Table 1.

Selected representative reports and studies of squamous histological transformation in EGFR-mutant lung adenocarcinoma after EGFR-TKI therapy.

Author/year	Cases	Initial EGFR mutation	EGFR-TKI before transformation	Transformation site	Molecular/pathological findings after transformation	Post-transformation treatment and outcome	Key relevance
Ye et al., 2022 (5)	1	L858R	Gefitinib	Local metastatic lung lesions	Retained EGFR L858R; MET amplification; high PD-L1 expression	Paclitaxel, carboplatin and pembrolizumab; disease control for 8 months	Suggests that chemoimmunotherapy may be active in selected PD-L1-high transformed cases
Xi et al., 2022 (8)	1	Exon 19 deletion	Icotinib followed by osimertinib	New lung lesion	Retained EGFR exon 19 deletion and T790M; MET amplification	Osimertinib-based combination therapy; later targeted and immunotherapy regimens; died approximately 12 months after SCC confirmation	Highlights repeat biopsy and molecular reassessment in transformation with concurrent resistance alterations
Park et al., 2019 (17)	4	L858R or exon 19 deletion	Gefitinib, afatinib, erlotinib, or osimertinib	Lymph node, pleura, skin/scalp, or bone/soft tissue	Retained initial EGFR mutation in all transformed SCC samples; PI3K/AKT/mTOR pathway alterations in selected cases	Treatment varied; selected cases received everolimus or osimertinib	Supports a shared tumor origin and possible adenocarcinoma-to-SCC lineage transition
Schoenfeld et al., 2020 (18)	5 SCC transformations among 62 paired cases	Various EGFR mutations	First-line or later-line osimertinib	Resistant tumor tissue after progression	Retained sensitizing EGFR mutation when evaluable; additional off-target alterations in selected cases	Subsequent treatment varied; outcomes were mixed	Identifies squamous transformation as an off-target resistance mechanism to osimertinib and supports tissue re-biopsy
Roca et al., 2019 (19)	17	Exon 19 deletion or L858R in most cases	Gefitinib, erlotinib, afatinib, or sequential EGFR-TKIs	Progressive SCC lesions at re-biopsy	Baseline EGFR mutation retained in transformed SCC lesions; acquired T790M in some cases	Chemotherapy, EGFR-TKI, or combined approaches; median OS after SCC onset was 3.5 months	Shows poor prognosis and limited efficacy of available therapies after SCC transformation
Qiu et al., 2025 (22)	1	Exon 19 deletion	Gefitinib followed by osimertinib	Left clavicular/subclavicular mass	EGFR driver mutation not detected in transformed SCC; p40/p63 positive and TTF-1/Napsin A negative	Carboplatin/docetaxel followed by tislelizumab plus carboplatin/docetaxel; extracranial PR but brain progression; OS after SCC transformation was 8 months	Demonstrates EGFR-positive adenocarcinoma transforming into EGFR-negative SCC with heterogeneous treatment response
Present case	1	Exon 19 deletion; TP53 c.713G>T (p.C238F)	Osimertinib	Left supraclavicular lymph node	Retained EGFR exon 19 deletion and TP53 mutation; MYC amplification; MSS; no MET amplification; PD-L1 TPS <1% and CPS <1	Carboplatin plus nab-paclitaxel and tislelizumab followed by tislelizumab maintenance; PR followed by stable disease	Supports acquired squamous transformation after long-term osimertinib; treatment response should be interpreted cautiously

This table presents a non-systematic selection of representative publications and is not intended to be exhaustive. CPS, combined positive score; EGFR, epidermal growth factor receptor; EGFR-TKI, epidermal growth factor receptor tyrosine kinase inhibitor; MSS, microsatellite stable; nab-paclitaxel, nanoparticle albumin-bound paclitaxel; OS, overall survival; PD-L1, programmed death-ligand 1; PR, partial response; SCC, squamous cell carcinoma; TKI, tyrosine kinase inhibitor; TPS, tumor proportion score.