Journal of Medical Cases, ISSN 1923-4155 print, 1923-4163 online, Open Access
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Case Report

Volume 15, Number 8, August 2024, pages 153-158

Synchronous Double Primary Lung Adenocarcinomas With EGFR L858R Point Mutation and MET Exon 14 Skipping Mutation

Figures

Figure 1.
Figure 1. Histology of bronchoscopic specimen from the tumor in the right upper lobe (hematoxylin and eosin stain, magnification, × 200).
Figure 2.
Figure 2. FDG-PET-CT showed the accumulation of FDG in the right S1 (SUVmax: 7.1) (shown by black arrow) and in the left S1+2 (SUVmax: 2.1) (shown by black arrowhead), and in the bilateral inferior paratracheal lymph nodes (SUVmax: 4.49) (shown by white arrow). FDG-PET-CT: 18F-fluorodeoxyglucose positron emission tomography-computed tomography.
Figure 3.
Figure 3. Chest computed tomography (CT) demonstrated nodular shadows in the right S1 and the left S1+2 at the diagnosis (in September 2020). These nodules changed before and 4 months after osimertinib administration (partial response in the right S1), and before and 8 months after capmatinib administration (partial response in the left S1+2 and progression disease in the right S1).
Figure 4.
Figure 4. Cytology of fine-needle aspiration from the left supraclavicular lymph nodes (papanicolaou stain, magnification, × 400).

Tables

Table 1. List of Positive Mutations Detected by FoundationOne® Liquid CDx Tumor Profiling Test
 
GeneMutationAllele fraction
EGFR: epidermal growth factor receptor; MET: mesenchymal-to-epithelial transition; TP53; Tumor Protein P53; VHL: von Hippel Lindau.
EGFRL858R0.0014
METSplice site 2888-21_2888-20 TT>AGA0.13
TP53Q331*0.04
TP53V143M0.5
VHLE10*0.03

 

Table 2. Summary of the Previous Case Reports of Acquired MET Exon 14 Skipping Mutation as a Resistance Mechanism to EGFR-TKIs
 
Authors (publication year)Age, sexHistologyEGFR mutationEGFR-TKIs (response, PFS)MET mutationRegimens after appearance of MET mutation
Ad: adenocarcinoma; AdSq: adenosquamous cell carcinoma; EGFR: epidermal growth factor receptor; Ex: exon; F: female; M: male; MET: mesenchymal-to-epithelial transition; mo: months, PD: progressive disease; PR: partial response; yr: years.
Xiang et al, 2023 [16]53MAdEx19delErlotinib, osimertinib (PR, 28 mo)Ex 14 skippingOsimertinib + capmatinib (PR, 7 mo)
Takamori et al, 2022 [15]76FAdL858R + T790MOsimertinib (PR, 14 mo)Ex 14 skippingTepotinib (PR, 8 mo)
Pinquie et al, 2022 [14]56MAdL858R → L858R+T790MGefitinib/erlotinib (PR, 12 mo) → osimertinib (PD, 5 mo)Ex 14 skippingCrizotinib (PR, 4 mo)
Ou et al, 2022 [13]63FAdEx18 G719D + Ex 21 L861QIcotinib (PR, 9 mo) → osimertinib (SD, 1 yr)CUX1-MET fusionIcotinib + crizotinib (PR, > 9 mo)
Jiao et al, 2021 [12]33MAdSqEGFR p.S768_D770dupAfatinib (PD, 1 mo) → anlotinib (PD, 1 mo)Germline MET Ex 14 skippingNone

 

Table 3. Summary of the Previous Case Reports of Lung Cancers Harboring Coexistence of EGFR Mutation and MET Exon 14 Skipping Mutations
 
Authors (publication year)Age, sexHistologyStage at diagnosisEGFR mutationMET mutationRegimen (response, PFS)
Ad: adenocarcinoma; del: deletion; EGFR: epidermal growth factor receptor; Ex: exon; F: female; M: male; MET: mesenchymal-to-epithelial transition; mo: months: PD: progressive disease; PFS: progression-free survival; PR: partial response.
Liu et al, 2023 [19]82FAdIVEx19 del + L858REx 14 skippingOsimertinib (PD) → osimertinib + crizotinib (death, 17 days)
Chen et al, 2022 [17]69MAdIIIBEx 20 insertionEx 14 skipping + amplificationCrizotinib (PR, 6 mo)
Zeng et al, 2019 [20]60MAdIVEx18 G750AEx 14 skippingAfatinib + crizotinib (PR, > 3mo)
Kauffmann-Guerrero et al, 2019 [18]53FAdIIIBEx19 delEx 14 skippingAfatinib (PD) → afatinib + crizotinib (PR, > 3mo)