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      Sarcoidosis mimicking metastases in an echinoderm microtubule-associated protein-like 4 anaplastic lymphoma kinase positive non-small-lung cancer patient: A case report

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          Abstract

          BACKGROUND

          Rearrangements of the anaplastic lymphoma kinase (ALK) gene (ALK-positive) represent an oncogenic driver in approximately 3%-5% of non-small-lung cancer (NSCLC) patients. Sarcoidosis is a multisystem disease, and its reported incidence in Asia is 1 or less per 100000 people per year. The co-occurrence of sarcoidosis and ALK-positive NSCLC is rare, and ALK-positive lung cancer is likely to spread quickly. Therefore, the co-occurrence of sarcoidosis is more easily misdiagnosed as metastatic lung cancer by radiological examination.

          CASE SUMMARY

          A 50-year-old man had a nodule in the left superior lobe, many small nodules in left superior and right lungs, and enlarged bilateral hilar, mediastinal, and right supraclavicular lymph nodes. Computed tomography-guided pulmonary biopsy of the nodule in the left superior lobe revealed echinoderm microtubule-associated protein-like 4 gene-ALK positive NSCLC with concomitant noncaseating granuloma. This patient was treated with crizotinib. Thirty days later, a chest computed tomography scan revealed a dramatic decrease in the size of the left superior lobe nodule; however, the lesions in the right lung progressed. The right supraclavicular lymph nodes showed granulomas, and no tumor cells were identified in the specimens. The angiotensin-converting enzyme level was high. After 1 wk of methylprednisolone treatment, a significant response of all lesions was revealed. Following radical resection of the lung cancer, noncaseating granulomas were observed in both lung tissues and lymph nodes, which resulted in a diagnosis of echinoderm microtubule-associated protein-like 4-ALK positive NSCLC accompanied with sarcoidosis.

          CONCLUSION

          Our experience illustrates that pathological evidence is needed to confirm metastatic disease, especially when some suspected metastatic lesions are negative for malignancy.

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          Most cited references19

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          Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer.

          Improvement in the clinical outcome of lung cancer is likely to be achieved by identification of the molecular events that underlie its pathogenesis. Here we show that a small inversion within chromosome 2p results in the formation of a fusion gene comprising portions of the echinoderm microtubule-associated protein-like 4 (EML4) gene and the anaplastic lymphoma kinase (ALK) gene in non-small-cell lung cancer (NSCLC) cells. Mouse 3T3 fibroblasts forced to express this human fusion tyrosine kinase generated transformed foci in culture and subcutaneous tumours in nude mice. The EML4-ALK fusion transcript was detected in 6.7% (5 out of 75) of NSCLC patients examined; these individuals were distinct from those harbouring mutations in the epidermal growth factor receptor gene. Our data demonstrate that a subset of NSCLC patients may express a transforming fusion kinase that is a promising candidate for a therapeutic target as well as for a diagnostic molecular marker in NSCLC.
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            Clinical features and outcome of patients with non-small-cell lung cancer who harbor EML4-ALK.

            The EML4-ALK fusion oncogene represents a novel molecular target in a small subset of non-small-cell lung cancers (NSCLC). To aid in identification and treatment of these patients, we examined the clinical characteristics and treatment outcomes of patients who had NSCLC with and without EML4-ALK. Patients with NSCLC were selected for genetic screening on the basis of two or more of the following characteristics: female sex, Asian ethnicity, never/light smoking history, and adenocarcinoma histology. EML4-ALK was identified by using fluorescent in situ hybridization for ALK rearrangements and was confirmed by immunohistochemistry for ALK expression. EGFR and KRAS mutations were determined by DNA sequencing. Of 141 tumors screened, 19 (13%) were EML4-ALK mutant, 31 (22%) were EGFR mutant, and 91 (65%) were wild type (WT/WT) for both ALK and EGFR. Compared with the EGFR mutant and WT/WT cohorts, patients with EML4-ALK mutant tumors were significantly younger (P < .001 and P = .005) and were more likely to be men (P = .036 and P = .039). Patients with EML4-ALK-positive tumors, like patients who harbored EGFR mutations, also were more likely to be never/light smokers compared with patients in the WT/WT cohort (P < .001). Eighteen of the 19 EML4-ALK tumors were adenocarcinomas, predominantly the signet ring cell subtype. Among patients with metastatic disease, EML4-ALK positivity was associated with resistance to EGFR tyrosine kinase inhibitors (TKIs). Patients in the EML4-ALK cohort and the WT/WT cohort showed similar response rates to platinum-based combination chemotherapy and no difference in overall survival. EML4-ALK defines a molecular subset of NSCLC with distinct clinical characteristics. Patients who harbor this mutation do not benefit from EGFR TKIs and should be directed to trials of ALK-targeted agents.
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              Metastatic sites and survival in lung cancer.

              Population-based data on metastatic sites and survival in site-specific metastases are lacking for lung cancer and for any cancer because most cancer registries do not record metastases. This study uses a novel population-based approach to identify metastases from both death certificates and national inpatient data to describe metastatic pathways in lung cancer patients.
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                Author and article information

                Contributors
                Journal
                World J Clin Cases
                WJCC
                World Journal of Clinical Cases
                Baishideng Publishing Group Inc
                2307-8960
                6 May 2021
                6 May 2021
                : 9
                : 13
                : 3140-3146
                Affiliations
                Department of Respiratory Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China
                Department of Respiratory Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China
                Department of Lung Transplantation, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China
                Positron Emission Tomography Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China
                Department of Pathology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China
                Department of Respiratory Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China
                Department of Respiratory Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China. drsyh@ 123456zju.edu.cn
                Author notes

                Author contributions: Chen X and Wang J wrote the original draft; Han WL, Zhao K, and Chen Z collected the data; Zhou JY, Chen X, and Wang J performed the investigation; Shen YH performed the project administration and wrote, reviewed, and edited the manuscript.

                Supported by The Zhejiang Provincial Natural Science Foundation of China, No. LQ17H160005.

                Corresponding author: Yi-Hong Shen, MD, Chief Doctor, Department of Respiratory Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, No. 79 Qingchun Road, Hangzhou 310003, Zhejiang Province, China. drsyh@ 123456zju.edu.cn

                Article
                jWJCC.v9.i13.pg3140
                10.12998/wjcc.v9.i13.3140
                8080747
                c6bff314-11b0-4304-957a-2d805d9e92fd
                ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.

                This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial.

                History
                : 17 December 2020
                : 7 February 2021
                : 4 March 2021
                Categories
                Case Report

                lung cancer,sarcoidosis,anaplastic lymphoma kinase,echinoderm microtubule-associated protein-like 4 anaplastic lymphoma kinase,metastasis,case report

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