Persistent Nausea and Vomiting in Pregnancy

Abstract

Question: A 23-year-old pregnant woman at 27 weeks gestation presented with 10 weeks of persistent nausea, emesis, and a 20-pound weight loss. On examination, she appeared ill and had epigastric tenderness. Laboratory assessment was notable for anemia (hemoglobin level, 7 g/dL). Hyperemesis gravidarum was entertained, but upper endoscopy revealed circumferential, edematous narrowing of the gastric antrum with ulceration (Figure A, arrow). Gastric biopsies were obtained (Figure B). Computed tomography showed intrauterine pregnancy (Figure C, thin arrow) and a thickened gastric wall (Figure C, thick arrow). What is the diagnosis? Look on page 323 for the answer and see the Gastroenterology web site (www.gastrojournal.org) for more information on submitting your favorite image to Clinical Challenges and Images in GI. Gastric biopsy (Figure B) demonstrates adenocarcinoma with signet ring cells (arrows). The thick arrow in Figure C shows circumferential gastric thickening consistent with linitis plastica. The patient subsequently acknowledged her father perished with gastric cancer at age 45 years. Hereditary diffuse gastric cancer (HDGC) was confirmed by CDH-1 gene mutation testing. Vaginal delivery was expedited and chemotherapy initiated. Unfortunately, the patient succumbed to metastatic disease. Gastric cancer during pregnancy is rare, but should be considered in women with hyperemesis late in pregnancy. HDGC is an autosomal-dominant, inherited gastric cancer syndrome characterized by germline mutation of CDH-1 gene, which encodes for the cell-to-cell adhesion protein E-cadherin. It is a relatively rare cancer syndrome but may account for approximately 1% of all cases of gastric carcinoma in populations with a low incidence of gastric cancer such as the United States, Canada, and the United Kingdom.1Blair V. Martin I. Shaw D. et al.Hereditary diffuse gastric cancer: diagnosis and management.Clin Gastroenterol Hepatol. 2006; 4: 262-275Abstract Full Text Full Text PDF PubMed Scopus (142) Google Scholar Diffuse-type gastric adenocarcinoma with signet-ring cells is the most common cancer in carriers of germline CDH-1 mutations. Genetic testing for mutations in the CDH-1 gene is widely available. However, only 30%–50% of families meeting diagnostic criteria carry a predisposing CDH-1 mutation.1Blair V. Martin I. Shaw D. et al.Hereditary diffuse gastric cancer: diagnosis and management.Clin Gastroenterol Hepatol. 2006; 4: 262-275Abstract Full Text Full Text PDF PubMed Scopus (142) Google Scholar The revised International Gastric Cancer Linkage Consortium diagnostic criteria for CDH-1 mutation testing in HDGC include (1) 2 gastric cancer cases in family, 1 confirmed diffuse gastric cancer under age 50, (2) 3 confirmed diffuse gastric cancer cases in first- or second-degree relatives independent of age, (3) diffuse gastric cancer in an individual under age of 40, and (4) personal or family history of diffuse gastric cancer and lobular breast cancer, 1 diagnosed under the age of 50.2Fitzgerald R.C. Hardwick R. Huntsman D. et al.Hereditary diffuse gastric cancer: updated consensus guidelines for clinical management and directions for future research.J Med Genet. 2010; 47: 436-444Crossref PubMed Scopus (412) Google Scholar The other malignancy that occurs at increased frequency in HDGC families is lobular breast carcinoma. It is unclear why germline CDH-1 mutation predisposes predominantly to gastric cancer. There is a high lifetime risk for advanced gastric cancer in HDGC of approximately 70% in men and 80% in women by 80 years of age.3Pharoah P. Guilford P. Caldas C. Consortium TIGCLIncidence of gastric cancer and breast cancer in CDH1 (E-cadherin) mutation carriers from hereditary diffuse gastric cancer families.Gastroenterology. 2001; 121: 1348-1353Abstract Full Text Full Text PDF PubMed Scopus (479) Google Scholar The risk for advanced gastric cancer is age-related and estimated to be <1% at 20 years and increasing to 4% at 30 years.3Pharoah P. Guilford P. Caldas C. Consortium TIGCLIncidence of gastric cancer and breast cancer in CDH1 (E-cadherin) mutation carriers from hereditary diffuse gastric cancer families.Gastroenterology. 2001; 121: 1348-1353Abstract Full Text Full Text PDF PubMed Scopus (479) Google Scholar Because most patients have advanced stage gastric carcinoma at diagnosis, prophylactic gastrectomy is recommended in asymptomatic CDH-1 mutation carriers over the age of 20 years to prevent the development of this lethal cancer. If prophylactic gastrectomy is declined, intensive gastroscopic surveillance should be performed with the patient informed of the limitations for endoscopic detection of early lesions in HDGC.