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Case Reports
. 2024 Apr 23:14:1395654.
doi: 10.3389/fonc.2024.1395654. eCollection 2024.

ALK-rearranged and EGFR wild-type lung adenocarcinoma transformed to small cell lung cancer: a case report

Rui Chen  1 , Yan Jian  2 , Yuzhen Liu  3 , Junping Xie  1
Affiliations
Case Reports

ALK-rearranged and EGFR wild-type lung adenocarcinoma transformed to small cell lung cancer: a case report

Rui Chen et al. Front Oncol. .

Abstract

Background: Cases of ALK-rearranged EGFR wild-type lung adenocarcinoma (LUAD) transforming into small cell lung cancer (SCLC) are rarely reported, and diagnosis is often delayed. The emergence of this transformation phenomenon is often regarded as a consequence of acquired resistance mechanisms.

Case presentation: A 47-year-old male diagnosed with poorly differentiated adenocarcinoma of the right middle lung (pT2N2M0, stage IIIA) achieved a 46-month progression-free survival (PFS) following surgery and adjuvant chemotherapy. During routine follow-up, tumor recurrence and metastasis was detected. Genetic testing revealed ALK rearrangement and wild-type EGFR, prompting treatment with ALK-TKIs. In May 2023, abdominal CT scans showed significant progression of liver metastases and abnormal elevation of the tumor marker NSE. Immunohistochemical results from percutaneous liver biopsy indicated metastatic SCLC.

Results: After resistance to ALK-TKIs and transformation to SCLC, the patient received chemotherapy combined with immunotherapy for SCLC, but the patient's disease progressed rapidly. Currently, the patient is being treated with albumin-bound paclitaxel in combination with oral erlotinib and remains stable.

Conclusion: Histological transformation emerges as a compelling mechanism of resistance to ALK-TKIs, necessitating the utmost urgency for repeat biopsies in patients displaying disease progression after resistance. These biopsies are pivotal in enabling the tailor-made adaptation of treatment regimens to effectively counteract the assorted mechanisms of acquired resistance, thus optimizing patient outcomes in the battle against ALK-driven malignancies.

Keywords: ALK-TKIs; liver metastasis; non-small cell lung cancer; small cell lung cancer; transformation.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Patient’s treatment history and medication details.
Figure 2
Figure 2
Changes in liver metastases on abdominal CT. (A) Images of liver metastases before monotherapy with crizotinib. (B) Images of the liver at the time of disease progression following treatment with TGRX-326. (C) Hepatic imaging of disease progression following use of 4 courses of chemotherapy combined with immunotherapy for SCLC.
Figure 3
Figure 3
The profile of NSE in serum.
Figure 4
Figure 4
Hematoxylin and eosin (H&E) staining and immunohistochemical staining (IHC) staining of the liver biopsy specimen. (A) H&E staining of the liver biopsy specimen. (B-D) IHC staining confirmed positive for TTF-1, CgA and CD56. IHC staining confirms (E) AFP-negative and (F-H) CK, CK7 and CK19-positive. IHC staining confirmed (I) CD10 positivity, (J) Napsin A negativity, (K) GPC-3 positivity, and (L) GS positivity. IHC staining confirmed (M) HepPar-1 negativity, (N) HSP70 positivity, (O) Ki-67 positivity, and (P) P40 negativity.
See this image and copyright information in PMC

References

    1. Shaw A, Bauer TM, de Marinis F, Felip E, Goto Y, Liu G, et al. . First-line lorlatinib or crizotinib in advanced ALK-positive lung cancer. New Engl J Med. (2020) 383:2018–29. doi: 10.1056/NEJMoa2027187 - DOI - PubMed
    1. Ettinger D, Wood D, Aisner D, Akerley W, Bauman J, Bharat A, et al. . Non-small cell lung cancer, version 3.2022, NCCN clinical practice guidelines in oncology. J Natl Compr Cancer Net. JNCCN. (2022) 20:497–530. doi: 10.6004/jnccn.2022.0025 - DOI - PubMed
    1. Katayama R. Drug resistance in anaplastic lymphoma kinase-rearranged lung cancer. Cancer Sci. (2018) 109:572–80. doi: 10.1111/cas.13504 - DOI - PMC - PubMed
    1. Schneider J, Lin J, Shaw A. ALK-positive lung cancer: a moving target. Nat Cancer. (2023) 4:330–43. doi: 10.1038/s43018-023-00515-0 - DOI - PMC - PubMed
    1. Liu Y. Small cell lung cancer transformation from EGFR-mutated lung adenocarcinoma: A case report and literatures review. Cancer Biol Ther. (2018) 19:445–9. doi: 10.1080/15384047.2018.1435222 - DOI - PMC - PubMed

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