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We report a case of a 64-year-old Filipino male who initially presented with chronic cough, easy fatigability, and weight loss. Work-ups lead to a diagnosis of lung adenocarcinoma with epidermal growth factor receptor (EGFR) exon 19 deletion. Patient was placed on targeted therapy with Afatinib. He was able to complete 17 months of targeted therapy with relatively stable disease before experiencing recurrence of easy fatigability. Work-ups then lead to a diagnosis of a high-grade neuroendocrine tumor consistent with small cell lung carcinoma (SCLC). Afatinib was then discontinued and the patient was started on Carboplatin and Etoposide. However, after only one cycle, the patient’s symptoms progressed and the patient eventually expired. Histological transformation of EGFR-mutant adenocarcinoma to SCLC as a mechanism of resistance to targeted therapy has been documented in literature since 2006. However, to our knowledge, this is the first fully-documented case of histologic transformation occurring in a Filipino patient. As molecular targeted therapy and immunotherapy become standard-of-care in our country, it is of paramount importance that clinicians and pathologists are aware of the various mechanisms of resistance that can occur as a result of these treatments.
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The Philippine Journal of Pathology is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Based on works made open access at http://philippinejournalofpathology.org
2. Mangum MD, Greco FA, Hainsworth JD, Hande KR, Johnson, DH. Combined small-cell and non-small-cell lung cancer. J Clin Oncol. 1989;7(5):607-12. PMID: 2540288. https://doi.org/10.1200/JCO.19184.108.40.2067.
3. Wallace AS, Arya M, Frazier SR, Westgate S, Wang Z, Doll D. Combined small-cell lung carcinoma: an institutional experience. Thorac Cancer. 2014;5(1): 57-62. PMID: 26766973. PMCID: PMC4704284. https://doi.org/10.1111/1759-7714.12059.
4. Oser MG, Niederst MJ, Sequist LV, Engelman JA. Transformation from non-small cell lung cancer to small cell lung cancer: molecular drivers and cells of origin. Lancet Oncol. 2015;16(4): e165-72. PMID: 25846096. PMCID: PMC4470698.https://doi.org/10.1016/S1470-2045(14)71180-5.
5. Suda K, Murakami I, Sakai K, et al. Small cell lung cancer transformation and T790M mutation: complimentary roles in acquired resistance to kinase inhibitors in lung cancer. Scientific Reports 5. 2015; Article number 14447. https://www.nature.com/articles/srep14447. Accessed 24 April 2019.
6. Chai CS, Liam CK, Pang YK. Case series of small cell lung cancer transformation post tyrosine kinase inhibitor failure. Ann Oncol. 2017;28(suppl 10):x153-4. https://oncologypro.esmo.org/Meeting-Resources/ESMO-Asia-2017-Congress/Case-Series-of-Small-Cell-Lung-Cancer-Transformation-Post-Tyrosine-Kinase-Inhibitor-Failure-498P. Accessed 30 April 2019.
7. Morgillo F, Della Corte CM, Fasano M, Ciardiello F. Mechanisms of resistance to EGFR-targeted drugs: lung cancer. ESMO Open. 2016; 1(3):e000060. PMID: 27843613 PMCID: PMC5070275. https://doi.org/10.1136/esmoopen-2016-000060.
8. Marcoux N, Gettinger SN, O’Kane G, et al. EGFR-mutant adenocarcinomas that transform to small-cell lung cancer and other neuroendocrine carcinomas: clinical outcomes. Journal of Clinical Oncology. 2019;37(4):278-85. PMID: 30550363. https://doi.org/10.1200/JCO.18.01585.
9. Zakowski MF, Ladanyi M, Kris, MG. EGFR mutations in small-cell lung cancers in patients who have never smoked. N Engl J Med. 2006;355(2):213–5. PMID: 16837691. https://doi.org/10.1056/NEJMc053610.
10. Fallet, V, Ruppert, A, Poulot, V, et al. Secondary resistance to erlotinib: acquired T790M mutation and small-cell lung cancer transformation in the same patient. J Thoracic Oncol. 2012;7(6): 1061-3. PMID: 22588159. https://doi.org/10.1097/JTO.0b013e31824fea45.
11. Kuiper JL, Heideman DA, Thunnissen E, et al. Incidence of T790M mutation in (sequential) rebiopsies in EGFR-mutated NSCLC-patients. Lung Cancer. 2014;85(1): 19-24. PMID: 24768581. https://doi.org/10.1016/j.lungcan.2014.03.016.
12. Lin Q, Cai G, Yang K, Yang L, Chen C, Li, Y. Case report: small cell transformation and metastasis to the breast in a patient with lung adenocarcinoma following maintenance treatment with epidermal growth factor receptor tyrosine kinase inhibitors. BMC Cancer. 2016;16:593. PMID: 27488410. PMCID: PMC4972970. https://doi.org/ 10.1186/s12885-016-2623-4.
13. Varghese, AM, Zakowski, MF, Yu, HA, et al. Small-cell lung cancers in patients who never smoked cigarettes. J Thorac Oncology. 2014; 9(6):892-6. PMID: 24828667. PMCID: PMC4199745. https://doi.org/10.1097/JTO.0000000000000142.
14. Watanabe S, Sone T, Matsui T, et al. Transformation to small-cell lung cancer following treatment with EGFR tyrosine kinase inhibitors in a patient with lung adenocarcinoma. Lung Cancer. 2013; 82(2): 370-2. https://doi.org/10.1016/j.lungcan.2013.06.003.
15. Zhang, B, Xu, J, Wang, S, et al. Characteristics and outcome of small cell lung cancer patients (SCLC) transformed from adenocarcinoma after tyrosine kinase inhibitors treatment. Annals of Oncology. 2018; 29 (Suppl 9): ix150-60. https://oncologypro.esmo.org/Meeting-Resources/ESMO-Asia-2018-Congress/Characteristics-and-outcome-of-small-cell-lung-cancer-patients-SCLC-transformed-from-adenocarcinoma-after-tyrosine-kinase-inhibitors-treatment. Accessed 30 April 2019.