A Novel Algorithm to Differentiate Between Multiple Primary Lung Cancers and Intrapulmonary Metastasis in Multiple Lung Cancers With Multiple Pulmonary Sites of Involvement

Abstract

Introduction: Differentiating between multiple primary lung cancer (MPLC) and intrapulmonary metastasis (IPM) is critical for developing a therapeutic strategy to treat multiple lung cancers with multiple pulmonary sites of involvement.Methods: We retrospectively included 252 lesions (126 pairs) from 126 patients with surgically resected multiple lung adenocarcinomas. Each pair was classified as MPLC or IPM based on histopathologic findings as the reference standard. A novel algorithm was established with four sequential decision steps based on the combination of computed tomography (CT) lesion types (step 1), CT lesion morphology (step 2), difference of maximal standardized uptake values on positron-emission tomography/CT (step 3), and presence of N2/3 lymph node metastasis or distant metastasis (step 4). The diagnostic accuracy of the algorithm was analyzed. Performances of 11 observers were assessed without and with knowledge of algorithm.Results: Among 126 pairs, 90 (71.4%) were classified as MPLCs and 36 (28.6%) as IPMs. On applying the diagnostic algorithm, the overall accuracy for diagnosis of IPM among conclusive cases up to step 4 was 88.9%, and 65 and 44 pairs were correctly diagnosed based on step 1 and step 2, respectively. Specificity and positive predictive value for diagnosis of IPM increased significantly in all observers compared with reading rounds without the algorithm.Conclusions: Application of the algorithm based on comprehensive information on clinical and imaging variables can allow differentiation between MPLCs and IPMs. When both of two suspected malignant lesions appear as solid predominant lesions without spiculation or airbronchogram on CT, IPM should be considered.

RETRACTED: Establishment of Criteria for Molecular Differential Diagnosis of MPLC and IPM

“…Imaging test can provide unique evidence for MPLC and IPM distinguishment. A recent study established the algorithm for distinguishing MPLC from IPM by combining characteristics of lesions from CT/PET imaging and achieved good diagnostic efficacy ( 24 ). Thirdly, the criteria established in this study were based on the 605-gene panel.…”

Clinical features and outcomes of patients with stage I multiple primary lung cancers

“…Application of the algorithm based on comprehensive information on clinical and imaging variables can also allow differentiation between MPLCs and IPMs. When both of two suspected malignant lesions appear as solid predominant lesions without spiculation or air‐bronchograms on CT, IPM should be considered 14,24 . Goto et al 25 showed that LC mutation analysis by targeted deep sequencing is useful for distinction of the clonality of individual pulmonary tumors.…”

Tumor microenvironment disparity in multiple primary lung cancers: Impact of non-intrinsic factors, histological subtypes, and genetic aberrations

“…The criteria based on tumor locations and pathological findings used to define MPLCs were initially published in 1975 [36] . Additionally, a novel algorithm to differentiate between MPLCs and intrapulmonary metastasis using clinical and imaging variables has been reported [38] . The algorithm showed combinations of lesion types on CT, and the presence of air-bronchogram and spiculation were the most accurate determinants for differentiation between MPLC and intrapulmonary metastasis.…”

“…We diagnosed MPLC based on the methods described in previous studies [36] , [37] , [38] . MPLC was diagnosed if (1) paired nodules were located in different segments, lobes, or lungs; (2) either of the paired nodules was adenocarcinoma in situ (AIS) or minimally invasive adenocarcinoma (MIA); (3) the histopathologic patterns, including subtypes, were different between paired nodules; (4) nodal or systemic metastases were absent; or (5) CT imaging showed the presence of an air-bronchogram or speculation in paired nodules.…”