Epidermal Growth Factor Receptor Mutation in a Patient with Squamous Cell Carcinoma of the Lung: Who Should Be Tested

We report the case of a 64-year-old ex-smoker with metastatic poorly differentiated squamous cell carcinoma (SCC) of the lung and an epidermal growth factor receptor (EGFR) mutation in exon 21 (p.L858R) who achieved prolonged clinical benefit from treatment with an EGFR tyrosine kinase inhibitor (TKI). The initial diagnosis of SCC of the lung obtained by bronchoscopic biopsy was based on immunohistochemical staining only with positivity for cytokeratin (CK) 5/6 and p63 because morphological diagnosis was not possible. Patients with non-small cell lung cancer (NSCLC), not otherwise specified (NOS) favouring SCC are usually not tested for the presence of EGFR mutations, and therefore may not receive EGFR TKI therapy. A bronchoscopic rebiopsy showed small nests of undifferentiated tumour cells with weak immunoreactivity of some tumour cells for CK5/6, p63 and no positivity of some tumour cells for thyroid transcription factor-1. These findings suggested a mixed squamous/glandular immunophenotype that has been missed at the initial biopsy. Our clinical case illustrates the problem of tumour heterogeneity encountered in small bronchoscopic biopsies and the difficulties of evaluating the histological subtype in poorly differentiated carcinomas. Initial bronchoscopy should be performed by an experienced pulmonologist who attempts to obtain sufficient material from different areas of the tumour. In the era of targeted therapy, a remote smoking history in a patient with NOS favouring SCC should also lead to EGFR mutation testing to allow highly effective therapy to be offered to mutation-positive patients