What's new in non-small cell lung cancer for pathologists: the importance of accurate subtyping, EGFR mutations and ALK rearrangements

A Special Author Introduction
Pathology
ISSN: 0031-3025 • Frequency: 7/year • Impact Factor 2.673 • Subscribe Now

By Wendy A. Cooper

Lung cancer is the leading cause of cancer death in Australia and other parts of the Western world. In the past, once a diagnosis of lung cancer was established the only critical point of distinction was between small cell carcinoma and non-small cell lung cancer (NSCLC) but this information alone may no longer be sufficient for clinical decision making. Recent clinical trials demonstrating differing efficacy and toxicity of specific treatments (namely the chemotherapeutic agent pemetrexed and the vascular endothelial growth factor antibody bevacizumab) according to specific histological subtypes of NSCLC has resulted in the need for accurate distinction between tumours with squamous and non-squamous histology. In addition, the emergence of new selective kinase inhibitors against EGFR (epidermal growth factor receptor) and ALK (anaplastic lymphoma kinase), has created a need to identify the subset of patients harbouring the specific genetic mutations associated with sensitivity to these agents. These mutations occur almost exclusively in adenocarcinomas and as such, histological subtyping assists in selection of cases appropriate to undergo mutation analysis. As most patients with NSCLC present with advanced stage disease which is not amenable to surgery, pathologists now face the challenge of accurately subtyping NSCLC in small biopsy and cytology samples. While morphological criteria remain the most important feature to distinguish NSCLC subtypes, use of mucin and immunohistochemical stains (particularly TTF-1, p63 and CK5/6) can be of assistance in difficult small biopsy cases.

In this paper, the importance of accurately subtyping NSCLC is reviewed along with a suggested approach for distinguishing histologic subtypes in small biopsy specimens. The significance of EGFR and ALK mutations in NSCLC and the impact of these genotypes on pathology and clinical practice are also discussed.

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This article was originally published in Pathology, to read more research in this field please visit: www.rcpa-pathologyjournal.com