Large Cell Neuroendocrine Carcinoma of the Lung: Is it Possible to Diagnose from Biopsy Specimens?

Abstract

We have recently proposed new diagnostic criteria for high-grade non-small cell neuroendocrine carcinoma, i.e. possible large cell neuroendocrine carcinoma, in biopsy specimens and have started a clinicopathological comparative study of high-grade neuroendocrine carcinomas in an advanced stage. This study aimed to elucidate the usefulness of our diagnostic criteria for inoperable advanced large cell neuroendocrine carcinoma and to know the true incidence of large cell neuroendocrine carcinoma among lung cancers. We reviewed all cancer lesions (1040 specimens) obtained by transbronchial lung biopsies in our hospital from 2002 to 2009 and selected 38 biopsy specimens that satisfied our diagnostic criteria for high-grade non-small cell neuroendocrine carcinoma. All 38 cases were clinicopathologically investigated and all biopsy specimens were precisely studied for their morphological characteristics. Clinicopathological information about the selected 38 cases was very similar to the clinicopathological characteristics of large cell neuroendocrine carcinoma reported. Of 38 cases, six were at Stage I, II or IIIA, underwent surgery, and the diagnosis was confirmed to be large cell neuroendocrine carcinoma using surgical tumor specimens. In the 38 biopsy specimens, features of neuroendocrine morphology such as organoid nesting, peripheral palisading and rosette formation were not frequent histological features and the majority of tumor cells contained nuclei with a fine chromatin pattern. Mitoses were difficult to find; however, immunohistochemical Ki-67/MIB1 labeling indices were quite useful for evaluating proliferative activity, which ranged from 43.4 to 99.0%. Our study showed the diagnostic potential of using biopsy specimens for large cell neuroendocrine carcinoma, and we herein proposed more simplified diagnostic criteria for possible large cell neuroendocrine carcinoma in practical diagnostic use.