Transformation of epidermal growth factor receptor T790M mutation‐positive adenosquamous carcinoma of the lung to small cell carcinoma and large‐cell neuroendocrine carcinoma following osimertinib therapy: an autopsy case report

Abstract

A 59‐year‐old man with relapsed epidermal growth factor receptor ( EGFR ) exon 19 deletion‐positive stage IA adenosquamous carcinoma after lobectomy was treated with erlotinib and bevacizumab for 1 year followed by erlotinib alone for 1 year. Because of mediastinal and supraclavicular lymphadenopathy and a nodule on the left anterior chest wall, the patient underwent repeat biopsy from the supraclavicular lymph node. Pathological analysis demonstrated adenosquamous carcinoma harbouring EGFR exon 19 deletion and T790M mutation. Osimertinib treatment was therefore started. Six months later, the patient underwent a second‐repeat biopsy from the mediastinal lymph nodes and liver metastases. Both specimens showed small cell lung carcinoma (SCLC). After chemotherapies for SCLC, he died from lung cancer. An autopsy demonstrated tumour heterogeneity, including histological types of adenosquamous, SCLC, and large‐cell neuroendocrine carcinoma. Repeat biopsies at the time of disease progression are useful to choose subsequent treatment for patients with EGFR mutation‐positive lung cancer.

An EGFR T790M-mutated lung adenocarcinoma undergoing large-cell neuroendocrine carcinoma transformation after osimertinib therapy: a case report

“…EGFR exon 19 deletion was identified in both the adenocarcinoma and LCNEC. To the best of our knowledge, this is the fourth description of adenocarcinoma transformation to LCNEC after osimertinib therapy [ 4 – 6 ]. One recent study investigating the mechanisms of resistance to osimertinib in 73 consecutive patients reported only small cell lung cancer (SCLC) transformation in 4 patients [ 7 ].…”

Transformation of advanced lung adenocarcinoma to acquired T790M resistance mutation adenosquamous carcinoma following tyrosine kinase inhibitor: a case report

“…Various histologic types including adenosquamous carcinoma, SCLC, and large cell neuroendocrine carcinoma were found at autopsy. 11 For patients with TKI resistance, repeated biopsy to identify pathologic types and gene mutations is critical for subsequent treatment.…”