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. 2019 Apr 18;9:288. doi: 10.3389/fonc.2019.00288

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Copyright © 2019 Ren, Huang, Dai, Xie, Zheng, Xie, Zheng, She, Zhou, Wang, Li, Fei, Jiang, Zhang, Su, Sweet-Cordero, Tran, Yang, Patel, Rolfo, Rocco, Cardona, Tuzi, Suter, Yang, Xu and Chen.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Proposed SM-GGN origination models. Five models plus an unknown process were hypothesized. These different originations could occur in different cases, or even mixed in one patient. There are evidence supporting the lymph metastasis SM-GGNs, aero metastasis SM-GGNs, Convergent SM-GGNs (CVG), and the inherent sporadic SM-GGNs (ISG). The independent clonal SM-GGNs (ICG) we hypothesize is prone to the deficient local immune microenvironment or presumably to the biochemical substances released from the primary tumor lesion.