Neurological Surgery 脳神経外科51巻5号

2023年09月発行

特集 臨床脳神経外科医にとってのWHO脳腫瘍分類第5版 Ⅲ 成人良性脳腫瘍

神経鞘腫，神経線維腫症2型，神経鞘腫症

著者： 長井健一郎¹ 藤井正純¹

所属機関： ¹福島県立医科大学脳神経外科学講座

ページ範囲：P.845 - P.857

Point
・WHO脳腫瘍分類は版を重ねるごとに分子診断の必要性が上がっているが，神経鞘腫に関して分子診断は必須ではなく，改訂第4版（WHO 2016分類）と第5版（WHO 2021分類）で大きな変化はない．
・WHO 2016分類でメラニン性シュワン細胞腫とされていた腫瘍は，WHO 2021分類からは悪性黒色神経鞘腫となり，神経鞘腫とは別のものとして扱われることになった．
・WHO 2021分類発行後の2022年に神経線維腫症2型（NF2）はNF2関連神経鞘腫症へと名称が変更され，NF2関連以外にも神経鞘腫症はSMARCB1，LZTR1関連神経鞘腫症など名称が加わった．
・NF2に対するベバシズマブの有効性は以前から言われており，本邦で多施設共同二重盲検無作為化比較試験（BeatNF2 trial）が施行され，近日中に結果が公表される予定である．

参考文献

1）Pilavaki M, et al：Imaging of peripheral nerve sheath tumors with pathologic correlation：pictorial review. Eur J Radiol 52：229-239, 2004

2）Skovronsky DM, Oberholtzer JC：Pathologic classification of peripheral nerve tumors. Neurosurg Clin N Am 15：157-166, 2004

3）Plotkin SR, et al；International Consensus Group on Neurofibromatosis Diagnostic Criteria（I-NF-DC）：Updated diagnostic criteria and nomenclature for neurofibromatosis type 2 and schwannomatosis：an international consensus recommendation. Genet Med 24：1967-1977, 2022

4）Evans DG：Neurofibromatosis type 2（NF2）：a clinical and molecular review. Orphanet J Rare Dis 4：16, 2009　doi:10.1186/1750-1172-4-16

5）Voltaggio L, et al：Gastric schwannoma：a clinicopathologic study of 51 cases and critical review of the literature. Hum Pathol 43：650-659, 2012

6）Preston DL, et al：Tumors of the nervous system and pituitary gland associated with atomic bomb radiation exposure. J Natl Cancer Inst 94：1555-1563, 2002

7）Ron E, et al：Tumors of the brain and nervous system after radiotherapy in childhood. N Engl J Med 319：1033-1039, 1988

8）Stemmer-Rachamimov AO, et al：Universal absence of merlin, but not other ERM family members, in schwannomas. Am J Pathol 151：1649-1654, 1997

9）Petrilli AM, Fernández-Valle C：Role of merlin/NF2 inactivation in tumor biology. Oncogene 35：537-548, 2016

10）Rouleau GA, et al：Alteration in a new gene encoding a putative membrane-organizing protein causes neuro-fibromatosis type 2. Nature 363：515-521, 1993

11）Trofatter JA, et al：A novel moesin-, ezrin-, radixin-like gene is a candidate for the neurofibromatosis 2 tumor suppressor. Cell 72：791-800, 1993

mutations in schwannomas. Genes Chromosomes Cancer 17：45-55, 1996

genetic alterations in sporadic vestibular schwannomas：clinical implications. Otol Neurotol 34：1355-1361, 2013

14）Oh JE, et al：Alterations in the NF2/LATS1/LATS2/YAP Pathway in Schwannomas. J Neuropathol Exp Neurol 74：952-959, 2015

15）Håvik AL, et al：Genetic landscape of sporadic vestibular schwannoma. J Neurosurg 128：911-922, 2018

16）McClatchey AI, Giovannini M：Membrane organization and tumorigenesis--the NF2 tumor suppressor, merlin. Genes Dev 19：2265-2277, 2005

17）Kissil JL, et al：Merlin, the product of the Nf2 tumor suppressor gene, is an inhibitor of the p21-activated kinase, Pak1. Mol Cell 12：841-849, 2003

18）Murthy A, et al：NHE-RF, a regulatory cofactor for Na（＋）-H＋ exchange, is a common interactor for merlin and ERM（MERM）proteins. J Biol Chem 273：1273-1276, 1998

19）Ren Y, et al：New developments in neurofibromatosis type 2 and vestibular schwannoma. Neurooncol Adv 3：vdaa153, 2020　doi:10.1093/noajnl/vdaa153

20）Agnihotri S, et al：The genomic landscape of schwannoma. Nat Genet 48：1339-1348, 2016

21）Nonaka D, et al：Sox10：a pan-schwannian and melanocytic marker. Am J Surg Pathol 32：1291-1298, 2008

22）Karamchandani JR, et al：Sox10 and S100 in the diagnosis of soft-tissue neoplasms. Appl Immunohistochem Mol Morphol 20：445-450, 2012

23）Koelsche C, et al：Melanotic tumors of the nervous system are characterized by distinct mutational, chromosomal and epigenomic profiles. Brain Pathol 25：202-208, 2015

24）Ackerman LV, Taylor FH：Neurogenous tumors within the thorax；a clinicopathological evaluation of forty-eight cases. Cancer 4：669-691, 1951

25）Woodruff JM, et al：Cellular schwannoma：a variety of schwannoma sometimes mistaken for a malignant tumor. Am J Surg Pathol 5：733-744, 1981

26）White W, et al：Cellular schwannoma. A clinicopathologic study of 57 patients and 58 tumors. Cancer 66：1266-1275, 1990

27）Pekmezci M, et al：Morphologic and immunohistochemical features of malignant peripheral nerve sheath tumors and cellular schwannomas. Mod Pathol 28：187-200, 2015

28）Erlich SA, et al：Cellular schwannoma of the abducens nerve：case report and review of the literature. Clin Neurol Neurosurg 111：467-471, 2009

29）Weller RO：Greenfield's neuropathology（8th edition）. Neuropathol Appl Neurobiol 34：573-574, 2008

30）Berg JC, et al：Plexiform schwannoma：a clinicopathologic overview with emphasis on the head and neck region. Hum Pathol 39：633-640, 2008

31）Fletcher CD, Davies SE：Benign plexiform（multinodular）schwannoma：a rare tumour unassociated with neurofibromatosis. Histopathology 10：971-980, 1986

32）Agaram NP, et al：Deep-seated plexiform schwannoma：a pathologic study of 16 cases and comparative analysis with the superficial variety. Am J Surg Pathol 29：1042-1048, 2005

33）Woodruff JM, et al：Congenital and childhood plexiform（multinodular）cellular schwannoma：a troublesome mimic of malignant peripheral nerve sheath tumor. Am J Surg Pathol 27：1321-1329, 2003

34）Jo VY, Fletcher CDM：SMARCB1/INI1 loss in epithelioid schwannoma：a clinicopathologic and immunohistochemical study of 65 cases. Am J Surg Pathol 41：1013-1022, 2017

35）Jo VY, Fletcher CD：Epithelioid malignant peripheral nerve sheath tumor：clinicopathologic analysis of 63 cases. Am J Surg Pathol 39：673-682, 2015

36）Liegl B, et al：Microcystic/reticular schwannoma：a distinct variant with predilection for visceral locations. Am J Surg Pathol 32：1080-1087, 2008

37）Luzar B, et al：Cutaneous microcystic/reticular schwannoma：a poorly recognized entity. J Cutan Pathol 43：93-100, 2016

38）Evans DG, et al：Incidence of vestibular schwannoma and neurofibromatosis 2 in the north west of England over a 10-year period：higher incidence than previously thought. Otol Neurotol 26：93-97, 2005

39）Bourn D, et al：Germline mutations in the neurofibromatosis type 2 tumour suppressor gene. Hum Mol Genet 3：813-816, 1994

40）Louis DN, et al：Neuropathology and molecular genetics of neurofibromatosis 2 and related tumors. Brain Pathol 5：163-172, 1995

41）MacCollin M, et al：Mutational analysis of patients with neurofibromatosis 2. Am J Hum Genet 55：314-320, 1994

gene. Genes Chromosomes Cancer 12：117-127, 1995

43）Sainz J, et al：High frequency of nonsense mutations in the NF2 gene caused by C to T transitions in five CGA codons. Hum Mol Genet 4：137-139, 1995

44）Evans DG, et al：Incidence of mosaicism in 1055 de novo NF2 cases：much higher than previous estimates with high utility of next-generation sequencing. Genet Med 22：53-59, 2020

45）Kluwe L, et al：Molecular study of frequency of mosaicism in neurofibromatosis 2 patients with bilateral vestibular schwannomas. J Med Genet 40：109-114, 2003

46）Hiruta R, Fujii M：Current topics on precision medicine for neurofibromatosis type 2. No Shinkei Geka 50：150-161, 2022

47）Neurofibromatosis. Conference statement. National institutes of health consensus development conference. Arch Neurol 45：575-578, 1988

48）Plotkin SR, et al：Update from the 2011 international schwannomatosis workshop：from genetics to diagnostic criteria. Am J Med Genet A 161A：405-416, 2013

49）Antinheimo J, et al：Population-based analysis of sporadic and type 2 neurofibromatosis-associated meningiomas and schwannomas. Neurology 54：71-76, 2000

50）Seppälä MT, et al：Multiple schwannomas：schwannomatosis or neurofibromatosis type 2? J Neurosurg 89：36-41, 1998

51）Rivera B, et al：DGCR8 microprocessor defect characterizes familial multinodular goiter with schwannomatosis. J Clin Invest 130：1479-1490, 2020

in schwannomatosis-associated schwannomas. Hum Mutat 29：227-231, 2008

53）Plotkin SR, et al：Bevacizumab for progressive vestibular schwannoma in neurofibromatosis type 2：a retrospective review of 31 patients. Otol Neurotol 33：1046-1052, 2012

54）Fujii M, et al：Bevacizumab therapy of neurofibromatosis type 2 associated vestibular schwannoma in Japanese patients. Neurol Med Chir（Tokyo）60：75-82, 2020

55）Fujii M, et al；On Behalf Of The BeatNF Trial Investigators：Rationale and design of beatNF2 trial：a clinical trial to assess the efficacy and safety of bevacizumab in patients with neurofibromatosis type 2 related vestibular schwannoma. Curr Oncol 28：726-739, 2021

56）Tamura R, et al：A VEGF receptor vaccine demonstrates preliminary efficacy in neurofibromatosis type 2. Nat Commun 10：5758, 2019　doi:10.1038/s41467-019-13640-1