There are two types of problems one encounters with respect to metastatic carcinomas of the colon. The first is determining if a tumor in the intestine is primary or secondary, and the second reflects the need to distinguish a colorectal carcinoma metastatic to other sites from a primary tumor in that site.

When colon cancers metastasize, particularly in individuals with multiple primary cancers, distinguishing a metastatic colonic tumor from either a primary lung tumor or a metastasis from another site may be histologically difficult. One histologic feature helpful in suggesting the presence of a colonic primary lesion is the presence of “dirty necrosis” (324,823). This feature is particularly helpful when present in biopsy specimens. It is less helpful in cytology specimens, since intact tissues are usually not obtained. More often, however, one relies on the use of a panel of antibodies to distinguish between a variety of possible primary sites of origin. A battery of immunostains may help resolve this clinical conundrum. Antibodies to specific cytokeratins may help delineate the site of the primary lesion. Colon carcinomas are usually negative for cytokeratin-7 but positive for cytokeratin-20 (824,825). Used alone, neither cytokeratin immunostaining nor cytokeratin-20 immunostaining reliably separates the tumors. For example, the immunophenotype of cytokeratin-7+ cytokeratin-20- occurs in 86% of pulmonary adenocarcinomas and 0% of colonic carcinomas. Conversely, the cytokeratin-7- cytokeratin-20+ immunophenotype occurs in 77% of colon cancers and 0% of pulmonary tumors (638). TTF-1 immunoreactivity may also aid in distinguishing primary lung from metastatic colon cancers.