Molecular Markers Help Characterize Neuroendocrine Lung Tumors

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Molecular Markers Help Characterize Neuroendocrine Lung Tumors Valerie W. Rusch, MD, David S. Klimstra, MD, Ennapadam S. Venkatraman, PhD The Annals of Thoracic Surgery Volume 62, Issue 3, Pages 798-810 (August 1996) DOI: 10.1016/S0003-4975(96)00435-3 Copyright © 1996 The Society of Thoracic Surgeons Terms and Conditions

Fig. 1 Histologic features of typical carcinoid tumor. At low power (A) the tumor has a nesting and trabecular architecture and lacks necrosis. At high power (B) the tumor cells have moderate to abundant cytoplasm, regular nuclei with a stippled chromatin pattern, and no mitoses. The Annals of Thoracic Surgery 1996 62, 798-810DOI: (10.1016/S0003-4975(96)00435-3) Copyright © 1996 The Society of Thoracic Surgeons Terms and Conditions

Fig. 2 Histologic features of small cell lung cancer. At low power (A) there is little architectural pattern. Large areas of necrosis are present, with hematoxylin staining around vessels (arrows), the so-called Azzopardi effect. At higher power (B) the cells are small with minimal cytoplasm, fusiform nuclei, and inapparent nucleoli. The Annals of Thoracic Surgery 1996 62, 798-810DOI: (10.1016/S0003-4975(96)00435-3) Copyright © 1996 The Society of Thoracic Surgeons Terms and Conditions

Fig. 3 Histologic features of atypical carcinoid tumor. At low power (A) there is a nesting pattern, with punctate foci of necrosis. At higher power (B) the tumor cells are uniform and resemble those of a typical carcinoid, although scattered mitoses are present (arrows). The Annals of Thoracic Surgery 1996 62, 798-810DOI: (10.1016/S0003-4975(96)00435-3) Copyright © 1996 The Society of Thoracic Surgeons Terms and Conditions

Fig. 4 Histologic features of large cell neuroendocrine carcinoma. The low-power appearance (A) shows a well-defined nesting pattern with peripheral palisading of the nuclei. Necrosis is evident. At high power (B) the cells have large nuclei with prominent nucleoli and there is abundant cytoplasm. Mitoses are numerous. The Annals of Thoracic Surgery 1996 62, 798-810DOI: (10.1016/S0003-4975(96)00435-3) Copyright © 1996 The Society of Thoracic Surgeons Terms and Conditions

Fig. 5 Histologic features of mixed small cell–large cell neuroendocrine carcinoma. The low-power pattern (A) resembles that of small cell carcinoma, showing abundant necrosis and marked hypercellularity. At higher power (B) there is an equal admixture of smaller fusiform cells with absent nucleoli and larger cells with more cytoplasm, vesicular chromatin, and prominent nucleoli (arrows). The Annals of Thoracic Surgery 1996 62, 798-810DOI: (10.1016/S0003-4975(96)00435-3) Copyright © 1996 The Society of Thoracic Surgeons Terms and Conditions

Fig. 6 Immunohistochemical staining for Ki67. In a low proliferative rate tumor (typical carcinoid) there is nuclear positivity in less than 5% of the cells (1+) (A), whereas in a high proliferative rate tumor (small cell lung cancer), more than 90% of the cells are positive (4+) (B). The Annals of Thoracic Surgery 1996 62, 798-810DOI: (10.1016/S0003-4975(96)00435-3) Copyright © 1996 The Society of Thoracic Surgeons Terms and Conditions

Fig. 7 Immunohistochemical staining for p53. In these two large cell neuroendocrine carcinomas, one (A) shows 4+ positivity, with nearly all of the nuclei staining; the other (B) is negative, with absent staining. The Annals of Thoracic Surgery 1996 62, 798-810DOI: (10.1016/S0003-4975(96)00435-3) Copyright © 1996 The Society of Thoracic Surgeons Terms and Conditions

Fig. 8 Immunohistochemical staining for EGFR. Diffuse cytoplasmic positivity (4+) is present in this large cell neuroendocrine carcinoma (A). In negative cases (B), only the basal layers of the normal respiratory epithelium stain. The Annals of Thoracic Surgery 1996 62, 798-810DOI: (10.1016/S0003-4975(96)00435-3) Copyright © 1996 The Society of Thoracic Surgeons Terms and Conditions

Fig. 9 Immunohistochemical staining for Rb. The normal pattern of staining varies with the proliferative rate. In a low proliferative rate tumor (atypical carcinoid), only focal staining of scattered tumor cell nuclei is present (A). In a high proliferative rate tumor (small cell lung cancer) there is more widespread positivity (B). In the presence of Rb abnormalities in a small cell lung cancer, no tumor cells stain (C), although reaction product is present in nonneoplastic endothelial cells (arrows), an essential internal positive control. The Annals of Thoracic Surgery 1996 62, 798-810DOI: (10.1016/S0003-4975(96)00435-3) Copyright © 1996 The Society of Thoracic Surgeons Terms and Conditions

Fig. 10 Overall survival by tumor histology. (AC = atypical carcinoma; LCNC = large cell carcinoma; MNC = mixed small-large cell neuroendocrine carcinoma; SCLC = small cell carcinoma; TC = typical carcinoma.) The Annals of Thoracic Surgery 1996 62, 798-810DOI: (10.1016/S0003-4975(96)00435-3) Copyright © 1996 The Society of Thoracic Surgeons Terms and Conditions

Fig. 11 Overall survival in the low- and intermediate-grade neu-roendocrine tumors (typical carcinoma and atpical carcinoma) versus the high-grade neuroendocrine tumors (large cell carcinoma and mixed small–large cell neuroendocrine carcinoma and small cell carcinoma). The p value was less than 0.01. The Annals of Thoracic Surgery 1996 62, 798-810DOI: (10.1016/S0003-4975(96)00435-3) Copyright © 1996 The Society of Thoracic Surgeons Terms and Conditions