Malignant Gastric Neoplasms Overview

Malignant Gastric Neoplasms

• Most common malignant tumors: Adenocarcinoma (95%), Lymphoma (4%), Malignant GIST (1%)
• Rare malignant tumors: Carcinoid tumor, Angiosarcoma, Carcinosarcoma, Squamous cell carcinoma
• Tumors that metastasize to the stomach: Melanoma, Breast Ca. Adenocarsinoma
• Age: 6th and 7th decades, Men/Women ratio 2/1
• Socioeconomic level: Increased risk with lower socioeconomic status
• Localization: Previously - 50% antral-pyloric, now there is an increased incidence of cardia tumors
• Increased risk factors: Dietary factors (nitrates, salt, fat), smoking, family history, pernicious anemia, radiation, A blood group, achlorhydria, familial polyposis, Helicobacter infection, EBV, Aflatoxin, Gastric ulcer
• Helicobacter infection: May lead to atrophic gastritis, intestinal metaplasia, dysplasia

Premalignant Lesions

• Polyps:
  • Insignificant: Inflammatory (0.43%), Hamartomatous, Heterotopic
  • Premalignant: Hyperplastic (2%), Adenoma (20%)
    • Adenoma: High risk with diameter greater than 2cm, associated with Familial Adenomatous Polyposis (FAP)
• Atrophic gastritis: Most common premalignant lesion, intestinal type (20%), 3 types: Autoimmune, Hypersecretory, Environmental
• Intestinal metaplasia: Complete type with small intestine type cells
• Benign gastric ulcer: May lead to gastric remnant cancers
• Gastric remnant cancers: Most commonly found after Billroth 2 surgery
• Menetrier's disease: Rare, may lead to gastric cancer

Pathology

• Gastric dysplasia: May lead to gastric adenocarcinoma
• Severe dysplasia: Resection if diffuse or multifocal, EMR if localized
• Mild dysplasia: Monitor with endoscopic biopsy surveillance and H.Pylori eradication

Early Gastric Cancer

• Confined to mucosa and submucosa: May have lymph node involvement (10%)
• Well differentiated: 70%
• Small intramucosal lesions: Treatable by EMR
• Morphology: Polypoid (good prognosis), Fungative (good prognosis), Ulcerative, Scirrhous cancers (linitis plastica) (poor prognosis)
• Location: 40% distal, 30% middle, 30% proximal

Histology (Lauren Classification)

• Intestinal type:
  • Develops from areas of intestinal metaplasia
  • Replacement of gastric epithelium with goblet-paneth cells
  • H.Pylori associated
  • 85% develop in hypochlorhydric stomachs
  • Risk directly proportional to metaplasia amount
  • Epidemic cancer
• Diffuse type:
  • Less related to environmental factors
  • Incidence increases with decrease in intestinal type
  • More common in young people
  • Independent of intestinal metaplasia
  • Whole stomach involvement
  • Single cell mutation
  • Poor prognosis

Clinic

• Most common findings: Loss of appetite, weight loss, early satiety, abdominal tenderness, palpable mass
• Symptoms: Dysphagia, Pain (cardiac dominant finding), Nausea, vomiting, bloating, anemia, stool occult blood positivity, massive hematemesis, paraneoplastic syndrome
• Paraneoplastic syndrome: Trousseau syndrome, Acanthosis nigricans, peripheral neuropathy

Diagnosis and Staging

• Suspicion:
  • Endoscopy: Best first-line investigation, Biopsy for diagnosis
  • Barium upper GI series: Single or double contrast, useful for linitis plastica
  • CT: For M phase
  • Endoscopic US: For T and N phase
  • Laparoscopy: For staging

Staging

• N0: No lymph node metastasis
• N1: 1-2 regional lymph node metastases
• N2: 3-6 regional lymph node metastases
• N3: 7 or more regional lymph node metastases (N3a: 7-15, N3b: more than 16)
• Virchow nodule: Left supraclavicular lymph node
• Sister joseph nodule: Palpable umbilical nodule
• Blumer's rectal shelf: Hard mass palpable on rectal examination

Treatment

• Radiotherapy and Chemotherapy: Limited benefit
• Surgery:
  • Palliative: Bleeding, Obstruction
  • Curative: Resection margins, EMR for early stomach cancer, Radical subtotal-total gastrectomy depending on location, Lymph node dissection

Prognosis

• 5-year survival: 22%
• Influenced by: Pathological stage, tumor differentiation, age, gender, tumor location, size, and depth

Gastric Lymphoma

• More than half of primary GI lymphomas occur in the stomach: 25% are multiple, 95% are Non-Hodgkin's B cell
• Location: Lesser curvature and antrum, on the HP floor
• Macroscopy:
  • Primary: Tumoral mass
  • Secondary: Submucosal lymphocytic disease (most common)
• Findings: Early satiety, loss of appetite, weight loss, bleeding is rare
• Diagnosis: Barium examination, Endoscopy and biopsy
• Treatment: Chemotherapy, H.Pylori eradication for Malt cell lymphoma, Surgery for complications or CT unresponsiveness, Subtotal gastrectomy, Adjuvant CT-RT
• Survival: 85% with combined treatments limited to the stomach, 40-50% with node involvement

Gastrointestinal Stromal Tumor (GIST)

• Most common in the stomach
• Pathology: Originates from cajal cells
• C-kit mutation: Tyrosine kinase activity
• Diagnosis: Endoscopy, Endoscopic USG, CT
• Treatment: Tyrosine kinase inhibitors, Wedge resection for local recurrence

Gastric Carcinoid Tumors

• 1% of all carcinoids
• Malignant potential
• Etiology: Pernicious anemia, Atrophic gastritis
• Location: Submucosal, slow-growing
• Diagnosis: EUS
• Treatment: Resection (endoscopic or open surgery)

Benign Gastric Neoplasms

• Leiomyoma: Hard, solitary, may be ulcerated and bleed, originates from smooth muscle, lesions <2cm are benign and often asymptomatic, follow-up recommended, enucleation or wedge resection for larger or symptomatic lesions
• Lipomas: Mostly benign and asymptomatic, typical EUS appearance, no intervention unless symptomatic
• Ectopic pancreas: Rare, antrum location, appears as a belly-shaped depression within the submucosa, may cluster, treatment is excision if malignancy is ruled out or symptoms are persistent

Hypertrophic Gastropathy (Menetrier's disease)

• Rare, inflammatory disease: Proximal stomach, epithelial hyperplasia, giant gastric folds
• Possible autoimmune etiology: Loss of plasma proteins due to epithelial permeability, hypochlorhydria
• Clinic: Epigastric pain, weight loss, diarrhea, hypoproteinemia
• Treatment: Good nutrition, symptom management, surgical intervention for rare hypoproteinemia
• Monitor for: Gastric cancer

Malignant Tumors of the Stomach

• The three most common malignant stomach neoplasms are adenocarcinoma (95%), lymphoma (4%), and malignant GIST (1%).
• Rare malignant stomach neoplasms include carcinoid tumors, angiosarcoma, carcinosarcoma and squamous cell carcinoma.
• Melanoma, breast adenocarcinoma, and other tumors can metastasize to the stomach.
• Gastric cancers are more common in the 6th and 7th decades of life.
• The ratio of men to women with gastric cancer is 2:1.
• The risk of gastric cancer increases as socioeconomic levels fall.
• Gastric cancer localization has shifted from predominantly antral location to more frequent cardia tumors.

Risk Factors

• Increased risk factors for gastric cancer include diet high in nitrates, salt and fat, smoking, family history, pernicious anemia, blood group A, achlorhydria, familial polyposis, radiation, environmental factors, EBV, aflatoxin, Helicobacter infection, atrophic gastritis, intestinal metaplasia, dysplasia, and gastric ulcers.

Premalignant Lesions

• Premalignant lesions include polyps, atrophic gastritis, and intestinal metaplasia.
• There are three types of atrophic gastritis: autoimmune, hypersecretory, and environmental.
• Intestinal metaplasia includes two types: small intestine and goblet cells.
• Intestinal metaplasia is associated with H. pylori.
• Hereditary nonpolyposis colorectal cancer is a rare but serious form of hereditary cancer that can impact the stomach.

Pathology

• Gastric dysplasia is a precancerous condition that can lead to gastric adenocarcinoma.
• Patients with severe dysplasia should undergo gastric resection if it is diffuse or multifocal, or endoscopic mucosal resection (EMR) if it is localized.
• Patients with mild dysplasia should be monitored with endoscopic biopsy surveillance and H. pylori eradication.

Early Gastric Cancer

• Early gastric cancer is confined to the mucosa and submucosa of the stomach, regardless of lymph node involvement.
• 10% of early gastric cancers metastasize to lymph nodes.
• 70% of early gastric cancers are well-differentiated.
• Small intramucosal lesions can be treated with EMR.
• Early gastric cancer morphology includes polypoid, fungative, ulcerative, and scirrhous (linitis plastica) forms, with varying prognoses.
• The location of early gastric cancer is 40% distal, 30% middle, and 30% proximal.

Histology (Lauren Classification)

• There are two main histological types of gastric cancer: intestinal and diffuse.
  • Intestinal type: Associated with H. pylori, develops from intestinal metaplasia, and is more common.
  • Diffuse type: Less associated with environmental factors, more common in young people, and has a poorer prognosis.

Clinic

• The most common symptoms of gastric cancer include loss of appetite, weight loss, early satiety, abdominal tenderness, and dysphagia.
• Pain, nausea, vomiting, bloating, anemia, stool occult blood positivity, and massive hematemesis can also occur.
• Paraneoplastic syndromes, such as Trousseau syndrome, acanthosis nigricans, and peripheral neuropathy, can be associated with gastric cancer.

Diagnosis and Staging

• Diagnosis of gastric cancer typically involves suspicion, endoscopy with biopsy, barium studies, CT, endoscopic ultrasound, and laparoscopy if needed.
• Staging includes evaluating lymph node involvement:
  • N0: No lymph node metastasis
  • N1: 1-2 regional lymph node metastasis
  • N2: 3-6 regional lymph node metastasis
  • N3: 7 or more regional lymph node metastases.
• Important physical exam findings include the Virchow node, Sister Joseph nodule, and Blumer's rectal shelf.

Treatment

• Treatment options include radiotherapy, chemotherapy, and surgery.
• Surgery can be palliative (for bleeding or obstruction) or curative (resection with clear margins).
• Lymph node dissection is a key part of surgical treatment.
• EMR is an option for early gastric cancer.

Prognosis

• For gastric cancer, the 5-year survival rate is 22%.
• Prognosis depends on factors such as pathological stage, tumor differentiation, age, gender, tumor location, tumor size and depth.

Gastric Lymphoma

• More than half of primary GI lymphomas occur in the stomach.
• 95% are Non-Hodgkin B cell lymphomas.
• Macroscopy reveals two types: primary tumoral mass and secondary submucosal lymphocytic disease.
• Common symptoms include early satiety, loss of appetite, and weight loss.
• Diagnosis involves barium examination, endoscopy, and biopsy.
• Treatment often involves chemotherapy, H. pylori eradication for MALT lymphoma, and surgery for complications or CT unresponsiveness.
• Survival rates are high with combined treatments that are limited to the stomach, but decrease significantly with lymph node involvement.

Gastrointestinal Stromal Tumor (GIST)

• GISTs most commonly occur in the stomach.
• They originate from Cajal cells and have a c-kit mutation.
• Diagnosis involves endoscopy, endoscopic ultrasound, and CT.
• Treatment includes tyrosine kinase inhibitor drugs, wedge resection, and management of local recurrence.

Gastric Carcinoid Tumor

• Gastric carcinoid tumors account for 1% of all carcinoid tumors.
• Some have malignant potential.
• Etiology is associated with pernicious anemia and atrophic gastritis.
• Diagnosis involves EUS.
• Treatment includes resection (endoscopic or open surgery).

Benign Gastric Neoplasms

• Leiomyomas: Hard, solitary, and often asymptomatic; may cause bleeding if ulcerated; treatment involves monitoring for small lesions, enucleation, or wedge resection.
• Lipomas: Benign and asymptomatic; visible on EUS; no intervention unless symptomatic.
• Ectopic Pancreas: Rare; usually in the antrum; diagnosis involves rule out malignancy and persistent symptoms; treatment involves excision.

Hypertrophic Gastropathy (Menetrier's Disease)

• Rare inflammatory disease of the proximal stomach characterized by epithelial hyperplasia and giant gastric folds.
• May be autoimmune.
• Pathology: Loss of plasma proteins and hypochlorhydria.
• Clinic: Epigastric pain, weight loss, diarrhea, hypoproteinemia.
• Treatment: Good nutrition, symptom-oriented practices, and surgical intervention if hypoproteinemia develops.
• Observation for stomach cancer is crucial.