Radiologic Response to Neoadjuvant Treatment Predicts Histologic Response in Thymic Epithelial Tumors Geoffrey B. Johnson, MD, PhD, Marie Christine Aubry,

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Radiologic Response to Neoadjuvant Treatment Predicts Histologic Response in Thymic Epithelial Tumors Geoffrey B. Johnson, MD, PhD, Marie Christine Aubry, MD, Eunhee S. Yi, MD, Chi Wan Koo, MD, Sarah M. Jenkins, MS, Yolanda I. Garces, MD, Randolph S. Marks, MD, Stephen D. Cassivi, MD, MSc, Anja C. Roden, MD Journal of Thoracic Oncology Volume 12, Issue 2, Pages 354-367 (February 2017) DOI: 10.1016/j.jtho.2016.09.118 Copyright © 2016 International Association for the Study of Lung Cancer Terms and Conditions

Figure 1 Morphologic findings in thymic epithelial tumors after neoadjuvant treatment. Tumor response grade (A–E) is scored as 1 (A), 2 (B), 3 (C), 4 (D), and 5 (E). Arrow (B insert) marks rare clusters of viable tumor cells. Morphologic findings after neoadjuvant treatment include fibrosis (A–D and G), calcifications within fibrosis (A and G) or tumor cell nests (F), necrosis (arrowhead in B and J), necrotizing granuloma (H), and acute hemorrhage (I). Hematoxylin and eosin staining; original magnification, ×12.5 (A–E), ×400 (B insert), ×100 (F–I), and ×20 (J). Journal of Thoracic Oncology 2017 12, 354-367DOI: (10.1016/j.jtho.2016.09.118) Copyright © 2016 International Association for the Study of Lung Cancer Terms and Conditions

Figure 2 Change of histologic tumor type with neoadjuvant treatment. (A–E) A pre–neoadjuvant treatment needle core biopsy (A) shows bland-appearing spindle cells (A [left] and B) and areas predominantly comprising small lymphocytes (A [right] and C); findings suggestive of a thymoma WHO type AB. The post–neoadjuvant treatment resection specimen (D) comprises bland-appearing spindle cells with only occasional lymphocytes (E), which is consistent with type A thymoma. (F–J) A biopsy specimen (F) comprises a mixture of epithelial tumor cells and small lymphocytes (G) consistent with type B2 thymoma. A posttreatment biopsy specimen from this patient (H) shows sheets of polygonal large epithelioid cells within a lobulated architecture suggestive of type B3 thymoma (I and J). (K–O) A biopsy specimen shows nests of cells against a fibrotic background (K). On high magnification, large epithelioid cells with a high nuclear-to-cytoplasmic ratio and dark nuclear chromatin are growing in a desmoplastic stromal reaction consistent with poorly differentiated carcinoma (L). Post–neoadjuvant treatment complete resection specimen, on low magnification, shows a lobulated mass that predominantly comprises lymphocytes with scattered tumor cells (M) consistent with type B2 thymoma. However, there is a focus with features similar to those of the pretreatment biopsy specimen and suggestive of a minor component of poorly differentiated carcinoma (N and O). (P–T) A biopsy specimen shows clusters of epithelial cells associated with fibrosis (P and Q). Whereas two pathologists considered the findings to be indicative of thymic carcinoma, one pathologist favored type B3 thymoma. The incomplete resection specimen after neoadjuvant therapy revealed a lobulated mass (R) comprising bland (S) and focally more atypical cells with clear cytoplasm (T), with some growing as single-file and small cell nests within collagen fibrosis (S). These morphologic findings were considered type B3 thymoma (two pathologists, one of which thought that there is a minor component of thymic carcinoma) or thymic carcinoma (one pathologist). Hematoxylin and eosin–stained slides; original magnification, ×40 (A, D, F, I, and K), ×400 (B, C, E, G, J, L, O, Q, and T), ×20 (H and M), ×100 (N, P, and S), and ×12.5 (R). Journal of Thoracic Oncology 2017 12, 354-367DOI: (10.1016/j.jtho.2016.09.118) Copyright © 2016 International Association for the Study of Lung Cancer Terms and Conditions

Figure 3 Clinicopathologic and radiologic-pathologic correlation. The proposed International Association for the Study of Lung Cancer (IASLC)/International Thymic Malignancy Interest Group (ITMIG) T-stage correlates with tumor regression grade (A) and percent viable tumor (B) after neoadjuvant therapy. Radiologic response as assessed by the Response Evaluation Criteria in Solid Tumors also correlates with tumor regression grade (C) and percent viable tumor (D). Computed tomography scan of a patient with pretreatment diagnosis of thymic carcinoma on the basis of a biopsy specimen had an anterior mediastinal mass of 8 cm in longest axial diameter (E [white line]). The patient was treated with chemoradiation. A post–neoadjuvant treatment computed tomography scan (F) revealed a partial response with a longest axial diameter of 4.4 cm (white line). The patient had a complete pathologic response (see Fig. 1A). Abbreviation: TRG, tumor response grade. Journal of Thoracic Oncology 2017 12, 354-367DOI: (10.1016/j.jtho.2016.09.118) Copyright © 2016 International Association for the Study of Lung Cancer Terms and Conditions

Figure 4 Correlation between radiologic response, type of thymic epithelial tumor, and pathologic tumor response grade. For the purpose of this figure, the tumor response grade recorded by the majority of reviewers was used. Journal of Thoracic Oncology 2017 12, 354-367DOI: (10.1016/j.jtho.2016.09.118) Copyright © 2016 International Association for the Study of Lung Cancer Terms and Conditions