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DOI: 10.1055/s-0038-1667180
Immunohistochemical Markers for Schwannomas, Neurofibromas and Malignant Peripheral Nerve Sheath Tumors—What Can the Recent Literature Tell Us?
Marcadores imuno-histoquímicos para schwannomas, neurofibromas e tumores malignos da bainha do nervo periférico—o que a literatura recente pode nos dizer?Publication History
29 March 2018
05 June 2018
Publication Date:
24 July 2018 (online)
![](https://www.thieme-connect.de/media/10.1055-s-00028832/201802/lookinside/thumbnails/10-1055-s-0038-1667180_1800027-1.jpg)
Abstract
Introduction Schwannomas and neurofibromas are the two most common benign neoplasms of the peripheral nerve sheath, and although they are generally easy to distinguish, in some cases, they can closely resemble one another. Furthermore, malignant peripheral nerve sheath tumors (MPNSTs), another example of peripheral nerve sheath neoplasm, may likewise constitute, due to their morphology and lack of specific immunohistochemical markers, a challenging diagnostic.
Objective To bring attention to new and promising biomarkers for schwannomas, neurofibromas and MPNSTs and to outline, based on the recent literature, a immunohistochemical profile for each neoplasm at hand, as well as to emphasize the need for further studies that could help us understand their diagnostic potential and disrupt our dependence of limited and nonspecific biomarkers.
Methods An overview of the recent literature published in English on both the classical promising immunohistochemical markers of schwannomas, neurofibromas and MPNSTs was performed. We discarded case reports.
Conclusions There is still a lack of specific biomarkers for peripheral nerve tumors. However, plenty of new immunohistochemical markers have been coming to light with presumed higher specificity and more diverse helpful uses than the classical ones. For example, Sox10 is a good biomarker for differentiating schwannomas and neurofibromas from sarcomas, calretinin schwannomas from neurofibromas, TLE1 and HMGA2 MPNSTs from sarcomas, and nestin, EGFR, p16 and Ki-67 MPNSTs from different types of schwannomas and neurofibromas. There is still need for further studies; however, the potential of some of these promising markers, among others, should not be disregarded.
Resumo
Introdução Schwannomas e neurofibromas são as duas neoplasias benignas mais comuns a acometer o tecido nervoso periférico, e apesar de geralmente serem facilmente distinguíveis, em alguns casos, elas podem ser muito semelhantes. Além disso, os tumores malignos da bainha dos nervos periféricos (TMBNPs), outro exemplo de neoplasia da bainha do nervo periférico, podem da mesma forma constituir, pela sua morfologia e falta de marcadores imuno-histoquímicos específicos, um diagnóstico desafiador.
Objetivo Chamar a atenção para novos e promissores biomarcadores para schwannomas, neurofibromas e TMBNPs e delinear, a partir da literatura atual, um perfil imuno-histoquímico para cada neoplasia em questão, além de enfatizar a necessidade de futuros estudos que possam elucidar-nos acerca de seu potencial diagnóstico e, por ventura, romper nossa dependência de biomarcadores inespecíficos e limitados.
Método Foi feita uma revisão da literatura recente incluindo artigos em língua inglesa sobre os marcadores imunohistoquímicos clássicos e os promissores para schwannomas, neurofibromas e TMBNPs. Descartamos relatos de caso.
Conclusão Ainda há uma falta de biomarcadores específicos para as neoplasias acima. Contudo, vários novos marcadores imuno-histoquímicos têm surgido, e com futuros estudos poderemos talvez definir biomarcadores específicos e indispensáveis para os casos desafiadores de neurofibromas, schwannomas e TMBNPs. Por exemplo, o Sox10 é um bom biomarcador para diferenciar schwannomas e neurofibromas de sarcomas; a calretinina é um bom marcador para diferenciar schwannomas de neurofibromas; os biomarcadores TLE1 e HMGA2 podem ajudar a diferenciar TMBNPs de sarcomas, e a nestina, o receptor do fator de crescimento epidérmico (EGFR), o gene p16 e a proteína Ki-67 podem diferenciar TMBNPs de diferentes tipos de schwannomas e neurofibromas. Ainda há necessidade de novos estudos; contudo, o potencial de alguns desses marcadores, dentre outros, não deveria ser negligenciado.
Keywords
immunohistochemistry - biomarker - nerve sheath neoplasm(s) - schwannoma - neurofibroma - malignant peripheral nerve sheath tumorPalavras-chave
imuno-histoquímica - biomarcador - tumor(es) do sistema nervoso periférico - schwannoma - neurofibroma - tumor maligno da bainha do nervoFinancial and Material Support
We did not receive any financial and/or material support from any granting organization or specific funding.
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References
- 1 Fine SW, McClain SA, Li M. Immunohistochemical staining for calretinin is useful for differentiating schwannomas from neurofibromas. Am J Clin Pathol 2004; 122 (04) 552-559
- 2 Shivane A, Parkinson DB, Ammoun S, Hanemann CO. Expression of c-Jun and Sox-2 in human schwannomas and traumatic neuromas. Histopathology 2013; 62 (04) 651-656
- 3 Le LQ, Liu C, Shipman T, Chen Z, Suter U, Parada LF. Susceptible stages in Schwann cells for NF1-associated plexiform neurofibroma development. Cancer Res 2011; 71 (13) 4686-4695
- 4 Thway K, Fisher C. Malignant peripheral nerve sheath tumor: pathology and genetics. Ann Diagn Pathol 2014; 18 (02) 109-116
- 5 Pekmezci M, Reuss DE, Hirbe AC. , et al. Morphologic and immunohistochemical features of malignant peripheral nerve sheath tumors and cellular schwannomas. Mod Pathol 2015; 28 (02) 187-200
- 6 Rodriguez FJ, Folpe AL, Giannini C, Perry A. Pathology of peripheral nerve sheath tumors: diagnostic overview and update on selected diagnostic problems. Acta Neuropathol 2012; 123 (03) 295-319
- 7 Guo A, Liu A, Wei L, Song X. Malignant peripheral nerve sheath tumors: differentiation patterns and immunohistochemical features - a mini-review and our new findings. J Cancer 2012; 3: 303-309
- 8 Naber U, Friedrich RE, Glatzel M, Mautner VF, Hagel C. Podoplanin and CD34 in peripheral nerve sheath tumours: focus on neurofibromatosis 1-associated atypical neurofibroma. J Neurooncol 2011; 103 (02) 239-245
- 9 Nonaka D, Chiriboga L, Rubin BP. Sox10: a pan-schwannian and melanocytic marker. Am J Surg Pathol 2008; 32 (09) 1291-1298
- 10 Miettinen M, McCue PA, Sarlomo-Rikala M. , et al. Sox10--a marker for not only schwannian and melanocytic neoplasms but also myoepithelial cell tumors of soft tissue: a systematic analysis of 5134 tumors. Am J Surg Pathol 2015; 39 (06) 826-835
- 11 Miettinen M. Immunohistochemistry of soft tissue tumours - review with emphasis on 10 markers. Histopathology 2014; 64 (01) 101-118
- 12 Skovronsky DM, Oberholtzer JC. Pathologic classification of peripheral nerve tumors. Neurosurg Clin N Am 2004; 15 (02) 157-166
- 13 Schulz A, Zoch A, Morrison H. A neuronal function of the tumor suppressor protein merlin. Acta Neuropathol Commun 2014; 2 (01) 82
- 14 Caltabiano R, Magro G, Polizzi A. , et al. A mosaic pattern of INI1/SMARCB1 protein expression distinguishes Schwannomatosis and NF2-associated peripheral schwannomas from solitary peripheral schwannomas and NF2-associated vestibular schwannomas. Childs Nerv Syst 2017; 33 (06) 933-940
- 15 Karamchandani JR, Nielsen TO, van de Rijn M, West RB. Sox10 and S100 in the diagnosis of soft-tissue neoplasms. Appl Immunohistochem Mol Morphol 2012; 20 (05) 445-450
- 16 Zhang HY, Yang GH, Chen HJ. , et al. Clinicopathological, immunohistochemical, and ultrastructural study of 13 cases of melanotic schwannoma. Chin Med J (Engl) 2005; 118 (17) 1451-1461
- 17 Kleinschmidt-DeMasters BK, Tihan T, Rodriguez F. Diagnostic Pathology: Neuropathology. Elsevier Health Sciences 2016; 528-545
- 18 Jett K, Friedman JM. Clinical and genetic aspects of neurofibromatosis 1. Genet Med 2010; 12 (01) 1-11
- 19 Johansson G, Peng PC, Huang PY. , et al. Soluble AXL: a possible circulating biomarker for neurofibromatosis type 1 related tumor burden. PLoS One 2014; 9 (12) e115916
- 20 Weiss SW, Goldblum JR, Folpe AL. Enzinger and Weiss' soft tissue tumors. Philadelphia: Saunders/Elsevier; 2014
- 21 Henderson SR, Guiliano D, Presneau N. , et al. A molecular map of mesenchymal tumors. Genome Biol 2005; 6 (09) R76
- 22 Ferner RE. Neurofibromatosis 1 and neurofibromatosis 2: a twenty first century perspective. Lancet Neurol 2007; 6 (04) 340-351
- 23 Hui P, Li N, Johnson C. , et al. HMGA proteins in malignant peripheral nerve sheath tumor and synovial sarcoma: preferential expression of HMGA2 in malignant peripheral nerve sheath tumor. Mod Pathol 2005; 18 (11) 1519-1526
- 24 Shimada S, Tsuzuki T, Kuroda M. , et al. Nestin expression as a new marker in malignant peripheral nerve sheath tumors. Pathol Int 2007; 57 (02) 60-67
- 25 Hayashi T, Hirose T, Nishimura Y, Fukuoka J, Kishikawa M. Hybrid schwannoma/perineurioma of the spinal nerve: multifocal occurrence, and recurrence as an intraneural perineurioma. Pathol Int 2013; 63 (07) 368-373
- 26 Fletcher CDM, Unni KK, Martens F. World Health Organization classification of tumors. Pathology and Genetics of Tumors of Soft Tissue and Bone. IARC Press; 2002