Malignant epithelial neoplasms of the large bowel

Colorectal cancer is a common clinical problem and a major contributor to the pathologist's workload. There are a number of important inherited syndromes leading to the disease and study of these has contributed significantly to our understanding of the biological basis of cancer. The aetiology of colorectal carcinoma is complex and probably depends on interplay between environmental and endogenous genetic factors. It is now recognised that, although cancer does usually develop from adenomatous polyps, there are several distinct pathways involving chromosomal instability, DNA methylation and mismatch repair defects. Distinct morphological pathways including the conventional adenoma-carcinoma sequence, as well as the serrated route to cancer, have been characterised. There have been major advances in recognition of the importance of macroscopic assessment and handling of cancer resection specimens. The pathologist has a key role in quality assurance of surgical treatment. Staging is best done through the TNM system but there are some problematic areas of disagreement regarding recent revisions of TNM in colorectal cancer. Microscopic prognostic features include tumour differentiation, margin involvement and venous invasion. Identification of tumour budding is a promising new tool in guiding prognosis. The advent of population screening for bowel cancer means that more cases are diagnosed at an early stage. Local resections are more common and the role of the pathologist is often to identify patients who will benefit from further excision. Molecular pathology has now arrived as part of the clinical assessment of the bowel cancer patient. Identification of microsatellite instability and immunohistochemical assessment of mismatch-repair protein expression may lead to detection of families with Lynch's syndrome. K-ras mutation analysis of tumour tissue is required in determining the likelihood of response to anti-epidermal growth factor receptor (EGFR) therapy with cetuximab.