94 - Neoplasia 3 Flashcards
*Four appearances of intraepithelial neoplasia
Process that precedes many carcinomas
Intraepithelial neoplasia
Most-common cancers
Carcinomas/epithelial cancers
Stages of intraepithelial neoplasia 1 2 3 4
1) Normal 2) Dysplasia (EG: simple columnar cell takes on several mutations) 3) In situ neoplasm 4) Invasive neoplasm
Stages of intraepithelial neoplasia 1 2 3 4
1) Normal 2) Dysplasia (EG: simple columnar cell takes on several mutations, increased mitotic activity, pleiomorphic nuclei. Changes are restricted to epithelial cells) 3) In situ neoplasm 4) Invasive neoplasm
Stages of intraepithelial neoplasia 1 2 3 4
1) Normal 2) Dysplasia (EG: simple columnar cell takes on several mutations, increased mitotic activity, pleiomorphic nuclei. Changes are restricted to epithelial cells) 3) In situ carcinoma (architecture is no longer organised) 4) Invasive neoplasm
Appearance of dysplasic cells
Increased mitotic activity. Pleiomorphic nuclei Large nucleoli Premalignant.
What is in situ carcinoma?
When dysplasic cells become malignant.
Dysplasia
Abnormality of development; alteration in size, shape and organisation ofcells
Meaning of grades of dysplasia
Higher the grade -> more likely to progress to malignancy (grades 1, 2 and 3)
Grade 3 dysplasia
In situ carcinoma. Non-invasive.
Differences between normal stratified squamous epithelium and squamous dysplasia
Dysplasic: Enlarged nuclei, pleomorphic nuclei, disorganised cells, increased proliferation, incomplete cellular maturation (should only have mitosis in basal layer)
Differences between normal stratified squamous epithelium and squamous dysplasia
Dysplasic: Enlarged nuclei, pleomorphic nuclei, disorganised cells, increased proliferation, incomplete cellular maturation (should only have mitosis in basal layer)
What do glandular dysplastic lesions arising from lining epithelium often form?
Polyps (protuberances of tissue into the lumen)
Difference between hyperplasia and neoplasia
Hyperplasia is controlled.
When can hyperplasia predispose to cancer?
Hyperplasia in certain situations can confer increased risk of malignancy (risk of mutations developing). NOT premalignant.
When can metaplasia predispose to neoplasia?
Influences that lead to pathologic metaplasia can also predispose to malignant transformation of metaplastic epithelium
Risk of intraepithelial neoplasias to become malignant
Reasonable risk (therefore considered premalignant). Greater risk than most other benign lesions
Risk of intraepithelial neoplasias to become malignant
Reasonable risk (therefore considered premalignant). Greater risk than most other benign lesions
Lymphadenopathy
Enlarged lymph nodes
Examples of effects of metastases 1 2 3 4
– Local lymphadenopathy (draining to local lymph node) – Bone pain or features related to hypercalcaemia – Jaundice (to liver) – Seizures (if in brain)
Examples of effects of metastases 1 2 3 4
– Local lymphadenopathy (draining to local lymph node) – Bone pain or features related to hypercalcaemia – Jaundice (to liver) – Seizures (if in brain)
Malignancies often associated with weight loss, fever
Late-stage
Where do TNFa and IL-1 come from in some cancers?
Produced by either tumour cells or cells in the tumour microenvironment (EG: macrophages)
Paraneoplastic effects
Effects of malignancy, not caused directly by tumour mass
Examples of paraneoplastic endocrine effects 1 2 3 4 5
1) Cushing’s syndrome 2) Inappropriate ADH syndrome 3) Hypercalcaemia 4) Hypoglycaemia 5) Polycythaemia
Cushing’s syndrome
ACTH (adrenocorticotropic hormone) release.
Hypercalcaemia in cancer
Squamous cell carcinoma releases parathyroid hormone-like substance.
Hypercalcaemia in cancer
Squamous cell carcinoma releases parathyroid hormone-like substance. Can lead to excessive breakdown of bone (increase osteoclast activity)
Immunological paraneoplastic effects 1 2 3 4
1) Dermatologic (rashes, lesions) 2) Neuropathy (injuries to nerves) 3) Inflammation of muscle (weakness) 4) Nephrotic syndrome
Paraneoplastic effects of lung cancer 1 2 3 4
Clubbing Hypertrophic osteoarthropathy Venous thrombosis Non-bacterial thrombotic endocarditis
Paraneoplastic effects 1 2 3 4
1) Clubbing 2) Hypertrophic osteoarthropathy 3) Venous thrombosis 4) Non-bacterial thrombotic endocarditis
Local effects of primary lung cancer 1 2 3 4 5 6
1) Cough 2) Haemoptysis 3) Wheeze 4) Dyspnoea 5) Pneumonia 6) Pancoast’s syndrome
Cancer that can lead to anaemia
Colon cancer (lose blood into colon)
Tests that can be useful in diagnosing cancers
1) Haemoglobin level 2) Liver function tests 3) Radiology (CXR, CT scan) 4) Endoscopy
Prostate specific antigen
Can be elevated in prostate, pancreatic cancer. Can also be elevated in non-malignant tumours, non-cancer conditions. Used in diagnosis, but is hard to use because of some non-specificity.
What can CXR be used for? 1 2 3
1) Investigation of primary cancer 2) Staging of cancer (progression) 3) Follow up (to see if there is remission, relapse, etc)
Tests that can be useful in diagnosing cancers 1 2 3 4
1) Haemoglobin level 2) Liver function tests 3) Radiology (CXR, CT scan) 4) Endoscopy
What can CXR be used for? 1 2 3
1) Investigation of primary cancer 2) Staging of cancer (progression) 3) Follow up (to see if there is remission, relapse, etc)
Uses of endoscopy
Visualisation and biopsy of suspicious-looking lesions
Anatomical pathologist
Specialises in looking at biopsy results under a microscope, diagnosing cancers.
Samples essential for diagnosis of cancer
Histopathological specimens
Two principle ways to biopsy a tumour
1) Histopathology 2) Cytology
Histopathology
Take a piece of tissue, stain it (HE, immunohistochemistry). Can see tissue architecture.
Cytology
Take fine needle aspiration, exfoliative cytology (scrape cells from a surface). Place cells onto a slide. Can’t see stroma, tissue architecture.
Examples of molecular, cytogenic techniques for diagnosing cancers 1 2 3 4
1) In situ hybridisation 2) PCR 3) Chromosomal rearrangements 4) Flow cytometry
Cytologic tissue sampling in lung tumours 1) 2) 3) 4)
• Sputum • Bronchial brush and wash at bronchoscopy • Endobronchial ultrasound transbronchial aspiration (EBUS-TBNA) • FNA under radiological guidance for more peripheral lesions
Tissue/histopathology specimens for diagnosing lung tumours 1) 2) 3) 4)
• Tissue core biopsy for peripheral lesions • Surgical resection specimen (if performed) • H&E • Immunohistochemistry: may help distinguish primary from metastatic lesions
Things we need to know once diagnosis of malignancy is made 1 2 3 4
• Specific tumour type and subtype (cell lineage) • Grade • Stage • Presence of lymphovascular invasion
Two broad groups of lung cancers
Non-small cell Neuroendocrine
Neuroendocrine carcinomas
Show features of neuroendocrine cells.
Small cell carcinoma
Very aggressive neuroendocrine cardcinoma
Main types of non-small cell carcinomas
Squamous cell carcinoma, adenocarcinoma, large-cell (undifferentiated) carcinoma
Most-common cancer in smokers and non smokers
Adenocarcinomas
Pre-neoplastic changes in squamous cell carcinoma (lung) 1 2 3 4
Stratified squamous cell epithelium present (in smokers) Large, pleomorphic nuclei. Necrosis Invasive
Pre-neoplastic changes in squamous cell carcinoma (lung) 1 2 3 4
Stratified squamous cell epithelium present (in smokers) Large, pleomorphic nuclei. Necrosis Invasive
Name for pre-malignancy of squamous cell carcinoma
Dysplasia-carcinoma sequence
Gross appearance of squamous cell carcinoma
Pale mass. Arise in main bronchi. Can form cavities.
Location of adenocarcinomas
In bronchiolar epithelial cells. More peripheral. Not in main airways.
Desmoplasia
When a lot of the tumour isn’t actually neoplastic cells, but stroma.
What determines how hard a tumour is?
Degree of desmoplasia (amount of stroma)
Classic histological feature of adenocarcinoma
Form ducts
Classic histological feature squamous cell carcinoma
Keratinisation
Degrees of cancer differentiation
Well-differentiated (resemble mature cells) Moderately-differentiated Poorly-differentiated (only poorly resemble mature cells, more aggressive)
Stage of cancer
Refers to progression of malignancy (in terms of local spread, metastasis)
What is used to determine stage of cancer?
Radiological and pathological assessment
TNM
T: Extent of primary tumour (1 - 4) N: Regional lymph node metastases (0 - 3) M: Presence or absence of metastases (0 or 1) These are combined to give a score out of four.
Histological suggestion of metastasis
Lympho-vascular invasion (even if can’t see metastases radiologically). Gives a poorer prognosis
Examples of predictive factors in breast cancers
HER2 amplification in breast cancer Oestrogen and progesterone receptors Predictive factors can suggest potential therapies
Examples of predictive factors in breast cancers
HER2 amplification in breast cancer Oestrogen and progesterone receptors Predictive factors can suggest potential therapies
Management of a tumour 1 2 3 4 5
1) Surgery 2) Radiotherapy 3) Chemotherapy 4) Targeted therapy 5) Immunotherapy, bone marrow transplant (these are less-widely applicable)
Things on a path report for a cancer 1 2 3 4 5 6
• Confirmation/further information on type and subtype of malignancy • Grade • Size of tumour/depth of invasion • Presence/absence of microscopic vascular invasion • Completeness of excision • Presence and number of lymph node metastases (which may only be microscopic so histologic examination is necessary)
Targeted therapy
Targeted therapies block the growth of cancer cells by interfering with the function of specific molecules (e.g. oncoproteins) resulting from genetic alterations that drive carcinogenesis and tumour growth
Advantages of targeted therapies
Less damaging to normal cells, target neoplastic cells
Two broad types of targeted therapies
Monoclonal antibodies Small molecules
Most important mutations in non-small cell carcinomas
EGFR ALK
EGFR
Transmembrane tyrosine kinase receptors Growth factor receptor. When stimulated, causes cell to divide.
Examples of anti-EGFR therapies
Gefitinib Erlotinib Both inhibit EGFR tyrosine kinase.
Examples of anti-EGFR therapies 1 2
Gefitinib Erlotinib Both inhibit EGFR tyrosine kinase.
Causes of death in cancer 1 2 3
1) Cachexia 2) Secondary infection from poor nutrition, effects of treatment (pneumonia is common) 3) Damage to vital organ or system by either primary or secondary tumour
