LAK局所療法施行中に腫瘍出血を伴う再発をきたした悪性星細胞腫の1例

Recurrence with Tumor Bleeding in a Patient with Malignant Astrocytoma During the Treatment with Intracranial Injection of Lymphokine-activated Killer Cells : A Case Report

　Lymphokine-activated killer（LAK）局所療法を施行中に，腫瘍出血を伴う腫瘍再発をきたした22歳女性の再発悪性神経膠腫の症例を報告した。13歳で初発，加療後完全寛解したが，9年後に右後頭葉に腫瘍が再発した。腫瘍亜全摘術にてastrocytoma grade 3と診断され，術後患者末梢血から固層化CD 3抗体下，interleukin−2にて誘導されたLAK細胞を，1回1-3×10⁹個，合計8回Ommaya貯留槽から腫瘍腔内局所投与した。6回目以降，腫瘍腔内貯留液は強い血性となり，8回目には明らかな腫瘍増大と脳圧亢進症状が出現し再手術を施行した。腫瘍腔表面には多数の新生血管，マクロファージ，リンパ球の浸潤を伴う硝子化の強い線維性結合組織が存在し，膜内部および深部に腫瘍の増生がみられ，Ommaya管先端部付近に多く血塊が認められた。腫瘍浸潤リンパ球は主にCD 3陽性のT cellであった。LAK局注療法においては血管新生を伴う腫瘍腔表面の肉芽形成が治療抵抗性に加え出血を惹起する可能性が考えられた。

A 22-year-old woman harboring recurrent malig-nant astrocytoma presented with intracranial hyper-tension by tumor hemorrhage during repeated administration of lymphokine - activated killer (LAK) cells via Ommaya's reservoir. She first suf-fered from the tumor located at the right occipital lobe at the age of 13. The tumor regressed comple-tely by subtotal removal of the tumor, followed by external irradiation. Nine years later, however, the occipital tumor recurred and was subtotally resect-ed. Pathological diagnosis was astrocytoma grade 3. Postoperatively, LAK cells induced from her periph-eral blood lymphocytes incubated with interleukin-2 and anti - CD3 antibody were injected into the tumor cavity via Ommaya's reservoir for eight times. At the end of the LAK therapy, the tumor regrew with massive hemorrhage in the tumor cav-ity causing intracranial hypertension. At the reope-ration, thick granulation tissue covered the surface of the recurrent tumor and dense deposits of clot were noted around the tip of the Ommaya's tube. Histologically the superficial layer of the tumor was infiltrated with macrophages and lymphocytes, mostly CD3-positive T cells, accompanied with capillary hyperplasia. Viable astrocytoma cells were abundant beneath the granulation layer. It should be considered that in local LAK therapy granulation tissue formation with hypervasculariza-tion at the surface of the tumor cavity may lead to tumor bleeding as well as resistance to the treat-ment.