Clinicopathologic and immunohistochemical study of small apparently "de novo" colorectal adenocarcinomas

Rarely, adenocarcinomas of the colorectum develop as small (< or =1.0 cm) rapidly invasive tumors without an obvious adenomatous or "in situ" component. These tumors have been termed "de novo" carcinomas. Although it is believed by some that these tumors are more aggressive than conventional large adenocarcinomas with an identifiable in situ component, little is known about the biologic characteristics and natural history of these lesions. The aim of this study was to evaluate and compare the pathologic features, biologic characteristics, and natural history of small apparently de novo invasive colorectal adenocarcinomas with conventional large (>1.0 cm) carcinomas. Routinely processed specimens from 20 patients (M/F ratio: 13/7; mean age: 65 y) with small apparently de novo invasive colorectal adenocarcinomas (all < or =1.0 cm in size) were evaluated for a variety of clinical and pathologic features. In addition, immunostains for p53, beta-catenin, DPC4, hMLH1, hMSH2, and MGMT were evaluated in all cases. The findings in this group of cases were compared with those from 20 control patients (M/F ratio: 8/12; mean age: 60 y) with stage-matched conventional "large" colorectal adenocarcinomas (all >1.0 cm in size). Patients were followed for a mean of 52.6 and 60.6 months, respectively, for the 2 groups. Small apparently de novo invasive adenocarcinomas were present in the left colon, transverse colon, and right colon in 85%, 10%, and 5% of cases, respectively. Their mean size was 7 mm (range: 3 to 10 mm). All cases were stage T1 and the majority were moderately differentiated (75%). Only 1 (5%) patient had lymph node metastases. Two (10%) cases were mucinous and only 1 (5%) showed prominent tumor infiltrating lymphocytes. Upon complete sectioning of the tissue blocks of tumor, residual foci of adenomatous epithelium were present in 16/20 (80%) cases, of which 75% contained foci of high-grade dysplasia. P53 and nuclear beta-catenin staining was present in 70% and 85% of cases, respectively, but only 5 cases (25%) showed loss of DPC4. Loss of MGMT expression was seen in 5 cases (25%), loss of hMSH2 in only 1 case (5%), and none showed loss of hMLH1. Only 2 patients (10%) developed visceral metastases upon follow-up. Control patients had similar demographic features, clinical outcome, anatomic distribution of tumors, degree of differentiation, and prevalence of positivity for the immunostains noted above, to the study cases. In our patient population, true small de novo colorectal adenocarcinomas, tumors that lack an identifiable adenomatous component, are exceedingly rare, because complete tissue sectioning reveals residual adenomatous tissue in the majority of cases. The biologic characteristics and natural history of small carcinomas with a minimal dysplastic component, and those with no identifiable adenomatous component, are similar to conventional large (>1 cm) adenocarcinomas, and, thus, they should probably be treated similarly.