发信人: USMedEdu (US_CMGs), 信区: Pre_Resident_Club
标 题: LzR: 医网情深： 病理实习笔记：胃癌
发信站: BBS 未名空间站 (Fri Sep 8 20:57:30 2017, 美东)
Pathology Externship Note on Gastric Carcinoma
This note is my homework and based on my pathology externship with Dr. He
who presented a gastric biopsy case to me.
Pic1: Gastric biopsy, 4X ; Pic2: 10X
a) Gastric cancer is part of the spectrum of malignancies in Lynch syndrome.
b) Incidence of gastric cancer was highest in Lynch syndrome patients with
MSH2 or MLH1 mutations.
c) MLH1 and MSH mutations have a high penetrance, with >80% of carriers
developing some form of cancer during their life time. PMS2 mutations are
associated with a lower penetrance and variable clinical phenotypes ranging
from early-or late-onset ,apparently sporadic colorectal cancer.
a) CK-7 is used to distinguish adenocarcinoma of distal esophagus (CK7+ /
CK19+: 90%, CK7+ / CK20-: 74%) from proximal stomach (CK7+ / CK19+: 44%, CK7
+ / CK20-: 24%);
b) CK19 belongs to a family of keratins, which are normally expressed in the
lining of the gastroenteropancreatic and hepatobiliary tracts.
Accounts for 7.8% of cancers worldwide,
High incidence in eastern Asia, eastern Europe and central and Latin America,
Low-incidence in North America, northern Europe, and most countries in
Africa and South-Eastern Asia.
“Intestinal” type is relatively predominant in high-incidence areas,
where antrum and pylorus are most common sites.
“Diffuse” type are relatively more common in low-incidence areas, where
proximal stomach (”cardia” ) is the most common site.
1). Gender (M>F);
2). Ethnicity (in the U.S, Hispanic Americans, African Americans, and Asian/
Pacific Islander> non-Hispanic whites);
3). Geography (Most common in Japan, China, Southern and Eastern Europe and
South and Central America);
4). H. pylori infection;
5). Stomach Lymphoma (MALT);
6). Diet (increased in people with diets that have large amounts of smoked
foods, salted fish and meat, pickled vegetables;6). Smoking;
7). previous stomach surgery;
8). pernicious anemia;
9). Type A blood;
10). Inherited cancer syndromes;
11). Family History;
12). Adenomatous polyps;
13). EBV infection ;
14). Certain occupations (workers in the coal , metal, and rubber industries
15). Common variable immune deficiency (CVID) for they cannot make enough
antibodies in response to germs.
Classified endoscopically according to growth pattern:
Early : 3 types: protruded (type 0-I); superficial (most common type, type 0
-II), excavated (type 0-III).
Histologically, most early gastric cancers have a tubular or papillary
PET in combination with CT : used to detect LN and liver metastases to
Tumour spread and staging:
Intestinal type preferentially metastasize haematogenously to the liver,
whereas carcinomas composed of poorly cohesive cells (“diffuse type”
preferentially metastasize to peritoneal surfaces;
Histopathology (WHO classification):
1) Tubular adenocarcinoma: dilated or slit-like and branching tubules of
2) Papillary adenocarcinoma: well-differentiated exophytic carcinoma with
elongated finger-like processes lined by cylindrical or cuboidal cells
supported by fibrovascular connective tissue cores;
3) Mucinous adenocarcinoma: composed of malignant epithelium and
extacellular mucinous pools;
4) Poorly cohesive carcinomas, including signet ring cell CA and other
variants: poorly cohesive CA are composed of neoplastic cells that are
isolated or arranged in a small aggregates. The latter is composed
predominantly or exclusively of signet-ring cells, characterized by a
central optically clear, globoid droplet of cytoplasmic mucin with an
eccentrically placed nucleus;
5) Mixed CA: a mixture of discrete morphologically identifiable glandular (
tubular/papillary)and signet ring/poorly-cohesive histological components.
Grading-applies primarily to tubular and papillary carcinomas (not other
Well-differentiated adenocarcinomas are composed of well-formed glands,
sometimes resembling metaplastic intestinal epithelium.
Precursor lesions- gastritis and intestinal metaplasia
1)Negative for intraepithelial neoplasia (dysplasia), indicating benign
changes like inflammatory, metaplastic, or reactive in nature;
2) Indefinite for intraepithelial neoplasia (dysplasia);
3) intraepithelial neoplasia, low-grade (well- and moderately differentiated
) or high-grade (poorly differentiated)
Intramucosal invasive neoplasia- invade the lamina propria;
Invasive neoplasia -beyond the lamina propria ,associated with nodal an
1). hereditary diffuse gastric cancer : germline mutation of the E-cadherin
2). Dominantly inherited cancer-predispostion syndromes such as FAP and
Lynch Syndrome: carriers of mutations in MSH2 have increased risk of gastric
cancer; germline mutation of TP53 in Li-Fraumeni Syndrome; germline
mutation of the LKB1 gene in sporadic Peutz-Jeghers syndrome (PJS) with
early -onset gastric cancer—from “WHO”book;
3). Hereditary diffuse gastric cancer-CDH gene mutations; HNPCC, also known
as Lynch Syndrome –increased risk of colorectal and stomach cancer, caused
by defect in either the MLH1 or MSH2 gene, see pic3-4; Familial adenomatous
polyposis (FAP)-APC gene mutation; BRCA1 and BRCA2; Li-Fraumeni syndrome –
TP53 gene mutations, Peutz-Jeghers Syndrome (PJS)-STK1 mutation—from
American Cancer Society website;
Molecular Pathology- genetic and epigenetic changes that affect oncogenes,
tumour suppressor genes, and DNA mismatch repair(MMR), MSI (Microsatellite
instability) is caused by defects in the MMR system. In gastric cancer, MSI
is mainly caused by epigenetic silencing (promoter methylation) of the MLH1
gene. MSI-high tumors show a better prognosis than do MSI-low.
Staging of advanced gastric cancer- TNM system remains the strongest
prognostic indicator. Prognosis and predictive factors:
The prognosis of patients with gastric cancer is related to tumor extent and
includes both nodal involvement and direct tumor extension beyond the
gastric wall. Tumor grade may also provide some prognostic information.
Early gastric cancers have a low incidence of vessel invasion and LN
metastasis and a good prognosis (90% of Patients survive 10 years). 5 year
survival is 60-80% for patients with tumors that invade the muscularis
propria, but 50% for those with tumors invading the subserosa. Even with
apparent localized disease, the 5-year survival rate of patients with
proximal gastric cancer is only 10% to 15%.