Extrapulmonary neuroendocrine carcinoma

Neuroendocrine carcinoma is a different disease from the well-differentiated tumours it shares a name with. The WHO classification defines it by poorly differentiated small-cell or large-cell morphology with a Ki-67 above 20 percent and usually far higher, and its genetics follow small-cell lung cancer, with loss of TP53 and RB1 rather than the MEN1, DAXX and ATRX mutations of neuroendocrine tumours; a subset of colorectal carcinomas carry BRAF V600E and a few are microsatellite unstable. Somatostatin receptor expression is usually weak, so FDG PET stages the disease where somatostatin receptor PET stages tumours, and mixed neuroendocrine-non-neuroendocrine neoplasms (MiNEN) combine a carcinoma component with adenocarcinoma or squamous carcinoma. Merkel cell carcinoma of the skin and neuroendocrine prostate cancer are covered on their own pages.

Treatment is borrowed wholesale from small-cell lung cancer. Moertel showed in 1991 that cisplatin with etoposide produced responses in most anaplastic neuroendocrine carcinomas, and platinum-etoposide has been first-line therapy since; the NORDIC NEC series (Annals of Oncology 2013) of 305 patients confirmed that most respond but relapse quickly, and found that carcinomas with a Ki-67 below 55 percent responded less often to platinum yet lived longer, an observation that helped separate grade 3 well-differentiated tumours from true carcinoma. Randomised evidence is scarce: the ECOG-ACRIN EA2142 trial compared capecitabine-temozolomide with platinum-etoposide in high-grade gastroenteropancreatic neoplasms and did not show the oral regimen superior, and the Italian SENECA trial found both CAPTEM and FOLFIRI active in the second line. Localised disease is resected or given chemoradiotherapy with perioperative platinum-etoposide, as in limited-stage small-cell lung cancer.