High-Grade Neuroendocrine Carcinoma with Bronchial Intraepithelial Tumor Spread Hideaki Kojima, MD, Reiko Watanabe, MD, PhD, Mitsuhiro Isaka, MD, PhD,

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High-Grade Neuroendocrine Carcinoma with Bronchial Intraepithelial Tumor Spread Hideaki Kojima, MD, Reiko Watanabe, MD, PhD, Mitsuhiro Isaka, MD, PhD, Reiko Shimizu, MD, Hiroyuki Kayata, MD, Naoko Miyata, MD, Tomohiro Maniwa, MD, Shoji Takahashi, MD, Ichiro Ito, MD, PhD, Toru Kameya, MD, PhD, Kazuhito Funai, MD, PhD, Yasuhisa Ohde, MD, PhD, Takashi Nakajima, MD, PhD Journal of Thoracic Oncology Volume 10, Issue 9, Pages 1337-1340 (September 2015) DOI: 10.1097/JTO.0000000000000616 Copyright © 2015 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 1 Radiographic findings of the tumor: Computed tomography of the chest reveals a well-defined and lobulated solid nodule measuring 2.4 cm in diameter in the left peripheral S1+2b segment. Journal of Thoracic Oncology 2015 10, 1337-1340DOI: (10.1097/JTO.0000000000000616) Copyright © 2015 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 2 Microscopic findings of high-grade neuroendocrine carcinoma: The tumor has a vast necrotic area in the center (right side) and variably sized tumor nests around the necrotic area. Bronchiole is completely replaced by tumor cells (single arrow) and vascular invasion is seen in the center (A). The tumor nests are a mix of small cells (single arrow) with fine hyperchromatic oval- to spindle-shaped nuclei and large cells (double arrows) with large round nuclei, small nucleoli, and scant cytoplasm (B). The tumor cells are positive for CD56 (B, inset). Apart from the primary tumor, the bronchial epithelium and bronchial glands in the B1+2b region have tumor cell invasion (C). Two to three layers of tumor cells occupying the basal bronchial epithelium and normal respiratory epithelial cells are present on the surface at the resected end of the left upper bronchus (D). Journal of Thoracic Oncology 2015 10, 1337-1340DOI: (10.1097/JTO.0000000000000616) Copyright © 2015 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 3 Microscopic findings of large-cell neuroendocrine carcinoma with bronchial intraepithelial spread (case 4 in Table 1): The primary tumor, composed of large polygonal cells, shows prominent rosette-like structures with massive necrosis (A). Outside the primary tumor, tumor cells invade the bronchial epithelium (B); tumor cells are immunohistochemically positive for CD56 (B, inset). Journal of Thoracic Oncology 2015 10, 1337-1340DOI: (10.1097/JTO.0000000000000616) Copyright © 2015 International Association for the Study of Lung Cancer Terms and Conditions