L4 - Overview of Neoplasia History and Classification Flashcards
Tumour
Swelling. Commonly used to describe neoplasia.
Neoplasm
A new and abnormal growth of tissue in a part of the body, especially as a characteristic of cancer
Hyperplasia
- Increase in number of cells.
* Benign, usually not neoplastic, reversible.
Hypertrophy
- Increase in size of cells
- No increase in number of cells
- May be physiological or pathological
- Not neoplastic
- e.g. skeletal muscle, cardiac muscle
Metaplasia
- Change from the normal cell type, to another cell type, in response to stimuli, usually noxious.
- Not neoplastic, but if the stimulus persists, may progress to neoplasia in some circumstances.
Dysplasia
- Abnormal cell growth.
- May be neoplastic and pre-malignant.
- May regress
- e.g. Colon adenoma.
Eponymous tumours
- Hodgkin lymphoma
- Burkitt Lymphoma
- Ewing sarcoma
- Kaposi sarcoma
Other neoplasms
• Melanoma, Lymphoma, Neuroblastoma, Nephroblastoma
Differentiation
- The extent to which tumour cells recapitulate normal cells in structure and/or function.
- Benign tumours are generally well differentiated, and are only recognised as tumours because of formation of an abnormal mass, or abnormalities in hormones or genetics
- Malignant tumours are classified as well, moderately, poorly differentiated, or undifferentiated/anaplastic.
Pleomorphism
- Variation in size and shape of the cell or the nucleus (or both).
- Pleomorphism increases with loss of differentiation.
Nuclear atypia of neoplastic cells
- Hyperchromasia
- Change in nuclear cytoplasmic ratio
- Mitotic activity
- Loss of polarity
Hyperchromasia
Dark nuclei due to increased amount of chromatin, in same volume of nucleus. (Increased “blueness” on H+ E stained sections).
Change in nuclear cytoplasmic ratio
Usually increased, ie the nucleus increases in size in relation to the cytoplasm
Mitotic activity
Usually more helpful in malignant tumours. Particularly if bizarre mitoses are present
Loss of polarity
Some cells shows polarity of the nucleus (eg glandular epithelial cells). In neoplasia, the cells may lose this polarity.
Benign Neoplasms
- Slow growing
- Locally confined
- Cause symptoms by mass effect, e.g. compression of adjacent structures, or production of hormones with distant effects.
- May be asymptomatic until very large in some sites.
- May cause significant problems, even when very small (eg pituitary adenomas)
- Cured by surgical excision.
- Unlikely to cause death, except where the mass effects or hormone production affect vital functions. (eg benign tumours in brain stem, functional pituitary adenomas).
Malignant Neoplasms
- Tumour is not confined
- Capable of invasion of adjacent organs/structures
- Capable of distant metastasis (spread)
- Only curable if completely excised before spread and/or sensitive to appropriate treatment.
- Cytologically more atypical than benign tumours
- May be more mitotically active than benign tumours, especially atypical mitoses.
Spread of malignant tumours
- Direct invasion
- Lymphatic invasion (to lymph nodes)
- Vascular invasion (to other organs in the vascular pathway, eg colonic adenocarcinoma spreading to the liver)
- Transcoelomic spread (eg gastric carcinoma spreading through the peritoneal cavity to the ovary “Krukenberg”tumour
Grade
A measure of how aggressively a tumour behaves
• Grade generally corresponds with differentiation and mitotic activity
Stage
How far the tumour has advanced at the time of diagnosis
- AJCC (TNM staging)
- Features of the Tumour (Size, extent of local invasion)
- Nodal involvement
- Metastasis
Tests for Lipoma vs Liposarcoma
- FISH for specific translocations
- Immunohistochemistry can be used as a surrogate (MDM2, CDK4)
- Cytogenetics
Lymphoma tests
- PCR; IgH gene rearrangements, T Cell receptor gene rearrangements to prove clonality.
- FISH, for specific translocations eg t14:18, in follicular lymphoma (over-expression of bcl2, which inhibits apoptosis)
Lung carcinomas and melanoma metastases
- Knowledge of the molecular basis of carcinogenesis can provide prognostic and therapeutic information
- Lung adenocarcinomas may be caused by EGFR mutations. There are targeted therapies available which provided therapeutic benefit if the mutation is present (gefitinib). (Although the drugs don’t work if Kras mutations also present.)
- Similar targeted therapy is available for melanomas that harbour BRAF mutations (eg vemurafinib).
Breast Carcinoma
- Tissue microarray (“Gene Chips”) were used in the reclassification of breast carcinoma into types based on the genetics of the tumours, rather than just the histologic appearance.
- Microarray technology also provides the basis for a move towards “personalised” cancer therapy, in which each cancer can be typed based on a large number of known mutations and matched against currently available targeted therapies.
