Risk Factors for Linitis Plastica
The primary risk factors for linitis plastica include germline CDH1 mutations (causing hereditary diffuse gastric cancer), diffuse-type gastric adenocarcinoma histology, signet ring cell morphology, and genetic predisposition. 1
Genetic Risk Factors
Linitis plastica is a specific form of gastric cancer characterized by diffuse infiltration of poorly differentiated cancer cells throughout the gastric wall, leading to wall thickening and rigidity. The key genetic risk factors include:
CDH1 gene mutations: Germline truncating mutations in the CDH1 gene, which codes for E-cadherin protein, are strongly associated with hereditary diffuse gastric cancer (HDGC) that often presents as linitis plastica 2, 3
Family history: Individuals with first-degree relatives diagnosed with diffuse gastric cancer have significantly increased risk 2
Lynch syndrome: Carriers of MSH2 and MSH6 mutations (Lynch syndrome) have increased risk of developing gastric cancer, including the diffuse type 2
Histopathological Risk Factors
Certain histopathological features are associated with the development of linitis plastica:
Diffuse-type gastric adenocarcinoma: According to the Lauren classification, the diffuse type is more likely to have a primary genetic etiology and progress to linitis plastica 2, 3
Signet ring cell morphology: The presence of signet ring cells is frequently associated with linitis plastica 1, 4
Poorly differentiated cells with discohesive pattern: This cellular pattern is characteristic of linitis plastica 1
Demographic and Environmental Factors
Unlike intestinal-type gastric cancer, which is strongly associated with environmental factors, linitis plastica shows different epidemiological patterns:
Geographic distribution: Interestingly, linitis plastica is more prevalent in low-risk areas for gastric cancer compared to high-incidence regions 1, 3
Helicobacter pylori infection: While H. pylori is associated with both intestinal and diffuse varieties of gastric cancer, its role in linitis plastica specifically is less prominent than in intestinal-type gastric cancer 3
Clinical Presentation and Diagnostic Challenges
Linitis plastica is notorious for its late presentation, which contributes to poor outcomes:
Late symptom development: Patients typically present with advanced disease due to the failure of linitis plastica to cause early symptoms 5
Advanced stage at diagnosis: Most patients (75.8%) present with stage IV disease, often with peritoneal involvement 6
Diagnostic difficulties: The diffuse nature of the disease often requires specialized imaging techniques and multiple biopsies for accurate diagnosis 1
Prognostic Implications
Understanding the risk factors is important because of the poor prognosis associated with linitis plastica:
Limited curative options: Most patients are offered palliative or supportive treatment due to advanced disease at diagnosis 5
Poor survival: Even after surgical intervention, patients with linitis plastica have significantly shorter overall survival compared to those with other forms of gastric cancer (median OS after gastrectomy: 21.8 vs. 91.0 months) 6
Clinical Implications
For patients with identified risk factors:
Genetic counseling and testing: Consider genetic testing for CDH1 mutations in individuals with family history of diffuse gastric cancer 2
Prophylactic gastrectomy: May be considered for individuals with confirmed CDH1 germline mutations given the difficulty in early diagnosis and poor prognosis 3
Comprehensive staging: When linitis plastica is suspected, comprehensive staging with CT, EUS, and laparoscopy with peritoneal washings is essential 1
Understanding these risk factors is crucial for early identification of high-risk individuals and implementation of appropriate surveillance strategies to improve outcomes in this aggressive form of gastric cancer.