You Just Can't Call it Lung Cancer Anymore

Abstract

The optimal treatment of lung cancer relies on accurate histopathologic diagnosis. This is usually accomplished with a limited amount of tissue, on which multiple tests must be performed to enable the histologic, immunohistochemical, and molecular characterization of tumors. In this issue of the journal, Travis1 has succeeded in his attempt to “think like the clinician” by better pathologically classifying adenocarcinoma. His success will facilitate the most appropriate treatment for patients with non-small cell lung cancer (NSCLC). Although interest in this subject must have been present for some time, several events accelerated the need for such a document. The first was the increased availability and use of chest computed tomography, which led to the identification of early-stage tumors with distinct radiographic features, some of which could not have been identified in the era of chest radiographs. A proportion of these lesions (e.g., ground glass opacities) could not be adequately defined by the previously available pathologic definitions. Further, the clinical behavior of these tumors was distinctly different when compared with the more commonly seen invasive cancers. Second, molecular aberrations with prognostic and predictive significance were identified and needed to be considered to optimize histopathological diagnoses.2,3 Third, the recent findings that commonly used therapeutic agents can selectively benefit patients with specific histologic phenotype, and molecular characteristics created the need for better definitions of NSCLC, particularly adenocarcinoma, which was addressed in this document.4–6 NSCLCs are clinically, pathologically, and molecularly heterogeneous entities. This diverse group, often with overlapping features, makes the demarcation of NSCLCs into histopathologically distinct subentities challenging. Nevertheless, successfully accomplishing this has never been so important because treatment selection is now integrally dependent on the histologic phenotype and the molecular genotype. The authors have attempted to accomplish this by tackling potential “areas of confusion” for practicing pathologists, radiologists, and clinicians. It is critically important to emphasize that obtaining adequate amounts of tissue at the time of diagnosis is essential, so that second interventional biopsies can be eliminated. Clinicians can no longer be satisfied with a diagnosis of NSCLC when making treatment decisions. Nevertheless, there are opposing forces at work as it relates to tissue acquisition and processing. On the one hand, minimally invasive access to tumor using technologies such as endobronchial ultrasound guided or transthoracic needle biopsy is increasing at a time when more tests need to be performed with each specimen. Reverting back to more invasive techniques for obtaining a larger volume of tissue for comprehensive testing is unrealistic. Therefore, the onus is on us to develop instruments that provide minimally invasive access while enabling pathologists to receive adequate tissue for analysis. The optimal utilization of tissue is also paramount. In most patients, histomorphological and molecular features can be appropriately characterized. The team must decide how to optimally use the available tissue. Travis tackled this problem by suggesting that pathologists minimize the use of immunohistochemical stains, so that more tissue is available for molecular diagnosis. We concur with this recommendation because treatment