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Invited Commentary

¹ Department of Radiologic Pathology, Armed Forces Institute of Pathology Washington, DC

The lung is a frequent site of origin for neuroendocrine carcinogenesis. Part of the etiology can be found in exposure to cigarette smoke and is associated with a partial deletion of the short arm of chromosome 3 in tumor cells. In 1999, an updated concept of neuroendocrine tumors was added to the World Health Organization (WHO) classification (1). At that time, the spectrum of pulmonary neuroendocrine neoplasia included typical carcinoid, atypical carcinoid, small cell lung carcinoma (SCLC), and a neuroendocrine variant of large cell carcinoma (LCNEC). Although these tumors share a variety of morphologic and immunohistochemical characteristics, they continue to be classified separately because of widely varying prognosis and response to therapy. Typical and atypical carcinoids are considered low-grade malignancies with a lower mitotic rate and better survival than SCLC and LC-NEC, which are high-grade malignancies. Atypical carcinoid is a more aggressive lesion than typical carcinoid and has a survival that is intermediate between that of typical carcinoid and those of the high-grade neuroendocrine malignancies SCLC and LCNEC (2). These concepts of neuroendocrine pulmonary tumors were continued in the newest release of the WHO classification in 2004 (3).

In general, recognition of well-differentiated neuroendocrine neoplasms in the lung is not difficult for the pathologist. The typical findings at light microscopy of an organoid growth pattern with uniform nests and rosette-like structures are sufficiently distinctive for a confident diagnosis. However, a more common and perplexing clinical scenario includes a lung mass or nodule in which the tumor demonstrates focal neuroendocrine features at light microscopy but is predominantly poorly differentiated and the clinical team requires additional input in order to make a diagnosis and determine optimum treatment. In addition, some lung tumors will demonstrate neuroendocrine differentiation at electron microscopy or immunohistochemistry alone without light microscopic confirmation. These tumors are referred to as non–small cell tumors with neuroendocrine differentiation (4). The clinical importance of this form of neuroendocrine differentiation is not currently known. It is in these circumstances that the imaging features may provide important clues to the diagnosis.

The preceding article by Chong et al (5) provides an excellent review of the key imaging features of neuroendocrine lung neoplasms. Both typical carcinoids and atypical carcinoids manifest as predominantly central, well-defined nodules. Atypical carcinoids tend to be larger and have a slightly greater tendency to be peripheral. However, there is substantial overlap. The findings in LCNEC are similar to those of other non–small cell lung carcinomas. The tumors are well defined and predominantly peripheral with an increasingly heterogeneous pattern of enhancement in larger examples. SCLCs have the most distinctive appearance with large central masses and mediastinal or hilar adenopathy in the majority.

The accurate diagnosis of lung neoplasms has always been complicated by their acknowledged heterogeneity. Lung tumors often exhibit mixtures of cell types, and as yet the clinical importance of neuroendocrine admixtures remains to be determined. In addition, it is unclear whether neuroendocrine differentiation confers a unique morphologic appearance at imaging. The histologic diagnosis, imaging features, and treatment of lung neoplasms with neuroendocrine features will require continued collaborative research if we are to unlock their true meaning.

	Footnotes

 
Financial Interest: The author has no financial relationships to disclose.

	References

Top References

 

1. Travis WD, Colby TV, Corrin B, et al. Histological typing of lung and pleural tumors. International Histological Classification of Tumors. 3rd ed. Berlin, Germany: Springer-Verlag, 1999.
2. Beasley MB, Frederik MD, Thunnissen BJ, et al. Pulmonary atypical carcinoid: predictors of survival in 106 cases. Hum Pathol 2000;31:1255–1265.[CrossRef][Medline]
3. Travis WD, Brambilla E, Muller-Hermelink HK, Harris CC. Pathology and genetics of tumours of the lung, pleura, thymus and heart. Lyon, France: IARC Press, 2004.
4. Travis WD, Linnoila RI, Tsokos MG, et al. Neuroendocrine tumors of the lung with proposed criteria for large-cell neuroendocrine carcinoma: an ultrastructural, immunohistochemical, and flow cytometric study of 35 cases. Am J Surg Pathol 1991; 15:529–553.[Medline]
5. Chong S, Lee KS, Chung MJ, Han J, Kwon OJ, Kim TS. Neuroendocrine tumors of the lung: clinical, pathologic, and imaging findings. RadioGraphics 2006;26:41–58.[Abstract/Free Full Text]

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