Discriminant Model for Cytologic Distinction of Large Cell Neuroendocrine Carcinoma from Small Cell Carcinoma of the Lung Rira Hoshi, CT, Noriyuki Furuta,

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Discriminant Model for Cytologic Distinction of Large Cell Neuroendocrine Carcinoma from Small Cell Carcinoma of the Lung Rira Hoshi, CT, Noriyuki Furuta, CT, Takeshi Horai, MD, Yuichi Ishikawa, MD, PhD, Satoshi Miyata, PhD, Yukitoshi Satoh, MD, PhD Journal of Thoracic Oncology Volume 5, Issue 4, Pages 472-478 (April 2010) DOI: 10.1097/JTO.0b013e3181ce3cdd Copyright © 2010 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 1 Photomicrographs illustrating cellular arrangement in transbronchial aspiration or histology specimens of LCNEC and SCLC cases. A, Large and three-dimensional clusters are conspicuous in a cytologic smear of an LCNEC case (Papanicolaou stain, ×20); B, tumor nests of an LCNEC case show palisading and Rosette-like formations in a histology specimen (hematoxylin and eosin stain, ×40); C, single cells are conspicuous in the cytologic smear of an SCLC case (Papanicolaou stain, ×20); and D, tumor cells of an SCLC case comprise irregular nests in a histology specimen (hematoxylin and eosin stain, ×40). Journal of Thoracic Oncology 2010 5, 472-478DOI: (10.1097/JTO.0b013e3181ce3cdd) Copyright © 2010 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 2 Frequencies of large clusters with tight cohesion in the LCNEC and SCLC groups (n = 55). Journal of Thoracic Oncology 2010 5, 472-478DOI: (10.1097/JTO.0b013e3181ce3cdd) Copyright © 2010 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 3 Histograms of cell areas in LCNEC and SCLC groups. Note that about 60% of the SCLC cells fall in the range of less than 120 µm2, as compared with about 25% for LCNEC cells (p < 0.0001). Journal of Thoracic Oncology 2010 5, 472-478DOI: (10.1097/JTO.0b013e3181ce3cdd) Copyright © 2010 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 5 Photomicrographs illustrating single cells and tissue architecture in LCNEC and SCLC cases. A) Tumor cells ≥120 µm2 and/or with prominent nucleoli are evident in a cytologic smear of an LCNEC case (Papanicolaou stain, ×100); B, nests of LCNEC cells are predominantly composed of large tumor cells with abundant cytoplasm and occasional prominent nucleoli (hematoxylin and eosin stain, ×40); C, tumor cells <120 µm2 without prominent nucleoli are evident in a cytologic smear of an SCLC case (Papanicolaou stain, ×100); D, nests of SCLC cells are predominantly composed of small tumor cells with scant cytoplasm without nucleoli (hematoxylin and eosin stain, ×40). Journal of Thoracic Oncology 2010 5, 472-478DOI: (10.1097/JTO.0b013e3181ce3cdd) Copyright © 2010 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 4 Frequencies of small tumor cells without prominent nucleoli in the LCNEC and SCLC groups (n = 55). Journal of Thoracic Oncology 2010 5, 472-478DOI: (10.1097/JTO.0b013e3181ce3cdd) Copyright © 2010 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 6 Logistic regression for frequencies of small tumor cells without prominent nucleoli and large clusters with tight cohesion. The scatter plot allows clear separation of LCNEC (•) and SCLC cases (▴) by the calculated discriminant line. Therefore, a discriminant model for LCNEC and SCLC, diagnosing as SCLCs if dots exist in the field above the line and as LCNECs if below the line, was made. All SCLC and LCNEC cases were discriminated correctly with the discriminant model based on logistic regression from cytologic frequencies, and sensitivity, specificity, and accuracy were all 100%. Journal of Thoracic Oncology 2010 5, 472-478DOI: (10.1097/JTO.0b013e3181ce3cdd) Copyright © 2010 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 7 Leave-one-out cross validation. Regarding each case as a new case, prediction of the error rate of the discriminant model was analyzed. Red dots show error discriminant cases on cross validation. Two of the LCNEC cases and one SCLC case were discriminated in error with the discriminant model, so that the prediction of error rate of the model was 0.00545. Journal of Thoracic Oncology 2010 5, 472-478DOI: (10.1097/JTO.0b013e3181ce3cdd) Copyright © 2010 International Association for the Study of Lung Cancer Terms and Conditions