Characteristics of major tumour types

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Blood Science Mind Map on Characteristics of major tumour types, created by maisie_oj on 29/04/2013.
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Mind Map by maisie_oj, updated more than 1 year ago
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Created by maisie_oj over 11 years ago
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Resource summary

Characteristics of major tumour types
  1. Commonest cancers
    1. Males
      1. Lung/bronchus
        1. Prostate
          1. Colorectal
            1. Pancreas
              1. Non-hodgkins lymphoma
              2. Females
                1. Breast
                  1. Lung/bronchus
                    1. Colorectal
                      1. Pancreas
                        1. Ovary
                      2. Lung cancer
                        1. Most common cause of cancer mortality
                          1. Major risk factor is smoking
                            1. Increasing in women (reflecting changing smoking patterns)
                            2. Outcome is uniformly poor - 5yr survival rate in ~15%
                            3. Aetiology and pathogenesis
                              1. Smoking!
                                1. Major carcinogens = polycyclic aromatic hydrocarbons, phenol derivatives and radioactive elements
                                  1. Associated with other tumours: Mouth, larynx, oesophagus, pancreas, kidney, cervix and bladder
                                2. Classification
                                  1. Squamous cell carcinoma - 25-40%
                                    1. Adenocarcinoma - 25-40%
                                      1. Small/"oat" cell carcinoma - 20-25%
                                        1. Large cell carcinoma - 10-15%
                                        2. Squamous cell carcinoma
                                          1. Occurs in the proximal lung
                                            1. Associated with precursor squamous metaplasia
                                              1. Molecular changes
                                                1. p53 mutation
                                                  1. EGFR over expression
                                                    1. Her2/neu over expression
                                                    2. Microscopically - Squamous cell mass often enclosing a keratin pearl
                                                    3. Adenocarcinoma
                                                      1. Occur in the distal lung
                                                        1. Increasing in frequency (particularly in women)
                                                          1. Related to low-tar cigarettes(?)
                                                            1. Metastasise widely
                                                              1. Less frequently associated with smoking than other types
                                                              2. Small cell (aka oat cell) carcinoma
                                                                1. Highly malignant neuroendocrine tumour
                                                                  1. Frequently produce ectopic hormones - e.g. ACTH (= ectopic/paraneocrine Cushing's disease)
                                                                  2. Proximal location - associated with smoking
                                                                    1. Molecular changes
                                                                      1. p53
                                                                        1. RB
                                                                        2. Surgery is ineffective - treated with chemotherapy
                                                                      2. Breast cancer
                                                                        1. Risk factors
                                                                          1. Female
                                                                            1. Age: 75% occur >50yrs, mean age is 64yrs
                                                                              1. Pregnancy: protected if full term, however increased risk of pregnant <30yrs
                                                                                1. Family histroy: Increases with each 1st degree relative
                                                                                  1. Race: lower incidence, but more aggressive disease in Africans
                                                                                  2. Aetiology
                                                                                    1. Uknnown
                                                                                      1. Genetic factors: 5% sue to inherited mutation: BRCA1, BRCA2 and p53
                                                                                        1. Estrogen exposure
                                                                                          1. Oophorectomy reduces risk
                                                                                            1. HRT increases risk - only if unopposed oestrogen
                                                                                            2. Lifestyle (diet, exercise, alcohol etc.)
                                                                                            3. Precursor lesions (progression of tumouregenesis)
                                                                                              1. Normal (non-proliferative changes)
                                                                                                1. Luminal cells, with myoepithelial cells
                                                                                                  1. Germline mutation
                                                                                                    1. Loss of apoptosis
                                                                                                      1. Proliferative disease
                                                                                                        1. Atypical hyperplasia
                                                                                                          1. Sel sufficient growth
                                                                                                            1. Carcinoma in situ
                                                                                                              1. Limitless replication
                                                                                                                1. Invasive carcinoma
                                                                                                                2. Angiogenesis
                                                                                                              2. Genome instability
                                                                                                                1. Loss of growth inhibition
                                                                                                          2. Classification of breast cancer
                                                                                                            1. In-situ
                                                                                                              1. Lobular (affects lobules)
                                                                                                                1. Ductal (ducts)
                                                                                                                  1. High grade DCIS
                                                                                                                    1. Cells no longer resemble normal breast tissue
                                                                                                                      1. Extensive growth within the lumen of the duct
                                                                                                                      2. Fast proliferation!
                                                                                                                      3. Intermediate grade DCIS
                                                                                                                        1. Low grade DCIS
                                                                                                                          1. Cells appear somewhat normal, but abnormal growth noticeable
                                                                                                                            1. Calcification within the lumen
                                                                                                                              1. Diagnostic (seen with microscope)
                                                                                                                            2. Two forms
                                                                                                                              1. Cribiform
                                                                                                                                1. Micropapillary
                                                                                                                              2. Paget's disease
                                                                                                                                1. Malignant, irregular cells (Pagte cells) found in the areola and niple tissue that indicate an underlying breast cancer
                                                                                                                            3. Invasive
                                                                                                                              1. Lobular
                                                                                                                                1. Low frequency (15%), with 54% 10yr survival
                                                                                                                                  1. Second most common brest tumour
                                                                                                                                    1. Multifocality
                                                                                                                                      1. Metastasises (to serous cavities and abdominal organs)
                                                                                                                                        1. Lacks E-cadherin (next lecture)
                                                                                                                                      2. Ductal
                                                                                                                                        1. No special type
                                                                                                                                          1. High frequency (47%) with 47% 10yr survival
                                                                                                                                            1. Poorest prognosis
                                                                                                                                            2. Special types
                                                                                                                                              1. Tubular
                                                                                                                                                1. Low frquency (2.3%), with good prognosis (90% 10yr survival)
                                                                                                                                                  1. Low grade tubules occupy >90% of the tumour
                                                                                                                                                    1. Sometimes with cribiform elements (<50%)
                                                                                                                                                    2. Excellent prognosis
                                                                                                                                                    3. Many others; with low frequency and mixed survival rates
                                                                                                                                              2. Prognostic factors in breast cancer
                                                                                                                                                1. Tumour type (invasive ductal vs. tubular form)
                                                                                                                                                  1. Tumour grade
                                                                                                                                                    1. Tubule formation - scored as: 1 (>75% tubules); 2 (50% tubules) and 3 (little-no tubules)
                                                                                                                                                      1. Nuclear pleomorphism - scored as: 1-3 (based on appearance and variation of cells)
                                                                                                                                                        1. Mitotic counts - scored as: 1-3 (depending on the mitotic activity)
                                                                                                                                                          1. Lower scores = better prognosis
                                                                                                                                                          2. Tumour size
                                                                                                                                                            1. 1-9mm is best prognosis
                                                                                                                                                              1. >20mm significantly reduced prognosis
                                                                                                                                                                1. >50mm worst prognosis
                                                                                                                                                                2. Tumour spread (lymph node involvement)
                                                                                                                                                                  1. Better prognosis if no involvement, worse the more lymph nodes involved and metastasis
                                                                                                                                                                  2. Biologcial markers
                                                                                                                                                                    1. HER2 / ER
                                                                                                                                                                      1. Tested by IHC and FISH
                                                                                                                                                                3. Colorectal cancer
                                                                                                                                                                  1. The majority of colorectal cancers are glandular
                                                                                                                                                                    1. Arise from benign adenomas (polyps)
                                                                                                                                                                    2. Well categorised, multistep progression
                                                                                                                                                                      1. Adeonomas
                                                                                                                                                                        1. Can be tubular or villous
                                                                                                                                                                          1. Tubular = classic polyp form (brocoli)
                                                                                                                                                                            1. Villous = hyperperplastic villous structure (finger-like)
                                                                                                                                                                            2. Behaviour of adenomas
                                                                                                                                                                              1. Precursor to carcinoma
                                                                                                                                                                                1. Likelyhood of progression
                                                                                                                                                                                  1. Villous > tubular
                                                                                                                                                                                    1. Size
                                                                                                                                                                                      1. Degree of dysplasia (disorganised structure)
                                                                                                                                                                                        1. Familial adenomatous polyposis (FAP)
                                                                                                                                                                                          1. Germline mutation in APC (involved in beta-catenin signalling)
                                                                                                                                                                                            1. Causes dysregulated growth of colorectal glandualr tissue - results in hundreds of polp-adenomas by an early age
                                                                                                                                                                                              1. Develop invasive carcinoma by mid-20's
                                                                                                                                                                                    2. Progression of colorectal cancer
                                                                                                                                                                                      1. Normal colon
                                                                                                                                                                                        1. Germline (inherited)/somatic (acquired) mutation of supressor genes (first hit)
                                                                                                                                                                                          1. E.g. APC
                                                                                                                                                                                            1. Mucosa at risk
                                                                                                                                                                                              1. Methylation abnormalities and inactivation of normal alleles
                                                                                                                                                                                                1. Adenoma (benign) formation
                                                                                                                                                                                                  1. Proto oncogene mutations (e.g. K-RAS)
                                                                                                                                                                                                    1. Homozygous loss (LOH) of additional supressor genes, with overexpression of COX-2
                                                                                                                                                                                                      1. E.g. p53
                                                                                                                                                                                                        1. Adenocarcinoma
                                                                                                                                                                                                          1. Additional mutations and gross chromosmal alterations (e.g. telomerase reactivation)
                                                                                                                                                                                                            1. Invades the deeper layers (e.g. submucosa, muscularis propria) of the bowel wall
                                                                                                                                                                                                              1. Staged using DUke's staging
                                                                                                                                                                                                                1. Strong relationship to the outcome
                                                                                                                                                                                                                  1. T(IS) - adenocarcinoma restricted to mucosa
                                                                                                                                                                                                                    1. T(1) - Breaches muscularis mucosae and enters the submucosa
                                                                                                                                                                                                                      1. T(2) - Breaches the muscularis propria (external muscle layer of the bowel wall)
                                                                                                                                                                                                                        1. T(3) - Breaches the external serosa (membrane surrounding the bowel)
                                                                                                                                                                                                    2. Second pathway
                                                                                                                                                                                                      1. Microsatelite instability pathway (mutations in mismatch repair genes)
                                                                                                                                                                                                        1. Causes hereditary non-polyposis coli carcinoma
                                                                                                                                                                                                          1. Not preceeded by adenoma formation
                                                                                                                                                                                                            1. Arises due to mutations in DNA mismatch repair genes
                                                                                                                                                                                                              1. When DNA replicates mismatch repair genes act as 'spell checkers'
                                                                                                                                                                                                                1. With mutated MMR genes - mistakes accumulate and results in numerous mutations to supressor genes and oncogenes
                                                                                                                                                                                                                2. Genes affected
                                                                                                                                                                                                                  1. MSH2, MSH6, MLH1 and PMS2
                                                                                                                                                                                                      2. Aetiology
                                                                                                                                                                                                        1. Age of greatest risk: 60-79yrs
                                                                                                                                                                                                          1. Dietary factors implicated (much lower incidence in South america and Africa
                                                                                                                                                                                                            1. Low fibre and high red meat diets most at risk
                                                                                                                                                                                                        2. Cervical carcinoma
                                                                                                                                                                                                          1. Occurs at the endocervical transformation zone
                                                                                                                                                                                                            1. Columnar epithelium of the vagina -> squamous epithelium of the cervix
                                                                                                                                                                                                            2. Development
                                                                                                                                                                                                              1. Normal
                                                                                                                                                                                                                1. Cervical intraepithelial neoplasia (CIN) 1
                                                                                                                                                                                                                  1. Very mil/mild dysplasia (proliferative phase, with immunosupression)
                                                                                                                                                                                                                    1. CIN 2
                                                                                                                                                                                                                      1. Moderate dysplasia, with pro-angiogenic epithelial-stromal genomic signature
                                                                                                                                                                                                                        1. CIN 3
                                                                                                                                                                                                                          1. Severe dysplasia -> carcinoma in situ
                                                                                                                                                                                                                            1. Invasive carcinoma
                                                                                                                                                                                                                    2. Cause = HPV (see cancer lectures)
                                                                                                                                                                                                                    3. Skin tumours
                                                                                                                                                                                                                      1. Commonest cancer, but generally the lowest mortality (except melanoma)
                                                                                                                                                                                                                        1. Important types are
                                                                                                                                                                                                                          1. Squamous cell carcinoma
                                                                                                                                                                                                                            1. Cancer arising in the epithelial tissue of the skin
                                                                                                                                                                                                                              1. Microscopically
                                                                                                                                                                                                                                1. Lymphocyte infiltration of the epidermis
                                                                                                                                                                                                                                  1. Reduced stromal tissue
                                                                                                                                                                                                                                    1. Nests of squamous cells with keratin pearls
                                                                                                                                                                                                                                      1. Abnormal cells (morphology, mitotic activity)
                                                                                                                                                                                                                                  2. Basal cell carcinoma
                                                                                                                                                                                                                                    1. Tumour arising from the basal layer of the epidermis
                                                                                                                                                                                                                                      1. Microscopically
                                                                                                                                                                                                                                        1. Clusters of tumour cells extending through the dermis
                                                                                                                                                                                                                                          1. Reduced stroma
                                                                                                                                                                                                                                            1. Normal appearance basal cells (in palisades at periphery of tumour cell nest) and spindle-shaped cells in the middle of tumour cell nests
                                                                                                                                                                                                                                          2. (Malignant) melanoma
                                                                                                                                                                                                                                            1. Benign = naevus (mole)
                                                                                                                                                                                                                                              1. Pigmented lesions
                                                                                                                                                                                                                                                1. Frequently asymptomatic
                                                                                                                                                                                                                                                  1. Change in size, colour or shape of a pigmented lesion may signal progression
                                                                                                                                                                                                                                                    1. The extent of the vertical growth phase dtermines the biological behaviour
                                                                                                                                                                                                                                                      1. Progression of melanocyte lesions
                                                                                                                                                                                                                                                        1. Normal skin
                                                                                                                                                                                                                                                          1. Spontaneous DNA mutation (UV exposure)
                                                                                                                                                                                                                                                            1. Naevus (benign)
                                                                                                                                                                                                                                                              1. Further mutations
                                                                                                                                                                                                                                                                1. PTEN, CDKN2A
                                                                                                                                                                                                                                                                  1. Radical growth phase (RGP) of melanocytes
                                                                                                                                                                                                                                                                    1. Further mutations
                                                                                                                                                                                                                                                                      1. E.g. AKT
                                                                                                                                                                                                                                                                        1. Vertical growth pahse (VGP), (through basement of epidermis -> into dermis)
                                                                                                                                                                                                                                                                          1. Metastatic melanoma
                                                                                                                                                                                                                                                                  2. E.g. N-RAS or BRAF
                                                                                                                                                                                                                                                                  3. Or epigenetic mutation (e.g. in APC)
                                                                                                                                                                                                                                                            2. Aetiology of SCC and BCC
                                                                                                                                                                                                                                                              1. Both arise in sun-exposed skin
                                                                                                                                                                                                                                                                1. DNA damage through UV light exposure
                                                                                                                                                                                                                                                                2. Immunosupressed individuals have a higher incidence
                                                                                                                                                                                                                                                                  1. Both tumours are invasive, but BCC is not metastatic
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