A Case of Lung Cancer Exhibiting Pleoymorphic Carcinoma Transformation Resistance Following Treatment With
Yoshiaki Nagai1,2, Hiromitsu Ohta2, Hikari Amari2
1Department of Respiratory Medicine, Saitama Medical University, Saitama, Japan.
Abstract:
Various studies have reported resistance mechanisms and treatment methods after epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor treatment; however, treatment policies have not yet been established, and few cases have reported transformation to pleomorphic carcinoma (PC) as the resistance mechanism. Herein, we report the case of a 66-year-old woman who was diagnosed with Stage 4A lung adenocarcinoma (cT2bN0M1b) through bronchoscopic biopsy. Genetic profiling revealed an EGFR L858R mutation; therefore, osimertinib was administered as the first-line therapy and achieved a partial response. After 46 months of osimertinib treatment, the metastases remained under control; however, the primary tumor enlarged and was therefore resected. Pathological examination confirmed the diagnosis of PC. Genetic testing of the surgical pathology specimen showed that the EGFR mutation L858R was retained, and the patient was considered drug-resistant owing to the histologic transformation to PC. The patient continued osimertinib therapy and had no recurrence at 9 months postoperatively. Transformation to PC following osimertinib administration is rare, and we report this unique case. This study was approved by the Jichi Medical University Saitama Medical Center Ethics Committee (S24-073), and written informed consent was obtained from the patient.
Insights
A rare case of lung adenocarcinoma transformed into pleomorphic carcinoma after epidermal growth factor receptor (EGFR) inhibitor treatment highlights a novel resistance mechanism. Continued treatment with osimertinib showed no recurrence, suggesting a potential management strategy for this rare transformation.
Area of Science:
- Oncology
- Molecular Biology
- Pathology
Background:
- Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) are standard treatments for EGFR-mutated non-small cell lung cancer.
- Resistance mechanisms to EGFR-TKIs are diverse, but histologic transformation is infrequently reported.
- Pleomorphic carcinoma (PC) is a rare subtype of non-small cell lung cancer.
Observation:
- A 66-year-old woman with EGFR L858R-mutated lung adenocarcinoma received first-line osimertinib.
- After 46 months of partial response, the primary tumor enlarged, revealing transformation to pleomorphic carcinoma upon resection.
- Genetic testing confirmed the EGFR L858R mutation persisted, indicating resistance due to histologic transformation.
Findings:
- Histologic transformation to pleomorphic carcinoma is a rare mechanism of resistance to osimertinib in EGFR-mutated lung adenocarcinoma.
- The EGFR L858R mutation was retained despite the transformation to PC.
- The patient remained recurrence-free for 9 months post-surgery while continuing osimertinib therapy.
Implications:
- This case expands the understanding of resistance mechanisms to EGFR-TKIs, specifically highlighting histologic transformation.
- It suggests that continued TKI therapy may be beneficial even after transformation to PC.
- Further research is needed to establish treatment policies for EGFR-TKI-resistant lung cancers with histologic transformation.
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