malignant tumours of git
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8/6/2019 Malignant Tumours of GIT
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a gnan umours o
Esophageal Carcinoma
Squamous Cell Carcinoma Adenocarcinoma
Risk Factors
Esophageal disorders
y Long-standing esophagitisy Achalasiay Plummer-Vinson syndrome
(retarded passage of food prolonging mucosal exposure to carcinogens)
Lifestyle (correlated with abnormal TP53 gene)
y Alcoholy Tobacco abuseDietary
y Deficiency ofVitamin A, C, Riboflavin, B1, B6, Trace metal Zn, molybdenumy Content ofnitrites, nitrosaminesAssociation with HPV
Molecular changes TP53 gene
K-RAS mutations
Barrett esophagus recognized precursor of esophageal adenocaricnoma
(30-40% risk to develop adenocarcinoma)
TP53mutation
Definition
Replacement ofnormal distal stratified squamous epithelium by
metaplastic goblet cellcontaining columnar epithelium (intestinal metaplasia)
Pathogenesis
Long, recurrent gastro-esophageal reflux
Inflammation
Ulceration
Healing by re-epithelialisation from reserve cells
Differentiate to columnar epithelium
(in acid environment)(caused by acid reflux)
Clinical
Insidious in onset
Dysphagia
Obstruction gradually, late
Weight loss
Anorexia
Fatigue
Pain on swallowing
Prognosis
Surgical excision is rarely curative
(extensive invasion of rich lymphatic
network of esophagus, adjacent
structures)
Morphology
Early Lesions Late Stage
Small
Gray-whitePlaque-like thickening
Elevation of mucosa
Polypoidal exophytic mass
Necrotising ulcer(erode bronchus, aorta)
Diffuse infiltrative
y Thick, rigid wally Narrowing of lumen
Site
Upper-third 20%
Mid-third 50%
Lower-third 30%
Morphology
Flat, raised patches
Large nodular masses, deep ulcerative, diffusely infiltrative
MicroscopicMucin producing glandular tumour (exhibiting intestinal-type features)
Site
Lower-third
May invade gastriccardia
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Gastric Carcinoma (Adenocarcinoma)
Most common malignancy in stomach (90-95%)
y Lymphoma (4%)y Carcinoid (3%)y Mesenchymal spindle cell tumour (2%)Types
Intestinal Diffuse
Chronic gastritis
Arise from gastric mucous cells
(undergone intestinal metaplasia)
Arise de novo from native gastric
mucous cells
Not associated with chronic gastritis
Occurs after 50 y/o Occurs in earlier age
Male : Female = 2 : 1 Poorly differentiated
Risk Factors
Intestinal Diffuse
Diet (nitrites)
Smoked fish
Pickled vegetables
Salt intake
Fruits, vegetables
(antioxidants inhibit nitrosation)
Chronic gastritis
(with intestinal metaplasia)
H. pylori infection
Pernicious anaemia
Altered anatomy
Subtotal distal gastrectomy
Rare inherited mutation E-cadherin
H. pylori (absent)
Chronic gastritis (absent)
Morphology
Site
Antrum (50-60%)
Cardia (25%)
Body, Fundus
Lesser curvature (40%)
Greater curvature (12%)
Early gastric carcinoma
Confined to mucosa, submucosa
Perigastric lymph node metastasis
Exophytic
Protrusion into lumen
Flat, Depressed
No obvious tumour mass
Effacement of surface mucosal pattern
Excavated
Resembles chronic peptic ulcer (but has heaped-up margins)
Linitis plasticLeather bottle stomach
Thick, rigid (due to diffuse infiltration)
Microscopic
Intestinal Diffuse
Malignant cells form intestinal glands
resembling colonic adenocarcinoma
Scattered signet-ring individual cells
Small clusters in infiltrative growth
Krukenberg tumour
Penetrate wall
Involve serosa, regional, distant lymph nodes, seed intraperitoneally
Clinical
Early Carcinoma Advanced Carcinoma
Asymptomatic (generally) Abdominal discomfort
Weight
Dysphagia (cardia)
Obstructive (pylorus)
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Intestinal Polyps
Polyp
Nodular mass that protrude into lumen of gut
May be sessile, pedunculated
Epithelial Mesenchymal
Non-Neoplastic (Benign)
Hyperplastic
Hammartomatous
Inflammatory
Lymphoid
Neoplastic
Benign adenoma
Malignant adenocarcinoma,
carcinoid, anal zone carcinoma
Gastrointestinal stromal tumours
(GIST)
Benign, malignant
Lipoma
Neuroma
Angioma
Kaposi sarcoma
Lymphoma
Familial Polyposis Syndromes
Uncommon autosomal dominant disorders
Familial adenomatous polyposis (FAP)
y Minimum 100 polyps for diagnosisy Typically 500-2500Appear during adolescence
Colon carcinoma 100% by midlife
Genetic defect in APC gene (chromosome 5q21)
Gardner syndrome, Turcot syndrome
y Occurrence of extraintestinal tumoursy Eg. osteoma, glioma, soft tissue tumoursAdenocarcinoma of Small Intestine
No of deaths 1% of GIT malignancies
Gross
Napkin-ring, polypoid fungating mass
Site
Duodenum (most arise)
Clinical
Cramping pain
Nausea
Vomiting
Weight
Penetrated bowel wall
y Invaded mesentery, other segmentsy Regional lymph nodes, distant sitesPeriampullary tumours (obstructive jaundice early)
Treatment
Wide en-block excision (yields 70%5 year survival rate)
Colorectal Carcinoma
Adenocarcinomas (98% ofcoloniccancers)
60-70 y/o (peak)
Coloniccarcinoma in young, associated with
y Ulcerative colitisy Polyposis syndromeDietary factors
y Vegetables (unabsorbable fibers)y Carbohydrates (refined)y Fat (meat)y Micronutrients Vitamins A, C, E (oxygen radical scavenger)Aspirin, NSAIDs (protective effect against colon cancer)
Clinical
Asymptomatic (for years)Right side fatigue, weakness, iron deficiency
Left side Occult bleeding, bowel habit change, left lower quadrant discomfort
Spread (By direct extension into adjacent organs)
Metastasis via lymphatic, blood regional l/n, liver, lung, bones
Single most important prognostic indicator - stage
Morphology (ColonicAdenocarcinoma)
Site
y Caecum, ascending colon (25%)y Rectum, distal sigmoid (25%)y Descending colon, proximal sigmoid (25%)y Scattered elsewhere (25%)Tumours
Proximal Colon Distal Colon
Polypoid, exophytic
Obstruction uncommon
Annular
Napkin-ring constrictions of bowel
Narrows lumina
Margins are heaped up
Microscopic
Well-differentiated
Moderately-differentiated
Undifferentiated
Most of them produce mucin
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GI Carcinoids
Derived from epithelial stem cells (in mucosal crypts)
Designated endocrine tumours
Common sites
Appendix (most common)
Small intestine (ileum)
Rectum
Stomach
Colon
Peak incidence
6th
decade
Clinical
Asymptomatic (frequently)
Rarely symptoms secondary to angulation, obstruction
Carcinoid syndrome
Gastric
y Zollinger-Ellison syndromey Cushingy HyperinsulinismAppendiceal, rectal carcinoids (metastasize infrequently)
Gross
Appendix Stomach, Ileal Carcinoids
Bulbous swelling of tip
Obliterate lumen
Multicentric (frequently)
Solitary elsewhere
Elsewhere
Intramural
Submucosal
Small polypoid
Plateau-like elevation (rarely > 3cm)
Solid yellow-tan appearance
Very firm (due to desmoplasia)
Histology
Discrete islands
Trabeculae
Strands
Glands
Sheets
Round-to-oval stippled nucleus
Scanty pink granular cytoplasm
Mitosis infrequent, absent
Most carcinoids contain chromogranin A, synaptophysin, NSE
Cytoplasmic dense-core granules (membrane-bound secretory granules)
GI Lymphomas
Gut is most common extranodal location of lymphomas (1-4% of all GI malign.)
Definition (primary)
No evidence of liver, spleen, bone marrow involvement at diagnosis
Regional lymph node involvement may present
MALT
Adults, equal sex
Sites
y Stomach (55%)y Small intestine (25-30%)y Proximal colon (10-15%)y Distal colon (10%)MALT lymphomas arise from B cells
Associated with H. pylori chronic gastritis
Coeliac disease (associated with risk of T-cell lymphomas)
Gastrointestinal Stromal Tumours (GIST)
Tumours of malignant potential
Derived from pacemaker cells of Cajal
Include vast majority of mesenchymal derived stromal tumours of entire GIT
Tumour cells express c-kit oncogene (CD 117)
y Encode tyrosine kinasey Regulate cell proliferation, apoptosisCriteria for malignancy size, necrosis,mitosis
Gastric GISTS tend to behave in a benign fashion
Small, large bowel GISTS are more commonly malignant
Pathology
Gastric GIST (mostly submucosal)
Whorled appearance
MicroscopicSpindle cells arranged in whorls
Interlacing bundles in collagenous stroma
Epitheloid with polyhedral cells
Eosinophiliccytoplasm
Treatment
Surgical excision
Tyrosine kinase inhibitorsSTI-571 (Gleevec)