Squamous cell transformation and T790M mutation as acquired resistance mechanisms in a patient with lung adenocarcinoma treated with a tyrosine kinase inhibitor: A case report.

The present case report describes the infrequent coexistence of squamous cell transformation and the epidermal growth factor receptor () T790M mutation as resistance mechanisms to first line treatment with tyrosine kinase inhibitors. The patient was a 44-year-old female, diagnosed with a primitive advanced lung adenocarcinoma with bone metastases. The tumor was positive for the exon 19 deletion, therefore the patient was treated with afatinib (40 mg/day, orally) and radiotherapy for bone lesions. After 16 months, the patient developed resistance. Cytological examination of the pleural effusion confirmed an adenocarcinoma positive for the exon 19 deletion and the T790M mutation within exon 20, while a biopsy from the upper left bronchus revealed a keratinizing squamous cell carcinoma positive for the exon 19 deletion. In addition, the mutations were concomitantly detected in circulating cell-free tumour DNA. Due to the presence of the T790M mutation, the patient underwent osimertinib therapy (80 mg/day, orally), which resulted in a partial tumour regression at the 2-month follow-up, whereas the squamous lesions were treated with radiotherapy. The adenocarcinoma and squamous carcinoma components may share the same origin, according to the presence of the exon 19 deletion in both lesions. More accurate characterization of resistance mechanisms may lead to the development of improved treatment regimens.