CEA-Producing Mucin-Negative Gastric Signet-Ring Cell Carcinoma With Neuroendocrine Markers

Abstract

Biopsy and autopsy materials excised from a 69-year-old woman were investigated. Serum carcinoembryonic antigen (CEA) showed a high value of 955 ng/mL. A plateaulike tumor was located in the gastric cardia and fundus to the entire gastric body. It showed severe proliferation and infiltration from the mucosa to the serosa. The tumor was comprised of signet-ring cells and poorly differentiated adenocarcinoma cells, which spread into the submucosa of the pylorus, duodenum, and jejunum. Signet-ring cells had a large, eccentric vesicular nucleus and a pale cytoplasmic inclusion. Poorly differentiated adenocarcinoma cells had a pleomorphic nucleus, small eosinophilic nucleolus, and abundant eosinophilic cytoplasm. Both neoplastic cells were positive for CEA, epithelial membrane antigen, Leu-7 (CD57), and neuron-specific enolase, and were negative for cytokeratin, vimentin, and periodic acid-Schiff, Alcian blue, and mucicarmine stains. Electron microscopy showed endocrine granules with a limiting membrane measuring approximately 238 nm in diameter in the cytoplasm. The authors diagnosed this patient as having mucin-negative gastric signet-ring cell carcinoma with neuroendocrine markers, which is suggested to exist among poorly differentiated adenocarcinoma, undifferentiated carcinoma, and signet-ring cell carcinoma.

Signet Ring Cells in Gastric Carcinomas Are Derived from Neuroendocrine Cells

“…Previously, two cases of gastric cancer with neuroendocrine differentiation in neutral and acid mucin-negative signet ring cells have been reported (Morii et al 1999;Sugihara et al 2004), and a few case reports have described mucin-positive gastric signet ring cells with neuroendocrine markers (Tahara et al 1975;Prade et al 1982).…”

“…This study demonstrates that in 8/11 diffuse gastric cancers with signet ring cells, a proportion of PAS-positive signet ring cells express one or more neuroendocrine markers, a finding previously reported to be rare. Previously, two cases of gastric cancer with neuroendocrine differentiation in neutral and acid mucin-negative signet ring cells have been reported (Morii et al 1999; Sugihara et al 2004), and a few case reports have described mucin-positive gastric signet ring cells with neuroendocrine markers (Tahara et al 1975; Prade et al 1982).…”

HER-2-positive primary neuroendocrine neoplasms of the breast with signet ring feature: A case report and review of literature

“…NENs with the signet ring feature is characterized by eccentric, pale, or eosinophilic intracytoplasmic vacuoles that lead to various terms from ‘‘paranuclear clear zone” ( 3 , 5 ), ‘‘signet cell” ( 4 , 7 – 9 , 15 , 16 ), to ‘‘rhabdoid” ( 10 – 14 ) according to their light microscopic appearances. These intracytoplasmic inclusions are presumed to be caused by abnormalities in the metabolism and organization of intermediate filament-cytokeratin ( 3 – 5 , 12 ).…”

Tumor Classification Should Be Based on Biology and Not Consensus: Re-Defining Tumors Based on Biology May Accelerate Progress, An Experience of Gastric Cancer

“…In another study, the neuroendocrine marker chromogranin A was expressed in an important portion of signet-ring cell carcinomas, and patients had better prognoses if chromogranin A was expressed in the cancer cells [72], indicating that this expression was lost during the process of malignancy. Moreover, signet-ring cells need not express PAS/Alcian-blue positivity but may be strongly positive for neuroendocrine markers [73,74]. Interestingly, signet-ring cell carcinoma secondary to hypergastrinemia has been described [75], further strengthening the assumption that signet-ring cell carcinomas are NECs and often of ECL cell origin.…”