Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2022, 166(4):451-454 | DOI: 10.5507/bp.2022.037
An EGFR-mutant lung adenocarcinoma that transformed into small-cell lung cancer. A case report
- a Department of Oncology, Specialised Hospital of St Zoerardus Zobor, Nitra, Slovak Republik
- b 1st Department of Oncology, Faculty of Medicine, Comenius University and St. Elisabeth Cancer Institute, Bratislava, Slovak Republik
- c Department of Pneumology and Phtiseology, Specialised Hospital of St Zoerardus Zobor, Nitra, Slovak Republik
- d Department of Pathological Anatomy, Jessenius Faculty of Medicine, Comenius University and University Hospital in Martin, Martin, Slovak Republik
- e Martin's Biopsy Centre Ltd, Martin, Slovak Republik
- f Department of Pathology, Faculty Hospital, Nitra, Slovak Republik
- g Radiology, Jessenius - Diagnostic Centre, Nitra, Slovak Republik
- h Department of Radiology, Faculty of Medicine, Comenius University and Slovak Medical University, University Hospital, Bratislava, Slovak Republic
Background: Transformation of EGFR (epidermal growth factor receptor) - mutant non-small cell lung cancer (NSCLC) into small-cell lung cancer (SCLC) is one mechanism of resistance to tyrosine kinase inhibitor (TKI) treatment, seen in approximately 3-10% cases. Such transformed SCLC often retains the original EGFR mutation (EGFRM), which is not otherwise observed in SCLC.
Case report: We present a 67 y/o woman with pulmonary adenocarcinoma (AC) and EGFRM deletion on exon 19. After initial treatment with whole brain radiotherapy and 7 months of TKI afatinib, progression was observed. Liquid biopsy detected deletion on exon 19 and T790M mutation. Chemotherapy carboplatin plus pemetrexed was administered, with no response. Genetics from a rebiopsy of lung revealed deletion on exon 19. After 12 months treatment with TKI osimertinib, a progression in lung and pancreas lesions was detected, docetaxel was used, with followig progression. The lung biopsy revealed SCLC. Significant elevation of serum markers carcinoembryonic antigen (CEA) and neuron-specific enolase (NSE) was observed at the time of the SCLC diagnosis. Treatment with carboplatin and etoposide was not effective. The next biopsy found two populations of cells: SCLC and AC. The biopsy from the pancreatic lesion revealed metastasis of SCLC. PCR confirmed EGFRM deletion on exon 19 in the lung SCLC tissue sample. The following treatment lines of topotecan, erlotinib were not effective. The patient survived 36 months from diagnosis, 7 months from detection of SCLC.
Conclusion: Screening for transformation of EGFR-mutant NSCLC to SCLC should be considered in resistance to TKI. In the presented case, this rare transformation was confirmed by histopathologic examination and by PCR. EGFRM in the lung SCLC, identical to that found in the original lung AC, was detected. Further, the observed elevation of serum tumor markers NSE and CEA can indicate this infrequent transformation and help to decide on rebiopsy.
Keywords: EGFR mutation, non-small cell lung cancer, small-cell lung cancer, transformation
Received: May 12, 2022; Revised: August 7, 2022; Accepted: August 10, 2022; Prepublished online: August 23, 2022; Published: December 7, 2022 Show citation
ACS | AIP | APA | ASA | Harvard | Chicago | Chicago Notes | IEEE | ISO690 | MLA | NLM | Turabian | Vancouver |
References
- Wu SG, Shih JY. Management of acquired resistance to EGFR TKI-targeted therapy in advanced non-small cell lung cancer. Mol Cancer 2018;17(1):38. doi:10.1186/s12943-018-0777-1
Go to original source...
Go to PubMed...
- Schoenfeld AJ, Chan JM, Rizvi H, Rizvi H, Rekhtman N, Daneshbod Y, Kubota D, Chang JC, Arcila ME, Ladanyi M, Somwar R, Kris MG, Pe'er D, Riely GJ, Yu HA. Tissue-based molecular and histological landscape of acquired resistance to osimertinib given initially or at relapse in patients with EGFR-mutant lung cancers. J Clin Oncol 2019;37(15_suppl):9028-9028. doi:10.1200/JCO.2019.37.15_suppl.9028
Go to original source...
- Yu HA, Arcila ME, Rekhtman N, Sima CS, Zakowski MF, Pao W, Kris MG, Miller VA, Ladanyi M, Riely GJ. Analysis of Tumor Specimens at the Time of Acquired Resistance to EGFR-TKI Therapy in 155 Patients with EGFR -Mutant Lung Cancers. Clin Cancer Res 2013;19(8):2240-47. doi:10.1158/1078-0432.CCR-12-2246
Go to original source...
Go to PubMed...
- Sequist LV, Waltman BA, Dias-Santagata D, Digumarthy S, Turke AB, Fidias P, Bergethon K, Shaw AT, Gettinger S, Cosper AK, Akhavanfard S, Heist RS, Temel J, Christensen JG, Wain JC, Lynch TJ, Vernovsky K, Mark EJ, Lanuti M, Iafrate AJ, Mino-Kenudson M, Engelman JA. Genotypic and Histological Evolution of Lung Cancers Acquiring Resistance to EGFR Inhibitors. Sci Transl Med 2011;3(75): 75ra26. doi:10.1126/scitranslmed.3002003
Go to original source...
Go to PubMed...
- Ferrer L, Giaj Levra M, Brevet M, Antoine M, Mazieres J, Rossi G, Chiari R, Westeel V, Poudenx M, Letreut J, Gervais R, Osman G, Girard N, Toffart AC, Novello S, Moro-Sibilot D. A Brief Report of Transformation From NSCLC to SCLC: Molecular and Therapeutic Characteristics. J Thorac Oncol 2019;14(1):130-34. doi:10.1016/j.jtho.2018.08.2028
Go to original source...
Go to PubMed...
- Offin M, Chan JM, Tenet M, Rizvi HA, Shen R, Riely GJ, Rekhtman N, Daneshbod Y, Quintanal-Villalonga A, Penson A, Hellmann MD, Arcila ME, Ladanyi M, Pe'er D, Kris MG, Rudin CM, Yu HA. Concurrent RB1 and TP53 Alterations Define a Subset of EGFR-Mutant Lung Cancers at risk for Histologic Transformation and Inferior Clinical Outcomes. J Thorac Oncol 2019;14(10):1784-93. doi:10.1016/j.jtho.2019.06.002
Go to original source...
Go to PubMed...
- Marcoux N, Gettinger SN, O'Kane G, Arbour KC, Neal JW, Husain H, Evans TL, Brahmer JR, Muzikansky A, Bonomi PD, Del Prete S, Wurtz A, Farago AF, Dias-Santagata D, Mino-Kenudson M, Reckamp KL, Yu HA, Wakelee HA, Shepherd FA, Piotrowska Z, Sequist LV. EGFR -Mutant Adenocarcinomas That Transform to Small-Cell Lung Cancer and Other Neuroendocrine Carcinomas: Clinical Outcomes. J Clin Oncol 2019;37(4):278-85. doi:10.1200/JCO.18.01585
Go to original source...
Go to PubMed...
- Yin X, Li Y, Wang H, Jia T, Wang E, Luo Y, Wei Y, Qin Z, Ma X. Small cell lung cancer transformation: From pathogenesis to treatment. Semin Cancer Biol. 2022 Mar 8:S1044-579X(22)00062-1. doi: 10.1016/j.semcancer.2022.03.006 Epub ahead of print
Go to original source...
Go to PubMed...
- Lee JK, Lee J, Kim S, Kim S, Youk J, Park S, An Y, Keam B, Kim DW, Heo DS, Kim YT, Kim JS, Kim SH, Lee JS, Lee SH, Park K, Ku JL, Jeon YK, Chung DH, Park PJ, Kim J, Kim TM, Ju YS. Clonal History and Genetic Predictors of Transformation Into Small-Cell Carcinomas From Lung Adenocarcinomas. J Clin Oncol 2017;35(26):3065-74. doi:10.1200/JCO.2016.71.9096
Go to original source...
Go to PubMed...
- Park CK, Oh IJ, Kim YC. Is transformed small cell lung cancer (SCLC) different from de novo SCLC? Transl Cancer Res 2019;8(2):346-49. doi:10.21037/tcr.2019.03.22
Go to original source...
Go to PubMed...
- Huang LS, Yan HY, Sun LQZ, Xu Y, Cai DH, Li XH, Chen XL, Luo XH, Duan CH. Choice of serum tumor markers in patients with small cell lung cancer: progastrin-releasing peptide, neuron-specific enolase, and carcinoembryonic antigen. J Bio-X Res 2018;1(1):12-17. doi:10.1097/JBR.0000000000000002
Go to original source...
This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International License (CC BY 4.0), which permits use, distribution, and reproduction in any medium, provided the original publication is properly cited. No use, distribution or reproduction is permitted which does not comply with these terms.