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Pathology of Pathology of The Stomach - 2The Stomach - 2

Dr.CSBR.Prasad, M.D.,

May-2015-CSBRP

Gastric Polyps and Tumors

• Polyps, nodules or masses that project above the level of the surrounding mucosa

• Polyps may develop as a result of: – Epithelial or stromal cell hyperplasia – Inflammation– Ectopia or

– Neoplasia

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Gastric Polyps and Tumors

• Most common are inflammatory or hyperplastic polyps (70%)

• 50 and 60 years of age

• In association with chronic gastritis

Note: Because the risk of dysplasia correlates with size, polyps larger than 1.5 cm should be resected and examined histologically

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Morphology

Gross:• Less than 1 cm in diameter • Often multiple• Ovoid in shape and have a smooth surfaceMicroscopically, polyps have: • Irregular, cystically dilated, and elongated

foveolar glands • Lamina propria is typically edematous• Variable acute and chronic inflammation and• Surface ulceration may be present

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FIGURE 17-16 Gastric polyps. A, Hyperplastic polyp containing corkscrew-shaped foveolar glands. B, Hyperplastic polyp with ulceration. C, Fundic gland polyp composed of cystically dilated glands lined by parietal, chief, and foveolar cells. D, Gastric adenoma recognized by the presence of epithelial dysplasia.

Gastric polyps

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FUNDIC GLAND POLYPS

• Sporadic

• FAP (familial adenomatous polyposis)

• Secondary to proton pump inhibitor Tx

• More common in females

• CF: Nausea, Vomiting or Epigastric pain

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ADENOMAS

Definition (WHO):

“A circumscribed benign neoplasm composed of tubular and / or villous structures lined by dysplastic epithelium"

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ADENOMAS

• Uncommon neoplasms in the stomach• Common in Japanese • They are almost always antral

Background:– FAP syndrome– Sporadically, (chronic atrophic gastritis)

Clinical Features:

Asymptomatic - accidentally discovered during endoscopy

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ADENOMAS

Gross Findings:

• Sessile / Pedunculated

• Solitary / Multiple

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Sessile & Pedunculated

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ADENOMAS

Microscopic Findings: • Arise within the surface and superficial pit

epithelia• Abnormal neoplastic epithelium is usually

confined to the superficial mucosa • The mid-mucosa contains cysts • Architectural classification (WHO): Patterns:

– Tubular– Villous &– Tubulovillous

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SESSILE TUBULAR ADENOMA

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VILLOUS ADENOMA

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TUBULAR ADENOMA & VILLOUS ADENOMA

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Dysplasias

Two types of dysplastic epithelium: 

• The intestinal type

• The gastric type

Note: These types of dysplasias can occur in adenomas and also in the flat mucosa

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INTESTINAL TYPE DYSPLASIA LOW GRADE / HIGH GRADE

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GASTRIC TYPE DYSPLASIA LOW GRADE / HIGH GRADE

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Malignant potential of Adenomas

• Adenomas <1cm - no malignant potential

• Adenomas >4cms - high malignant potential

• Adenomas with prominent villous component – more malignant potential

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CaseCase: Identify the abnormality. Give your differentials.

Marcos Duarte Siosaki, M.D., and Ana Tarsila Souza, M.D.N Engl J Med 2013; 368:e7February 7, 2013DOI: 10.1056/NEJMicm1204740

Diagnosis:

• Supraclavicular mass - Virchow’s node

• Gatric primary (Gastric carcinoma)

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CaseCase: Identify the abnormality. Give your differentials.

Marcos Duarte Siosaki, M.D., and Ana Tarsila Souza, M.D.N Engl J Med 2013; 368:e7February 7, 2013DOI: 10.1056/NEJMicm1204740

Virchow's node

or Troisier's node

Gastric CarcinomaGastric Carcinoma

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Carcinoma of the stomach is one of the most common

neoplasms in the world, and most are adenocarcinomas

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Gastric Adenocarcinoma

Def: Malignant epithelial tumor with glandular differentiation

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Incidence

• High in Japan (80 cases per 100,000), Costa Rica, Columbia, Chile, and Finland

• Very low in Thailand and many parts of Africa

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Pathogenesis

Dietary Factors:– High salt consumption – Low intake of fresh fruits / vegetables– Smoking / Alcohol– Nitrosamines– Trace elements: selenium, zinc, copper, iron, and

manganese (part of antioxidants)Genetic Factors • Blood group A • Gastric carcinomas display some of the same

genetic alterations observed in other carcinomas

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PathogenesisGastric carcinomas display some of the same genetic alterations

observed in other carcinomas:– mutations in CDH1, which encodes E-cadherin (50% of sporadic cases)– BRCA2 mutations – Microsatellite instability – p53 mutations – hypermethylation of several genes:

• TGFβRII• BAX• IGFRII and • p16/INK4a

• Tumor invasion and metastasis: The synchronous expression of EGF, TGF-alpha and ras p21

• Poorly differentiated gastric carcinomas resulting in linitis plastica: overexpression of TGF-beta, IGF, and PDGF

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Pathogenesis

Predisposing Conditions:• H. pylori infection• Atrophic gastritis• Subtotal gastrectomy with gastrojejunal anastomosis• Immunodeficiency syndromes• Chronic gastric ulcers and • Menetrier's disease

Severe Atrophic Gastritis and Intestinal Metaplasia - by far the most important precursor lesions of gastric carcinoma

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Pathogenesis - H. pylori infection

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Pathogenesis - H. pylori infection

• Cag genes (IL-8 - severe gastritis)

• Vac A (epithelial cell damage)

• fldA gene (MALTOMA)

• H.pylori adhere to Lewis blood group antigen

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Clinical features

• Mean age of presentation is 55 years• M:F = 2:1• Pain abdomen, unrelieved by food• Anorexia• Weight loss• Gastric outlet obstruction

• Virchow's node • Sister Mary Joseph’s nodule

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Gastric Adenocarcinoma

Two major subtypes: 1. Early gastric cancer and 2. Advanced gastric cancer

1. Early gastric carcinoma - which is confined to the mucosa and submucosa, with / without lymph node metastases

2. Advanced gastric cancers - cancers that have invaded into or beyond the muscularis propria, with / without lymph node metastases

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EARLY & ADVANCED GASTRIC CARCINOMA

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EARLY GASTRIC CARCINOMA

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EARLY GASTRIC CARCINOMA

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EARLY GASTRIC CARCINOMA

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ADVANCED GASTRIC CANCER:

POLYPOID LESION

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ADVANCED GASTRIC CANCER

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• Although overall incidence of gastric adenocarcinoma is falling, cancer of the gastric cardia is on the rise

• This is probably related to:– Barrett esophagus, chronic GERD and – Obesity

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Classifications for the gross appearance of gastric carcinoma

• There are a number of classifications. The most widely adopted is that of Borrmann

• Gastric carcinomas are subdivided into four types:– Type I for the well-circumscribed polypoid lesions– Type II for polypoid tumors with marked central ulceration– Type III for the ulcerated tumors with infiltrative margins and– Type IV for the linitis plastica

• The main value of Borrmann's classification is that it eliminates the need of excessive verbal description of the gross appearance of the tumor

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Gastric adenocarcinoma. A, Intestinal-type adenocarcinoma. B, Linitis plastica. May-2015-CSBRP

FIGURE 17-18 Gastric adenocarcinoma. A, Intestinal-type adenocarcinoma composed of columnar, gland-forming cells infiltrating through desmoplastic

stroma. B, Signet-ring cells can be recognized by their large cytoplasmic mucin vacuoles and peripherally displaced, crescent-shaped nuclei.

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Gastric carcinoma

Prognostic indicators:• The depth of invasion and • The extent of nodal and distant metastasis

• Virchow's node

• Sister Mary Joseph’s nodule

• Krukenberg’s tumorMay-2015-CSBRP

Virchow's node

Marcos Duarte Siosaki, M.D., and Ana Tarsila Souza, M.D.N Engl J Med 2013; 368:e7February 7, 2013DOI: 10.1056/NEJMicm1204740

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Sister Mary Joseph’s nodule Sister Mary Joseph first noticed that a

'nodule' in the umbilicus was often associated with advanced malignancy

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Krukenberg’s tumor

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Krukenberg’s tumor

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Complications

• Bleeding / anemia

• Perforation

• Mets and associated complications

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E N D

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• The synchronous expression of EGF, TGF-alpha and ras p21 is associated with tumor invasion and metastasis, and overexpression of TGF-beta, IGF, and PDGF is associated with collagen synthesis in poorly differentiated gastric carcinomas resulting in linitis plastica .

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