First Case of Combined Small-Cell Lung Cancer with Adenocarcinoma Harboring EML4- ALK Fusion and an Exon 19 EGFR Mutation in Each Histological Component

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First Case of Combined Small-Cell Lung Cancer with Adenocarcinoma Harboring EML4- ALK Fusion and an Exon 19 EGFR Mutation in Each Histological Component Gouji Toyokawa, MD, PhD, Kenichi Taguchi, MD, PhD, Taro Ohba, MD, PhD, Yosuke Morodomi, MD, PhD, Tomoyoshi Takenaka, MD, PhD, Fumihiko Hirai, MD, PhD, Masafumi Yamaguchi, MD, PhD, Takashi Seto, MD, PhD, Mitsuhiro Takenoyama, MD, PhD, Kenji Sugio, MD, PhD, FACS, Yukito Ichinose, MD, PhD Journal of Thoracic Oncology Volume 7, Issue 12, Pages e39-e41 (December 2012) DOI: 10.1097/JTO.0b013e3182762bcb Copyright © 2012 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 1 A, Computed tomography showing an irregular nodule in the right lower lobe of lung. B, Cut sections of the tumor are seen by the encircled part. Journal of Thoracic Oncology 2012 7, e39-e41DOI: (10.1097/JTO.0b013e3182762bcb) Copyright © 2012 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 2 Microscopic findings. A, Microscopic findings of the tumor consisting of SCLC (arrow) surrounded by adenocarcinoma with papillary, acinar and lepidic components (asterisk). Highly magnified images of (B) the SCLC (asterisk), the adenocarcinoma (arrow), and (C) the lepidic components. SCLC, small-cell lung cancer. Journal of Thoracic Oncology 2012 7, e39-e41DOI: (10.1097/JTO.0b013e3182762bcb) Copyright © 2012 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 3 A direct sequence analysis revealing (A) a deletion in exon 19 of EGFR in the adenocarcinoma and (B) a variant 1 mutation of EML4-ALK in the SCLC. Immunoreactivity of the lepidic component to the deletion in exon 19 of EGFR using an antibody that specifically detects deleted EGFR (E746-A750del) (6B6, Cell Signaling, Danvers, MA) (C) and of the SCLC to ALK using primary antibody against ALK (5A4, Nichirei, Tokyo, Japan) (D). A polymer method was used for the immunohistochemical analysis, specifically, an intercalating antibody-enhanced polymer method was used for the detection of ALK. E, Gene mapping of the driver mutations in each component. EGFR, epidermal growth factor receptor; EML4-ALK, echinoderm microtubule-associated protein-like 4; SCLC, small-cell lung cancer; ALK, anaplastic lymphoma kinase. Journal of Thoracic Oncology 2012 7, e39-e41DOI: (10.1097/JTO.0b013e3182762bcb) Copyright © 2012 International Association for the Study of Lung Cancer Terms and Conditions