Molecular and Cellular Pathology of Lung Cancer

Despite advances in imaging techniques and the molecular
characterization of lung tumors described elsewhere in this
volume, the histopathology of lung cancer remains the basis
for diagnosis and treatment of the disease and is essential for
the interpretation of imaging studies and molecular analyses.
Histopathology has recently taken on added importance as it
has been recognized that targeted agents affect specific lung
tumor subtypes differently and that successful treatment may
depend on histological distinctions that have been previously
unrecognized or ignored. Historically, the classification of lung
cancer rested on the expertise of individual pathologists but
in 1967, an international panel was first assembled through
the World Health Organization (WHO) to create a standard
nomenclature for lung cancer. This classification with its periodic
revisions has become the most widely used standard for
diagnosis and treatment and is provided in Appendix A. The
most recent edition of the WHO morphological classification
was published in 2004 and is more comprehensive than previous
editions’ description of the classification, taking into account
molecular data as well as morphology. 1 The purpose of
this chapter is not so much to recapitulate the details of the
WHO classification but rather to provide an understanding of
the main categories of lung carcinoma, to highlight potential
pitfalls in histopathological diagnosis of lung cancer, to summarize
current information on molecular properties and cellular
origin of individual lung tumor types, to relate pathology
to biological behavior, and to provide review guidelines for
reporting and pathological staging of lung cancer.
Nearly all lung cancers exhibit the morphological and molecular
features of epithelial cells (described later) and are accordingly
classified as carcinomas. The cells of origin of virtually
all lung cancers reside in the epithelial lining of the airways.
As more is learned about the origin of lung carcinoma, it is
increasingly clear that the biology of lesions arising in the central
airways is distinct from that of peripheral airway lesions.
In addition, there are important distinctions between tumors
from the two sites in histopathological appearances, molecular
profiles, and diagnostic approaches. While the dichotomy
between central and peripheral is not a sharp one, it is nevertheless
useful to consider tumors of the central airways separately
from peripheral tumors.