伴<em>H3</em> K27M和<em>BRAF</em> V600E双突变的弥漫性中线胶质瘤

doi:10.3969/j.issn.1672-6731.2020.04.012

摘要/Abstract

摘要：

目的探讨H3 K27M突变型弥漫性中线胶质瘤的临床病理学特点、免疫表型、分子遗传学改变、诊断与鉴别诊断及预后。方法与结果 男性患者，21岁，因烦渴、多饮多尿就诊。临床表现为双侧视敏感度减弱，视野无缺损；MRI呈鞍上T₁WI等、低信号，T₂WI等、高信号占位，病灶呈不均匀强化。术后组织病理学观察肿瘤细胞呈短梭形或椭圆形，较高或中等密度，呈束状、旋涡状排列，或形成血管周围假菊形团样结构；可见少量核分裂象、小灶性坏死及微血管增生。肿瘤细胞弥漫表达H3 K27M、胶质纤维酸性蛋白、少突胶质细胞转录因子2、波形蛋白、微管相关蛋白-2、S-100蛋白、突触素、巢蛋白和P53，Ki-67抗原标记指数为10%~20%。全基因组测序存在H3 K27M和BRAF V600E双突变；整合病理诊断为鞍区H3 K27M突变型弥漫性中线胶质瘤（WHOⅣ级），患者于术后11个月死亡。结论 H3K27M突变型弥漫性中线胶质瘤是2016年WHO中枢神经系统肿瘤分类第四版修订版中新增肿瘤分型（WHOⅣ级），组织学改变宽泛（WHOⅡ~Ⅳ级），极易误诊，诊断应以发病年龄（儿童为主）、发生部位（中线）、弥漫性生长及特征性H3 K27M突变作为重要依据。

关键词: 神经胶质瘤, 组蛋白类, DNA突变分析, 病理学, 免疫组织化学

Abstract:

Objective To explore the clinicopathological features, immunophenotype, molecular genetics, differential diagnosis and prognosis of diffuse midline glioma, H3 K27M mutant. Methods and Results A 21-year-old male patient suffered from polydipsia and polyuria. Physical examination showed that the visual sensitivity on both sides was weakened, the visual field was complete, and other signs were negative. Brain MRI showed that T₁WI iso-low signal and T₂WI iso-high signal occupied the suprasellar space, and enhanced unevenly. The patient underwent surgical treatment, with a greyish-red colour, soft texture and abundant blood supply. The tumor was partially resection. Histological findings showed the tumor was mainly composed of spindle shaped and ellipsoidal cells with occasionally typical mitotic activity, which were arranged in fascicularis, swirly or perivascular pseudorosettes patterns, with the moderate-to high-density. Small focal areas of necrosis and proliferation of microvessel also could be seen. Immunohistochemical staining showed the nuclei of tumor cells was diffusely positive for histone H3 K27M mutant protein (H3 K27M), oligodendrocytes transcription factor-2 (Olig-2) and P53, cytoplasm was positive for glial fibrillary acidic protein (GFAP), vimentin (Vim), microtubule-associated protein-2 (MAP-2), synaptophysin (Syn) and nestin (Nes), cytoplasm and nuclei were positive for S-100 protein (S-100). Ki-67 labeling index was 10%-20%. Whole genome sequencing (WGS) revealed the presence of H3 K27M and BRAF V600E gene mutations. Integrational diagnosis was diffuse midline glioma, H3 K27M mutant (WHO Ⅳ) lied in saddle area. The patient died 11 months after surgery. Conclusions Diffuse midline glioma, H3 K27M mutant is a group of primary brain neoplasm of recent acquisition in the 2016 WHO classification of central nervous system tumors, with the diverse histological appearance (WHOⅡ-Ⅳgrade), which was misdiagnosed easily. The most important clues for diagnosis were age (mostly in child), location (midline of the brain), diffusely growth pattern, and harbored histone H3 K27M mutation.

Key words: Glioma, Histones, DNA mutational analysis, Pathology, Immunohistochemistry

吴楠, 王璇, 魏雪, 吴晋蓉, 章如松, 石群立, 李南云. 伴H3 K27M和BRAF V600E双突变的弥漫性中线胶质瘤[J]. 中国现代神经疾病杂志, 2020, 20(4): 323-329.

WU Nan, WANG Xuan, WEI Xue, WU Jin-rong, ZHANG Ru-song, SHI Qun-li, LI Nan-yun. Diffuse midline glioma with co-occurrence of H3 K27M and BRAF V600E mutations[J]. Chinese Journal of Contemporary Neurology and Neurosurgery, 2020, 20(4): 323-329.

http://journal11.magtechjournal.com/cjcnn/CN/Y2020/V20/I4/323

参考文献

[1] Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Ellison DW, Figarella-Branger D, Perry A, Reifenberger G, Von Deimling A. (2016) WHO classification of tumours of the central nervous system[M]. 4th ed. Lyon:IARC Press, 2016:57-59.
[2] Solomon DA, Wood MD, Tihan T, Bollen AW, Gupta N, Phillips JJ, Perry A. Diffuse midline gliomas with histone H3-K27M mutation:a series of 47 cases assessing the spectrum of morphologic variation and associated genetic alterations[J]. Brain Pathol, 2016, 26:569-580.
[3] Fisher PG, Breiter SN, Carson BS, Wharam MD, Williams JA, Weingart JD, Foer DR, Goldthwaite PT, Tihan T, Burger PC. A clinicopathologic reappraisal of brain stem tumor classification. Identification of pilocystic astrocytoma and fibrillary astrocytoma as distinct entities[J]. Cancer, 2000, 89:1569-1576.
[4] Kramm CM, Butenhoff S, Rausche U, Warmuth-Metz M, Kortmann RD, Pietsch T, Gnekow A, Jorch N, Janssen G, Berthold F, Wolff JE. Thalamic high-grade gliomas in children:a distinct clinical subset[J]? Neuron Oncol, 2011, 13:680-689.
[5] Ye H, He P, Sun YH, Guan H, Xia J. Diffuse midline gliomas with histone H3-K27M mutation:a study of four cases and literature review[J]. Ying Xiang Zhen Duan Yu Jie Ru Fang She, 2018, 27:380-383.[叶海, 何品, 孙艳花, 关弘, 夏军. 弥漫性中线胶质瘤伴H3K27M突变四例报告并文献复习[J]. 影像诊断与介入放射, 2018, 27:380-383.]
[6] Aboian MS, Solomon DA, Felton E, Mabray MC, Villanueva-Meyer JE, Mueller S, Cha S. Imaging characteristics of pediatric diffuse midline gliomas with histone H3 K27M mutation[J]. Am J Neuroradiol, 2017, 38:795-800.
[7] Herrlinger U, Jones DT, Glas M, Hattingen E, Gramatzki D, Stuplich M, Felsberg J, Bähr O, Gielen GH, Simon M, Wiewrodt D, Schabet M, Hovestadt V, Capper D, Steinbach JP, von Deimling A, Lichter P, Pfister SM, Weller M, Reifenberger G. Gliomatosis cerebri:no evidence for a separate brain tumor entity[J]. Acta Neuropathol, 2016, 131:309-319.
[8] Bechet D, Gielen GG, Korshunov A, Pfister SM, Rousso C, Faury D, Fiset PO, Benlimane N, Lewis PW, Lu C, David Allis C, Kieran MW, Ligon KL, Pietsch T, Ellezam B, Albrecht S, Jabado N. Specific detection of methionine 27 mutation in histone 3 variants (H3-K27M) in fixed tissue from high-grade astrocytoma[J]. Acta Neuropathol, 2014, 128:733-741.
[9] Hochart A, Escande F, Rocourt N, Grill J, Koubi-Pick V, Beaujot J, Meignan S, Vinchon M, Maurage CA, Leblond P. Long survival in a child with a mutated K27M-H3.3 pilocytic astrocytoma[J]. Ann Clin Transl Neurol, 2015, 2:439-443.
[10] Orillac C, Thomas C, Dastagirzada Y, Hidalgo ET, Golfinos JG, Zagzag D, Wisoff JH, Karajannis MA, Snuderl M. Pilocytic astrocytoma and glioneuronal tumor with histone H3 K27M mutation[J]. Acta Neuropathol Commun, 2016, 4:84.
[11] Yuen BT, Knoepfler PS. Histone H3.3 mutations:a variant path to cancer[J]. Cancer Cell, 2013, 24:567-574.
[12] Lewis PW, Müller MM, Koletsky MS, Cordero F, Lin S, Banaszynski LA, Garcia BA, Muir TW, Becher OJ, Allis CD. Inhibition of PRC2 activity by a gain-of-function H3 mutation found in pediatric glioblastoma[J]. Science, 2013, 340:857-861.
[13] Chan KM, Fang D, Gan H, Hashizume R, Yu C, Schroeder M, Gupta N, Mueller S, James CD, Jenkins R, Sarkaria J, Zhang Z. The histone H3.3K27M mutation in pediatric glioma reprograms H3K27 methylation and gene expression[J]. Genes Dev, 2013, 27:985-990.
[14] Nikbakht H, Panditharatna E, Mikael LG, Li R, Gayden T, Osmond M, Ho CY, Kambhampati M, Hwang EI, Faury D, Siu A, Papillon-Cavanagh S, Bechet D, Ligon KL, Ellezam B, Ingram WJ, Stinson C, Moore AS, Warren KE, Karamchandani J, Packer RJ, Jabado N, Majewski J, Nazarian J. Spatial and temporal homogeneity of driver mutations in diffuse intrinsicpontine glioma[J]. Nat Commun, 2016, 7:11185.
[15] Karremann M, Gielen GH, Hoffmann M, Wiese M, Colditz N, Warmuth-Metz M, Bison B, Claviez A, van Vuurden DG, von Bueren AO, Gessi M, Kühnle I, Hans VH, Benesch M, Sturm D, Kortmann RD, Waha A, Pietsch T, Kramm CM. Diffuse high-grade gliomas with H3 K27M mutations carry a dismal prognosis independent of tumor location[J]. Neuro Oncol, 2018, 20:123-131.
[16] Pagès M, Beccaria K, Boddaert N, Saffroy R, Besnard A, Castel D, Fina F, Barets D, Barret E, Lacroix L, Bielle F, Andreiuolo F, Tauziède-Espariat A, Figarella-Branger D, Puget S, Grill J, Chrétien F, Varlet P. Co-occurrence of histone H3 K27M and BRAF V600E mutations in paediatric midline grade Ⅰ ganglioglioma[J]. Brain Pathol, 2018, 28:103-111.
[17] Grasso CS, Tang Y, Truffaux N, Berlow NE, Liu L, Debily MA, Quist MJ, Davis LE, Huang EC, Woo PJ, Ponnuswami A, Chen S, Johung TB, Sun W, Kogiso M, Du Y, Qi L, Huang Y, Hütt-Cabezas M, Warren KE, Le Dret L, Meltzer PS, Mao H, Quezado M, van Vuurden DG, Abraham J, Fouladi M, Svalina MN, Wang N, Hawkins C, Nazarian J, Alonso MM, Raabe EH, Hulleman E, Spellman PT, Li XN, Keller C, Pal R, Grill J, Monje M. Functionally defined therapeutic targets in diffuse intrinsic pontine glioma[J]. Nat Med, 2015, 21:555-559.
[18] Hashizume R, Andor N, Ihara Y, Lerner R, Gan H, Chen X, Fang D, Huang X, Tom MW, Ngo V, Solomon D, Mueller S, Paris PL, Zhang Z, Petritsch C, Gupta N, Waldman TA, James CD. Pharmacologic inhibition of histone demethylation as a therapy for pediatric brainstem glioma[J]. Nat Med, 2014, 20:1394-1396.

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2 伴H3 K27M和BRAF V600E双突变的弥漫性中线胶质瘤

Diffuse midline glioma with co-occurrence of H3 K27M and BRAF V600E mutations

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2 伴H3 K27M和BRAF V600E双突变的弥漫性中线胶质瘤

Diffuse midline glioma with co-occurrence of H3 K27M and BRAF V600E mutations

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