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━━ Background. The recommended primary therapy for ALK-positive lung cancer is crizotinib. While remains effective for a long time for some patients, it eventually becomes ineffective and leads to an enlargement of the tumor in many other patients. Case. The patient was a 71-year-old woman who was diagnosed with pulmonary adenocarcinoma in 2012 (cT2aN3M1b, stage IV, ALK-positive). During chemotherapy, several cystic lesions without contrast enhancement were found on contrast-enhanced cranial MRI and their progress was observed. After chemotherapy became ineffective in May 2013, the treatment was changed to the oral administration of crizotinib, which resulted in the shrinkage of the primary lesion. Nine months from the start of crizotinib treatment, the patient’s cerebral lesions were enlarged, while the primary lesion was observed to have shrunk. Craniotomy was therefore performed to conduct a biopsy. The definitive diagnosis of the biopsy specimen was metastasis to the brain from pulmonary adenocarcinoma. After whole brain irradiation, an exacerbation of bone metastasis occurred and the oral administration of alectinib was initiated in September 2014. A significant reduction of the metastatic lesions was observed on contrast-enhanced cranial MRI at one month after the start of alectinib treatment and the tumor reduction effect continues to be effective at 19 months after the start of alectinib treatment. Conclusion. In this case, alectinib was effective for treating brain metastasis for which crizotinib was ineffective. This is partly because there is a difference in the degree of transitivity of both drugs to the central nervous system. Moreover, because metastasis to the brain from mucinous tumors may provide atypical imaging findings--as occurred in this case--sufficient observation and a definitive histology-based diagnosis are vital. (JJLC. 2017;57:23-28) KEY WORDS━━ALK-positive lung cancer, Brain metastases, Mucoid tumors, Crizotinib, Alectinib Corresponding author: Yukari Tsubata. Received June 13, 2016; accepted November 14, 2016. 要旨━━背景.ALK陽性肺癌に対する一次治療にはク リゾチニブが推奨されており,長期有効例もあるが,無 効となり腫瘍の増大を認める症例が多く存在する.症 例.71 歳,女性.2012 年に肺腺癌(cT2aN3M1b,stage IV,ALK融合遺伝子陽性)と診断した.化学療法継続中 に頭部造影MRI で造影効果のない嚢胞性病変を複数個 認め,経過観察していた.2013 年 5 月に化学療法が無効 となりクリゾチニブ内服に治療を変更し,原発巣の縮小 を認めた.内服開始から 9か月後,原発巣は縮小したま まであったが脳病変が増大したことから確定診断のため 開頭生検術を実施し,肺腺癌の脳転移と診断した.全脳 照射後,骨転移の増悪を認め 2014 年 9 月にアレクチニブ 島根大学医学部 1医学科,2内科学講座呼吸器・臨床腫瘍学. 論文責任者:津端由佳里. 受付日:2016 年 6 月 13 日,採択日:2016 年 11 月 14 日. (肺癌.2017;57:23-28) 2017 The Japan Lung Cancer Society Atypical Brain Metastases in ALK-positive Lung Cancer―Mitarai et al 24 Japanese Journal of Lung Cancer―Vol 57, No 1, Feb 20, 2017―www.haigan.gr.jp の内服を開始した.投与開始 1か月後の頭部造影MRI で脳転移巣の著明な縮小を認め,内服開始 19 か月の時点 で腫瘍縮小効果は継続している.結論.本症例ではクリ ゾチニブが無効であった脳転移に対してアレクチニブが 有効であった.著効を得た一因として,両薬剤の中枢神 経系への移行性の程度の差異があると考えられた.また, 粘液産生性腫瘍の脳転移巣は本症例のように非典型的な 画像所見を呈する場合があり,十分な観察と組織学的な 確定診断が重要である. 索引用語━━ALK陽性肺癌,脳転移,粘液産生性腫瘍, クリゾチニブ,アレクチニブ

A Case of ALK-positive Lung Cancer in Which Brain Metastasis Was Surgically Diagnosed and Alectinib Was Found to be Remarkably Effective