Neoplasia Flashcards
What percentage of Australians die from maligancy? What about cardiovascular disease?
30% and 33% respectively
What does transcoelomic metastasis refer to?
Metatasis into pleural, peritoneal or mediastinal cavity
What cell lineage does adeno refer to?
Glandular
What does carcinoma refer to?
Malignant epithelial cell
Is a benign tumour a cancer?
NO, Cancers are malignant lesions
What histological features do tumours of glandular origins sometimes exhibit?
Glandular lumen
Formation of mucin
Signet ring cells
What histological features do tumours of squamous origins sometimes exhibit?
Keratinisation
Intercalated bridges
Eosinophilic cytoplasm
What types of proteins can carcinogenic mutations effect?
Growth factors
Growth factor receptors
Protein involved in signal transduction
Nucleur-regulatory proteins
Cell cycle regulators
What is the difference between a proto-oncogene and an oncogene?
A oncogene is a mutated form of an proto-oncogene that no longer requires normal growth-promoting signals
What are some common features of malignant tumours?
Locally invasive, destructive growth
Often not well circumsized growth
Frequently induce desmoplasia in stroma they invade
Sometimes have necrosis
Variable differentiation - poor, moderate and well
Potential to metatasize
Define dysplasia
Dysplasia is a general term for abnormal growth (alteration in size, growth or organisation of cells), can is used not only in the context of tumours
How is epigenetic control exerted on TSGs?
DNA is methylated so that the TSG can not be expressed
What are two important factors in angiogenesis?
VEGFs and VEGF-Rs
What is a adenocarcinoma?
Neoplasia of a epithelium of glandular origin
What features do well differentiated cell have?
Resemble their cell of origin well
Low cytological atpyia
Low architectural disorganisation
What cytotic features do neoplasic cells demonstrate?
Larger nuclei
Hyperchromatic nuclei
Pleomorphic nuclei
Prominent necleoli
Coarser nuclear chromatin
More mitosis, abnormal mitotic figures
Architectural disorganisation
What type of genes are BRCA1 and BRCA2?
Genes involved in DNA repair and that are associated with increased risk of breast cancer
What are some common TSGs?
P53, Rb, APC, PTEN
What are some histological features of adenocarcinomas?
They tend to form lumens and attempt to secrete mucus
What are some common features of benign tumours?
Local expansile,
Slow growthing,
Often well circumscribed
Unable to metastasize
Rarely life threatening (unless they’re in a critial position)
Well differentiated cells (ie look like mature cells)
What is a surgical resection
When part or all of an organ is removed to prevent spread of a cancer
Define paraneoplastic effects?
Unusual effects that a tumour produces for unknown reasons and that aren’t normally associated with their cell type.
What is the supposed mechanism of weight loss in cancer patients?
TNF-alpha and IL-1 produced by tumour cells or within their local environment causes an increase in the basal metabolic rate.
What is a lymphona?
Cancer of T or B cells
What are the top 5 most common cancers in Australian women?
Brest
Bowel
Melanoma
Lung
Lymphoma
What types of DNA mutation can occur?
Point mutations
Replication in the number of genes
Chromosomal rearrangements
What features do poorly differentiated cell have?
Do not resemble their cells of origin well
High cytological atypia
High architectural disorganisation
What are some common sites of tumour metastasis?
Liver, Brain, Bone, Lung, LNs
Which are more aggressive malignancies, well or poorly differentiated cells?
Poorly are more aggressive
What is targeted therapy?
A method of treating malignancies where specific cell factors such an ongene products are targeted to block their carcinogenic effect. This is less toxic to normal cells cf to tradition chemotherapy. It depends on the genotype/phenotype of the individual tumour. Small molecules or antibodies can be used.
What are some investigations used to detect/diagnose cancer?
History and clinical examination
Blood - full blood, liver enzyme, Tumour markers (generally used for follow ups)
Radiology - xray, CT
Endoscopy
Tissue sampling
How do tumour cells achieve replicative immortality?
Activated Telomerase to increase the length of chromosomal telomeres therefore allowing mitosis to continue.
What are some examples of paraneoplastic effects?
Hypercalaemia in SCC lung cancers
Dermatologic in SCC
Clubbing in lung cancer
Cushing’s syndrome
What is a polyp?
Glandular, dysplasic lesion often arising from epithelia
What are the emerging hallmarks of cancer?
Immune evasion
Promote inflammation
Genome instability and mutation
Deregulating cellular energies
What types of lung cancers are typically located centrally in the lung? What type are more peripheral?
SSC and small small cell carcinomas are central and adenocarcinomas peripheral
How can a metastasis to the pertioneal cavity present?
Swelling of the abdomen due to overproduction of serous fluid
What are some histological features of small cell carcinomas?
small cells , not particularly pleomorphic, fine chromatin, not necessarily nucleoli.
Which cytokine is released to help a tumour to produce stroma?
TGF-beta
What is the average tumour doubling time for clinically detectable lung and bowel cancer?
2 to 3 months
What is the name given to tumour stroma?
Desmoplasic stroma
What are the 4 mains types of lung carcinomas?
Adenocarcinoma
Small cell carcinoma
Large cell (undifferentiated) carcinoma
Squamous cell carcinoma
What cell lineage does leiomyo refer to?
Smooth muscle
What is the most common lung cancer in non-smokers?
Adenocarcinomas
What are the top 5 most common cancers in Australian men?
Prostate
Bowel
Lung
Melanoma
Lymphoma
What are some common paediatric cancers?
Certain leukaemias
Certain brain cancers
Neuroblastoma
Wilm’s tumor
Certain lymphomas
Which type of neoplasia demonstrates a greater amount of cytological atypia?
Malignant
What are some histological features of large cell carcinomas?
Large sheets of undifferentiated epithelial cells.
What are some high growth factor tumours?
Lymphona, small cell carcinoma, leukaemias
What are some source of genetic mutations that contribute to neoplasm?
Carcinogenic agents
- microbes
- radiation
- chemical eg cigarette smoke
Inherited
- abnoral tumour suppressor genes
- Defective DNA repair
Can surgery be used to treat small cell carcinomas?
No, they are very aggressive
What is a neoplasia?
A new, uncontrolled growth. Includes benign growths.
What are some histological features of squamous cell carcinomas?
They can have keratinization and a lot of eosinophilic cytoplasm
What percentage of world wide cancer deaths are lung cancer?
18%
What is the mechanism of metastasis?
Cellular adherins are disrupted allowing cells to escape their normal niche. Ie. Cadherins, beta-catenin and connexins
What suffix is given to benign cells?
-oma
What are the four classes of normal regulatory genes are that mutated in carcinogenesis?
Growth promoting proto-ongenes
Growth suppressing tumour suppressor genes
Genes that regulate apoptosis
Genes involved in DNA repair
What can IHC do used for in neoplasm investigation?
Differentiating primary from metastatic tumours
Identifying certain proteins for specific treatments
What is the clinical presentation of lung cancer?
Cough, dyspnoea, wheeze, haemoptysis, pneumonia, anorexia, fatigue
Intraepithelial neoplasia is another term for what type of lesions?
Premalignant epithelial lesions
What does tumour stroma typically contain?
Fibroblasts, immune cells, ECM, endothelial cells, soluble molecules
How does mutant RAS act as a oncogene?
Mutant RAS is not normally inactivated after responding to a growth factor therefore there is sustained activation of transcription factors for cell cylce progression.
What do you need to know once diagnosis of malignancy is made?
Cell linear
Grade
Stage
Presence of lymphovascular invasion
What are the classic hallmarks of cancer?
Sustaining proliferative signals
Avoid apoptosis
Induce angiogenesis
Facilitation of invasion and metastasis
Replicative Immortality
Avoid growth suppressors
How many copies of the an oncogene must be abnormal cf to TSGs?
1 allele compared to both alleles for TSGs
What are some ways in which cancer causes death?
Cachexia
Secondary infection
Damage to a vital organ directly caused by the primary or secondary tumour
What does sarcoma refer to?
Cancer of mesenchymal origin
What are some common oncogene?
Ras, Myc and Her2-neu
What are some clinical features indicative of metastasis?
Jaundice
Lymphadenopathy
Bone pain or features related to hypercalcaemia
Seizures
What does the “stage” of a cancer refer to?
The progression of a maligancy in terms of local spread and metastasis
