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A Rare Histologic Transformation from EGFR-Positive Lung Adenocarcinoma to EGFR-Negative Squamous Cell Carcinoma
Mengli Qiu1, Peiwen Guo1, Jieheng Lin2
1The First Clinical School, Guangzhou University of Chinese Medicine, Guangzhou, People's Republic of China.
Abstract:
Lung adenocarcinoma (ADC) harboring epidermal growth factor receptor (EGFR) mutations rarely transforms into squamous cell carcinoma (SCC) following resistance to targeted therapy. Here, we present a case of EGFR-positive ADC that transformed into EGFR-negative SCC after developing resistance to EGFR tyrosine kinase inhibitors (TKIs). The patient experienced progressive disease after one cycle of chemotherapy and subsequently underwent five courses of tislelizumab combined with chemotherapy. Although the primary tumor showed a partial response to this combined regimen, intracranial metastases continued to progress, ultimately leading to the patient's death. Notably, the patient survived for 8 months after SCC transformation with immuno-chemotherapy, a significantly longer duration than the previously reported median survival of 3.5 months. This case underscores the occurrence of genomic instability, histological transformation, and dissociated response (DR) following treatment with EGFR-TKIs in EGFR-positive lung ADC. We hypothesize that these phenomena may be driven by tumor heterogeneity and the dynamic variability within the tumor microenvironment (TME).
Insights
EGFR-mutated lung adenocarcinoma rarely transforms into squamous cell carcinoma after resistance to targeted therapy. This case highlights genomic instability and histological transformation, offering insights into treatment resistance in lung cancer.
Area of Science:
- Oncology
- Genetics
- Cancer Biology
Background:
- Lung adenocarcinoma (ADC) with epidermal growth factor receptor (EGFR) mutations is typically treated with EGFR tyrosine kinase inhibitors (TKIs).
- Acquired resistance to TKIs is a significant clinical challenge, often involving complex genomic alterations and tumor evolution.
Observation:
- A rare case of EGFR-positive lung ADC transforming into EGFR-negative squamous cell carcinoma (SCC) after TKI resistance is presented.
- The patient exhibited progressive disease despite chemotherapy and subsequent immuno-chemotherapy with tislelizumab.
- Intracranial metastases progressed despite a partial response in the primary tumor, indicating a dissociated response.
Findings:
- Histological transformation from ADC to SCC occurred alongside EGFR negativity.
- Genomic instability and dissociated response were observed following EGFR-TKI treatment.
- The patient survived 8 months post-transformation with immuno-chemotherapy, exceeding the typical 3.5-month median survival.
Implications:
- This case demonstrates the potential for histological transformation and genomic instability in EGFR-mutated lung ADC under TKI pressure.
- Tumor heterogeneity and the tumor microenvironment (TME) may drive these adaptive changes.
- Understanding these mechanisms is crucial for developing novel therapeutic strategies for resistant lung cancer.
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