Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Case Reports
. 2020 May 15;59(10):1291-1294.
doi: 10.2169/internalmedicine.3542-19. Epub 2020 Feb 26.

Combined Small and Squamous Transformation in EGFR-mutated Lung Adenocarcinoma

Taiki Hakozaki  1 , Miyako Kitazono  2 , Mikio Takamori  2 , Takahiro Kiriu  3
Affiliations
Case Reports

Combined Small and Squamous Transformation in EGFR-mutated Lung Adenocarcinoma

Taiki Hakozaki et al. Intern Med. .

Abstract

Histologic transformation has been described as an acquired mechanism of resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). We herein report the case of a woman with stage IV lung adenocarcinoma harboring EGFR exon 19 deletions who was initially treated with EGFR-TKIs; several cytotoxic chemotherapeutic regimens were used when resistance developed. A lymph node re-biopsy revealed histologic transformation of the tumor to combined small-cell lung cancer and squamous cell carcinoma with retained EGFR exon 19 deletions. Following sequential chemotherapy appropriate for transformed histology, a clinical response was achieved.

Keywords: EGFR mutation; acquired resistance; histologic transformation; non-small-cell lung cancer.

PubMed Disclaimer

Conflict of interest statement

Author's disclosure of potential Conflicts of Interest (COI).

Mikio Takamori: Honoraria, AstraZeneca, Eli Lilly Japan, Taiho Pharmaceutical, Chugai Pharmaceutical, Ono Pharmaceutical, Bristol-Myers Squibb, Boehringer Ingelheim Japan, Merck Sharp & Dohme, Kyorin Pharmaceutical, Kyowa Hakko Kirin, Novartis, Astellas and Qiagen.

Figures

Figure 1.
Figure 1.
A cytology specimen from a primary tumor confirmed the diagnosis of adenocarcinoma. A repeated evaluation did not reveal any component of small-cell or squamous cell lung carcinoma. (A) Hematoxylin and Eosin staining (200×). (B) Thyroid transcription factor-1 (TTF-1) (200×).
Figure 2.
Figure 2.
Chest computed tomography at the time small-cell and squamous cell transformation was detected (A-C). After four cycles of carboplatin+etoposide (D-E).
Figure 3.
Figure 3.
Morphologic features and immunohistochemical staining of a biopsy specimen from a right hilar lymph node obtained by endobronchial ultrasound transbronchial needle aspiration confirming histologic transformation to both small-cell and squamous cell lung carcinoma. (A) Hematoxylin and Eosin staining (200×). (B) Synaptophysin (200×). (C) p40 (200×). (D) Cytokeratin AE1/AE3.
See this image and copyright information in PMC

References

    1. Li W, Ren S, Li J, et al. . T790M mutation is associated with better efficacy of treatment beyond progression with EGFR-TKI in advanced NSCLC patients. Lung Cancer 84: 295-300, 2014. - PubMed
    1. Brugger W, Thomas M. EGFR-TKI resistant non-small cell lung cancer (NSCLC): new developments and implications for future treatment. Lung Cancer 77: 2-8, 2012. - PubMed
    1. Cretella D, Saccani F, Quaini F, et al. . Trastuzumab emtansine is active on HER-2 overexpressing NSCLC cell lines and overcomes gefitinib resistance. Mol Cancer 13: 143, 2014. - PMC - PubMed
    1. Li Y, Yang Z, Li W, et al. . TOPK promotes lung cancer resistance to EGFR tyrosine kinase inhibitors by phosphorylating and activating c-Jun. Oncotarget 7: 6748-6764, 2016. - PMC - PubMed
    1. Lin Y, Wang X, Jin H. EGFR-TKI resistance in NSCLC patients: mechanisms and strategies. Am J Cancer Res 4: 411-435, 2014. - PMC - PubMed

Publication types

MeSH terms