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.