Histological Classification of Gastric Cancer: Diffuse vs. Intestinal Type
Statement 1 is correct: Diffuse-type gastric cancer is characterized by CDH1 mutations, particularly in hereditary diffuse gastric cancer (HDGC) syndrome.
Analysis of Each Statement
Statement 1: CDH1 Mutation in Diffuse-Type Cancer ✓ TRUE
- Diffuse-type gastric cancer is strongly associated with CDH1 (E-cadherin) mutations, particularly in hereditary cases where CDH1 germline mutations define hereditary diffuse gastric cancer (HDGC) syndrome 1.
- CDH1 mutations are a defining molecular feature of diffuse gastric cancer, along with RHOA alterations 2, 3.
- The 2020 IGCLC guidelines specifically list CDH1 and CTNNA1 mutations as causative for HDGC 1.
Statement 2: Intestinal-Type Lacks Cohesion ✗ FALSE
- This is backwards: diffuse-type cancer is characterized by lack of cohesion, not intestinal-type 1.
- The NCCN guidelines explicitly state that diffuse-type is "characterized by poorly differentiated and discohesive tumor cells with a signet-ring or non-signet-ring morphology" 1.
- The WHO classification recognizes "poorly cohesive" carcinomas (including signet ring cell) as part of the diffuse category 1.
- Intestinal-type forms cohesive glandular structures with tubular or glandular patterns 1.
Statement 3: Diffuse-Type Affects Older People ✗ FALSE
- Diffuse-type gastric cancer typically affects younger patients, not older people 1, 4.
- Intestinal-type cancer is associated with advancing age and occurs more frequently in older individuals 5.
- The diffuse subtype has a substantially increasing incidence rate in younger populations in Europe and the USA 4.
- The 2020 HDGC guidelines include age-specific criteria, with DGC diagnosed <50 years as an individual testing criterion 1.
Statement 4: Intestinal-Type Has Worse Prognosis ✗ FALSE
- Diffuse-type gastric cancer has a significantly worse prognosis than intestinal-type 6.
- A comprehensive meta-analysis of 73 studies including 61,468 patients demonstrated that diffuse-type histology is associated with worse overall survival (HR 1.23; 95% CI, 1.17-1.29; P<0.0001) 6.
- This survival disadvantage persists in both loco-regional confined disease (HR 1.21) and advanced disease (HR 1.25), across both Asian and Western populations 6.
- Diffuse-type is characterized by aggressive behavior including rapid invasion, chemoresistance, and peritoneal metastasis 4, 3.
Statement 5: Intestinal-Type Has Ring-Seal Pattern ✗ FALSE
- Signet ring cell morphology is a feature of diffuse-type cancer, not intestinal-type 1.
- The NCCN guidelines clearly state that diffuse-type is characterized by "signet-ring or non-signet-ring morphology" 1.
- The WHO classification includes signet ring cell carcinoma as a subtype of "poorly cohesive" adenocarcinomas, which belong to the diffuse category 1.
- Intestinal-type is characterized by tubular or glandular patterns with scattered goblet cells, not signet ring cells 1.
Key Clinical Distinctions
Diffuse-Type Characteristics:
- Molecular: CDH1, RHOA mutations; genomically stable (GS) subtype 1, 2, 3
- Histology: Poorly cohesive, signet ring cells, discohesive infiltration 1
- Demographics: Younger age, more prevalent in low-risk geographic areas 1, 4
- Prognosis: Worse survival, aggressive behavior, peritoneal spread 6, 3