Discordance of Histologic Grade Between Primary and Metastatic Neuroendocrine Carcinomas

Background. The prognosis and management of neuroendocrine carcinoma are largely driven by histologic grade as assessed by mitotic activity. The authors reviewed their institutional experience to determine whether the histologic grade of neuroendocrine carcinoma can differ between primary and metastatic tumors. Methods. This study examined patients who underwent operative resection of both primary and metastatic foci of neuroendocrine carcinoma. Resected tumors were independently reviewed and categorized as low, intermediate, or high grade as determined by mitotic count. Results. The authors identified 20 patients with metastatic neuroendocrine carcinoma treated at their institution between 1997 and 2013 for whom complete pathologic review of primary and metastatic tumors was possible. Primary lesions were found in the small intestine (n = 12), pancreas (n = 7), ampulla (n = 1), stomach (n = 1), and rectum (n = 1). The timing of hepatic metastasis was synchronous in 15 cases and metachronous in 5 cases. The histologic grade was concordant between primary and metastatic tumors in 9 cases and discordant in 11 cases. Among the discordant cases, 7 had a higher metastatic grade than primary grade, and 4 had a lower metastatic grade than primary grade. Metachronous presentation was associated with a higher likelihood of grade discordance (p = 0.03). The histologic grade of all metachronous metastases differed from that of the primary tumors. Conclusion. There is a high prevalence of histologic grade discordance between primary and metastatic foci of neuroendocrine carcinoma, particularly among patients with a metachronous metastatic presentation. Given the importance of histologic grade in disease prognostication and treatment planning, this finding may be informative for the management of patients with metastatic neuroendocrine carcinoma.