Intestinal epithelial lesions associated with signet ring cell carcinoma of the colon and small intestine

Aims: The purpose of this study was to investigate the epithelial lesions associated with signet ring cell carcinoma (SRCC) of the colon and small intestine and the possible mechanism of tumour development. Methods: Twenty-seven cases of adenocarcinoma with a signet ring cell (SRC) component of the colon and small intestine were divided into three groups depending on the association of the SRCC with: (1) epithelium without definite epithelial dysplasia, (2) adenoma, and (3) common type of adenocarcinoma (CTCA) with SRCC component occupying more than 50%, 30%, or less than 30% of the tumour. Results: Most carcinomas were of T3 or T4 type, using the TNM standard staging system. The SRCC component was histopathologically similar in all groups. In group 1 (four cases, linitis plastica type), the overlying epithelium was normal or showed indefinite epithelial dysplasia and occasionally contained intra-epithelial SRCs. In groups 2 and 3 (two and 21 cases, respectively), seven cases contained multiple foci of intra-epithelial SRCs in areas separated from the invasive carcinoma. Transitional areas between SRCC and adenoma or CTCA were also identified. Immunostaining for p53 showed a varied extent of positive reactivity in 23 SRCC. The degree and the extent of reactivity appeared to increase with the stage of the carcinoma. Most intraepithelial SRCs were immunoreactive for p53. Linitis plastica SRCC was associated with extensive p53 reactivity of the 'atypical' and the adjacent 'normal' epithelium. Conclusions: SRCC may arise from either CTCA, adenoma, 'atypical' epithelium or a combination of these epithelia. SRCC accounts for the bulk of carcinoma in each of these categories. In linitis plastica SRCC, positive reactivity for p53 is extensive in the adjacent 'normal' colonic epithelium and extends as far as 3cm from the microscopically identified SRCC margin.