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There have been profound and fundamental changes in the significance of the histologic classification of bronchogenic carcinoma since the previous edition of this book. The past practice of simply dividing lung tumors into non–small-cell and small-cell lung carcinoma, particularly when evaluating small specimens in patients with advanced disease, was nearly always sufficient for providing the clinically relevant pathologic information that was necessary for treatment purposes. The development of new classes of drugs and targeted therapy for lung cancer has not only prompted an extensive reevaluation of the pathologic classification but has also affected strategies for tissue acquisition and routine processing. Rather than diminishing the traditional role of the pathologist in lung cancer treatment, the advent of what has been termed “personalized” or “precision” medicine has only made pathologic assessment more crucial to patient management.1,2 This chapter focuses on the major histologic subtypes of malignant pulmonary epithelial tumors and includes carcinoid tumors, sarcomatoid carcinoma, and salivary gland tumors. Other unusual tumors, both benign and malignant, are covered in a separate chapter and there is a separate chapter on the genetic and molecular changes in lung cancer. The extremely rapid pace of developments in molecular diagnostics and therapy makes it quite difficult to make enduring summary statements about the prognostic and therapeutic implications for specific histologic subtypes. The overall intent of the chapter is to provide a broad overview of the current histologic classification with its controversies and to provide a deeper understanding of the current issues regarding the preanalytic steps of sampling, processing, and evaluating lung cancer specimens for molecular analysis.

General Considerations in Histologic Classification and the Current Classification of Lung Tumors

Pathologic assessments are continually refined to reflect changes in surgical and medical management, as well as to incorporate an improved understanding of basic tumor biology. Once the diagnosis of malignancy has been made, the pathologic evaluation of lung cancer has traditionally focused on histologic subtyping and, for the minority of patients undergoing surgical resection, determining the extent of disease. Histologic classification is essentially predicated on the assumption that the quantitative predominance of a particular histologic pattern reflects distinctive biologic characteristics. It has been gratifying to note that concurrent developments in other disciplines such as molecular biology have substantiated many aspects of the currently accepted framework for histologic classification. The 2004 World Health Organization (WHO) classification of lung tumors was the first edition to extensively summarize the molecular biology of different tumor subtypes.3 Nevertheless, the main purpose of the 2004 WHO classification was to provide reproducible criteria to pathologists worldwide by using recognizable architectural patterns and individual cellular features that can be appreciated by routine light microscopy and standard hematoxylin- and eosin-stained slides. The use of ancillary techniques, such as immunohistochemistry or molecular biology, is not required in most instances, thereby making the classification accessible to all pathologists for diagnosis and fostering consistency in treatment and research protocols. ...

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