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Background  Adenosquamous carcinoma (ADSC) of the lung, a rare but aggressive subtype of non-small cell lung cancer (NSCLC), is defined as a carcinoma containing components of adenocarcinoma (ADC) and squamous cell carcinoma (SqCC). Mutations of epidermal growth factor receptor (EGFR) are found at a frequency of 15 to 44% in Asian ADSC, and EGFR tyrosine kinase inhibitors (EGFR-TKIs) are a more effective treatment for EGFR-mutated ADSC compared to chemotherapy. However, ADSC in small lung biopsies could be misdiagnosed as SqCC or non-small cell carcinoma (NSCC) favor SqCC due to undersampling, which may result in neglecting of  EGFR  mutation testing and affecting patients’ clinical management, particularly in Asian patients that relatively have high prevalence of  EGFR  mutation.    Methods  A total of 148 small lung biopsy cases with pathological diagnosis of SqCC or NSCC favor SqCC were retrospectively enrolled. The frequency of  EGFR  mutations and the correlation between patients’  EGFR  mutation status and clinicopathological characteristics were evaluated.    Results   EGFR  mutations were found in 8.8% (13 /148) of all cases with 5.2% (7/135) in SqCC and 46.2% (6/13) in NSCC favor SqCC. There were 7 (53.8%) L858R mutation, 4 (30.8%) exon 19 deletions, and 2 (15.4%) cases with coexistent L858R and T790 M mutations. Multivariate analysis showed that  EGFR  mutations were more prevalent in never-smokers (83.3% versus 16.7%,  p  = 0.006) and patients diagnosed as NSCC favor SqCC (46.2% versus 5.2%,  p  = 0.001). Moreover, 75% (3/4) of  EGFR  mutation-positive cases with subsequent surgical resection or rebiopsy were further diagnosed as ADSC.    Conclusions   EGFR  mutation testing should be performed in Asian patients with SqCC diagnosed from small lung biopsies, especially in never-smokers and patients with diagnosis of NSCC favor SqCC, which have a high probability of being ADSC.

diagnostic pathology

The importance of EGFR mutation testing in squamous cell carcinoma or non-small cell carcinoma favor squamous cell carcinoma diagnosed from small lung biopsies