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Tumours of the GIT - Coggle Diagram

- - - - Hyperplastic
      - Fundic Gland
      - Adenoma
  - - - Mean age 55
      - Male 2:1
    - - Mean age 48
      - Equal sex
  - - - Diet
      - Low socio-economic status
      - Smoking
    - - Chronic gastritis
      - Partial gastrectomy
      - Adenomas
    - - Blood group A
      - Family hx of gastric cancer
      - HNPCC syndrome
  - - - Depth of invasion
      - Macroscopic growth pattern
      - Histological subtype
- - - - Hyperplastic polyps
        
        Morphology
        
        Small
        
        Sessile (immobile)
        
        Rectum 50% - left sided
        
        Serrated
        
        No dysplasia or malignant potential
        
        Right sided
        
        Less common
        
        Large
        
        K-RAS mutation
      - Juvenile polyps
        
        Morphology
        
        Peduncled with ulceration
        
        Hamartomatous
        
        Rectum
        
        Juvenile Polyposis syndrome
        
        Autosomal dominant
        
        ↑Risk of GI carcinoma
      - Peutz-Jeghers Polyps
    - - Adenoma
        
        Tubular Adenoma
        
        Tubulovillous adenoma
        
        Villous adenoma
  - - - Neuroendocrine (Carcinoid Tumours)
      - Lymphoma
      - Mesenchymal Tumours
      - Adenocarcinoma
    - - Peak 60-79 ys
      - 10% of cancer deaths in the US
      - 1-3% ass with Familial syndrome or Ulcerative colitis
      - Arise in polyps and produce symptoms early
    - - Chromosomal Instability (CIN)
        
        Inherited mutation of APC Gene = FAP
        
        Aquired / sporadic
      - Microsatellite Instability (MSI)
        
        Inherited of mismatch repair genes
        
        HNPCC / Lynch syndrome
        
        Aquired/ Sporadic
      - CIMP and Serrated pathways
  - - - Classic Form (>100 polyps)
      - Attenuated Form (>30 polyps)
      - Garndener Syndrome
        
        Classic + osteomas, epidermal cysts, fibromatosis
      - Turcot Syndrome
        
        Classic + brain tumours
    - - Genetics
        
        5 mismatch repair genes
        
        HMSH2
        
        HMLH1
        
        MSH6
        
        HPMS1
        
        HPMS2
      - Pathogenesis
        
        Mutation results in microsatelite instability
        
        Rapid progression from incident adenoma to cancer
        
        Distinc pathological features
        Right sided
        Mucinous
        Poorly differentiated
        Lymphocytic host response
        
        Extra intestinal tumours
        Endometrium
        Stomach
  - - - Large Genomic Alterations
        
        Aneuploidy
        
        Gain and loss of chromosomal regions
      - Mutation requirement for malignancy
        4-10 mutations
        
        APC (Adenomatous polyposis coli)
        
        DCC (Deleted in Colorectal Cancer)
        
        KRAS (Kirsten rat sarcoma viral oncogene homolog)
        
        Prevalence
        
        10% of adenoma
        
        50% of adenomas with severe dysplasia
        
        35-45% carcinomas
        
        Larger polyps
        
        Mutation Sites
        
        Codon 12, 13, 61
        
        Dowstream effector of EGFR (Epithelial growth factor regulator)
        
        Clinical Significance
        
        Predictive marker for effectiveness of
        
        Cetuximab
        
        Panitumumab
        
        TP53 (Tumour protein p53)
    - - Mechanism
        
        Inactivation of DNA mismatch repair proteins leads to mutation accumulation
      - Sporadic Colon Carcinoma
        
        MSI due to loss of MLH1 expression by MLH1 promoter methylation
        
        Poorly differentiated
        
        Mucinous origin
        
        Proximal colon compared to HNPCC
        
        Serrated adenomas are precursor lesions
      - HNPCC (Hereditary Nonpolyposis Colorectal cancer)
        
        Inherited mutation of DNA repair gene
      - Prevalence
        
        15-20% of Sporadic colorectal cancers
      - BRAF Mutation
        
        Associated with MSI Pathway
- - - - Hyperplastic
      - Hamartomatous
    - - Adenoma
        
        Ampulla of Vater
        
        25% of small intestine tumours
        
        Occult blood loss
        
        Extend into orifice
  - - - Adenocarcinoma
      - Carcinoid tumour (Neuroendocrine cell tumour)
        
        Location
        
        Appendix > Ileum > Rectum > Stomach
        
        Malignant Predictors
        
        Site
        
        Depth of local penetration
        
        Size (>2cm)
        
        Grade
        
        Clinical Features
        
        Many asymptomatic
        
        Obstruction
        
        Endocrinopathies / syndromes
        
        Zollinger - Ellison syndrome
        
        Cushing syndrome
        
        Carcinoid syndrome (Excess 5-HT)
    - - GIST
        
        Presentation
        
        Non-sepcific symptoms
        
        Epidemiology
        
        50s-60s
        
        Male = female
        
        Malignant Predictors
        
        Site
        
        Size (>5cm)
        
        Miotic count
        
        Miettenin lasota
        
        Pathology
        
        Well circumscribed submucosal
        
        Spindle cell / epitheliod
        
        Activating mutation of proto-oncogene C-KIT
        Overexpression of Tyrosine Kinase receptor CD117
        Tyrosine kinase PDGFRA
        
        Resistant mutations to targeted therapy
      - Lipoma
      - Neuroma
  - - - Genetics
        
        Autosomal Dominant
      - Presentation
        
        Hamartomatous polyps throughout GIT
        
        Melanotic mucosal and cutaneous pigmentation
        
        ↑ Risk of carcinomas of the pancreas, breast, lung, uterus
- - - - Risk Factors
        
        Chronic Irritation
        
        Smoking
        
        Achalasia
        
        Oesophageal diverticuli
        
        Genetic
        
        Tylosis: Hoewl-Evans syndrome
        
        Others
        
        Plummer-vinson syndrome AKA Paterson-Brown-Kelly syndrome or Sideropenic dysplasgia
        
        Deficiency of Vit A,C, Riboflavin
      - Pathogenesis
        
        Nutritional deficiencies potentiate environmantal carcinogens
        
        More than 50% p53 point mutations
        
        Mutations in p16, allelic loss in other chromosomes
        
        No role for K-RAS or APC mutations
      - Morphology
        
        20% upper 1/3
        50% middle
        30% lower 1/3
        
        Exphytic 60%
        Flat 15%
        Excavated 35%
        
        Most moderately-well differentiated
    - - Risk Factors
        
        GERD / GORD
        
        Genetic
        
        Functional inactivation of p53
        
        7% familial
        
        Obesity
        
        Barrett's oesophagus
        
        White
        
        Male
        
        Over 50yrs
        
        Over 5 yr hx GORD
      - Barrett's Oesophagus
        
        Metaplastic columnar epithelium replaces normal squamous epithelium of distal oesophagus
        
        8-11% with symptomatic GORD
        
        Visible at endoscopy as red, velvety mucosa
        
        Short or long segment
        
        Risk of Dysplasia + Adenocarcinoma
        
        Low grade 4% per yr
        
        High grade 1% per yr
        
        Adenocarcinoma 0.5% per yr
      - Morphology
        
        Lower 1/3 of oesophagus
        
        Often invade gastric cardia
        
        Nodular or diffusely infiltrative masses
        
        Mucin-producing intestinal-type adenocarcinoma
      - Clinical Features
        
        Late syptoms
        
        Dysphagia
        
        Weight loss
        
        Odynophagia
        
        Aspiration
        
        Quick spread
        
        50% diagnosed unsectable or with mets