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International Journal of Clinical Oncology

Published in:

01-04-2019 | Original Article

Histologic transformation of non-small-cell lung cancer in brain metastases

Authors: Meng Jiang, Xiaolong Zhu, Xiao Han, Haiyan Jing, Tao Han, Qiang Li, Xiao Ding

Published in: International Journal of Clinical Oncology | Issue 4/2019

Abstract

Background

Treatment strategies differ substantially for small-cell lung cancer (SCLC), adenocarcinoma and squamous-cell cancer (SCC). Therefore, it is of important significance to identify histologic transformation. There are no reports on histologic transformation in brain metastases (BM) to date. The aim of this study was to analyze the histologic transformation in BM for the first time.

Methods

Medical records were reviewed and patients with both resected BM and primary tumors were examined retrospectively. The histologic diagnosis was confirmed by H&E staining, and additional diagnostic immunohistochemical stains were performed at the discretion of the pathologists. Characteristics of histologic transformation in BM were analyzed.

Results

3 of 24 patients (12.5%) with both resected BM and primary non-small-cell lung cancers (NSCLCs) had evidence of histologic transformation in BM. One case with SCC transformed to adenocarcinoma in brain, one case with adenocarcinoma transformed to SCLC, and another case with adenocarcinoma transformed to SCC. The three cases of histologic transformation were all spontaneous and had not tested gene status.

Conclusions

We disclosed the histologic transformation of NSCLC in BM at a frequency not as low as expected, and speculated it as an evolution promoted by intratumor heterogeneity, though it warrants further prospective multi-institution investigations with comprehensive molecular analysis. Our findings provided further impetus for surgery when the metastatic or recurrent lesion is resectable, and repeated pathologic evaluation to help tailor individualized treatment.

Kim TM, Song A, Kim DW, Kim S, Ahn YO, Keam B et al (2015) Mechanisms of acquired resistance to AZD9291: a mutation-selective, irreversible EGFR inhibitor. J Thorac Oncol 10(12):1736–1744. https://doi.org/10.1097/JTO.0000000000000688 CrossRefPubMed

Norkowski E, Ghigna MR, Lacroix L, Le Chevalier T, Fadel E, Dartevelle P et al (2013) Small-cell carcinoma in the setting of pulmonary adenocarcinoma: new insights in the era of molecular pathology. J Thorac Oncol 8(10):1265–1271. https://doi.org/10.1097/JTO.0b013e3182a407fa CrossRefPubMed

Sequist LV, Waltman BA, Dias-Santagata D, Digumarthy S, Turke AB, Fidias P et al (2011) Genotypic and histological evolution of lung cancers acquiring resistance to EGFR inhibitors. Sci Transl Med 3(75):75ra26. https://doi.org/10.1126/scitranslmed.3002003 CrossRefPubMedPubMedCentral

Yu HA, Arcila ME, Rekhtman N, Sima CS, Zakowski MF, Pao W et al (2013) 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 19(8):2240–2247. https://doi.org/10.1158/1078-0432.CCR-12-2246 CrossRefPubMedPubMedCentral

Alam N, Gustafson KS, Ladanyi M, Zakowski MF, Kapoor A, Truskinovsky AM et al (2010) Small-cell carcinoma with an epidermal growth factor receptor mutation in a never-smoker with gefitinib-responsive adenocarcinoma of the lung. Clin Lung Cancer 11(5):E1–E4. https://doi.org/10.3816/CLC.2010.n.046 CrossRefPubMed

Popat S, Wotherspoon A, Nutting CM, Gonzalez D, Nicholson AG, O’Brien M (2013) Transformation to “high grade” neuroendocrine carcinoma as an acquired drug resistance mechanism in EGFR-mutant lung adenocarcinoma. Lung Cancer 80(1):1–4. https://doi.org/10.1016/j.lungcan.2012.12.019 CrossRefPubMed

Ma AT, Chan WK, Ma ES, Cheng T, Cheng PN (2012) Small cell lung cancer with an epidermal growth factor receptor mutation in primary gefitinib-resistant adenocarcinoma of the lung. Acta Oncol 51(4):557–559. https://doi.org/10.3109/0284186X.2011.636757 CrossRefPubMed

van Riel S, Thunnissen E, Heideman D, Smit EF, Biesma B (2012) A patient with simultaneously appearing adenocarcinoma and small-cell lung carcinoma harbouring an identical EGFR exon 19 mutation. Ann Oncol 23(12):3188–3189. https://doi.org/10.1093/annonc/mds525 CrossRefPubMed

Morinaga R, Okamoto I, Furuta K, Kawano Y, Sekijima M, Dote K et al (2007) Sequential occurrence of non-small cell and small cell lung cancer with the same EGFR mutation. Lung Cancer 58(3):411–413. https://doi.org/10.1016/j.lungcan.2007.05.014 CrossRefPubMed

10.

Lee JK, Lee J, Kim S, Kim S, Youk J, Park S et al (2017) Clonal history and genetic predictors of transformation into small-cell carcinomas from lung adenocarcinomas. J Clin Oncol 35(26):3065–3074. https://doi.org/10.1200/JCO.2016.71.9096 CrossRefPubMed

11.

Niederst MJ, Sequist LV, Poirier JT, Mermel CH, Lockerman EL, Garcia AR et al (2015) RB loss in resistant EGFR mutant lung adenocarcinomas that transform to small-cell lung cancer. Nat Commun 6:6377. https://doi.org/10.1038/ncomms7377 CrossRefPubMed

12.

Lin Q, Cai GP, Yang KY, Yang L, Chen CS, Li YP (2016) 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 16:593. https://doi.org/10.1186/s12885-016-2623-4 CrossRefPubMedPubMedCentral

13.

Kim WJ, Kim S, Choi H, Chang J, Shin HJ, Park CK et al (2015) Histological transformation from non-small cell to small cell lung carcinoma after treatment with epidermal growth factor receptor-tyrosine kinase inhibitor. Thorac Cancer 6(6):800–804. https://doi.org/10.1111/1759-7714.12217 CrossRefPubMed

14.

Takegawa N, Hayashi H, Iizuka N, Takahama T, Ueda H, Tanaka K et al (2016) Transformation of ALK rearrangement-positive adenocarcinoma to small-cell lung cancer in association with acquired resistance to alectinib. Ann Oncol 27(5):953–955. https://doi.org/10.1093/annonc/mdw032 CrossRefPubMed

15.

Fujita S, Masago K, Katakami N, Yatabe Y (2016) Transformation to SCLC after treatment with the ALK inhibitor alectinib. J Thorac Oncol 11(6):e67–e72. https://doi.org/10.1016/j.jtho.2015.12.105 CrossRefPubMed

16.

Cha YJ, Cho BC, Kim HR, Lee HJ, Shim HS (2016) A Case of ALK-rearranged adenocarcinoma with small cell carcinoma-like transformation and resistance to crizotinib. J Thorac Oncol 11(5):e55–e58. https://doi.org/10.1016/j.jtho.2015.12.097 CrossRefPubMed

17.

Watanabe S, Sone T, Matsui T, Yamamura K, Tani M, Okazaki A et al (2013) Transformation to small-cell lung cancer following treatment with EGFR tyrosine kinase inhibitors in a patient with lung adenocarcinoma. Lung Cancer 82(2):370–372. https://doi.org/10.1016/j.lungcan.2013.06.003 CrossRefPubMed

18.

Hsieh MS, Jhuang JY, Hua SF, Chou YH (2015) Histologic evolution from adenocarcinoma to squamous cell carcinoma after gefitinib treatment. Ann Thorac Surg 99(1):316–319. https://doi.org/10.1016/j.athoracsur.2014.02.075 CrossRefPubMed

19.

Levin PA, Mayer M, Hoskin S, Sailors J, Oliver DH, Gerber DE (2015) Histologic transformation from adenocarcinoma to squamous cell carcinoma as a mechanism of resistance to EGFR inhibition. J Thorac Oncol 10(9):e86–e88. https://doi.org/10.1097/JTO.0000000000000571 CrossRefPubMedPubMedCentral

20.

Scher KS, Saldivar JS, Fishbein M, Marchevsky A, Reckamp KL (2013) EGFR-mutated lung cancer with T790M-acquired resistance in the brain and histologic transformation in the lung. J Natl Compr Cancer Netw 11(9):1040–1044CrossRef

21.

Longo L, Mengoli MC, Bertolini F, Bettelli S, Manfredini S, Rossi G (2017) Synchronous occurrence of squamous-cell carcinoma “transformation” and EGFR exon 20 S768I mutation as a novel mechanism of resistance in EGFR-mutated lung adenocarcinoma. Lung Cancer 103:24–26. https://doi.org/10.1016/j.lungcan.2016.11.012 CrossRefPubMed

22.

Kobayashi Y, Sakao Y, Ito S, Park J, Kuroda H, Sakakura N et al (2013) Transformation to sarcomatoid carcinoma in ALK-rearranged adenocarcinoma, which developed acquired resistance to crizotinib and received subsequent chemotherapies. J Thorac Oncol 8(8):e75–e78. https://doi.org/10.1097/JTO.0b013e318293d96f CrossRefPubMed

23.

Le T, Sailors J, Oliver DH, Mayer M, Hoskin S, Gerber DE (2017) Histologic transformation of EGFR mutant lung adenocarcinoma without exposure to EGFR inhibition. Lung Cancer 105:14–16. https://doi.org/10.1016/j.lungcan.2017.01.005 CrossRefPubMed

24.

Peifer M, Fernandez-Cuesta L, Sos ML, George J, Seidel D, Kasper LH et al (2012) Integrative genome analyses identify key somatic driver mutations of small-cell lung cancer. Nat Genet 44(10):1104–1110. https://doi.org/10.1038/ng.2396 CrossRefPubMedPubMedCentral

25.

Hsu CL, Chen KY, Kuo SW, Chang YL (2017) Histologic transformation in a patient with lung cancer treated with chemotherapy and pembrolizumab. J Thorac Oncol 12(6):e75–e76. https://doi.org/10.1016/j.jtho.2017.02.006 CrossRefPubMed

26.

Brastianos PK, Carter SL, Santagata S, Cahill DP, Taylor-Weiner A, Jones RT et al (2015) Genomic characterization of brain metastases reveals branched evolution and potential therapeutic targets. Cancer Discov 5(11):1164–1177. https://doi.org/10.1158/2159-8290.CD-15-0369 CrossRefPubMedPubMedCentral

27.

Paik PK, Shen R, Won H, Rekhtman N, Wang L, Sima CS et al (2015) Next-generation sequencing of stage IV squamous cell lung cancers reveals an association of PI3K aberrations and evidence of clonal heterogeneity in patients with brain metastases. Cancer Discov 5(6):610–621. https://doi.org/10.1158/2159-8290.CD-14-1129 CrossRefPubMedPubMedCentral

28.

Jamal-Hanjani M, Wilson GA, McGranahan N, Birkbak NJ, Watkins TBK, Veeriah S et al (2017) Tracking the evolution of non-small-cell lung cancer. N Engl J Med 376(22):2109–2121. https://doi.org/10.1056/NEJMoa1616288 CrossRefPubMed

29.

de Bruin EC, McGranahan N, Mitter R, Salm M, Wedge DC, Yates L et al (2014) Spatial and temporal diversity in genomic instability processes defines lung cancer evolution. Science 346(6206):251–256. https://doi.org/10.1126/science.1253462 CrossRefPubMedPubMedCentral

30.

Zhang J, Fujimoto J, Zhang J, Wedge DC, Song X, Zhang J et al (2014) Intratumor heterogeneity in localized lung adenocarcinomas delineated by multiregion sequencing. Science 346(6206):256–259. https://doi.org/10.1126/science.1256930 CrossRefPubMedPubMedCentral

Title: Histologic transformation of non-small-cell lung cancer in brain metastases
Authors: Meng Jiang
Xiaolong Zhu
Xiao Han
Haiyan Jing
Tao Han
Qiang Li
Xiao Ding
Publication date: 01-04-2019
Publisher: Springer Singapore
Published in: International Journal of Clinical Oncology / Issue 4/2019
Print ISSN: 1341-9625
Electronic ISSN: 1437-7772
DOI: https://doi.org/10.1007/s10147-018-1369-1

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Abstract

Background

Methods

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