GASTRIC TUMORS 3.
Adenomas:
True neoplasms
Benign Mucosal: Gastric Hyperplastic polyps (75%), Fundic gland (10%) Associated with [Link] with atrophy & intestinal metaplasia.
tumors polyps(Relatively Neoplastic/ Adenomatous polyps (10%). Contain dysplastic epithelium (L/H-grade).
& tumor uncommon) Hamartomatous polyps (PJS) Risk of malignant transformation increases with polyp size (>2cm).
like Mesenchymal Leiomyoma: Benign SMC, rare in stomach Malignant potential of gastric adenomas > colonic counterparts.
conditions Lipoma (submucosal, mature adipocytes) Carcinoma may be present in up to 30% of gastric adenomas.
Hemangioma
Malignant:
Granular cell tumour, Ectopic pancreatic rests.
Malignat Gastric CA (90%), Malignant lymphoma (5%), Carcinoid (3%), GIST (2%) 1. Gastric carcinoma:
Epidemiology:
Benign:
Variable geographic distribution
1. Hyperplastic (Inflammatory) polyps: High incidence in Japan, southern Korea, Chile, Costa Rica, Russia.
Not true neoplasm → exuberant response to chronic gastritis 3% of all cancer; dismally poor prognosis.
If associated with H. pylori gastritis, may regress after eradication. There is a steady decline in overall incidence and mortality
Risk of dysplasia increased with polyps larger than 1.5 cm.
Factors Associated with Increased Incidence of Gastric CA:
Hyperplastic mucosal epithelium and an inflamed edematous stroma.
Environmental Factors:
2. Fundic gland polyps:
H. pylori: Present in most cases of intestinal-type carcinoma
Small collections of dilated body/corpus-type glands Diet:
Asymptomatic and incidental.
Nitrites derived from nitrates (water, preserved food)
Polyps occur in body & fundus, often are multiple.
Smoked & salted foods, pickled vegetables, chili peppers
Sporadically, due to excessive use of PPIs, why?
Lack of fresh fruit and vegetables
May occur in persons with FAP (may show dysplasia)
Don’t have neoplastic potential with FAP even with dysplasia. Low socioeconomic status & Cigarette smoking
Host Factors:
Chronic gastritis:
Hypochlorhydria: favors colonization with H. pylori
Intestinal metaplasia is a precursor lesion
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Gastric adenomas: Carcinoma, undifferentiated,
40% harbor cancer at time of diagnosis Large cell carcinoma with rhabdoid phenotype8014/3
30% have adjacent cancer at time of diagnosis Pleomorphic carcinoma 8022/3
Partial gastrectomy: reflux of bilious, alkaline intestinal fluid Sarcomatoid carcinoma 8033/3
Barrett esophagus: ↑ risk of GEJ tumors Carcinoma with osteoclast-like giant cells8035/3
Genetic Factors:
Familial gastric carcinoma syndrome (E-cadherin mutation) Lauren classification:
Slightly increased risk with blood group A Intestinal type: 5M + DHP
Family history of gastric cancer More common, in high-risk population
HNPCC syndrome: MSI = MSH/MLH More in Age of 50
Classification: Males > Females
More differentiated (Better)
WHO Classification (5th edition, 2019):
Risk factors:
Adenocarcinoma, NOS:
[Link]: [Link] → [Link]→ dysplasia
Tubular adenocarcinoma Pernicious anemia (Autoimmune gastritis)
Parietal cell carcinoma Partial gastrectomy
Adenocarcinoma with mixed subtypes Diets: foods → nitrites → nitrosamines & nitrosamides
Papillary adenocarcinoma
Smoked foods, pickled vegetables
Micropapillary carcinoma, NOS
Excessive salt intake
Mucoepidermoid carcinoma
Mucinous adenocarcinoma: ↓ fresh vegetables intake & fruits (antioxidants
present in these foods may inhibit nitrosation)
Signet ring cell carcinoma
Poorly cohesive carcinoma, NOS Malignant cells forming neoplastic glands & tubules
Medullary carcinoma with lymphoid stroma resembling those of colonic adenocarcinoma
Hepatoid adenocarcinoma Diffuse type:
Paneth cell carcinoma
Less common. Uniform incidence among populations
Squamous cell carcinoma, NOS Earlier age, M=F & Undefined Risk factors
Adenosquamous carcinoma
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Arise de novo from native gastric mucous cells Gross Morphology:
Infection with H. pylori & chronic gastritis: Absent Location:
No definite mass, poorly differentiated
Pylorus & antrum (50-60%) > Cardia (25%) > body & fundus.
May lead to hardening of the wall (linitis plastica)
Lesser curvature (antropyloric region) > Greater curvature.
linitis plastica: 2-3 cm like leather bag
Composed of poorly cohesive gastric-type cells invading Classification (depth of invasion):
the wall in infiltrative pattern (NO gland formation). Early gastric CA:
Some cells contain mucous “signet-ring" cells.
Confined to the mucosa & submucosa.
Rare inherited mutation of E-cadherin (CDH1 gene)
Carry an Excellent prognosis
Hereditary diffuse gastric cancer (HDGC) Commonly diagnosed in japan: routine screening
AD associated cancer syndrome. Advanced gastric CA: Rare cases in Jordan
Associated with DGC & invasive lobular breast CA.
Below the submucosa = poor prognosis
Inactivating mutations in CDH1 (E cadherin).
Usually with diffuse type.
For cases diagnosed with poorly cohesive
Evoke a desmoplastic Rxn & wall hardening
carcinoma/ diffuse carcinoma GENETIC
May mimic chronic peptic ulcer
COUNSELLING is recommended to exclude
Heaped-up (raised) margins
hereditary diffuse gastric cancer.
Treatment: Prophylactic total gastrectomy Clinical Features:
Early gastric CA: Usually asymptomatic, Abdominal
Tumor spread:
discomfort, dyspepsia & nausea.
Direct spread (through the wall to serosa). Advanced carcinoma:
Distant metastasis (mainly to liver).
May be asymptomatic.
Regional and distant LNs.
IDA, anorexia, bleeding, weight loss.
The Earliest LN mets may involve a Symptoms related to mets.
supraclavicular LN (Virchow node).
Tumors of the cardia may cause dysphagia.
Intraperitoneal spread: Tumors of pylorus may cause gastric outlet obstruction.
Ex: Krukenberg tumor
Tumor in females: may involve both ovaries
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Prognosis: Clinical picture: Asymptomatic → mass effect + mucosal ulceration.
Stage (TNM): Most important Prognostic factor Prognosis: Low to High risk; depending on:
Type: Signet ring & diffuse type carry a poor prognosis. Location, Tumor Size
5-year survival is: Early CA (90%), Advanced CA (< 20) Mitotic count/ 50HPF.
Treatment: Mets: appear > 20 y after removal of original tumor, mainly to liver.
Surgical resection remains the preferred treatment. Rx: Surgery (L. grade), Targeted therapy - TK (IMATINIB MESYLATE).
Beside surgery also CTX & individualized therapies:
3. GI Lymphoma:
(EGFR-HER2 overexpression: inhibit HER2 signaling)
Systemic dissemination of NHL
2. Gastrointestinal Stromal Tumors (GIST): Primary GI lymphoma:
The most common mesenchymal tumor of the abdomen. The gut is the most common extra-nodal site.
Arise from interstitial cells of Cajal which control the GI peristalsis Stomach: most common site of extranodal lymphomas (20%).
Site: Stomach (>50%), Small & large intestine & Esophagus (rare). MALToma: most common form in Western countries (B in origin)
Pathogenesis: 2nd most common is diffuse large B cell lymphoma (DLBCL).
No evidence of liver, spleen, BM involvement at the time of Dx.
Gain-of-function mutation in the c-KIT (CD117) gene
~ 5% of all GI malignancies.
95%: positive for CD117 (c-KIT) immunostaining.
Regional lymph nodes may be involved
which encodes a tyrosine kinase receptor-TKR (75%-85%)
Can be of B- or T-cell origin.
8% have mutations that activate a related TK (PDGFRA).
Genes encoding mitochondrial succinate dehydrogenase (SDH) in Others:
cases with no c-KIT or PDGFRA mutations lymphomatoid polyposis.: 3M
Wide range of morphology: M: mantle cell lymphoma (MCL) of the GIT.
Spindle cells, epithelioid cells, mixed. M: More in male
SMC (common) or neural differentiation. M: mean age 61 years.
Looks like Leiomyoma Involves colon, stomach and small intestine.
Nodular, sessile or polypoid lesions
Cajal = Carvajal Enteropathy associated T-cell lymphoma in Celiac disease.
Burkitt lymphoma.
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Marginal zone lymphoma of MALT type: Morhphology:
A sporadic low grade B cell lymphoma of the GI MALT. Solid yellow - tan submucosal mass
Usually arises in a background of: Islands, trabeculae, glands, or sheets of uniform cells with scant,
Helicobacter-associated chronic gastritis cytoplasm & around stippled nucleus. (salt & pepper).
OR Show t(11;18) translocation. Clinical Features of GI NETs:
Usually affects adults, M=F. Usually asymptomatic.
50% may regress with antibiotic treatment for H. pylori. Can be functional (H producing) and non-functional
Site: Anywhere in GI (Stomach (55-60%) > SI > colon). Rarely, local symptoms (angulation / obstruction = SI intussusception).
Microscope: Infiltration of small atypical lymphocytes in the The secretory products of some carcinoids can produce a variety
glands (lymphoepithelial lesions) and in the lamina propria of syndromes or endocrinopathies (CARCINOID sy).
Prognosis: relatively good Carcinoid syndrome:
Rx: antibiotics, surgery, chemo. Occurs in <10% of patients
Strongly associated with mets (liver) disease:
primary GI lymphomas have Better prognosis
than lymphoma of other sites & GI carcinoma. Inactivation of hormones occur in the liver
Treatment: Combined surgery, chemotherapy, and radiation. By mets, liver will be damaged causing symptoms
Due to vasoactive substances (serotonin, histamine)
4. Neuroendocrine tumors (NETs) Carcinoids:
Cutaneous flushing, sweating, bronchospasm, colicky
Origin: Neuroendocrine cells. abdominal pain, diarrhea, & right-sided cardiac valvular
Site: fibrosis
GIT (majority): Appendix (most common) > Small
Intestine (ileum) > rectum > stomach > colon. Zollinger-Ellison syndrome:
Pancreas & Biliary tree.
Tracheobronchial tree & lungs.
All NETs are potentially malignant, may mets to LNs or distant sites
Gastric NET tumors may be associated with endocrine cell hyperplasia
as seen in chronic atrophic gastritis and in Zollinger-Ellison syndrome
Behavior/ Prognosis correlates with:
The site: Midgut > foregut > Hind gut (appendix rarely mets)
Depth and local invasion / The size of the tumor (> 2 cm).
The Grade of the tumor.
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