Dysplasia of Nonmetaplastic Gastric Mucosa

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Abstract
In a review of 192 gastric resections, histological changes believed to represent dysplasia of nonmetaplastic gastric epithelium were observed. This paper presents a proposal for their classification. The main feature of this dysplasia is replacement of the differentiated cells lining the glands by undifferentiated cells with varying degrees of cytological abnormalities and cellular pleomorphism, but with absence of architectural glandular derangement. The classification is justified by cytokinetic and histologic observations in experimental gastric arcinogenesis and early human gastric carcinoma. The severity of the changes is graded, first, by the extent of involvement of the gland (crypt) as measured from the proliferative zone (PZ), and, second, by the degree of cytological abnormality. It utilizes a modificaton of the terminology of Riddell et al. (45) for dysplasia in inflammatory bowel disease wherein the term "dysplasia" denotes intraepithelial neoplasia. The changes are classified into (a) negative for dysplasia, (b) atypical, i.e., indefinite for dysplasia, and (c) positive for dysplasia. Changes negative for dysplasia are considered regenerative and consist of enlargement and vesicular transformation of the nucleus in the cells of the PZ and adjacent part of the crypt. Atypical changes consist of equivocal lesions difficult to classify as definitely regenerative or definitely dysplastic, and are hence called indefinite for dysplasia. They consist of loss of cytoplasmic differentiation of the cells lining the glands (i.e., mucus production and parietal and chief cell differentiation) with increased nuclear-cytoplasmic ratio and moderate cytological atypically. Based on the extent of gland involvement, the group with atypical mucosa is subdivided into two categories.sbd.atypical, probably negative for dysplasia (AtN) and atypical, probably positive for dysplasia (AtP). Mucosa exhibiting unequivocal cytological features of neoplsia with cellular and nuclear pleomorphism is classified as positive for dysplasia (D). This is subdivided into low-grade and high-grade dysplasia, the latter representing carcinoma in situ. Glandular architecture remains undisturbed in all stages and the cells remain cuboidal, without transformation into intestinal-type cells. This type of dysplasia was found in a significantly higher number of difffuse-type carcinomas than in intestinal-type carcinomas. The previously well-recognized adenomatous or metaplastic dysplasia was significantly more prevalent in intestinal-type carcinoma than in diffuse-type. We believe that this non-metaplastic dysplasia represents a second pathay in the genesis of gastric carcinoma, possibly the diffuse type, and would thus serve as an additional indicator of individuals at risk for gastric cancer. Our findings suggest that the Pz is the site of origin of this dysplasia.

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