A variant of early gastric carcinoma. Histologic and histochemical studies of early signet ring cell carcinomas discovered beneath preserved surface epithelium

Abstract

Gastric carcinomas hidden beneath flat and intact mucosal surface epithelium are rarely discovered. Such a tumor in the early stage is at best diagnosed as an incidental finding, so that the diagnosis is probably always a surprise to the clinician. Six such cases of early gastric carcinoma were presented. Four were intramucosal lesions and the remaining two were invasive with submucosal extension. All the tumors are composed purely of signet-ring cells (diffuse-type by Lauren's classification). Histologic examination of the six cases revealed that certain features, which are not characteristically observed in ordinary signet-ring cell carcinomas, were commonly recognized. These included compact nests of uniform signet-ring cells sharing a common cytoplasmic wall, lack of desmoplastic stromal response, and intracytoplasmic mucin predominantly composed of neutral mucopolysaccharide. These six tumors are considered to be an incipient stage of signet-ring cell carcinoma. The findings also suggest a close histogenetic relationship between these tumors and the mucous neck cells in the basal region of gastric glands. The grossly unremarkable mucosal surface and histologically innocuous appearance associated with this form of tumor are emphasized for diagnosis.

Nonneoplastic signet-ring cells in the gallbladder and uterine cervix. A potential source of overdiagnosis

“…The signet-ring cell appearance, which is usually due to the accumulation of mucin in the cytoplasm of malignant glandular cells accompanied by nuclear deformation and lateral displacement, has been classically considered the hallmark of a distinctive type of adenocarcinoma of the stomach (also known as diffuse carcinoma and linitis plastica) [2] and breast (thought to be in most cases a variant of lobular carcinoma) [3]. It later became apparent that adenocarcinomas with a similar morphology and intracellular mucin content could develop in a large number of epithelial-lined organs (Table 1).…”

“…The term signet-ring cell adenocarcinoma has been traditionally applied to a subtype of aggressive high-grade adenocarcinoma typically located in the stomach (also known as diffuse carcinoma and linitis plastica) [2] and breast [3]. Signet ring-cell adenocarcinomas with a similar appearance have subsequently been described in a large number of epitheliallined organs (Table 1).…”

The maturation of mucus-secreting gastric epithelial progenitors into digestive-enzyme secreting zymogenic cells requires Mist1

“…An exigency for studying neck-to-ZC differentiation is that this developmental pathway is aberrant in the precancerous state of chronic gastric atrophy (Houghton et al, 2004;Katz et al, 2005;Nomura et al, 2005;Shiotani et al, 2005), and mucous neck-like cells form the bulk of tumor cells in diffuse-type, signet ring adenocarcinomas (Yamashina, 1986;Charlton et al, 2004). Despite the abundant evidence for aberrant ZC differentiation in carcinogenesis, little is known about the molecular and cellular details of the defects.…”

Hereditary diffuse gastric cancer

“…DGCs identified in patients with HDGC are characterized by multiple infiltrates of malignant signet ring cells that may underlie the normal mucosa. [32][33][34] The wide distribution and small size of the malignant foci make them difficult to identify with random endoscopic biopsy. 32 Chromoendoscopy-aided biopsies have been used, but this approach only detects lesions >4 mm and, thus, has limited utility in diagnosing early HDGC.…”