Pulmonary Neuroendocrine Tumors: Carcinoid Tumors, Atypical Carcinoids, Large Cell Neuroendocrine Carcinoma, and Small Cell (Undifferentiated) Carcinoma

Abstract

The spectrum of pulmonary neuroendocrine tumors is very wide, encompassing several diagnostic entities. Their classification is quite complex, as is the terminology. Some neoplasms are encountered more frequently than are others. Not all are identified in cytologic specimens, especially the preneoplastic neuroendocrine lesions that are included in the most recent World Health Organization (WHO) and International Association for the Study of Lung Cancer (IASLC) classification of the lung tumors. This chapter will focus only on neoplasms that are more frequently encountered, including: (1) typical carcinoid tumor; (2) atypical carcinoid tumor; (3) large cell neuroendocrine carcinoma; and (4) small cell (undifferentiated) carcinoma. These four neoplasms present a spectrum of morphologic features ranging from benign-appearing uniform cellular patterns to highly anaplastic ones. Their biologic behavior likewise ranges from that of a benign protracted course in typical carcinoid to an aggressive one with a fatal outcome, as seen in large cell neuroendocrine and small cell carcinomas. Despite the differences, pulmonary neuroendocrine tumors share several features: namely, their origin (Kulchitsky cells), certain morphologic features (e.g., neuroendocrine growth patterns), and positive reactivity to most neuroendocrine markers. They all ultrastructurally exhibit dense core neurosecretory granules, and some are associated with ectopic hormone production.