High-grade Neuroendocrine Carcinoma of the Lung With Carcinoid Morphology: A Study of 12 Cases

Twelve lung neuroendocrine tumors with morphologic features of carcinoid tumors but with mitotic count >10/2 mm are reported. There were 7 males and 5 females, with age ranging from 56 to 78 years. Four cases were from never-smokers. All tumors showed architectural and cytomorphologic features of carcinoid tumor, including organoid nesting, insular, trabecular, or acinar growth, and tumor cells with low nucleocytoplasmic ratio, abundant cytoplasm, ovoid to round nuclei, and salt and pepper chromatin. Angulated or confluent nesting, insular or lobular growth pattern was also seen. Nuclear irregularities and anisonucleosis were focally present. Mitotic count ranged from 11 to 61/2 mm. Punctate-type necrosis was present in 8 tumors. Anaplastic cytology, large infarct-type necrosis, desmoplasia, or marked inflammatory infiltrate was not found in any of the tumors. One tumor occurred in the background of diffuse idiopathic pulmonary neuroendocrine hyperplasia. All tumors were treated by resection, and all but 1 patient subsequently developed metastasis, and 7 died of the tumor. For metastatic tumors, 4 patients were treated by platinum-based chemotherapy with no apparent response, whereas 3 other patients were treated by combined capecitabine and temozolomide—novel chemotherapy for well-differentiated neuroendocrine tumor/carcinoid tumor—2 of them responded. This subset of tumor would be classified as large cell neuroendocrine carcinoma according to the current WHO classification scheme, but their clinical and pathologic features appear to have more in common with the carcinoid tumor group than large cell neuroendocrine carcinoma, therefore, identification of this subset may be relevant for further therapeutic management.