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The development of new classes of drugs and targeted therapy for lung cancer prompted an extensive reevaluation of the pathologic classification of bronchogenic carcinoma but did not diminish the significance and impact of the histologic classification of bronchogenic carcinoma. Rather than marginalizing 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 The clinical necessity of providing rapid and concurrent molecular/immunologic analysis along with a histologic diagnosis has placed the anatomic pathologist in the additional central strategic management role of tumor tissue processing and evaluation, in addition to frequent consultation on optimal sample acquisition. 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 another 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. New molecular and immunologic insights are leading to entirely new classes of drugs that are continuously impacting, and in some cases dramatically improving, overall survival statistics. The intent of this chapter, therefore, is to provide a broad overview of the current histologic classification and to provide a deeper understanding of the critical issues regarding the preanalytic steps of sampling, processing, and evaluating lung cancer specimens for molecular analysis.


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 had been made, the pathologic evaluation of lung cancer had traditionally focused on histologic subtyping and, for the selected subset of patients undergoing surgical resection, determining the pathologic stage 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, was not required in most instances, thereby making the classification accessible to all pathologists for diagnosis and fostering consistency ...

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