Histologic transformation of non-small-cell lung cancer in brain metastases
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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.
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.
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.
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.
KeywordsHistologic transformation Non-small-cell lung cancer Brain metastases Small-cell lung cancer Surgery
This work was supported by the Research Award Fund for outstanding Young-Middle aged Scientists of Shandong Province, China [BS2014YY004]; and Shandong Provincial Natural Science Foundation, China [ZR2014HQ064, ZR2014HP042]. The funders had no role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the article for publication.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
- 5.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 Google Scholar
- 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 Google Scholar
- 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 Google Scholar
- 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):1040–1044Google Scholar
- 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 Google Scholar
- 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 Google Scholar
- 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 Google Scholar