Case 63

A 45 year old female with weight loss and abdominal pain, here is the gastric biopsy.

1.Poorly cohesive carcinomas (PCCs) account for what percentage of gastric cancers (GCs), and in which patient population are higher frequencies reported?

A. 20–54% of GCs, with higher frequencies in Japanese patients

B. 10–20% of GCs, with higher frequencies in European patients

C. 5–10% of GCs, with higher frequencies in North American patients

D. 60–80% of GCs, with higher frequencies in African patients

Answer

A

2.What does poorly cohesive carcinoma belong to in the TCGA molecular classification?

A: EBV-positive

B: MSI- unstable

C: Gnomically stable

D: Chromosomal unstable

Answer

Subtype

Histological Features

Molecular/Genetic Characteristics

EBV-positive

GC with lymphoid stroma or lymphoepithelioma-like

PIK3CA and ARID1A mutations; genome-wide hypermethylation; amplification of CD274 (PD-L1)

Microsatellite-unstable

Not specifically defined histologically

Mutations or promoter methylation of mismatch repair genes (e.g., MLH1); exhibits global hypermethylation

Genomically stable

Predominantly diffuse-type

Lower frequency of genetic aberrations; subset shows RHOA mutations or fusions involving RHO-family GTPase-activating proteins

Chromosomally unstable

Mostly intestinal-type

Extensive DNA copy-number abnormalities; amplification of receptor tyrosine kinase genes (e.g., ERBB2, EGFR, MET, FGFR2)

References: https://tumourclassification.iarc.who.int/chaptercontent/31/29

Case credit: UCSD Pathology

Author: Wangpan Jackson Shi, MD