69: Role of the Pathologist and Pathology- Specific Treatment of Lung Cancer

Introduction

A pathologist experienced in thoracic oncology is an essential member of the thoracic team. Surgical resection related to lung cancer and other pulmonary pathology accounts for the largest proportion of current thoracic practice. The goals of pathologic analysis of surgical lung specimens are to classify the lung cancer, determine the extent of its invasion (i.e., pleural, lymphovascular, soft tissue, or chest wall), and establish the status of the surgical margins for cancer involvement.¹ Accurate disease identification and staging are of pinnacle importance to the decision-making process and influence the diagnosis (benign or malignant), course of treatment, selection of optimal surgical approach, and pursuit of appropriate adjuvant and neoadjuvant therapies such as chemotherapy, radiation, and other innovative approaches to treatment. Further, determination of the specific molecular abnormalities of the tumor is critical for predicting sensitivity or resistance to a growing number of drugable targets primarily tyrosine kinase inhibitors (TKIs).^2,3 After a malignancy has been identified, the pathologist must determine whether the tumor is primary or metastatic. Most tumors found in the lung represent metastatic foci from distant primaries, such as breast and colon cancer, as opposed to a primary lung malignancy. While the pathologic features of metastatic versus primary adenocarcinoma may be similar, for example, the treatment course is not. Immunohistochemistry (IHC) is required to make the distinction and has proved to be an invaluable diagnostic adjunct. Primary malignant tumors of the lung are most often of epithelial or mesenchymal origin. The epithelial tumors are broadly divided into small-cell lung cancer (SCLC) and non–small-cell lung cancer (NSCLC). NSCLC is further classified as squamous cell carcinoma (SCC), adenocarcinoma, and large-cell carcinoma (LCC).⁴ The World Health Organization (WHO) tumor classification system has historically provided the foundation for the classification of lung tumors, including histologic types, clinical features, staging considerations as well as the molecular, genetic, and epidemiologic aspects of lung cancer.^4–6

The pathologist plays a fundamental role in the preoperative, intraoperative, and postoperative evaluation. The preoperative evaluation includes examination of one of the following specimens: bronchial brushings, bronchial washings, fine-needle aspiration biopsy, core needle biopsy, endobronchial biopsy, and transbronchial biopsy. Because lung tumors demonstrate a great deal of heterogeneity, accurate classification depends on sampling technique: If the pathology sample is limited, sometimes the only categorization that can be made is the distinction between NSCLC and SCLC. The generic term “non–small-cell lung cancer (NSCLC)” should be avoided as a single diagnostic term. In small biopsy samples of poorly differentiated carcinomas where IHC is used, the following terms are acceptable: “NSCLC favor adenocarcinoma” or “NSCLC favor SCC.”^6,7 Mutational testing (e.g., epidermal growth factor receptor [EGFR], anaplastic lymphoma kinases [ALKs]) should be performed in this setting. Lymph node status is one of the most important prognostic features in patients with NSCLC.^8,9 Since mediastinoscopy with pathologic examination of lymph nodes remains the “gold standard” for the evaluation of lymph node status in ...