多形肺癌を合併した超新星性自己免疫性脳炎の剖検例

Paraneoplastic autoimmune encephalitis associated with pleomorphic lung carcinoma: An autopsy case report.

• Takashi Ando
• Yoji Goto
• Kazuo Mano
• Fumio Nomura
• Masako Kurashige
• Masafumi Ito
• Maya Mimuro
• Yasushi Iwasaki
• Masahisa Katsuno
• Mari Yoshida

抄録

64歳の男性が急性発症の意識障害で入院した．脳脊髄液検査では多血球症と蛋白質の上昇を認め，培養とPCRは陰性であった．自己免疫性脳炎の血清抗体も陰性であった。脳磁気共鳴画像検査（MRI）は異常なしであったが、全身CT検査では左肺下葉に腫瘍が認められた。気管支ブラシ細胞診では悪性細胞のクラスターが認められ，F-フルオロデオキシグルコースポジトロン断層撮影では肺腫瘍に多発性の病変が認められた．臨床的にはステージIVの肺癌で、T3N3M1b（OSS）と診断された。ステロイド療法の効果は限定的であったが、化学療法により神経症状は劇的に改善した。そのため、腫瘍性神経症の診断基準に基づき、腫瘍性傍神経症性自己免疫性脳炎と診断された。14ヵ月後に病状の進行により死亡した。死後の剖検では左肺に白色の不定形結節を認め、他の臓器にも同様の結節を認めた。脳の固定前の体重は1500gで、右心前回に結節が認められた。顕微鏡的には肺腫瘍は腺癌成分を含む多形癌であった。大脳皮質、灰白質接合部、基底核に微小軟化（500μm以下）が複数認められ、大脳辺縁系と非大脳辺縁系の両方にびまん性に分布していた。大脳皮質内の血管には軽度のリンパ球浸潤が認められた。右心前回に腫瘍転移はほとんど認められなかった。多発する微小軟化は、腫瘍性自己免疫性脳炎の慢性的な神経病理学的変化を反映している可能性がある。これらの病変は脳MRIで検出するには小さすぎた。しかし、これらの病変は多くの解剖学的部位で観察されたため、急性期の神経症状を引き起こす可能性がある。自己免疫性脳炎の神経病理を推定する際には、微小軟化などの微妙な所見に注意を払う必要がある。本疾患の特徴的な神経病理を理解するためには、さらなる検討が必要である。

A 64-year-old man was admitted with acute onset disturbed consciousness. Cerebrospinal fluid analysis revealed pleocytosis and elevated protein, with negative cultures and PCR. Serum antibodies for autoimmune encephalitis were also negative. Brain magnetic resonance imaging (MRI) was unremarkable, but whole-body CT scan showed a tumor in the left lower lung lobe. Bronchial brush cytology demonstrated clusters of malignant cells, and F-fluorodeoxyglucose positron emission tomography showed multiple lesions and increased uptake in the lung tumor. Clinically the patient had a stage IV lung carcinoma, graded as T3N3M1b (OSS). Steroid therapy had limited efficacy, but chemotherapy dramatically improved his neurological symptoms. Therefore, he was diagnosed with paraneoplastic autoimmune encephalitis based on the diagnostic criteria for paraneoplastic neurological syndromes. He died due to disease progression 14 months later. Subsequent postmortem examination revealed white ill-defined nodules in the left lung, with similar nodules in other organs. The brain weighed 1500 g before fixation, and a nodule was observed in the right precentral gyrus. Microscopically, the lung tumor was a pleomorphic carcinoma with an adenocarcinoma component. Multiple areas of micro-softening (≤500 μm) were identified in the cerebral cortex, gray-white matter junction and basal ganglia, and were distributed diffusely in both the limbic and non-limbic systems. Mild lymphocytic infiltrates were observed involving few intraparenchymal vessels. Few tumor metastases were observed in the right precentral gyrus. The multiple micro-softenings may reflect a chronic neuropathologic change of paraneoplastic autoimmune encephalitis. They were too small to be detected by brain MRI. However, these lesions may have the potential to cause the neurological symptoms in the acute phase because they were observed in many anatomical regions. We should pay attention to subtle findings such as micro-softenings when estimating the neuropathology of autoimmune encephalitis. Further investigations are needed to understand the characteristic neuropathology of this condition.

© 2018 Japanese Society of Neuropathology.