Lung cancer with concurrent EGFR mutation and ROS1 rearrangement: a case report and review of the literature

Abstract

ROS1 rearrangement has recently emerged as a new molecular subtype in non-small cell lung cancer, and is predominantly found in lung adenocarcinomas compared with other oncogenes such as EGFR, KRAS, or ALK. Patients who have both mutations are extremely rare. Here we report a 50-year-old female diagnosed with adenocarcinoma with sarcomatoid differentiation, who was shown to have EGFR and ROS1 mutations. The patient was treated surgically and received three cycles of adjuvant postoperative chemotherapy. In addition, we reviewed the previously reported cases and related literature. This presentation will provide further understanding of the underlying molecular biology and optimal treatment for non-small cell lung cancer patients with more than one driver mutation.

Keywords: EGFR gene mutation; ROS1 fusion gene; non-small cell lung cancer.

Figure 1

Treatment of lung adenocarcinoma with sarcomatoid differentiation using different chemotherapy regimens and results of monitoring the CEA levels. Notes: (A–D) Lung CT scans from (A) November 2015, (B) December 2015, (C) January 2016, and (D) February 2016. (E–H) CT scans of the mediastinum from (E) November 2015, (F) December 2015, (G) January 2016, and (H) February 2016. Abbreviations: CEA, carcinoembryonic antigen; CT, computed tomography.

Figure 2

The hematoxylin-eosin staining and the immunohistochemistry in the part of adenocarcinoma and sarcomatoid differentiation. Notes: (A) The hematoxylin–eosin staining revealed that tumor cells were lung adenocarcinoma (×100). (B) The hematoxylin–eosin staining revealed that tumor cells were sarcomatoid differentiation (×100). (C) Immunohistochemical examination revealed that tumor cells were positive for monoclonal anti-CK7 antibody in a portion of the adenocarcinoma (×100). (D) Immunohistochemical examination revealed that tumor cells were positive for monoclonal anti-CK7 antibody in a portion of the sarcomatoid differentiation (×100). (E) Immunohistochemical examination revealed that tumor cells were positive for monoclonal anti-TTF-1 antibody in a portion of the adenocarcinoma (×100). (F) Immunohistochemical examination revealed that tumor cells were positive for monoclonal anti-TTF-1 antibody in a portion of sarcomatoid differentiation (×100). (G) Immunohistochemical examination revealed that tumor cells were positive for monoclonal antivimentin antibody in a portion of adenocarcinoma (×100). (H) Immunohistochemical examination revealed that tumor cells were positive for monoclonal antivimentin antibody in a portion of sarcomatoid differentiation (×100).

Figure 3

Schema shows tumor with dual drivers (CD74-ROS1 fusion gene by polymerase chain reaction and EGFR exon 21 L858R point mutation by next-generation sequencing) in a portion of the adenocarcinoma (1), and tumor with no driver or unknown driver in a portion of the sarcomatoid differentiation (2).