Malignant Tumours of GIT

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)

Documents

Malignant Tumours of GIT