Neurological Surgery 脳神経外科44巻2号

2016年02月発行

連載 脳腫瘍Update

（4）Oligodendroglial tumors（乏突起膠細胞系腫瘍)

著者： 宇塚岳夫¹ 大谷亮平¹ 植木敬介¹²

所属機関： ¹獨協医科大学脳神経外科 ²獨協医科大学腫瘍センター

ページ範囲：P.161 - P.170

Ⅰ．乏突起膠細胞系腫瘍（oligodendroglial tumors）とは？—その歴史と現在—
　乏突起膠腫（oligodendroglioma）という名称は，BaileyとCushingが1926年に初めて用いたもので，主に成人の大脳半球に発生するグリオーマのうち，組織形態をみた時に腫瘍細胞の形態が乏突起膠細胞（oligodendrocyte）に似ている腫瘍の一群が存在することが認識され，この名が付けられた．彼らの命名法は，細胞の形態的な特徴から腫瘍が発生する母体細胞を推定し，それを腫瘍の名称に用いるというものである．このような，細胞形態による仮想の母体細胞（presumed origin）による分類は，Bailey/Cushingの分類全体を貫いたprincipleであり，もっと遡ればおそらくVirchowの細胞病理学に起源がある．この分類は臨床経過との相関が比較的良好であったために，広く受け容れられ，今日に至っている．しかし，乏突起膠腫は，確かに細胞の形態は乏突起膠細胞に似ているものの，例えば乏突起膠細胞がもつ髄鞘形成作用が証明されたことはなく，母体細胞が何であるのか本当は明らかではない．
　現在用いられているWHO 2007分類においてもBailey/Cushingのこの基本的な定義と概念は踏襲されているが，組織形態上は，1つの腫瘍の中に乏突起膠細胞に似た細胞だけでなく星状膠細胞（astrocyte）に似た腫瘍細胞がさまざまな程度やパターンで混在していることも多く，それらは2つの系統の腫瘍（乏突起膠腫と星細胞腫（astrocytoma））が混在した腫瘍と考えられてきた．その結果，乏突起膠細胞系腫瘍（oligodendroglial tumors）の中に乏突起膠腫（oligodendroglioma：OD，Grade Ⅱ），退形成性乏突起膠腫（anaplastic oligodendroglioma：AOD, Grade Ⅲ），乏突起星細胞腫（oligoastrocytoma：OA, Grade Ⅱ），退形成性乏突起星細胞腫（anaplastic oligoastrocytoma：AOA, Grade Ⅲ）の4つの腫瘍名が列記されている．それぞれの定義は組織形態によって記載されている¹⁰⁾．

参考文献

1) Bettegowda C, Agrawal N, Jiao Y, Sausen M, Wood LD, Hruban RH, Rodriguez FJ, Cahill DP, McLendon R, Riggins G, Velculescu VE, Oba-Shinjo SM, Marie SK, Vogelstein B, Bigner D, Yan H, Papadopoulos N, Kinzler KW：Mutations in CIC and FUBP1 contribute to human oligodendroglioma. Science 333：1453-1455, 2011

2) Cairncross JG, Macdonald DR：Successful chemotherapy for recurrent malignant oligodendroglioma. Ann Neurol 23：360-364, 1988

3) Cairncross JG, Ueki K, Zlatescu MC, Lisle DK, Finkelstein DM, Hammond RR, Silver JS, Stark PC, Macdonald DR, Ino Y, Ramsay DA, Louis DN：Specific genetic predictors of chemotherapeutic response and survival in patients with anaplastic oligodendrogliomas. J Natl Cancer Inst 90：1473-1479, 1998

4) Cairncross G, Wang M, Shaw E, Jenkins R, Brachman D, Buckner J, Fink K, Souhami L, Laperriere N, Curran W, Mehta M：Phase Ⅲ trial of chemoradiotherapy for anaplastic oligodendroglioma：long-term results of RTOG 9402. J Clin Oncol 31：337-343, 2013（Epub 2012 Oct 15）

5) Cancer Genome Atlas Research Network, Brat DJ, Verhaak RG, Aldape KD, Yung WK, Salama SR, Cooper LA, Rheinbay E, Miller CR, Vitucci M, Morozova O, Robertson AG, Noushmehr H, Laird PW, Cherniack AD, Akbani R, Huse JT, Ciriello G, Poisson LM, Barnholtz-Sloan JS, Berger MS, Brennan C, Colen RR, Colman H, Flanders AE, Giannini C, Grifford M, Iavarone A, Jain R, Joseph I, Kim J, Kasaian K, Mikkelsen T, Murray BA, O'Neill BP, Pachter L, Parsons DW, Sougnez C, Sulman EP, Vandenberg SR, Van Meir EG, von Deimling A, Zhang H, Crain D, Lau K, Mallery D, Morris S, Paulauskis J, Penny R, Shelton T, Sherman M, Yena P, Black A, Bowen J, Dicostanzo K, Gastier-Foster J, Leraas KM, Lichtenberg TM, Pierson CR, Ramirez NC, Taylor C, Weaver S, Wise L, Zmuda E, Davidsen T, Demchok JA, Eley G, Ferguson ML, Hutter CM, Mills Shaw KR, Ozenberger BA, Sheth M, Sofia HJ, Tarnuzzer R, Wang Z, Yang L, Zenklusen JC, Ayala B, Baboud J, Chudamani S, Jensen MA, Liu J, Pihl T, Raman R, Wan Y, Wu Y, Ally A, Auman JT, Balasundaram M, Balu S, Baylin SB, Beroukhim R, Bootwalla MS, Bowlby R, Bristow CA, Brooks D, Butterfield Y, Carlsen R, Carter S, Chin L, Chu A, Chuah E, Cibulskis K, Clarke A, Coetzee SG, Dhalla N, Fennell T, Fisher S, Gabriel S, Getz G, Gibbs R, Guin R, Hadjipanayis A, Hayes DN, Hinoue T, Hoadley K, Holt RA, Hoyle AP, Jefferys SR, Jones S, Jones CD, Kucherlapati R, Lai PH, Lander E, Lee S, Lichtenstein L, Ma Y, Maglinte DT, Mahadeshwar HS, Marra MA, Mayo M, Meng S, Meyerson ML, Mieczkowski PA, Moore RA, Mose LE, Mungall AJ, Pantazi A, Parfenov M, Park PJ, Parker JS, Perou CM, Protopopov A, Ren X, Roach J, Sabedot TS, Schein J, Schumacher SE, Seidman JG, Seth S, Shen H, Simons JV, Sipahimalani P, Soloway MG, Song X, Sun H, Tabak B, Tam A, Tan D, Tang J, Thiessen N, Triche T Jr, Van Den Berg DJ, Veluvolu U, Waring S, Weisenberger DJ, Wilkerson MD, Wong T, Wu J, Xi L, Xu AW, Yang L, Zack TI, Zhang J, Aksoy BA, Arachchi H, Benz C, Bernard B, Carlin D, Cho J, DiCara D, Frazer S, Fuller GN, Gao J, Gehlenborg N, Haussler D, Heiman DI, Iype L, Jacobsen A, Ju Z, Katzman S, Kim H, Knijnenburg T, Kreisberg RB, Lawrence MS, Lee W, Leinonen K, Lin P, Ling S, Liu W, Liu Y, Liu Y, Lu Y, Mills G, Ng S, Noble MS, Paull E, Rao A, Reynolds S, Saksena G, Sanborn Z, Sander C, Schultz N, Senbabaoglu Y, Shen R, Shmulevich I, Sinha R, Stuart J, Sumer SO, Sun Y, Tasman N, Taylor BS, Voet D, Weinhold N, Weinstein JN, Yang D, Yoshihara K, Zheng S, Zhang W, Zou L, Abel T, Sadeghi S, Cohen ML, Eschbacher J, Hattab EM, Raghunathan A, Schniederjan MJ, Aziz D, Barnett G, Barrett W, Bigner DD, Boice L, Brewer C, Calatozzolo C, Campos B, Carlotti CG Jr, Chan TA, Cuppini L, Curley E, Cuzzubbo S, Devine K, DiMeco F, Duell R, Elder JB, Fehrenbach A, Finocchiaro G, Friedman W, Fulop J, Gardner J, Hermes B, Herold-Mende C, Jungk C, Kendler A, Lehman NL, Lipp E, Liu O, Mandt R, McGraw M, Mclendon R, McPherson C, Neder L, Nguyen P, Noss A, Nunziata R, Ostrom QT, Palmer C, Perin A, Pollo B, Potapov A, Potapova O, Rathmell WK, Rotin D, Scarpace L, Schilero C, Senecal K, Shimmel K, Shurkhay V, Sifri S, Singh R, Sloan AE, Smolenski K, Staugaitis SM, Steele R, Thorne L, Tirapelli DP, Unterberg A, Vallurupalli M, Wang Y, Warnick R, Williams F, Wolinsky Y, Bell S, Rosenberg M, Stewart C, Huang F, Grimsby JL, Radenbaugh AJ, Zhang J：Comprehensive, integrative genomic analysis of diffuse lower-grade gliomas. N Engl J Med 372：2481-2498, 2015

6) Coons SW, Johnson PC, Scheithauer BW, Yates AJ, Pearl DK：Improving diagnostic accuracy and interobserver concordance in the classification and grading of primary gliomas. Cancer 79：1381-1393, 1997

7) Eckel-Passow JE, Lachance DH, Molinaro AM, Walsh KM, Decker PA, Sicotte H, Pekmezci M, Rice T, Kosel ML, Smirnov IV, Sarkar G, Caron AA, Kollmeyer TM, Praska CE, Chada AR, Halder C, Hansen HM, McCoy LS, Bracci PM, Marshall R, Zheng S, Reis GF, Pico AR, O'Neill BP, Buckner JC, Giannini C, Huse JT, Perry A, Tihan T, Berger MS, Chang SM, Prados MD, Wiemels J, Wiencke JK, Wrensch MR, Jenkins RB：Glioma groups based on 1p/19q, IDH, and TERT promoter mutations in tumors. N Engl J Med 372：2499-2508, 2015

8) Giannini C, Scheithauer BW, Weaver AL, Burger PC, Kros JM, Mork S, Graeber MB, Bauserman S, Buckner JC, Burton J, Riepe R, Tazelaar HD, Nascimento AG, Crotty T, Keeney GL, Pernicone P, Altermatt H：Oligodendrogliomas：reproducibility and prognostic value of histologic diagnosis and grading. J Neuropathol Exp Neurol 60：248-262, 2001

9) Jenkins RB, Blair H, Ballman KV, Giannini C, Arusell RM, Law M, Flynn H, Passe S, Felten S, Brown PD, Shaw EG, Buckner JC：A t（1；19）（q10；p10）mediates the combined deletions of 1p and 19q and predicts a better prognosis of patients with oligodendroglioma. Cancer Res 66：9852-9861, 2006

10) Louis DN, Ohgaki H, Wiestler OD, Cavenee WK：WHO Classification of tumours of the central nervous system. IARC, Lyon, 2007

11) Louis DN, Perry A, Burger P, Ellison DW, Reifenberger G, von Deimling A, Aldape K, Brat D, Collins VP, Eberhart C, Figarella-Branger D, Fuller GN, Giangaspero F, Giannini C, Hawkins C, Kleihues P, Korshunov A, Kros JM, Beatriz Lopes M, Ng HK, Ohgaki H, Paulus W, Pietsch T, Rosenblum M, Rushing E, Soylemezoglu F, Wiestler O, Wesseling P；International Society Of Neuropathology--Haarlem：International Society Of Neuropathology--Haarlem consensus guidelines for nervous system tumor classification and grading. Brain Pathol 24：429-435, 2014

12) Panageas KS, Iwamoto FM, Cloughesy TF, Aldape KD, Rivera AL, Eichler AF, Louis DN, Paleologos NA, Fisher BJ, Ashby LS, Cairncross JG, Roldán Urgoiti GB, Wen PY, Ligon KL, Schiff D, Robins HI, Rocque BG, Chamberlain MC, Mason WP, Weaver SA, Green RM, Kamar FG, Abrey LE, Deangelis LM, Jhanwar SC, Rosenblum MK, Lassman AB：Initial treatment patterns over time for anaplastic oligodendroglial tumors. Neuro Oncol 14：761-767, 2012

13) Parsons DW, Jones S, Zhang X, Lin JC, Leary RJ, Angenendt P, Mankoo P, Carter H, Siu IM, Gallia GL, Olivi A, McLendon R, Rasheed BA, Keir S, Nikolskaya T, Nikolsky Y, Busam DA, Tekleab H, Diaz LA Jr, Hartigan J, Smith DR, Strausberg RL, Marie SK, Shinjo SM, Yan H, Riggins GJ, Bigner DD, Karchin R, Papadopoulos N, Parmigiani G, Vogelstein B, Velculescu VE, Kinzler KW：An integrated genomic analysis of human glioblastoma multiforme. Science 321：1807-1812, 2008

14) Sahm F, Reuss D, Koelsche C, Capper D, Schittenhelm J, Heim S, Jones DT, Pfister SM, Herold-Mende C, Wick W, Mueller W, Hartmann C, Paulus W, von Deimling A：Farewell to oligoastrocytoma：in situ molecular genetics favor classification as either oligodendroglioma or astrocytoma. Acta Neuropathol 128：551-559, 2014

15) Shinozaki N, Uchino Y, Yoshikawa K, Matsutani T, Hasegawa A, Saeki N, Iwadate Y：Discrimination between low-grade oligodendrogliomas and diffuse astrocytoma with the aid of 11C-methionine positron emission tomography. J Neurosurg 114：1640-1647, 2011

16) Suzuki H, Aoki K, Chiba K, Sato Y, Shiozawa Y, Shiraishi Y, Shimamura T, Niida A, Motomura K, Ohka F, Yamamoto T, Tanahashi K, Ranjit M, Wakabayashi T, Yoshizato T, Kataoka K, Yoshida K, Nagata Y, Sato-Otsubo A, Tanaka H, Sanada M, Kondo Y, Nakamura H, Mizoguchi M, Abe T, Muragaki Y, Watanabe R, Ito I, Miyano S, Natsume A, Ogawa S：Mutational landscape and clonal architecture in grade Ⅱ and Ⅲ gliomas. Nat Genet 47：458-468, 2015

17) Turcan S, Rohle D, Goenka A, Walsh LA, Fang F, Yilmaz E, Campos C, Fabius AW, Lu C, Ward PS, Thompson CB, Kaufman A, Guryanova O, Levine R, Heguy A, Viale A, Morris LG, Huse JT, Mellinghoff IK, Chan TA：IDH1 mutation is sufficient to establish the glioma hypermethylator phenotype. Nature 483：479-483, 2012

18) Ueki K, Nishikawa R, Nakazato Y, Hirose T, Hirato J, Funada N, Fujimaki T, Hojo S, Kubo O, Ide T, Usui M, Ochiai C, Ito S, Takahashi H, Mukasa A, Asai A, Kirino T：Correlation of histology and molecular genetic analysis of 1p, 19q, 10q, TP53, EGFR, CDK4, and CDKN2A in 91 astrocytic and oligodendroglial tumors. Clin Cancer Res 8：196-201, 2002

19) van den Bent MJ, Brandes AA, Taphoorn MJ, Kros JM, Kouwenhoven MC, Delattre JY, Bernsen HJ, Frenay M, Tijssen CC, Grisold W, Sipos L, Enting RH, French PJ, Dinjens WN, Vecht CJ, Allgeier A, Lacombe D, Gorlia T, Hoang-Xuan K：Adjuvant procarbazine, lomustine, and vincristine chemotherapy in newly diagnosed anaplastic oligodendroglioma：long-term follow-up of EORTC brain tumor group study 26951. J Clin Oncol 31：344-350, 2013（Epub 2012 Oct 15）

20) Yan H, Parsons DW, Jin G, McLendon R, Rasheed BA, Yuan W, Kos I, Batinic-Haberle I, Jones S, Riggins GJ, Friedman H, Friedman A, Reardon D, Herndon J, Kinzler KW, Velculescu VE, Vogelstein B, Bigner DD：IDH1 and IDH2 mutations in gliomas. N Engl J Med 360：765-773, 2009