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━━ Background. Driver gene mutations, including epidermal growth factor receptor (EGFR) gene mutations, and immune escape mechanisms, including the programmed death-ligand 1 (PD-L1) pathway, have attracted attention as therapeutic targets for lung cancer. Case. A 57-year-old man was found to have a 35-mm mass in the right upper lobe, a 17-mm nodule in the right lower lobe, and swollen supraclavicular and mediastinal lymph nodes. A mediastinal lymph node biopsy led to the diagnosis of lung adenocarcinoma (cT4N3M0: Stage IIIC), which arose from the right upper lobe. The tumor was EGFR gene mutation (exon21 L858R)-positive and PD-L1-negative. After the initiation of afatinib treatment, the tumor in the right lower lobe and supraclavicular and mediastinal lymph nodes shrank; however, the tumor in the right upper lobe continued to grow. Another biopsy from the tumor in the right upper lobe revealed adenocarcinoma that was EGFR gene mutation-negative and PD-L1-positive (90%). Subsequently, the tumor in the right upper lobe was diagnosed as lung adenocarcinoma (cT2aN0M0: Stage IB), with strong PD-L1 positivity but no EGFR gene mutation. In contrast, the tumor in the right lower lobe was lung adenocarcinoma (cT1aN3M0: Stage IIIC), with an EGFR gene mutation (exon21 L858R) but no expression of PD-L1. This led to the diagnosis of multiple lung cancers. Conclusion. In cases in which multiple tumor sites show heterogeneous treatment responses, it is advisable to collect as many pathological specimens as possible in consideration of the possibility of multiple cancers or transformation. (JJLC. 2018;58:984-988) KEY WORDS━━ EGFR, PD-L1, Multiple primary lung cancers Corresponding author: Yasuyuki Hayashi. Received August 21, 2018; accepted October 2, 2018. 要旨━━背景.肺癌領域において EGFR遺伝子変異に 代表されるドライバー遺伝子変異や,PD-L1を介した免 疫逃避機構が注目されている.症例.57歳,男性.右上 葉の 35 mm大の腫瘤,右下葉の 17 mm大の結節,鎖骨上 窩と縦隔の多発リンパ節腫大を認め,縦隔リンパ節から 生検を行い右上葉原発の肺腺癌 cT4N3M0 Stage IIIC (EGFR exon21 L858R陽性,PD-L1陰性)と診断した.ア ファチニブ内服を開始したところ右下葉の腫瘍と鎖骨上 窩や縦隔のリンパ節は縮小した一方,右上葉の腫瘍は増 大を続けた.右上葉の腫瘍から生検を行った結果,再び 腺癌が検出されたが EGFR遺伝子変異は陰性で PD-L1 が 90%陽性であった.右上葉腫瘍は肺腺癌 cT2aN0M0 Stage IB(EGFR遺伝子変異陰性,PD-L1強陽性),右下 葉腫瘍は肺腺癌 cT1aN3M0 Stage IIIC(EGFR exon21 L858R陽性,PD-L1陰性)という,多発肺癌と診断した. 結論.複数の病変の間で治療に対する反応性が異なる場 合,多発癌や形質転換などを考慮して積極的に病理組織 を採取することが望ましい. 索引用語━━ EGFR,PD-L1,多発肺癌 1京都桂病院呼吸器センター呼吸器内科. 論文責任者:林 康之. 受付日:2018年 8月 21日,採択日:2018年 10月 2日. (肺癌.2018;58:984-988) 2018 The Japan Lung Cancer Society Multiple Primary Lung Cancers―Hayashi et al Japanese Journal of Lung Cancer―Vol 58, No 7, Dec 20, 2018―www.haigan.gr.jp 985 Figure 1. Chest X-ray obtained at the initial visit. A mass shadow contacting the mediastinum was detected in the right upper lung field. はじめに 非小細胞肺癌の薬物治療において,epidermal growth factor receptor(EGFR)遺伝子変異や anaplastic lymphoma kinase(ALK)融合遺伝子を代表とするドライ バー遺伝子変異が報告され,それら遺伝子変異をター ゲットとする阻害薬が広く使用されるようになった.一 方で programmed death-ligand 1(PD-L1)は免疫逃避機 構として働き,その発現率が治療効果を予測する因子に なることが指摘されている.今回我々は,EGFR遺伝子変 異陽性で PD-L1陰性の肺癌と EGFR遺伝子変異陰性で PD-L1陽性の肺癌を合併した 1例を経験した.同様の症 例は検索しうる限り報告がなく,稀な 1例と考えたため 文献的考察を含めて報告する.

Multiple Primary Lung Cancers Containing Adenocarcinoma with EGFR Gene Mutation and Adenocarcinoma with Strong PD-L1 Positivity