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An Extremely Rare Type of Gastric Carcinoma in a Teenager Male Diana Moya 1 , John S. Corns 2 , Wendy L. Taylor 1 , Clarisa Cuevas 1 , M. Samer Ammar 1 , Susan E. Spiller 2 , Youhanna Al-Tawil 1 - PowerPoint PPT PresentationTRANSCRIPT
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.
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.
Background Case Presentation Case Presentation Summary
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 Subbiah V, et al. Gastric adenocarcinoma in children and adolescents. Pediatric Blood and Cancer. 2011;57(3):524-527.
References
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
disease to 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).
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
palative paracentesis and thoracostomy and developed pleural and
hepatic metastasis. He was not a candidate for cytoreductive
surgery of peritoneal disease, neither for hyperthermic
intraperitoneal 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.
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
Colonoscopy: coffee ground material and nodular changes.EGD: Nodular gastritis, large fundic mass (arrow).
Figure 2. Upper Endoscopy and Colonoscopy
Benign gland
Signet ring cell
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.
Figure 3. Pathology
Abdominal MRI: diffuse ascites (head arrows), thick-walled small bowel (arrow).
Figure 1. CT
PET/CT: Metastatic disease to peritoneal cavity.