Tumour Pathology Flashcards
Describe the balance between cell proliferation and apoptosis in cancer.
In cancer, accumulation of proliferating cells (cell survival/proliferation»_space; cell death)
Is the level of cell proliferation the same everywhere in the body ?
No.
Lots of proliferation in hair and nails, very little or none in neurons
Define the term neoplasm.
A new and abnormal growth of tissue in a part of the body, especially as a characteristic of cancer.
Describe the type of cells making up tumours.
- Neoplastic cells, which are present in stroma
2. Stroma (connective tissue, blood vessels, inflammatory cells)
Why are tumours said to be autonomous ?
Because response to physiological stimuli lost or abnormal, allowing unregulated growth
What is the main risk factor for cancer ? Why is that ?
Age
Because long time for most cancers to grow + for cumulative changes in tumour cells to have clinical effects
Which kind of tissue do the most common kinds of cancer arise in ?
Epithelial Tissues
Distinguish between the most common cancers in men and women.
MEN
- Prostate
- Lung
- Large bowel
- Bladder
WOMEN
- Breast
- Large bowel
- Lung
- Ovary
Why are cancers (i.e. cells proliferating too much) a problem ?
Because cancer cells do not obey strong borders, infiltrate other areas and cause chaos in surrounding material
What are the hallmarks of cancer ?
- Evading apoptosis
- Self-sufficiency in growth signals (Must able to grow autonomously without signals, because will get signals telling it to stop growing)
- Insensitivity to anti-growth signals
- Tissue invasion and metastasis
- Limitless replicative potential (Molecular clock inside normal cells only allow limited amount of cell cycles which is programmed at the end of chromosomes (telomeres). Cancer cells extend telomeres by activating telomerase allowing them to have limitless numbers of cell cycle).
- Sustained angiogenesis (to get supply of oxygen and nutrients)
Describe the main events in cancer timeline, including the diagnosis.
- Initiation/Promotion (some DNA event in some cell)
- Growth
- Diagnosis/Excision (of some bit of cancer tissue. Biopsy it to reveal which kind of cancer, course of treatment, and
prognosis) - Cure/relapse/metastasis/death
Distinguish malignant from benign tumours.
BENIGN • Well circumscribed • Slow growth • No necrosis • Non-invasive • No metastasis -Intact surface -Exophytic growth -Homogeneous cut surface -Circumscribed or encapsulated edge (does not move to the layer down) • Resemble tissue of origin • Well circumscribed • Well differentiated • Minimal nuclear pleomorphism • Mitotic figures normal • No necrosis
MALIGNANT
• Poorly circumscribed
• Rapid growth
• Often necrotic
• Invasive
• Metastasis
-Heterogeneous cut surface due to necrosis
-Ulcerated surface
-Endophytic growth (Growing down into next tissue layer)
-Vascular permeation
-Irregular infiltrative edge
• Variable resemblance to tissue of origin
• Variable differentiation (Some cells look like tissue or origin, some do not)
• Variable pleomorphism may be anaplastic
• Mitotic figures abnormal
• High nucleo-cytoplasmic ratio
• Nuclear hyperchromasia (increase in chromatin in cell nuclei)
• Nuclear pleomorphism (variability in the size and shape of cells and/or their nuclei)
• Abnormal chromatin structure
What are possible clinical effects of benign tumours ?
Do NOT invade or metastasise BUT not always clinically benign! (may still cause problems)
1) Space occupying effects
• Obstruction
• Epilepsy (when in the brain)
• Conduction abnormalities
2) Haemorrhage (if in blood supply)
• Pulmonary
• Gastrointestinal
3) Hormone production
• Pituitary
• Adrenal
• Endocrine pancreas
How do malignant tumours spread ?
- Directly invade locally
- Via the lymphatics
- Via the bloodstream (haematological)
- Through body cavities (transcoelomic)
Do all tumours metastasise in the same manner/ with the same distribution ? Explain, giving examples.
No, some of tumour cells have a preference about secondary site where want to grow (preferentially growing there).
Prostate –> bone
Lung –> brain, adrenals
Breast –> lung, liver, bone, brain
Ovary –> peritoneal cavity
Identify the types of tumours structurally. State whether each kind tends to be benign or malignant.
Sessile: More bengign
E.g. skin cancer
Pedunculated: More benign
E.g. colorectal cancer
Papillary: More benign
Fungating: More malignant
Ulcerated: More malignant
Annular: grows centripetally
E.g. within vessels
Define dysplasia.
Presence of cells of an abnormal type within a tissue, which may signify a stage preceding the development of cancer.
Define Koilocytosis.
Presence of koilocytes in a specimen (squamous epithelial cell that has undergone a number of structural changes,)
How are tumours classified histologically ? Why is this important ?
BY GRADE
-Depends on resemblance to tissue of origin (differentiation, determine histologically)
Grade I: Well Differentiated
Grade II: Moderately Differentiated
Grade III: Poorly Differentiated
Grade IV: Nearly aplastic
Important because grade correlates broadly with clinical behaviour, so precise classification important for planning treatment
How is the extent of spread of different tumours classified ?
By STAGE
-E.g. TNM staging (Tumour Node Metastasis)
1. Tumour size Tis= In situ, non-invasive (confined to epithelium) T1 T2 T3 T4
2. Lymph Node Involvement N0= No lymph node involvement N1= Nearby lymph node involvement N2= Regional lymph node involvement N3= More distant lymph node involvement
- Metastases
M0= No distant metastases
M1= Distant metastases present
Describe the mechanism of bone metastasis.
- Primary malignant neoplasm leads to new vessel formation
- Neoplasm invades vessel
- Embolism of tumour cells
- Arrest in distant capillary bed in bone
- Adhere to capillary walls
- Extravasation
- Response to microenvironment
- Tumour-cell proliferation
- Bone metastases
Describe the mechanism by which a blood vessel neoplasm may spread.
- Haematogenous spread to liver (blood)
- Lymphatic spread to lymph nodes
- Transcoelomic spread to peritoneum
What system is there to describe the stage of Colorectal Cancer ? Describe it ?
Dukes’ Staging System for Colorectal Cancer
- A - confined to bowel wall
- B - through bowel wall but no lymph node involvement
- C - lymph nodes involved
- D - distant spread
What is the suffix of all cancers ?
-oma
What is the nomenclature for Benign epithelial tumours ?
Either papillomas (squamous, transitional) or adenomas
What is the nomenclature for Benign connective tissue (mesenchymal) tumours ?
Begin with term denoting cell of origin e.g. lipoma (adipocytes)
What is the nomenclature for malignant epithelial tumours ?
Carcinomas
What is the nomenclature for malignant connective tissue (mesenchymal) tumours ?
Sarcomas
What are the possible tissue origins of tumours ?
- Epithelial origin (most)
- Connective tissue origin (mesenchymal)
- Lymphoid / haematopoetic origin (e.g. (Lymphomas and Leukemias)
Identify the name of malignant and benign tumours for the following epithelial cells:
Squamous cell
Transitional
Basal cell
Glandular
- Squamous cell
Benign: Squamous cell papilloma
Malignant: Squamous cell carcinoma - Transitional
Benign: Transitional cell papilloma
Malignant: Transitional cell carcinoma - Basal cell
Benign: Basal cell papilloma
Malignant: Basal cell carcinoma - Glandular
Benign: Adenoma
Malignant: Adenocarcinoma
Identify the name of malignant and benign tumours for the following mesenchymal cells:
Smooth muscle Striated muscle Adipose tissue Blood vessels Bone Cartilage Mesothelium Synovium
Smooth muscle
Benign: Leiomyoma
Malignant: Leiomyosarcoma
Striated muscle
Benign: Rhabdomyoma
Malignant: Rhabdomyosarcoma
Adipose tissue
Benign: Lipoma
Malignant: Liposarcoma
Blood vessels
Benign: Angioma
Malignant: Angiosarcoma
Bone
Benign: Osteoma
Malignant: Osteosarcoma
Cartilage
Benign: Chondroma
Malignant: Chondrosarcoma
Mesothelium
Benign: Benign mesothelioma
Malignant: Malignant mesothelioma
Synovium
Benign: Synovioma
Malignant: Synovial sarcoma
What is a carcinoma ? What are some common carcinomas ?
Malignant epithelial tumour
Squamous cell carcinoma
Transitional cell carcinoma
Adenocarcinoma
Which kinds of tumours may be associated with a non-invasive precursor ? What does this mean ? Give examples of non-invasive precursors.
Epithelial Tumours
It means that the involved tissues are a cancer-setting, but not a clinical problem at this point (Somewhere in the middle of benign and malignant tumours)
Some cancers will go on to progress into more
aggressive cancers which will become a problem
Examples:
– Carcinoma in situ
– Intraepithelial neoplasia
Give examples of benign mesenchymal tumours.
– Lipoma
– Haemangioma (vascular lesions)
Give examples of malignant mesenchymal tumours.
– Liposarcoma
– Haemangiosarcoma
Are mesenchymal tumours usually associated with a non-invasive precursor ?
No
Define the following: • Melanoma • Lymphoma • Teratoma • Embryonal tumours (‘blastomas’) • Carcinoid tumours • Cysts
- Melanoma= Tumour from melanocytes
- Lymphoma= Tumour from lymphocytes
- Teratoma= ‘Tumor made up of several different types of tissue, such as hair, muscle, or bone’
- Embryonal tumours (‘blastomas’)= Tumours which arise during embryonic development (affects v young children)
- Carcinoid tumours= “slow-growing cancer that can arise in several places throughout your body”
- Cysts= “small sac filled with air, fluid, or other material”
Identify the following:
- Tumour from melanocytes
- Tumour from lymphocytes
- Tumours which arise during embryonic development (affects v young children)
- “Small sac filled with air, fluid, or other material”
- “Slow-growing cancer that can arise in several places throughout your body”
- ‘Tumor made up of several different types of tissue, such as hair, muscle, or bone’
- Melanoma
- Lymphoma
- Embryonal tumours (blastomas)
- Cysts
- Carcinoid tumours
- Teratoma
Describe the main features of a teratoma.
- Contains elements of all three embryonic germ cell layers
- Of germ cell origin
- Has both benign and malignant forms
- Ovarian – almost always benign
- Testicular – more often malignant
What are the important features of tumours to consider as a physician ?
- Incidence
- Age
- Sex
- Geographical distribution
- Predisposing factors
- Macroscopic features
- Microscopic features
- Spread
- Prognosis
= In a Surgeon’s Gown Physicians May Make Some Progress
What is meant by monoclonal origin of cancer ?
A theory which states that in general, neoplasms arise from a single cell of origin.
What is an experiment which shows that many tumours have a clonal origin ?
- Gene for Glucose 6 phosphate dehydrogenase (G-6PD) is on X chromosome
- Two forms of the enzyme which can be separated using chromotography (A and B forms)
- For women with particular cancer, can look into tissue to see if A form or B form. Since X inactivation (one of the two X chromosomes randomly switched off in the cells, Lyon inactivation hypothesis), within particular cell, should only express one or the other
- Using chromatography, may separate the two forms of the enzyme in body tissues
- Normal tissue, express both, so is a 50 : 50 mixture of both enzyme markers (assuming that one parent has XA and the other has XB), 50% cells express A and 50% express B, child will be heterozygous (but individual cells 100% one or the other)
- If the tumour arises from a single cell i.e. is clonal in origin, then all the Tumour cells will have the same enzyme marker (because all origin from a single cell)
Are all tumour cells equal ? How so or how not ?
No: Once got a tumour mass, not all cells the same and not all cells act in the same way.
-For instance, try an experiment whereby subject basal cell or squamous cell carcinoma to radiation treatment.
-From size can calculate the number of tumour cells
-From radiation data can calculate how many cells are killed
-PROBLEM: number of cells in the tumour VASTLY exceeds the number capable of being killed by radiation
(sub-treshold dose of radiation)
-CONCLUSION: Only 1 in 10^3 - 10^4 cells can repopulate the tumour. These are TUMOUR STEM CELLS
-Proof is that if separate different cells from a tumour mass, some can proliferate (tumour stem cells) but other cannot and just die
What are tumour stem cells ?
“Rare cells within a tumour that can both self-renew by dividing and give rise to many cell types that constitute the tumour, and can therefore form tumours” (rather than just being part of tumour mass) (Important note: They are not actually stem cells)
