IllnessSignet ring cell carcinoma, gastric; differential diagnosis

NGS +

[Sanger]

Gastric cancer (GC) is classified into two main histological types, diffuse and intestinal, plus an undetermined mixed type. The intestinal and diffuse types exhibit numerous differences in etiology and prognosis, the diffuse type having worse prognosis. Since 1990, signet-ring cell carcinoma (SRCC), previously classified as diffuse type, constitutes a specific histotype. While the incidence of GC has decreased worldwide, the incidence of SRCC is constantly increasing accounting for 8-30% of GC. Hereditary diffuse gastric cancer (HDGC) is an autosomal dominant disorder. 40% of HDGC families have germline mutations in the CDH1 gene, and the cumulative risk of GC for CDH1 mutation carriers by age 80 is 70% for men and 56% for women, the latter with a 50%-risk of breast cancer. Somatic CDH1 alterations have also been found in 30% of all patients with GC. As CDH1 is a tumor suppressor gene, second somatic hits include promoter methylation, somatic mutation or loss of heterozygosity. Due to their high number and the difficulty to demonstrate their functional role in vivo, many mutations remain clinically uncertain. GC associated with CDH1 mutation is highly penetrant, presents at early age and severe in course. The diagnostic yield is at most 50%, thus negative mutation test results do not exclude the clinical diagnosis.

Reference: https://www.ncbi.nlm.nih.gov/books/NBK1139/

• Alias: Hereditäres diffuses Magenkarzinom
• Alias: Siegelring-Karzinom
• Allelic: Acrodysostosis 1, with/-out hormone resistance (PRKAR1A) 3
• Allelic: Adenomatous polyposis coli (APC)
• Allelic: Adrenocortical carcinoma, pediatric (TP53)
• Allelic: Basal cell carcinoma 7 (TP53)
• Allelic: Blepharocheilodontic syndrome 1 (CDH1)
• Allelic: Bone marrow failure syndrome 5 (TP53)
• Allelic: Brain tumor-polyposis syndrome 2 (APC)
• Allelic: Breast cancer, lobular (CDH1)
• Allelic: Breast cancer, male, susceptibility to (BRCA2)
• Allelic: Breast cancer, somatic (TP53)
• Allelic: Breast cancer, susceptibility to (CHEK2)
• Allelic: Breast cancer, susceptibility to (PALB2)
• Allelic: Breast-ovarian cancer, familial, 2 (BRCA2)
• Allelic: Choroid plexus papilloma (TP53)
• Allelic: Colorectal cancer (TP53)
• Allelic: Colorectal cancer, susceptibility to (CHEK2)
• Allelic: Desmoid disease, hereditary (APC)
• Allelic: Diarrhea 5, with tufting enteropathy, congenital (EPCAM)
• Allelic: Endometrial cancer, familial (MSH6)
• Allelic: Endometrial carcinoma, somatic (CDH1)
• Allelic: Exudative vitreoretinopathy [MONDO:0019516] (CTNNA1)
• Allelic: Gardner syndrome (APC)
• Allelic: Glioblastoma 3 (BRCA2)
• Allelic: Glioma susceptibility 1 (TP53)
• Allelic: Glioma susceptibility 2 (PTEN)
• Allelic: Hepatocellular carcinoma, somatic (TP53)
• Allelic: Macrocephaly/autism syndrome (PTEN)
• Allelic: Macular dystrophy, patterned, 2 (CTNNA1)
• Allelic: Medulloblastoma (BRCA2)
• Allelic: Melanoma + neural system tumor syndrome (CDKN2A)
• Allelic: Melanoma, cutaneous malignant, 2 (CDKN2A)
• Allelic: Melanoma-pancreatic cancer syndrome (CDKN2A)
• Allelic: Meningioma (PTEN)
• Allelic: Myxoma, intracardiac (PRKAR1A)
• Allelic: Nasopharyngeal carcinoma, somatic (TP53)
• Allelic: Osteosarcoma (TP53)
• Allelic: Ovarian cancer, somatic (CDH1)
• Allelic: Pancreatic cancer 2 (BRCA2)
• Allelic: Pancreatic cancer, somatic (TP53)
• Allelic: Pancreatic cancer, susceptibility to, 3 (PALB2)
• Allelic: Pigmented nodular adrenocortical disease, primary, 1 (PRKAR1A)
• Allelic: Prostate cancer (BRCA2)
• Allelic: Prostate cancer, familial, susceptibility to (CHEK2)
• Allelic: Prostate cancer, susceptibility to (CDH1)
• Allelic: Wilms tumor (BRCA2)
• Ataxia-telangiectasia (ATM)
• Carney complex, type 1 (PRKAR1A)
• Cowden syndrome 1 (PTEN)
• Fanconi anemia, complementation group D1 (BRCA2)
• Fanconi anemia, complementation group N (PALB2)
• Gastric adenocarcinoma + proximal polyposis of the stomach (APC)
• Gastric cancer, hereditary diffuse, with/-out cleft lip and/or palate (CDH1)
• Hereditary diffuse gastric cancer [D-guideline] (CTNNA1)
• Lhermitte-Duclos disease (PTEN)
• Li-Fraumeni syndrome (TP53)
• Li-Fraumeni syndrome 2 (CHEK2)
• Lynch syndrome 1 (MSH2)
• Lynch syndrome 2 (MLH1)
• Lynch syndrome 4 (PMS2)
• Lynch syndrome 5 (MSH6)
• Lynch syndrome 8 (EPCAM)
• Mismatch repair cancer syndrome 1 (MLH1)
• Mismatch repair cancer syndrome 2 (MSH2)
• Mismatch repair cancer syndrome 3 (MSH6)
• Mismatch repair cancer syndrome 4 (PMS2)
• Muir-Torre syndrome (MLH1, MSH2)
• Peutz-Jeghers syndrome (STK11)