Abstract
BackgroundAdenosquamous 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.MethodsA 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.ResultsEGFR 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.ConclusionsEGFR 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.
Highlights
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)
Patients’ clinical characteristics One hundred and forty-eight patients diagnosed as SqCC or non-small cell carcinoma (NSCC) favor SqCC from small biopsies were enrolled in this study
The current guideline of College of American Pathologists (CAP)/IASLC/Association for Molecular Pathology (AMP) suggests that testing for epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) translocations should be recommended for adenocarcinomas and mixed lung cancers with an adenocarcinomatous component, regardless of histologic grade, and are not recommended in lung cancers that lack any adenocarcinoma component, such as “pure” SqCC, “pure” Small cell lung cancer (SCLC), or large cell carcinomas lacking any IHC evidence of adenocarcinoma differentiation [20]
Summary
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). Non-small cell lung cancer (NSCLC), accounting for approximately 80–85% of all the cases, is further divided into major histological subtypes including adenocarcinoma (ADC), squamous cell carcinoma (SqCC), large cell carcinoma (LCC), and other rare tumors including adenosquamous carcinoma (ADSC) [1]. The poor prognosis of ADSC has raised the demand for more effective treatment approaches such as targeted therapy. The development of targeted therapy toward oncogenic “driver mutations” has revolutionized the clinical management of patients with NSCLC including ADSC [6, 7]
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