H3 K27M突变型弥漫性中线胶质瘤11例临床病理分析
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摘要
目的探讨H3 K27M突变型弥漫性中线胶质瘤的临床病理特征、免疫组化、诊断与鉴别诊断。方法分析11例H3 K27M突变型弥漫性中线胶质瘤的临床表现、影像学资料、组织病理学特征及免疫组化表型,并复习相关文献。结果 11例患者中,男性4例,女性7例,发病年龄为9～70岁,中位年龄27岁。临床表现为头晕头痛、恶心呕吐、肢体乏力、视物不清等颅内占位症状。组织学上形态多样,主要呈星形细胞瘤样或少突胶质细胞瘤样,少见情况下呈多形性黄色星形细胞瘤样和毛黏液样型星形细胞瘤样。免疫组化示瘤细胞均表达H3 K27M和Olig2(+),不同程度的ATRX、GFAP和p53(+),IDH-1和H3 K27me3(-)。结论 H3 K27M突变型弥漫性中线胶质瘤是好发于儿童和青少年中线部位的高级别胶质瘤,呈浸润性生长,肿瘤形态多样,预后差。诊断时应结合发病部位、影像学资料、组织学形态和免疫标记综合分析判断。
Objective To investigate the clinicopathological features, immunohistochemical features of diffuse midline gliomas with histone H3 K27 M mutation with emphasis on diagnosis and differential diagnosis. Methods The clinical manifestations, radiological appearance, pathological and immunohistochemical findings of 11 patients were analyzed, and the literatures were also reviewed. Results Among the 11 patients, there were 4 males and 7 females ranged in age from 9-70 years(median=27). The clinical features included dizziness, headache, nausea and vomiting, limb weakness and unclear vision. Histologically, a wide morphologic spectrum was encountered, including astrocytoma-like and oligdendroglioma-like, rarely pleomorphic xanthoastrocytoma-like and pilomyxoid astrocytoma-like patterns. The tumor cells showed immunoreactivity for H3 K27 M and Olig2, ATRX, GFAP and p53 were variably expressed, but none was positive for IDH-1 and H3 K27 me3. Conclusion The diffuse midline gliomas with histone H3 K27 M mutation is a high-grade glioma arising in midline of children and young adults, and characterized by aggressiveness and poor prognosis. Intergrative analysis of location, radiology, histomorphology and immunohistochemistry will help accuracy diagnosis of diffuse midline gliomas with histone H3 K27 M mutation
Objective To investigate the clinicopathological features, immunohistochemical features of diffuse midline gliomas with histone H3 K27 M mutation with emphasis on diagnosis and differential diagnosis. Methods The clinical manifestations, radiological appearance, pathological and immunohistochemical findings of 11 patients were analyzed, and the literatures were also reviewed. Results Among the 11 patients, there were 4 males and 7 females ranged in age from 9-70 years(median=27). The clinical features included dizziness, headache, nausea and vomiting, limb weakness and unclear vision. Histologically, a wide morphologic spectrum was encountered, including astrocytoma-like and oligdendroglioma-like, rarely pleomorphic xanthoastrocytoma-like and pilomyxoid astrocytoma-like patterns. The tumor cells showed immunoreactivity for H3 K27 M and Olig2, ATRX, GFAP and p53 were variably expressed, but none was positive for IDH-1 and H3 K27 me3. Conclusion The diffuse midline gliomas with histone H3 K27 M mutation is a high-grade glioma arising in midline of children and young adults, and characterized by aggressiveness and poor prognosis. Intergrative analysis of location, radiology, histomorphology and immunohistochemistry will help accuracy diagnosis of diffuse midline gliomas with histone H3 K27 M mutation
引文
[1] Louis DN, Perry A, Reifenberger G, et al. The 2016 World Health Organization classification of tumors of the central nervous system: a summary [J]. Acta Neuropathol, 2016, 131(6):803-820.
[2] Lee J, Solomon DA, Tihan T. The role of histone modifications and telomere alterations in the pathogenesis of diffuse gliomas in adults and children [J]. J Neurooncol, 2017, 132(1):1-11.
[3] Louis DN, Giannini C, Capper D, et al. cIMPACT-NOW update 2: diagnostic clarifications for diffuse midline glioma, H3 K27M mutant and diffuse astrocytoma/anaplastic astrocytoma, IDH-mutant [J]. Acta Neuropathol, 2018, 135(4):639-642.
[4] Aihara K, Mukasa A, Gotoh K, et al. H3F3A K27M mutations in thalamic gliomas from young adult patients [J]. Neuro Oncol, 2014, 16(1):140-146.
[5] Solomon DA, Wood MD, Tihan T, et al. 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(2):569-580.
[6] Caretti V, Bugiani M, Freret M, et al. Subventricular spread of diffuse intrinsic pontine glioma [J]. Acta Neuropathol, 2014, 128(4):605-607.
[7] Aboian MS, Solomon DA, Felton E, et al. Imaging characteristics of pediatric diffuse midline gliomas with histone H3K27M mutation [J]. Am J Neuroradiol, 2017, 38(4):795-800.
[8] López G, Oberheim Bush NA, Berger MS, et al. Diffuse non-midline glioma with H3F3A K27M mutation: a prognostic and treatment dilemma [J]. Acta Neuropathol Commun, 2017, 5(1):38.
[9] Yoshimoto K, Hatae R, Sangatsuda Y, et al. Prevalence and clinicopathological features of H3.3 G34-mutant high-grade gliomas: a retrospective study of 411 consecutive glioma cases in a single institution [J]. Brain Tumor Pathol, 2017, 34(3):103-112.
[10] Banan R, Christians A, Bartels S, et al. Absence of MGMT promoter methylation in diffuse midline glioma, H3 K27M-mutant [J]. Acta Neuropathol Commun, 2017, 5(1):98.
[11] Hochart A, Escande F, Rocourt N, et al. Long survival in a child with a mutated K27M-H3.3 pilocytic astrocytoma [J]. Ann Clin Transl Neurol, 2015, 2(4):439-443.
[12] von Bueren AO, Karremann M, Gielen GH, et al. A suggestion to introduce the diagnosis of "diffuse midline glioma of the pons, H3 K27 wildtype (WHO grade IV)"[J]. Acta Neuropathol, 2018, 136(1):171-173.
[13] Karremann M, Gielen GH, Hoffmann M, et al. Diffuse high-grade gliomas with H3 K27M mutations carry a dismal prognosis independent of tumor location [J]. Neuro Oncol, 2018, 20(1):123-131.
[14] Feng J, Hao S, Pan C, et al. The H3.3 K27M mutation results in a poorer prognosis in brainstem gliomas than thalamic gliomas in adults [J]. Hum Pathol, 2015, 46(11):1626-1632.
[15] Ramaswamy V, Remke M, Taylor MD. An epigenetic therapy for diffuse intrinsic pontine gliomas [J]. Nat Med, 2014, 20(12):1378-1379.
[16] Long W, Yi Y, Chen S, et al. Potential new therapies for pediatric diffuse intrinsic pontine glioma [J]. Front Pharmacol, 2017, 8(1):495-507.
[17] Mohammad F, Weissmann S, Leblanc B, et al. EZH2 is a potential therapeutic target for H3K27M- mutant pediatric gliomas [J]. Nat Med, 2017, 23(4):483-492.
[18] Wiese M, Schill F, Sturm D, et al. No significant cytotoxic effect of the EZH2 inhibitor tazemetostat (EPZ-6438) on pediatric glioma cells with wildtype histone 3 or mutated histone 3.3 [J]. Klin Padiatr, 2016, 228(3):113-117.
[2] Lee J, Solomon DA, Tihan T. The role of histone modifications and telomere alterations in the pathogenesis of diffuse gliomas in adults and children [J]. J Neurooncol, 2017, 132(1):1-11.
[3] Louis DN, Giannini C, Capper D, et al. cIMPACT-NOW update 2: diagnostic clarifications for diffuse midline glioma, H3 K27M mutant and diffuse astrocytoma/anaplastic astrocytoma, IDH-mutant [J]. Acta Neuropathol, 2018, 135(4):639-642.
[4] Aihara K, Mukasa A, Gotoh K, et al. H3F3A K27M mutations in thalamic gliomas from young adult patients [J]. Neuro Oncol, 2014, 16(1):140-146.
[5] Solomon DA, Wood MD, Tihan T, et al. 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(2):569-580.
[6] Caretti V, Bugiani M, Freret M, et al. Subventricular spread of diffuse intrinsic pontine glioma [J]. Acta Neuropathol, 2014, 128(4):605-607.
[7] Aboian MS, Solomon DA, Felton E, et al. Imaging characteristics of pediatric diffuse midline gliomas with histone H3K27M mutation [J]. Am J Neuroradiol, 2017, 38(4):795-800.
[8] López G, Oberheim Bush NA, Berger MS, et al. Diffuse non-midline glioma with H3F3A K27M mutation: a prognostic and treatment dilemma [J]. Acta Neuropathol Commun, 2017, 5(1):38.
[9] Yoshimoto K, Hatae R, Sangatsuda Y, et al. Prevalence and clinicopathological features of H3.3 G34-mutant high-grade gliomas: a retrospective study of 411 consecutive glioma cases in a single institution [J]. Brain Tumor Pathol, 2017, 34(3):103-112.
[10] Banan R, Christians A, Bartels S, et al. Absence of MGMT promoter methylation in diffuse midline glioma, H3 K27M-mutant [J]. Acta Neuropathol Commun, 2017, 5(1):98.
[11] Hochart A, Escande F, Rocourt N, et al. Long survival in a child with a mutated K27M-H3.3 pilocytic astrocytoma [J]. Ann Clin Transl Neurol, 2015, 2(4):439-443.
[12] von Bueren AO, Karremann M, Gielen GH, et al. A suggestion to introduce the diagnosis of "diffuse midline glioma of the pons, H3 K27 wildtype (WHO grade IV)"[J]. Acta Neuropathol, 2018, 136(1):171-173.
[13] Karremann M, Gielen GH, Hoffmann M, et al. Diffuse high-grade gliomas with H3 K27M mutations carry a dismal prognosis independent of tumor location [J]. Neuro Oncol, 2018, 20(1):123-131.
[14] Feng J, Hao S, Pan C, et al. The H3.3 K27M mutation results in a poorer prognosis in brainstem gliomas than thalamic gliomas in adults [J]. Hum Pathol, 2015, 46(11):1626-1632.
[15] Ramaswamy V, Remke M, Taylor MD. An epigenetic therapy for diffuse intrinsic pontine gliomas [J]. Nat Med, 2014, 20(12):1378-1379.
[16] Long W, Yi Y, Chen S, et al. Potential new therapies for pediatric diffuse intrinsic pontine glioma [J]. Front Pharmacol, 2017, 8(1):495-507.
[17] Mohammad F, Weissmann S, Leblanc B, et al. EZH2 is a potential therapeutic target for H3K27M- mutant pediatric gliomas [J]. Nat Med, 2017, 23(4):483-492.
[18] Wiese M, Schill F, Sturm D, et al. No significant cytotoxic effect of the EZH2 inhibitor tazemetostat (EPZ-6438) on pediatric glioma cells with wildtype histone 3 or mutated histone 3.3 [J]. Klin Padiatr, 2016, 228(3):113-117.