Colorectal glandular-neuroendocrine mixed tumor: pathologic spectrum and clinical implications

Colorectal glandular-neuroendocrine mixed tumor is an uncommon entity with ill-defined clinicopathologic characteristics. We describe the clinicopathology of 23 new cases and review 67 previously reported cases. Clinically, patients (mean age, 61.9 y; male: female, 1.0:1.1) presented with a positive fecal occult blood test or visible rectal bleeding (44%), abdominal pain or change in bowel movement pattern (25%), bowel obstruction (19%), or weight loss (19%). Endoscopically, the tumors presented as a polypoid lesion (57%), a mass lesion (30%), or an ulcerating lesion (9%). Tumors were located in the right colon (56%), transverse colon (3%), and left colon (41%). Surgical resection was the treatment of choice in 83% of cases. After follow-up for an average of 20 months, the tumor-related death rate was 68%. Histologically, 42% were classified as composite tumors and 58% were classified as collision tumors. An adenoma to carcinoma, and then carcinoma to mixed tumor progression through the APC/β-catenin pathway was seen in a majority of cases. Both the glandular and the neuroendocrine components of the mixed tumor can show a spectrum of differentiation, and each component can metastasize separately regardless of its percentage volume. On the basis of the combined analysis of the pathologic spectrum and the clinical behavior of our series and previously reported cases, we propose a new classification system that reflects the differentiation of each component in colorectal glandular-neuroendocrine mixed tumor to facilitate uniform reporting and to better predict its clinical behavior.