Response

Abstract

We are grateful for the comments of Song and Lin on our publication regarding tumor spread through air spaces (STAS) in lung pleomorphic carcinoma (PC).1Yokoyama S. Murakami T. Tao H. et al.Tumor spread through air spaces identifies a distinct subgroup with poor prognosis in surgically resected lung pleomorphic carcinoma.Chest. 2018; 154: 838-847Abstract Full Text Full Text PDF PubMed Scopus (29) Google Scholar They raised some valid concerns about our pathologic approach and statistical analysis. We appreciate their interest in our study, and our response to their concerns is as follows. Very few studies have described STAS in PC, probably because of the rarity of the tumor. Moreover, researchers may be hesitant to assess STAS in PC because of the difficulty in pathologic evaluation, as experienced in our study. First, it is uncertain whether spindle cells can retain their unique shape in alveolar spaces. This precludes atypical cells in alveolar spaces from being distinguished between epithelial and sarcomatoid cells based on morphology. Second, immunohistochemical studies of STAS are often impossible because STAS cells are frequently lost during tissue sectioning because of their smallness, especially single-cell STAS. Therefore, to simplify, we classified STAS cells into three morphologic subtypes. It is premature to define all STAS in PC being from epithelial components other than sarcomatoid components. Improved understanding of underlying mechanisms of STAS through further immunohistochemical and molecular analysis along with advanced pathologic techniques should help resolve this issue. Analysis of correlations between STAS and the pathologic features in PC should be carefully interpreted because PC contains more diverse components of epithelial and sarcomatoid cells than other non-small cell lung carcinomas. We could not determine any statistical correlations between STAS and the histologic subtypes, including solid adenocarcinoma and micropapillary adenocarcinoma. Although any claims that lung PC accompanying such high-risk epithelial elements contributed to poor prognosis could not be found,2Okuda K. Oda R. Suzuki A. et al.Clinicopathological factors influenced the prognosis of surgically resected pulmonary pleomorphic carcinoma.J Thorac Dis. 2017; 9: 1295-1302Google Scholar further studies need to be addressed as being insufficiently explored. Contrastingly, our data suggest that STAS in PC is associated with necrosis. Because necrosis has been linked to poor outcome,3Mochizuki T. Ishii G. Nagai K. et al.Pleomorphic carcinoma of the lung: clinicopathologic characteristics of 70 cases.Am J Surg Pathol. 2008; 32: 1727-1735Crossref PubMed Scopus (157) Google Scholar elucidating molecular interactions between STAS and necrosis may be emphasized to develop STAS in clinical settings. In survival analysis, although a certain level of significance was observed, we were limited by a small number of patients. One patient, who had multiple recurrent tumors in the residual lung, died of acute exacerbation of underlying interstitial pneumonia. Survival analysis was performed based on overall survival because it was difficult to conclude whether the recurrent tumors influenced patient death in this patient. As for chemotherapy, only one patient showed EGFR mutation-positive tumor and received erlotinib therapy after recurrence. This patient died 18 months after surgery. In conclusion, further studies, including a larger cohort of patients, are necessary to confirm our findings. Could Tumor Spread Through Air Spaces Identify Distinct Subgroup With Poor Prognosis in Lung Pleomorphic Carcinoma?CHESTVol. 156Issue 3PreviewWe read with great interest the study by Yokoyama et al1 in CHEST (October 2018). In the retrospective study, tumor spread through air spaces (STAS) in patients with lung pleomorphic carcinoma (PC) was associated with high recurrence rates and poor survival after surgical resection, and regarded as a predictor of postoperative survival. However, we would like to raise the following comments. Full-Text PDF Tumor Spread Through Air Spaces Identifies a Distinct Subgroup With Poor Prognosis in Surgically Resected Lung Pleomorphic CarcinomaCHESTVol. 154Issue 4PreviewTumor spread through air spaces (STAS) has recently been reported as a novel form of lung adenocarcinoma invasion that can negatively affect survival; however, its role in pleomorphic carcinoma remains unclear. The goal of this study was to characterize tumor STAS in pleomorphic carcinoma, including its association with clinicopathologic features and prognosis. Full-Text PDF