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Stomach

Carcinoma

General


Reviewers: Elliot Weisenberg, M.D. (see Reviewers page)
Revised: 12 October 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
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● In 2012, estimated 21,320 cases in US (American Cancer Society)
● U.S. rates declining due to lower rates of intestinal type; rates for diffuse type unchanged
● Worldwide, 8% of all cancers, more deaths than lung cancer, but incidence declining since 1995
● 90% of malignant tumors in stomach are carcinomas

Epidemiology
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● High incidence in Japan, Chile, Northern Italy, China, Portugal, Russia
● 2/3 men
● Associated with lower socioeconomic groups
● In young patients, associated with radiation therapy or chemotherapy for other malignancies

Clinical features
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● Usually asymptomatic until late
● Symptoms: weight loss, abdominal pain, nausea, vomiting, altered bowel habits
● Metastases to supraclavicular nodes (Virchow’s node) may be first clinical manifestation
● Sites: pylorus and antrum > cardia; lesser > greater curvature
● Japan: mass endoscopy programs led to 35% early gastric cancers vs. 10% in US
● Well differentiated tumors may grow very slowly (Arch Pathol Lab Med 1990;114:1046)
● Rarely occurs in gastric stump after partial gastrectomy for ulcer (Arch Pathol Lab Med 1985;109:958)
● Minute (< 5 mm) poorly differentiated tumors may show no gross features, however, chromoendoscopy increases their detectability (Arch Pathol Lab Med 1989;113:926)

Treatment and prognosis
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● Treatment: gastrectomy, chemotherapy, trastuzumab for HER2+ tumors
● 5 year survival is 95% for surgically treated early gastric carcinoma; overall only 20% or less
● Nodal involvement may not alter survival in early gastric cancer
● Locally invades esophagus (proximal carcinomas), duodenum (distal carcinomas), omentum, colon, pancreas, spleen
● Death may occur due to widespread seeding of peritoneum and lung/liver metastases
● Also distant metastases to adrenal gland, peritoneum, ovary, spleen (#2 cause of splenic metastases, Arch Pathol Lab Med 2000;124:526)
● Kruckenberg tumor: metastases of diffuse or signet ring types to one or both ovaries, rarely tubular pattern (Am J Surg Pathol 1981;5:225)
● Depth of invasion most important prognostic factor
● Poor prognostic factors: younger age (usually diffuse histology, more advanced disease), proximal half of stomach, deep invasion, infiltrative margin, diffuse histologic type, positive surgical margins (predicts local recurrence), lymph node metastases

Phenotypes
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● Intestinal: majority, arise from complete-type intestinal metaplasia; pattern of genetic alterations resembles colon carcinoma
● Diffuse: arise directly from gastric foveolar epithelium, poorer prognosis
● Microsatellite instability phenotype cancers: 10% prevalence, associated with fewer lymph node metastases, possibly improved survival (Mod Pathol 2002;15:632), minimal desmoplasia (Mod Pathol 1999;12:15); 18% with both gastric and colorectal cancers have this phenotype (Mod Pathol 2001;14:543)

Classification
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● Early: confined to mucosa or mucosa and submucosa, regardless of perigastric nodal metastases
● Advanced: muscularis propria invasion

Borman classification of advanced gastric cancer:
● Type 1, polypoid
● Type 2, fungating
● Type 3, Ulcerated
● Type 4, Infiltrative

Laurén classification
● Diffuse
● Intestinal
● Mixed
● Indeterminate

WHO classification

● Tubular adenocarcinoma
● Papillary adenocarcinoma
● Mucinous adenocarcinoma, tumor shows >50% mucin
● Poorly cohesive carcinomas, including signet ring cell carcinoma

Rare variants:
● Adenosquamous carcinoma
● Carcinoma with lymphoid stroma
● Choriocarcinoma
● Embryonal carcinoma
● Endodermal sinus tumor
● Hepatoid carcinoma
● Malignant rhabdoid tumor
● Mixed adeno-neuroendocrine carcinoma
● Mucoepidermoid carcinoma
● Oncocytic adenocarcinoma
● Paneth cell carcinoma
● Parietal cell carcinoma
● Undifferentiated carcinoma

Clinical images
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Virchows Node

Cytology images
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Gastric adenocarcinoma

Positive stains
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● CDX2 (Am J Surg Pathol 2003;27:303), CK7 (71%, Hum Pathol 2002;33:1078), CK20 (41%)

Negative stains
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● CD44 (Arch Pathol Lab Med 2000;124:212)
● EBV (except for lymphoepithelioma-like carcinomas and rarely classic carcinomas, Mod Pathol 1999;12:873)

Molecular features
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● c-met: 20-40% in both intestinal and diffuse types
● APC: 30-40% in intestinal type, < 2% in diffuse type
● Kras: 1-28% in intestinal type, < 1% in diffuse type
● HER2/ERBB2: 5-15% in intestinal type, < 1% in diffuse type
● p53: 25-40% in intestinal type, 0-21% in diffuse type

End of Stomach > Carcinoma > General


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