Clinicopathologic Aspects of Neuroendocrine Tumors of the Lung

The WHO classification published in 1999 defines four major subtypes of pulmonary neuroendocrine tumor: typical carcinoid, atypical carcinoid, large cell neuroendocrine carcinoma, and small cell carcinoma. Although the clinicopathologic characteristics of each subtype (especially large cell neuroendocrine carcinoma) have been in dispute, some of them were recently clarified by a Japanese multicenter study. Accurate histopathologic diagnosis of these tumors requires correct recognition of neuroendocrine morphology, ancillary examinations such as immunohistochemistry, strict application of histopathologic criteria, and understanding of the clinicopathologic significance of each subtype. Diagnostic accuracy in distinguishing low-from high-grade tumors seems to be high, whereas it is low for differential diagnosis between large cell carcinoma and small cell carcinoma. Because the latter two subtypes also closely resemble one another in demographic and molecular aspects, their separation in the classification scheme will likely be discussed and reconsidered in the future. As large cell neuroendocrine carcinoma is known to have a poor prognosis after surgery alone, a standard adjuvant therapy should be established based on the accurate pathologic diagnosis of this subtype, not only postoperatively but also preoperatively.