Case Report: EGFR-Positive Early-Stage Lung Adenocarcinoma Transforming to Squamous Cell Carcinoma After TKI Treatment

Abstract

The histological transformation from epidermal growth factor receptor (EGFR)-mutated adenocarcinoma (ADC) to squamous cell carcinoma (SCC) after tyrosine kinase inhibitor (TKI) treatment is rare. We present a case of a patient who transitioned from early-stage primary lung ADC with partial squamous differentiation, EGFR mutation and amplification, to adrenal gland metastasis as SCC with EGFR amplification disappearance 115-months after surgery, during which gefitinib and local radiotherapy were utilized for the metastasis in the right femoral head and mediastinal lymph nodes. This case might indicate a possible mechanism of EGFR inhibition resistance with SCC transition and EGFR amplification loss from the initially well-responding ADC, especially those with SCC or partial squamous differentiation. The optimal post-progression therapy for ADC-SCC patients is challenging and further studies are needed.

Drug resistance mechanisms and progress in the treatment of EGFR‑mutated lung adenocarcinoma (Review)

“…Transformation to lung squamous cell carcinoma (SCC). In recent years, several cases of transformation of EGFR-mutated NSCLC to SCC have been reported (117)(118)(119)(120)(121), and some reports indicate the association between the T790M mutation and SCC transformation (122,123). As this morphological transformation is rare, the mechanism is unclear, although it has been shown that it may be related to changes in the PI3K/AKT/mTOR pathway during EGFR-TKI therapy (124).…”

“…For patients with drug-resistant lung SCC, the prognosis is usually poor, and the mOS is only ~3.5 months ( 120 ). It is difficult to choose follow-up treatments due to the low incidence; Liao et al ( 121 ) reported the case of a patient who received almonertinib for 6 months after detection of the SCC phenotype. At the time of writing the study, the patient was continuing almonertinib monotherapy and the disease was stable.…”