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Article

Rare sequential EGFR and ALK mutations in non‑small cell lung cancer: A case report and literature review

  • Authors:
    • Hung Van Nguyen
    • Chi Huyen Do
    • Bach Trung Tran
    • Huy Le Trinh
  • View Affiliations / Copyright

    Affiliations: Oncology Center, Hanoi Medical University Hospital, Hanoi 100000, Vietnam, Department of Oncology, Hanoi Medical University, Hanoi 100000, Vietnam
  • Article Number: 398
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    Published online on: June 18, 2025
       https://doi.org/10.3892/ol.2025.15144
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Abstract

In non‑small cell lung cancer, the two main genetic alterations are epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangements. The presence of both mutations in a single patient or genetic mutation discrepancies between primary tumors and metastases is uncommon. Therefore, at present, there are no guidelines on the optimal approach and treatment for this group of patients. This report presents the case of a 58‑year‑old woman with EGFR‑mutated regional lung cancer who underwent surgery followed by adjuvant chemotherapy. Upon disease recurrence, the response to EGFR‑tyrosine kinase inhibitor therapy was poor. Further analysis of metastatic pleural fluid revealed an ALK mutation. The patient was then treated with anti‑ALK therapy, resulting in long‑term disease stability. In conclusion, the coexistence of EGFR and ALK mutations in lung cancer is rare, likely due to tumor heterogeneity and prior treatments. Resistance to targeted therapies can develop through new molecular alterations during disease progression. Re‑biopsies at progression are crucial for detecting these changes and optimizing treatment based on the updated molecular profile.
View Figures

Figure 1

Chest CT scan 2 months after
chemoradiation. The white arrow indicates nodular pleural
thickening.

Figure 2

Chest CT scan 3 months after epidermal
growth factor receptor-tyrosine kinase inhibitor therapy. A large
amount of left pleural effusion was noted.

Figure 3

Hematoxylin and eosin staining of the
left pleural effusion cell block. (A) High-magnification view
showing clusters of malignant cells with glandular formation, large
basophilic nuclei and a high nucleus-to-cytoplasm ratio
(magnification, ×40). (B) High-magnification field demonstrating
similar cytological features (magnification, ×40). (C)
Low-magnification view showing the overall architecture of the cell
block with tumor cell clusters in a background of fibrin and
inflammatory cells (magnification, ×10).

Figure 4

Immunohistochemical staining of the
histological biopsy from the left pleural fluid cell block. Cells
are arranged in clusters with epithelioid morphology suggesting
glandular, papillary structures; the cells exhibit large,
basophilic nuclei and a high nucleus-to-cytoplasm ratio. (A)
Cluster tumor cells showing strong CK7 expression, confirming
epithelial origin (magnification, ×40). (B) Tumor cells showing a
loss of CK20 expression (magnification, ×40). (C) Atypical
epithelioid cells exhibiting strong nuclear transcription
termination factor 1 expression, indicative of lung adenocarcinoma
(magnification, ×40). (D) Absence of calretinin expression, ruling
out mesothelial differentiation (magnification, ×40).

Figure 5

Chest CT scan after the first 3 months
of treatment with anaplastic lymphoma kinase-tyrosine kinase
inhibitor. The pleural fluid was notably decreased.

Figure 6

Chest CT scan collected February 2025
(stable disease for 50 months).

Figure 7

Clinical course of the diagnosis and
treatment history of the patient. Dx, diagnosis; Tx, treatment; AC,
adjuvant chemotherapy; HPE, histopathologic examination; EGFR,
epidermal growth factor receptor; CRT, chemoradiotherapy; ALK,
anaplastic lymphoma kinase; EML4, EMAP like 4.
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Copy and paste a formatted citation
Spandidos Publications style
Nguyen HV, Do CH, Tran BT and Trinh HL: Rare sequential EGFR and ALK mutations in non‑small cell lung cancer: A case report and literature review. Oncol Lett 30: 398, 2025.
APA
Nguyen, H.V., Do, C.H., Tran, B.T., & Trinh, H.L. (2025). Rare sequential EGFR and ALK mutations in non‑small cell lung cancer: A case report and literature review. Oncology Letters, 30, 398. https://doi.org/10.3892/ol.2025.15144
MLA
Nguyen, H. V., Do, C. H., Tran, B. T., Trinh, H. L."Rare sequential EGFR and ALK mutations in non‑small cell lung cancer: A case report and literature review". Oncology Letters 30.2 (2025): 398.
Chicago
Nguyen, H. V., Do, C. H., Tran, B. T., Trinh, H. L."Rare sequential EGFR and ALK mutations in non‑small cell lung cancer: A case report and literature review". Oncology Letters 30, no. 2 (2025): 398. https://doi.org/10.3892/ol.2025.15144
Copy and paste a formatted citation
x
Spandidos Publications style
Nguyen HV, Do CH, Tran BT and Trinh HL: Rare sequential EGFR and ALK mutations in non‑small cell lung cancer: A case report and literature review. Oncol Lett 30: 398, 2025.
APA
Nguyen, H.V., Do, C.H., Tran, B.T., & Trinh, H.L. (2025). Rare sequential EGFR and ALK mutations in non‑small cell lung cancer: A case report and literature review. Oncology Letters, 30, 398. https://doi.org/10.3892/ol.2025.15144
MLA
Nguyen, H. V., Do, C. H., Tran, B. T., Trinh, H. L."Rare sequential EGFR and ALK mutations in non‑small cell lung cancer: A case report and literature review". Oncology Letters 30.2 (2025): 398.
Chicago
Nguyen, H. V., Do, C. H., Tran, B. T., Trinh, H. L."Rare sequential EGFR and ALK mutations in non‑small cell lung cancer: A case report and literature review". Oncology Letters 30, no. 2 (2025): 398. https://doi.org/10.3892/ol.2025.15144
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