Current concepts in the diagnosis and management of poorly differentiated gastrointestinal neuroendocrine carcinomas

Abstract

Poorly differentiated neuroendocrine carcinomas (PDNEC) are rare tumours that can originate from any site of the gastrointestinal tract exhibiting an overall aggressive behaviour that may vary between tumours according to the degree of cellular proliferation. The majority of PDNEC are locally advanced or metastatic at presentation, and are only infrequently associated with secretory hormonal syndromes. PDNEC exhibit aggressive histological features (high mitotic rate, high Ki67 labelling index and presence of necrosis) and are further subdivided into two morphological subgroups, small and large cell variants. As PDNEC express somatostatin receptors less frequently, somatostatin receptor scintigraphy is usually negative, whereas 18F-fluorodeoxyglucose positron emission tomography appears to be the best method of evaluating disease spread and guiding further treatment. PDNEC have traditionally been treated similarly to small cell lung carcinoma, although they show a number of different clinical and histopathologic features. First line systemic chemotherapy with a platinum-based agent and etoposide is used for patients with metastatic disease, leading to variable response rates that are often of relative short duration. Sequential or concurrent chemoradiation is recommended for patients with locoregional disease. In patients with localised disease, complete surgical resection should be offered followed by adjuvant treatment (chemotherapy with or without radiotherapy); the value of neoadjuvant chemotherapy has not been evaluated as yet. The role of second line therapies is evolving, with temozolomide being a promising agent. However, the majority of data regarding PDNEC is hampered by the small number of series and their retrospective nature, making it important that multicentre co-operative studies be performed.