smooth Muscle -‐ leiomyoma
Sarcoma
A malignant tumour derived from connective tissue (mesenchymal) cells
The prefix is the site of the tumour e.g. osteosarcoma (bone)
Types of sarcoma:
prefixes are used for all medical conditions
- Fat = liposarcoma
- Bone = osteosarcoma
- Cartilage = chondrosarcoma
- Striated Muscle = rhabdomyosarcoma
- Smooth Muscle = leiomyosarcoma
- Nerve Sheath = Malignant Peripheral Nerve Sheath Tumour
Leukemia and lymphoma
These are both tumours of white blood cells
Leukaemia -‐ malignant tumour of BONE MARROW derived cells which circulate in the blood
Lymphoma -‐ malignant tumour of LYMPHOCYTES (usually) IN LYMPH NODES
NOTE: lymphocytes are produced by the bone marrow and the are found in lymph nodes so in some cases you can get a mix of both lymphoma and leukaemia
Laukemia of lymphocytes - but when it is within the lymphocytes
Teratoma
- A tumour derived from GERM CELLS, which has the potential to develop into tumours of ALL THREE germ cell layers
- Three Layers: Ectoderm, Mesoderm + Endoderm
- All the slides on the left are from ONE tumour
- There are loads of different cell types in one teratoma
IMPORTANT NOTE:
Gonadal teratomas in MALES are almost ALL MALIGNANT
Gonadal teratomas in females are mostly benign
MAle - malignant
Female - benign
Hamartoma
Definition: localised overgrowth of cells and tissues NATIVE TO THE ORGAN
- In other words: the tissues that are present are appropriate for that particular part of the body but the way that they are architecturally arranged is inappropriate
- The cells are mature but architecturally abnormal
- This is common in children, and should stop growing when they stop growing
- Example above:
- This is a section of liver showing the bile ducts
- A normal portal tract only contains ONE bile duct
- Here there are loads of bile ducts
- Normal bile ducts are round but these ones are a little misshapen
- Though there are no issues cytologically
- These bile ducts are abnormally arranged
List five morphological features which allow assessment of the differentiation of a tumour
- Tumours are graded (how well differentiated they are) and staged (how far they’ve spread)
- Staging is MORE IMPORTANT
- High grade tumours generally have a high stage
- If you find a tumour you need to find out whether it is a primary tumour or if it is a secondary
- This can be done by inspecting the tumour histologically and looking for evidence of normal function still present e.g.:
- Keratin is made by squamous cells
- Mucin is produced by glandular epithelium (adenocarcinoma)
- Bile is made by hepatocytes
- Hormones e.g. insulin is made by the pancreas
There are specific grading systems for some cancers:
- Breast -‐ Nottingham scoring system
- Prostate -‐ Gleason classification
Tumours that show little or no differentiation are described as being ANAPLASTIC
TNM - staging
- The grade of a tumour describes its degree of differentiation
- The stage of a tumour describes how far it has spread or how big the tumour is
- Tumours of higher grade tend to be of higher stage
- Overall STAGE > grade in determining prognosis
- The TNM classification can be applied, and individualised, to tumours in all sites
TNM stage:
A: Limited to submucosa
B: muscularis propira
C: enteruc nodes
D: metastasis
Summarise incidence and mortality rates of the major adult tumours as well as their spatial distribution and temporal trends.
Cancer Incidence & Mortality
- Ischaemic heart disease and stroke lend to the highest global causes of death (not cancer).
- Death rates from CVS disease have dropped over the years.
- Death rates from cancer have remained stable/increased-slightly over the years.
- Developed countries have a greater incidence of cancer than undeveloped countries.
- Males – prostate and lung cancers are the most common cancers.
- Females – breast and cervix uteri cancers are the most common cancers.
- Cancer incidence can show a geographical variation:
- I.E. Melanoma is most common in AUS/NZ and colorectal cancer is most common in Japan.
- Incidence is increasing for common cancer sites in both high-income (with plateau/decrease) and low-income countries (still some infectious causes)– effects of earlier diagnosis, screening and changes in risk factors.
- Rapid increases in incidence may be due to the introductions of official screening procedures.
- High income countries tend to show an increasing and then rapid increase followed by a plateau of cancer incidence due to introduction of screening procedures.
Mortality is decreasing (earlier detection, better treatment0 in high-income countries but NOT low-income: Survival is increasing
Total burden of cancer is increasing because of demographic changes
- If changes in cancer incidences or mortality are too rapid, there cannot have been genetic changes.
Discuss how Migration Studies have been used to demonstrate the environmental contribution to cancer
Migrant Studies – to study cancer incidence:
- Rapid change in risk following migration -> lifestyle and environmental factors act late in carcinogenesis.
- Slow change -> exposures early in life are more relevant.
- Persistence of rates -> genetic susceptibility is important in determining risk.
Graph shows that people born in japan get the most stomach cancer as people born in Hawaii and elsewhere have a lower incidence.
Discuss the epidemiological evidence for cancer causation.
Hereditary inclination (5-10% of cases).
OLD AGE (not Acute Lymphoblastic L) Smoking, obesity (3 oxydative radical from diet), infection, reproductive hormone, alcohol, occupation (order of attributive risk highest to lowest).
- 45% (men) and 40% (women) of cancers could have been prevented by reducing risk.
- Smoking – 30% of cancer death, increases risk for >15 cancers, 90% (men) and 80% (women) of lung cancer causes.
- Diet – colorectal cancer chance increased with low fibrous diet.
- Alcohol – synergistic with tobacco, mechanism is poorly understood and is also associated with liver, oral cavity, pharynx, larynx and oesophageal cancer. Has a preventative effect for CHD.
– Anthropometry – study of measurements and proportions of the human body:
World cancer research fund guidelines for dietary prevention: (obesity is an inflammatory disease connected with a huge increase in inflammatory cytokines)
- Be lean without being underweight.
- Be physically active for at least 30 minutes a day.
- Avoid sugary drinks.
- Eat a variety of fruit/veg.
- Limit consumption of red meat (<500g/week) and avoid processed meat.
- Limit alcoholic drinks.
- Limit consumption of salty foods.
Breast cancers:
- Sex steroids can increase cancer risk.
Westernisation of lifestyle (more energy-rich diets, low physical diets, etc.) can promote cancer.
Infectious causes of cancer - ~16% of cancer is from an infectious cause (25% in Africa and <10% in EU).
- E.G. HPV (cervix cancer), EBV (Hodgkin’s/Burkett’s Lymphoma), HCV/HBV (liver cancer), H. pylori (stomach cancer).
