Large Cell Neuroendocrine Carcinoma of the Lung: In Search for a Better Definition

Pulmonary large cell neuroendocrine carcinoma (LCNEC) represents a controversial entity that has been associated with difficulties for diagnosis. The sources for these difficulties are multiple, including lack of stringent morphologic criteria, variable immunohistochemical profile, and variable molecular profile that share overlap with other tumors of the lung. There appears to exist a spectrum of lesions in the lung that have the potential to overlap with LCNEC, compounding the difficulties inherent in making a diagnosis for what is essentially a rare lesion that most general pathologists have limited experience with. Moreover, the broad definition of LCNEC by the World Health Organization (WHO) has the potential for classifying tumors that may not clearly belong in this group under this category. Herein we will discuss the criteria for light microscopic, immunohistochemical, and molecular diagnostic features of LCNEC along with a discussion of some of the problems encountered in the interpretation of these tumors. The differential diagnosis is also discussed, including tumors that may show similar neuroendocrine-like morphology.