Background

1. An Extremely Rare Type of Gastric Carcinoma in a Teenager Male Diana Moya1, John S. Corns2, Wendy L. Taylor1, Clarisa Cuevas1, M. Samer Ammar1, Susan E. Spiller2, Youhanna Al-Tawil1 1GI for Kids, PLLC. Pediatric Gastroenterology - East Tennessee Children’s Hospital. 2 Pediatric Hematology/Oncology - East Tennessee Children’s Hospital Case Presentation Case Presentation Summary Background Pediatric gastric carcinoma is extremely rare, highly malignant and has a poor prognosis. Data is limited in regards of clinical presentation, treatment and outcomes in children. GAC is most frequently located in the antro-pyloric region. Symptoms can developed depending on the location of the tumor, presence of bleeding, ulceration, metastasis or systemic manifestations of malignancy. Family history of gastric and colorectal carcinoma have been linked to GAC. H. Pylori infection constitutes an additional risk factor. Our patient did not have polyposis or a prior history of carcinoma. He tested negative for germ line mutations, specifically CDH1, thus it was likely a de novo occurrence carcinoma. Therapeutic regimens for children are based on adult oncology experience and remain a significant challenge. Radical surgery is an essential treatment for children affected with GAC. Perioperative chemotherapy may improve the prognosis of this fatal condition. Large multi-institutional studies are not possible given the infrequent occurrence of GAC in children. Gastrointestinal tract (GIT) malignancies in children represent around 5% of all neoplasms in pediatrics. Primary gastric carcinoma is extremely rare, accounting for only 0.05% of GIT tumors1. Signet ring-cell is one type of gastric adenocarcinoma (GAC). It is an infiltrative tumor with isolated malignant cells that contains intracytoplasmic mucin2. Special stains, including mucin stains (PAS, mucicarmine, or alcian blue) or immunohistochemical stains with antibodies to cytokeratin are important markers for histologic diagnosis2. The majority of GAC arises sporadically. Occasionally, it occurs in families with germline mutations in TP53, BRCA2 and ATM5 genes. Germline mutations in the gene encoding the cell adhesion protein E-cadherin (CDH1) lead to hereditary diffuse gastric carcinoma (HDGC)3. Additionally, GAC can develop as part of the hereditary non-polyposis colon cancer (HNPCC) syndrome or as part of the GIT polyposis syndromes including familial adenomatous polyposis (APC and MUTYH genes) and Peutz-Jeghers syndrome2. Infection with Helicobacter pylori (H. Pylori) have been linked to GAC, especially vasAs1-, vasAm1- and cagA-positive genotypes4. Clinically, children can develop abdominal pain, anorexia, emesis, hematemesis, melena, anemia or abdominal distention secondary to ascites and bowel obstruction. Upper GIT endoscopy with biopsy is used as part of the initial evaluation. Radiographic studies aid the diagnosis and surgical strategy. We present a case of a teenager who was diagnosed with a poorly differentiated metastatic signet-ring cell GAC. Esophageal biopsies showed Candida esophagitis. Gastric biopsies confirmed H. Pylori gastritis, and an invasive signet-ring cell adenocarcinoma (Figure 3). Colonic biopsies were normal. Paracentesis confirmed signet-cell gastric adenocarcinoma and pleural fluid yielded signet-ring cells. Gene sequence analysis of APC, MUTYH, CDH1, TP53, and juvenile polyposis syndromes (BMPR1A and SMAD4 mutations) were negative. Human epidermal growth factor receptor 2 (HER-2/neu) overexpression was negative by fluorescence in situ hybridization (FISH) and immunohistochemical analysis. The patient developed severe gastroparesis and ileus. He needed palativeparacentesis and thoracostomy and developed pleural and hepatic metastasis. He was not a candidate for cytoreductive surgery of peritoneal disease, neither for hyperthermicintraperitoneal chemotherapy (HIPEC). He was treated with four cycles of neoadjuvant chemotherapy with ECF (epirubicin, cisplatin and fluorouracil) and a cycle of paclitaxel. His outcome was fatal 3-months after his initial diagnosis. A 15-year-old male previously healthy, presented with a 3 week history of abdominal pain and intermittent fever. Two weeks later, he developed abdominal distention and was treated for constipation. Family history was negative for hereditary gastric and colorectal malignancies. Abdominal MRI revealed massive ascites and pleural effusion with suspected omental caking of carcinomatosis. Abdominal positron emission tomography (PET/CT) scan was consistent with metastatic diseaseto peritoneal cavity (Figure 1). Upper endoscopy showed esophagitis, nodular gastritis, and a large gastric mass in the fundus invading the gastric wall. Colonoscopy exhibited coffee ground material in the right colon and nodular changes throughout the colon (Figure 2). Figure 3. Pathology Signet ring cell EGD: Nodular gastritis, large fundic mass (arrow). PET/CT: Metastatic diseaseto peritoneal cavity. Figure 1. CT Figure 2. Upper Endoscopy and Colonoscopy Benign gland Signet ring cell Invasive signet-ring cell adenocarcinoma. Tumor cells contain clear vacuoles filled with mucus that push the nuclei to the cell periphery creating a classical signet ring cell appearance. Abdominal MRI: diffuse ascites (head arrows), thick-walled small bowel (arrow). References 1 McGill TW, et al. Gastric carcinoma in children. J Pediatr Surg. 1993 Dec;28(12):1620-1. 2 Hamilton S.R., Aaltonen L.A. (Eds.): World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of the Digestive System. IARC Press: Lyon 2000 3 Huntsman, D, et al. Early gastric cancer in young, asymptomatic carriers of germ-line e-cadherin mutations. N Engl J Med. 2001; 344(25). 4 SubbiahV, et al. Gastric adenocarcinoma in children and adolescents. Pediatric Blood and Cancer. 2011;57(3):524-527. Colonoscopy: coffee ground material and nodular changes.