Advertisement

Acta Neuropathologica

, Volume 123, Issue 3, pp 295–319 | Cite as

Pathology of peripheral nerve sheath tumors: diagnostic overview and update on selected diagnostic problems

  • Fausto J. RodriguezEmail author
  • Andrew L. Folpe
  • Caterina Giannini
  • Arie Perry
Review

Abstract

Peripheral nerve sheath tumors are common neoplasms, with classic identifiable features, but on occasion, they are diagnostically challenging. Although well-defined subtypes of peripheral nerve sheath tumors were described early in the history of surgical pathology, controversies regarding the classification and grading of these tumors persist. Advances in molecular biology have provided new insights into the nature of the various peripheral nerve sheath tumors, and have begun to suggest novel targeted therapeutic approaches. In this review, we discuss current concepts and problematic areas in the pathology of peripheral nerve sheath tumors. Diagnostic criteria and differential diagnosis for the major categories of nerve sheath tumors are proposed, including neurofibroma, schwannoma, and perineurioma. Diagnostically challenging variants, including plexiform, cellular and melanotic schwannomas are highlighted. A subset of these affects the childhood population, and has historically been interpreted as malignant, although current evidence and outcome data suggest they represent benign entities. The growing current literature and the author's experience with difficult to classify borderline or “hybrid tumors” are discussed and illustrated. Some of these classification gray zones occur with frequency in the gastrointestinal tract, an anatomical compartment that must always be entertained when examining these neoplasms. Other growing recent areas of interest include the heterogeneous group of pseudoneoplastic lesions involving peripheral nerve composed of mature adipose tissue and/or skeletal muscle, such as the enigmatic neuromuscular choristoma. Malignant peripheral nerve sheath tumors (MPNST) represent a diagnostically controversial group; difficulties in grading and guidelines to separate “atypical neurofibroma” from MPNST are provided. There is an increasing literature of MPNST mimics which neuropathologists must be aware of, including synovial sarcoma and ossifying fibromyxoid tumor. Finally, we discuss entities that are lacking from the section on cranial and paraspinal nerves in the current WHO classification, and that may warrant inclusion in future classifications. In summary, although the diagnosis and classification of most conventional peripheral nerve sheath tumors are relatively straightforward for the experienced observer, yet borderline and difficult-to-classify neoplasms continue to be problematic. In the current review, we attempt to provide some useful guidelines for the surgical neuropathologist to help navigate these persistent, challenging problems.

Keywords

Peripheral nerve Neurofibroma Schwannoma Perineurioma MPNST 

Notes

Acknowledgments

The authors would like to thank Dr. James Woodruff for critically reviewing the manuscript and helpful suggestions. They also thank Norm Baker for assistance with graphics, as well as Drs. Robert Spinner and James Garrity for contributing intraoperative figures.

References

  1. 1.
    Adamiak A, Lee CH, Nielsen TO, Webber D, O’Connell JX (2009) Duodenal epithelioid gastrointestinal stromal tumor with prominent granular cell features. Hum Pathol 40:599–602PubMedCrossRefGoogle Scholar
  2. 2.
    Agaimy A, Wuensch PH (2005) Perineurioma of the stomach. A rare spindle cell neoplasm that should be distinguished from gastrointestinal stromal tumor. Pathol Res Pract 201:463–467PubMedCrossRefGoogle Scholar
  3. 3.
    Agaimy A, Markl B, Kitz J, Wunsch PH, Arnholdt H, Fuzesi L, Hartmann A, Chetty R (2010) Peripheral nerve sheath tumors of the gastrointestinal tract: a multicenter study of 58 patients including NF1-associated gastric schwannoma and unusual morphologic variants. Virchows Arch 456:411–422PubMedCrossRefGoogle Scholar
  4. 4.
    Agaram NP, Prakash S, Antonescu CR (2005) Deep-seated plexiform schwannoma: a pathologic study of 16 cases and comparative analysis with the superficial variety. Am J Surg Pathol 29:1042–1048PubMedGoogle Scholar
  5. 5.
    Ahrens WA, Ridenour RV 3rd, Caron BL, Miller DV, Folpe AL (2008) GLUT-1 expression in mesenchymal tumors: an immunohistochemical study of 247 soft tissue and bone neoplasms. Hum Pathol 39:1519–1526PubMedCrossRefGoogle Scholar
  6. 6.
    Aldabagh B, Azmi F, Vadmal M, Neider S, Usmani AS (2009) Plexiform pattern in cutaneous granular cell tumors. J Cutan Pathol 36:1174–1176PubMedCrossRefGoogle Scholar
  7. 7.
    Allison KH, Patel RM, Goldblum JR, Rubin BP (2005) Superficial malignant peripheral nerve sheath tumor: a rare and challenging diagnosis. Am J Clin Pathol 124:685–692PubMedCrossRefGoogle Scholar
  8. 8.
    Antonescu CR, Woodruff JM, Scheithauer BW (2012) Tumors of the peripheral nervous system, 4th edn. American Registry of Pathology, Washington DCGoogle Scholar
  9. 9.
    Ariza A, Bilbao JM, Rosai J (1988) Immunohistochemical detection of epithelial membrane antigen in normal perineurial cells and perineurioma. Am J Surg Pathol 12:678–683PubMedCrossRefGoogle Scholar
  10. 10.
    Beert E, Brems H, Daniels B, De Wever I, Van Calenbergh F, Schoenaers J, Debiec-Rychter M, Gevaert O, De Raedt T, Van Den Bruel A, de Ravel T, Cichowski K, Kluwe L, Mautner V, Sciot R, Legius E (2011) Atypical neurofibromas in neurofibromatosis type 1 are premalignant tumors. Genes Chromosomes Cancer 50:1021–1032PubMedCrossRefGoogle Scholar
  11. 11.
    Berg JC, Scheithauer BW, Spinner RJ, Allen CM, Koutlas IG (2008) Plexiform schwannoma: a clinicopathologic overview with emphasis on the head and neck region. Hum Pathol 39:633–640PubMedCrossRefGoogle Scholar
  12. 12.
    Brems H, Park C, Maertens O, Pemov A, Messiaen L, Upadhyaya M, Claes K, Beert E, Peeters K, Mautner V, Sloan JL, Yao L, Lee CC, Sciot R, De Smet L, Legius E, Stewart DR (2009) Glomus tumors in neurofibromatosis type 1: genetic, functional, and clinical evidence of a novel association. Cancer Res 69:7393–7401PubMedCrossRefGoogle Scholar
  13. 13.
    Brown RW, Tornos C, Evans HL (1992) Angiosarcoma arising from malignant schwannoma in a patient with neurofibromatosis. Cancer 70:1141–1144PubMedCrossRefGoogle Scholar
  14. 14.
    Carney JA (1990) Psammomatous melanotic schwannoma. A distinctive, heritable tumor with special associations, including cardiac myxoma and the Cushing syndrome. Am J Surg Pathol 14:206–222PubMedCrossRefGoogle Scholar
  15. 15.
    Carroll S (2012) Molecular mechanisms promoting the pathogenesis of Schwann cell neoplasms. Acta Neuropathol. doi: 10.1007/s00401-011-0928-6
  16. 16.
    Carter JM, O’Hara C, Dundas G, Gilchrist D, Collins MS, Eaton K, Judkins AR, Biegel JA, Folpe AL (2012) Epithelioid malignant peripheral nerve sheath tumor arising in a schwannoma, in a patient with “Neuroblastoma-like” schwannomatosis and a novel germline SMARCB1 mutation. Am J Surg Pathol 36:154–160Google Scholar
  17. 17.
    Casadei GP, Scheithauer BW, Hirose T, Manfrini M, Van Houton C, Wood MB (1995) Cellular schwannoma. A clinicopathologic, DNA flow cytometric, and proliferation marker study of 70 patients. Cancer 75:1109–1119PubMedCrossRefGoogle Scholar
  18. 18.
    Cha JH, Kwon JW, Cho EY, Lee CS, Yoon YC, Choi SH (2008) Ossifying fibromyxoid tumor invading the spine: a case report and review of the literature. Skeletal Radiol 37:1137–1140PubMedCrossRefGoogle Scholar
  19. 19.
    Chaubal A, Paetau A, Zoltick P, Miettinen M (1994) CD34 immunoreactivity in nervous system tumors. Acta Neuropathol 88:454–458PubMedCrossRefGoogle Scholar
  20. 20.
    Chen JY, Hruby G, Scolyer RA, Murali R, Hong A, Fitzgerald P, Pham TT, Quinn MJ, Thompson JF (2008) Desmoplastic neurotropic melanoma: a clinicopathologic analysis of 128 cases. Cancer 113:2770–2778PubMedCrossRefGoogle Scholar
  21. 21.
    Christensen WN, Strong EW, Bains MS, Woodruff JM (1988) Neuroendocrine differentiation in the glandular peripheral nerve sheath tumor. Pathologic distinction from the biphasic synovial sarcoma with glands. Am J Surg Pathol 12:417–426PubMedCrossRefGoogle Scholar
  22. 22.
    Coindre JM, Terrier P, Guillou L, Le Doussal V, Collin F, Ranchere D, Sastre X, Vilain MO, Bonichon F, N’Guyen Bui B (2001) Predictive value of grade for metastasis development in the main histologic types of adult soft tissue sarcomas: a study of 1240 patients from the French Federation of Cancer Centers Sarcoma Group. Cancer 91:1914–1926PubMedCrossRefGoogle Scholar
  23. 23.
    Coindre JM (2006) Grading of soft tissue sarcomas: review and update. Arch Pathol Lab Med 130:1448–1453PubMedGoogle Scholar
  24. 24.
    Daimaru Y, Hashimoto H, Enjoji M (1985) Malignant peripheral nerve-sheath tumors (malignant schwannomas). An immunohistochemical study of 29 cases. Am J Surg Pathol 9:434–444PubMedCrossRefGoogle Scholar
  25. 25.
    Damiani S, Manetto V, Carrillo G, Di Blasi A, Nappi O, Eusebi V (1991) Malignant peripheral nerve sheath tumor arising in a “de novo” ganglioneuroma. A case report. Tumori 77:90–93PubMedGoogle Scholar
  26. 26.
    DiCarlo EF, Woodruff JM, Bansal M, Erlandson RA (1986) The purely epithelioid malignant peripheral nerve sheath tumor. Am J Surg Pathol 10:478–490PubMedCrossRefGoogle Scholar
  27. 27.
    Downs-Kelly E, Goldblum JR, Patel RM, Weiss SW, Folpe AL, Mertens F, Hartke M, Tubbs RR, Skacel M (2008) The utility of fluorescence in situ hybridization (FISH) in the diagnosis of myxoid soft tissue neoplasms. Am J Surg Pathol 32:8–13PubMedCrossRefGoogle Scholar
  28. 28.
    Doyle LA, Moller E, Dal Cin P, Fletcher CD, Mertens F, Hornick JL (2011) MUC4 is a highly sensitive and specific marker for low-grade fibromyxoid sarcoma. Am J Surg Pathol 35:733–741PubMedCrossRefGoogle Scholar
  29. 29.
    Ducatman BS, Scheithauer BW (1983) Postirradiation neurofibrosarcoma. Cancer 51:1028–1033PubMedCrossRefGoogle Scholar
  30. 30.
    Ducatman BS, Scheithauer BW (1984) Malignant peripheral nerve sheath tumors with divergent differentiation. Cancer 54:1049–1057PubMedCrossRefGoogle Scholar
  31. 31.
    Ducatman BS, Scheithauer BW, Piepgras DG, Reiman HM (1984) Malignant peripheral nerve sheath tumors in childhood. J Neurooncol 2:241–248PubMedCrossRefGoogle Scholar
  32. 32.
    Emanuel P, Pertsemlidis DS, Gordon R, Xu R (2006) Benign hybrid perineurioma-schwannoma in the colon. A case report. Ann Diagn Pathol 10:367–370PubMedCrossRefGoogle Scholar
  33. 33.
    Emory TS, Scheithauer BW, Hirose T, Wood M, Onofrio BM, Jenkins RB (1995) Intraneural perineurioma. A clonal neoplasm associated with abnormalities of chromosome 22. Am J Clin Pathol 103:696–704PubMedGoogle Scholar
  34. 34.
    Enzinger FM, Weiss SW, Liang CY (1989) Ossifying fibromyxoid tumor of soft parts. A clinicopathological analysis of 59 cases. Am J Surg Pathol 13:817–827PubMedCrossRefGoogle Scholar
  35. 35.
    Fanburg-Smith JC, Majidi M, Miettinen M (2006) Keratin expression in schwannoma; a study of 115 retroperitoneal and 22 peripheral schwannomas. Mod Pathol 19:115–121PubMedCrossRefGoogle Scholar
  36. 36.
    Feany MB, Anthony DC, Fletcher CD (1998) Nerve sheath tumours with hybrid features of neurofibroma and schwannoma: a conceptual challenge. Histopathology 32:405–410PubMedCrossRefGoogle Scholar
  37. 37.
    Ferner RE, Golding JF, Smith M, Calonje E, Jan W, Sanjayanathan V, O’Doherty M (2008) [18F]2-fluoro-2-deoxy-d-glucose positron emission tomography (FDG PET) as a diagnostic tool for neurofibromatosis 1 (NF1) associated malignant peripheral nerve sheath tumours (MPNSTs): a long-term clinical study. Ann Oncol 19:390–394PubMedCrossRefGoogle Scholar
  38. 38.
    Ferry JA, Dickersin GR (1988) Pseudoglandular schwannoma. Am J Clin Pathol 89:546–552PubMedGoogle Scholar
  39. 39.
    Fetsch JF, Miettinen M (1997) Sclerosing perineurioma: a clinicopathologic study of 19 cases of a distinctive soft tissue lesion with a predilection for the fingers and palms of young adults. Am J Surg Pathol 21:1433–1442PubMedCrossRefGoogle Scholar
  40. 40.
    Fetsch JF, Michal M, Miettinen M (2000) Pigmented (melanotic) neurofibroma: a clinicopathologic and immunohistochemical analysis of 19 lesions from 17 patients. Am J Surg Pathol 24:331–343PubMedCrossRefGoogle Scholar
  41. 41.
    Fine SW, McClain SA, Li M (2004) Immunohistochemical staining for calretinin is useful for differentiating schwannomas from neurofibromas. Am J Clin Pathol 122:552–559PubMedCrossRefGoogle Scholar
  42. 42.
    Fletcher CD, Davies SE (1986) Benign plexiform (multinodular) schwannoma: a rare tumour unassociated with neurofibromatosis. Histopathology 10:971–980PubMedCrossRefGoogle Scholar
  43. 43.
    Fletcher CD, Davies SE, McKee PH (1987) Cellular schwannoma: a distinct pseudosarcomatous entity. Histopathology 11:21–35PubMedCrossRefGoogle Scholar
  44. 44.
    Foley KM, Woodruff JM, Ellis FT, Posner JB (1980) Radiation-induced malignant and atypical peripheral nerve sheath tumors. Ann Neurol 7:311–318PubMedCrossRefGoogle Scholar
  45. 45.
    Folpe AL, Billings SD, McKenney JK, Walsh SV, Nusrat A, Weiss SW (2002) Expression of claudin-1, a recently described tight junction-associated protein, distinguishes soft tissue perineurioma from potential mimics. Am J Surg Pathol 26:1620–1626PubMedCrossRefGoogle Scholar
  46. 46.
    Folpe AL, Weiss SW (2003) Ossifying fibromyxoid tumor of soft parts: a clinicopathologic study of 70 cases with emphasis on atypical and malignant variants. Am J Surg Pathol 27:421–431PubMedCrossRefGoogle Scholar
  47. 47.
    Foo WC, Cruise MW, Wick MR, Hornick JL (2011) Immunohistochemical staining for TLE1 distinguishes synovial sarcoma from histologic mimics. Am J Clin Pathol 135:839–844PubMedCrossRefGoogle Scholar
  48. 48.
    Giannini C, Scheithauer BW, Jenkins RB, Erlandson RA, Perry A, Borell TJ, Hoda RS, Woodruff JM (1997) Soft-tissue perineurioma. Evidence for an abnormality of chromosome 22, criteria for diagnosis, and review of the literature. Am J Surg Pathol 21:164–173PubMedCrossRefGoogle Scholar
  49. 49.
    Gibson JA, Hornick JL (2009) Mucosal Schwann cell “hamartoma”: clinicopathologic study of 26 neural colorectal polyps distinct from neurofibromas and mucosal neuromas. Am J Surg Pathol 33:781–787PubMedCrossRefGoogle Scholar
  50. 50.
    Giovannini M, Robanus-Maandag E, van der Valk M, Niwa-Kawakita M, Abramowski V, Goutebroze L, Woodruff JM, Berns A, Thomas G (2000) Conditional biallelic Nf2 mutation in the mouse promotes manifestations of human neurofibromatosis type 2. Genes Dev 14:1617–1630PubMedGoogle Scholar
  51. 51.
    Goldblum JR, Beals TF, Weiss SW (1994) Neuroblastoma-like neurilemoma. Am J Surg Pathol 18:266–273PubMedCrossRefGoogle Scholar
  52. 52.
    Gonzalez-Campora R, Delgado MD, Amate AH, Gallardo SP, Leon MS, Beltran AL (2011) Old and new immunohistochemical markers for the diagnosis of gastrointestinal stromal tumors. Anal Quant Cytol Histol 33:1–11PubMedGoogle Scholar
  53. 53.
    Graadt van Roggen JF, McMenamin ME, Belchis DA, Nielsen GP, Rosenberg AE, Fletcher CD (2001) Reticular perineurioma: a distinctive variant of soft tissue perineurioma. Am J Surg Pathol 25:485–493PubMedCrossRefGoogle Scholar
  54. 54.
    Graham RP, Dry S, Li X, Binder S, Bahrami A, Raimondi SC, Dogan A, Chakraborty S, Souchek JJ, Folpe AL (2011) Ossifying fibromyxoid tumor of soft parts: a clinicopathologic, proteomic, and genomic study. Am J Surg Pathol 35:1615–1625PubMedCrossRefGoogle Scholar
  55. 55.
    Halling KC, Scheithauer BW, Halling AC, Nascimento AG, Ziesmer SC, Roche PC, Wollan PC (1996) p53 expression in neurofibroma and malignant peripheral nerve sheath tumor. An immunohistochemical study of sporadic and NF1-associated tumors. Am J Clin Pathol 106:282–288PubMedGoogle Scholar
  56. 56.
    Hebert-Blouin MN, Amrami KK, Scheithauer BW, Spinner RJ (2010) Multinodular/plexiform (multifascicular) schwannomas of major peripheral nerves: an underrecognized part of the spectrum of schwannomas. J Neurosurg 112:372–382PubMedCrossRefGoogle Scholar
  57. 57.
    Hebert-Blouin MN, Scheithauer BW, Amrami KK, Durham SR, Spinner RJ (2011) Fibromatosis: a potential sequela of neuromuscular choristoma. J Neurosurg 116:399–408Google Scholar
  58. 58.
    Hirose T, Sumitomo M, Kudo E, Hasegawa T, Teramae T, Murase M, Higasa Y, Ikata T, Hizawa K (1989) Malignant peripheral nerve sheath tumor (MPNST) showing perineurial cell differentiation. Am J Surg Pathol 13:613–620PubMedCrossRefGoogle Scholar
  59. 59.
    Hirose T, Scheithauer BW, Sano T (1998) Perineurial malignant peripheral nerve sheath tumor (MPNST): a clinicopathologic, immunohistochemical, and ultrastructural study of seven cases. Am J Surg Pathol 22:1368–1378PubMedCrossRefGoogle Scholar
  60. 60.
    Hollmann TJ, Hornick JL (2011) INI1-deficient tumors: diagnostic features and molecular genetics. Am J Surg Pathol 35:e47–e63PubMedCrossRefGoogle Scholar
  61. 61.
    Hornick JL, Fletcher CD (2005) Soft tissue perineurioma: clinicopathologic analysis of 81 cases including those with atypical histologic features. Am J Surg Pathol 29:845–858PubMedCrossRefGoogle Scholar
  62. 62.
    Hornick JL, Fletcher CD (2005) Intestinal perineuriomas: clinicopathologic definition of a new anatomic subset in a series of 10 cases. Am J Surg Pathol 29:859–865PubMedCrossRefGoogle Scholar
  63. 63.
    Hornick JL, Bundock EA, Fletcher CD (2009) Hybrid schwannoma/perineurioma: clinicopathologic analysis of 42 distinctive benign nerve sheath tumors. Am J Surg Pathol 33:1554–1561PubMedCrossRefGoogle Scholar
  64. 64.
    Hruban RH, Shiu MH, Senie RT, Woodruff JM (1990) Malignant peripheral nerve sheath tumors of the buttock and lower extremity. A study of 43 cases. Cancer 66:1253–1265PubMedCrossRefGoogle Scholar
  65. 65.
    Hummel TR, Jessen WJ, Miller SJ, Kluwe L, Mautner VF, Wallace MR, Lazaro C, Page GP, Worley PF, Aronow BJ, Schorry EK, Ratner N (2010) Gene expression analysis identifies potential biomarkers of neurofibromatosis type 1 including adrenomedullin. Clin Cancer Res 16:5048–5057PubMedCrossRefGoogle Scholar
  66. 66.
    Jhanwar SC, Chen Q, Li FP, Brennan MF, Woodruff JM (1994) Cytogenetic analysis of soft tissue sarcomas. Recurrent chromosome abnormalities in malignant peripheral nerve sheath tumors (MPNST). Cancer Genet Cytogenet 78:138–144PubMedCrossRefGoogle Scholar
  67. 67.
    Jokinen CH, Dadras SS, Goldblum JR, van de Rijn M, West RB, Rubin BP (2008) Diagnostic implications of podoplanin expression in peripheral nerve sheath neoplasms. Am J Clin Pathol 129:886–893PubMedCrossRefGoogle Scholar
  68. 68.
    Kawahara E, Oda Y, Ooi A, Katsuda S, Nakanishi I, Umeda S (1988) Expression of glial fibrillary acidic protein (GFAP) in peripheral nerve sheath tumors. A comparative study of immunoreactivity of GFAP, vimentin, S-100 protein, and neurofilament in 38 schwannomas and 18 neurofibromas. Am J Surg Pathol 12:115–120PubMedCrossRefGoogle Scholar
  69. 69.
    Kazakov DV, Pitha J, Sima R, Vanecek T, Shelekhova K, Mukensnabl P, Michal M (2005) Hybrid peripheral nerve sheath tumors: Schwannoma-perineurioma and neurofibroma-perineurioma. A report of three cases in extradigital locations. Ann Diagn Pathol 9:16–23PubMedCrossRefGoogle Scholar
  70. 70.
    Kelesidis T, Tarbox A, Lopez M, Aish L (2009) Perineurioma of esophagus: a first case report. Am J Med Sci 338:230–232PubMedCrossRefGoogle Scholar
  71. 71.
    Keller SM, Papazoglou S, McKeever P, Baker A, Roth JA (1984) Late occurrence of malignancy in a ganglioneuroma 19 years following radiation therapy to a neuroblastoma. J Surg Oncol 25:227–231PubMedCrossRefGoogle Scholar
  72. 72.
    Kindblom LG, Ahlden M, Meis-Kindblom JM, Stenman G (1995) Immunohistochemical and molecular analysis of p53, MDM2, proliferating cell nuclear antigen and Ki67 in benign and malignant peripheral nerve sheath tumours. Virchows Arch 427:19–26PubMedCrossRefGoogle Scholar
  73. 73.
    Kindblom LG, Meis-Kindblom JM, Havel G, Busch C (1998) Benign epithelioid schwannoma. Am J Surg Pathol 22:762–770PubMedCrossRefGoogle Scholar
  74. 74.
    Knosel T, Heretsch S, Altendorf-Hofmann A, Richter P, Katenkamp K, Katenkamp D, Berndt A, Petersen I (2010) TLE1 is a robust diagnostic biomarker for synovial sarcomas and correlates with t(X;18): analysis of 319 cases. Eur J Cancer 46:1170–1176PubMedCrossRefGoogle Scholar
  75. 75.
    Kosemehmetoglu K, Vrana JA, Folpe AL (2009) TLE1 expression is not specific for synovial sarcoma: a whole section study of 163 soft tissue and bone neoplasms. Mod Pathol 22:872–878PubMedCrossRefGoogle Scholar
  76. 76.
    Kourea HP, Cordon-Cardo C, Dudas M, Leung D, Woodruff JM (1999) Expression of p27(kip) and other cell cycle regulators in malignant peripheral nerve sheath tumors and neurofibromas: the emerging role of p27(kip) in malignant transformation of neurofibromas. Am J Pathol 155:1885–1891PubMedCrossRefGoogle Scholar
  77. 77.
    Kourea HP, Orlow I, Scheithauer BW, Cordon-Cardo C, Woodruff JM (1999) Deletions of the INK4A gene occur in malignant peripheral nerve sheath tumors but not in neurofibromas. Am J Pathol 155:1855–1860PubMedCrossRefGoogle Scholar
  78. 78.
    Kurtkaya-Yapicier O, Scheithauer BW, Woodruff JM, Wenger DD, Cooley AM, Dominique D (2003) Schwannoma with rhabdomyoblastic differentiation: a unique variant of malignant triton tumor. Am J Surg Pathol 27:848–853PubMedCrossRefGoogle Scholar
  79. 79.
    Ladanyi M, Woodruff JM, Scheithauer BW, Bridge JA, Barr FG, Goldblum JR, Fisher C, Perez-Atayde A, Dal Cin P, Fletcher CD, Fletcher JA (2001) Re: O’Sullivan MJ, Kyriakos M, Zhu X, Wick MR, Swanson PE, Dehner LP, Humphrey PA, Pfeifer JD: malignant peripheral nerve sheath tumors with t(X;18). A pathologic and molecular genetic study. Mod pathol 2000;13:1336-46. Mod Pathol 14:733–737Google Scholar
  80. 80.
    Laskin WB, Weiss SW, Bratthauer GL (1991) Epithelioid variant of malignant peripheral nerve sheath tumor (malignant epithelioid schwannoma). Am J Surg Pathol 15:1136–1145PubMedCrossRefGoogle Scholar
  81. 81.
    Lasota J, Wasag B, Dansonka-Mieszkowska A, Karcz D, Millward CL, Rys J, Stachura J, Sobin LH, Miettinen M (2003) Evaluation of NF2 and NF1 tumor suppressor genes in distinctive gastrointestinal nerve sheath tumors traditionally diagnosed as benign schwannomas: s study of 20 cases. Lab Invest 83:1361–1371PubMedCrossRefGoogle Scholar
  82. 82.
    Le LQ, Shipman T, Burns DK, Parada LF (2009) Cell of origin and microenvironment contribution for NF1-associated dermal neurofibromas. Cell Stem Cell 4:453–463PubMedCrossRefGoogle Scholar
  83. 83.
    Lewin MR, Dilworth HP, Abu Alfa AK, Epstein JI, Montgomery E (2005) Mucosal benign epithelioid nerve sheath tumors. Am J Surg Pathol 29:1310–1315PubMedCrossRefGoogle Scholar
  84. 84.
    Liegl B, Bennett MW, Fletcher CD (2008) Microcystic/reticular schwannoma: a distinct variant with predilection for visceral locations. Am J Surg Pathol 32:1080–1087PubMedCrossRefGoogle Scholar
  85. 85.
    Lin BT, Weiss LM, Medeiros LJ (1997) Neurofibroma and cellular neurofibroma with atypia: a report of 14 tumors. Am J Surg Pathol 21:1443–1449PubMedCrossRefGoogle Scholar
  86. 86.
    Lodding P, Kindblom LG, Angervall L (1986) Epithelioid malignant schwannoma. A study of 14 cases. Virchows Arch A Pathol Anat Histopathol 409:433–451PubMedCrossRefGoogle Scholar
  87. 87.
    Louis DN, Ohgaki H, Wiestler OD, Cavenee WK (eds) (2007) WHO Classification of Tumours of the Central Nervous System, edn. International Agency for Research on Cancer, LyonGoogle Scholar
  88. 88.
    Maher CO, Spinner RJ, Giannini C, Scheithauer BW, Crum BA (2002) Neuromuscular choristoma of the sciatic nerve. Case report. J Neurosurg 96:1123–1126PubMedCrossRefGoogle Scholar
  89. 89.
    Matsuyama A, Hisaoka M, Shimajiri S, Hayashi T, Imamura T, Ishida T, Fukunaga M, Fukuhara T, Minato H, Nakajima T, Yonezawa S, Kuroda M, Yamasaki F, Toyoshima S, Hashimoto H (2006) Molecular detection of FUS-CREB3L2 fusion transcripts in low-grade fibromyxoid sarcoma using formalin-fixed, paraffin-embedded tissue specimens. Am J Surg Pathol 30:1077–1084PubMedGoogle Scholar
  90. 90.
    Mauermann ML, Amrami KK, Kuntz NL, Spinner RJ, Dyck PJ, Bosch EP, Engelstad J, Felmlee JP (2009) Longitudinal study of intraneural perineurioma–a benign, focal hypertrophic neuropathy of youth. Brain 132:2265–2276PubMedCrossRefGoogle Scholar
  91. 91.
    Mauermann ML, Scheithauer BW, Spinner RJ, Amrami KK, Nance CS, Kline DG, O’Connor MI, Dyck PJ, Engelstad J (2010) Inflammatory pseudotumor of nerve: clinicopathological characteristics and a potential therapy. J Peripher Nerv Syst 15:216–226PubMedCrossRefGoogle Scholar
  92. 92.
    McCarron KF, Goldblum JR (1998) Plexiform neurofibroma with and without associated malignant peripheral nerve sheath tumor: a clinicopathologic and immunohistochemical analysis of 54 cases. Mod Pathol 11:612–617PubMedGoogle Scholar
  93. 93.
    McMenamin ME, Fletcher CD (2001) Expanding the spectrum of malignant change in schwannomas: epithelioid malignant change, epithelioid malignant peripheral nerve sheath tumor, and epithelioid angiosarcoma: a study of 17 cases. Am J Surg Pathol 25:13–25PubMedCrossRefGoogle Scholar
  94. 94.
    Meis-Kindblom JM, Enzinger FM (1994) Plexiform malignant peripheral nerve sheath tumor of infancy and childhood. Am J Surg Pathol 18:479–485PubMedCrossRefGoogle Scholar
  95. 95.
    Meis JM, Enzinger FM, Martz KL, Neal JA (1992) Malignant peripheral nerve sheath tumors (malignant schwannomas) in children. Am J Surg Pathol 16:694–707PubMedCrossRefGoogle Scholar
  96. 96.
    Mennemeyer RP, Hallman KO, Hammar SP, Raisis JE, Tytus JS, Bockus D (1979) Melanotic schwannoma. Clinical and ultrastructural studies of three cases with evidence of intracellular melanin synthesis. Am J Surg Pathol 3:3–10PubMedCrossRefGoogle Scholar
  97. 97.
    Menon AG, Anderson KM, Riccardi VM, Chung RY, Whaley JM, Yandell DW, Farmer GE, Freiman RN, Lee JK, Li FP et al (1990) Chromosome 17p deletions and p53 gene mutations associated with the formation of malignant neurofibrosarcomas in von Recklinghausen neurofibromatosis. Proc Natl Acad Sci USA 87:5435–5439PubMedCrossRefGoogle Scholar
  98. 98.
    Michal M, Kazakov DV, Belousova I, Bisceglia M, Zamecnik M, Mukensnabl P (2004) A benign neoplasm with histopathological features of both schwannoma and retiform perineurioma (benign schwannoma-perineurioma): a report of six cases of a distinctive soft tissue tumor with a predilection for the fingers. Virchows Arch 445:347–353PubMedCrossRefGoogle Scholar
  99. 99.
    Miettinen M, Saari A (1988) Pheochromocytoma combined with malignant schwannoma: unusual neoplasm of the adrenal medulla. Ultrastruct Pathol 12:513–527PubMedCrossRefGoogle Scholar
  100. 100.
    Miettinen M, Finnell V, Fetsch JF (2008) Ossifying fibromyxoid tumor of soft parts—a clinicopathologic and immunohistochemical study of 104 cases with long-term follow-up and a critical review of the literature. Am J Surg Pathol 32:996–1005PubMedCrossRefGoogle Scholar
  101. 101.
    Miller SJ, Jessen WJ, Mehta T, Hardiman A, Sites E, Kaiser S, Jegga AG, Li H, Upadhyaya M, Giovannini M, Muir D, Wallace MR, Lopez E, Serra E, Nielsen GP, Lazaro C, Stemmer-Rachamimov A, Page G, Aronow BJ, Ratner N (2009) Integrative genomic analyses of neurofibromatosis tumours identify SOX9 as a biomarker and survival gene. EMBO Mol Med 1:236–248PubMedCrossRefGoogle Scholar
  102. 102.
    Min KW, Clemens A, Bell J, Dick H (1988) Malignant peripheral nerve sheath tumor and pheochromocytoma. A composite tumor of the adrenal. Arch Pathol Lab Med 112:266–270PubMedGoogle Scholar
  103. 103.
    Mori T, Orikasa H, Shigematsu T, Yamazaki K (2006) An ultrastructural and immunohistochemical study of a combined submucosal granular cell tumor and lipoma of the colon showing a unique nodule-in-nodule structure: putative implication of CD34 or prominin-2-positive stromal cells in its histopathogenesis. Virchows Arch 449:137–139PubMedCrossRefGoogle Scholar
  104. 104.
    Naber U, Friedrich RE, Glatzel M, Mautner VF, Hagel C (2011) Podoplanin and CD34 in peripheral nerve sheath tumours: focus on neurofibromatosis 1-associated atypical neurofibroma. J Neurooncol 103:239–245PubMedCrossRefGoogle Scholar
  105. 105.
    Nascimento AF, Fletcher CD (2007) The controversial nosology of benign nerve sheath tumors: neurofilament protein staining demonstrates intratumoral axons in many sporadic schwannomas. Am J Surg Pathol 31:1363–1370PubMedCrossRefGoogle Scholar
  106. 106.
    Nielsen GP, Stemmer-Rachamimov AO, Ino Y, Moller MB, Rosenberg AE, Louis DN (1999) Malignant transformation of neurofibromas in neurofibromatosis 1 is associated with CDKN2A/p16 inactivation. Am J Pathol 155:1879–1884PubMedCrossRefGoogle Scholar
  107. 107.
    Nonaka D, Chiriboga L, Rubin BP (2008) Sox10: a pan-schwannian and melanocytic marker. Am J Surg Pathol 32:1291–1298PubMedCrossRefGoogle Scholar
  108. 108.
    Ogawa K, Oguchi M, Yamabe H, Nakashima Y, Hamashima Y (1986) Distribution of collagen type IV in soft tissue tumors. An immunohistochemical study. Cancer 58:269–277PubMedCrossRefGoogle Scholar
  109. 109.
    Panagopoulos I, Storlazzi CT, Fletcher CD, Fletcher JA, Nascimento A, Domanski HA, Wejde J, Brosjo O, Rydholm A, Isaksson M, Mandahl N, Mertens F (2004) The chimeric FUS/CREB3l2 gene is specific for low-grade fibromyxoid sarcoma. Genes Chromosomes Cancer 40:218–228PubMedCrossRefGoogle Scholar
  110. 110.
    Perentes E, Nakagawa Y, Ross GW, Stanton C, Rubinstein LJ (1987) Expression of epithelial membrane antigen in perineurial cells and their derivatives. An immunohistochemical study with multiple markers. Acta Neuropathol 75:160–165PubMedCrossRefGoogle Scholar
  111. 111.
    Perry A, Roth KA, Banerjee R, Fuller CE, Gutmann DH (2001) NF1 deletions in S-100 protein-positive and negative cells of sporadic and neurofibromatosis 1 (NF1)-associated plexiform neurofibromas and malignant peripheral nerve sheath tumors. Am J Pathol 159:57–61PubMedCrossRefGoogle Scholar
  112. 112.
    Perry A, Kunz SN, Fuller CE, Banerjee R, Marley EF, Liapis H, Watson MA, Gutmann DH (2002) Differential NF1, p16, and EGFR patterns by interphase cytogenetics (FISH) in malignant peripheral nerve sheath tumor (MPNST) and morphologically similar spindle cell neoplasms. J Neuropathol Exp Neurol 61:702–709PubMedGoogle Scholar
  113. 113.
    Plaza JA, Wakely PE Jr, Suster S (2006) Lipoblastic nerve sheath tumors: report of a distinctive variant of neural soft tissue neoplasm with adipocytic differentiation. Am J Surg Pathol 30:337–344PubMedGoogle Scholar
  114. 114.
    Ricci A Jr, Parham DM, Woodruff JM, Callihan T, Green A, Erlandson RA (1984) Malignant peripheral nerve sheath tumors arising from ganglioneuromas. Am J Surg Pathol 8:19–29PubMedCrossRefGoogle Scholar
  115. 115.
    Rodriguez FJ, Scheithauer BW, Abell-Aleff PC, Elamin E, Erlandson RA (2007) Low grade malignant peripheral nerve sheath tumor with smooth muscle differentiation. Acta Neuropathol 113:705–709PubMedCrossRefGoogle Scholar
  116. 116.
    Rodriguez FJ, Erickson-Johnson MR, Scheithauer BW, Spinner RJ, Oliveira AM (2008) HMGA2 rearrangements are rare in benign lipomatous lesions of the nervous system. Acta Neuropathol 116:337–338PubMedCrossRefGoogle Scholar
  117. 117.
    Rodriguez FJ, Stratakis CA, Evans DG (2012) Genetic predisposition to peripheral nerve neoplasia: diagnostic criteria and pathogenesis of neurofibromatoses, Carney complex, and related syndromes. Acta Neuropathol. doi: 10.1007/s00401-011-0935-7
  118. 118.
    Rose DS, Wilkins MJ, Birch R, Evans DJ (1992) Malignant peripheral nerve sheath tumour with rhabdomyoblastic and glandular differentiation: immunohistochemical features. Histopathology 21:287–290PubMedCrossRefGoogle Scholar
  119. 119.
    Sangala JR, Park P, Blaivas M, Lamarca F (2010) Paraspinal malignant ossifying fibromyxoid tumor with spinal involvement. J Clin Neurosci 17:1592–1594PubMedCrossRefGoogle Scholar
  120. 120.
    Scheithauer BW, Woodruff JM, Erlandson RA (1997) Tumors of the peripheral nervous system. Armed Forces Institute of Pathology, Washington D.CGoogle Scholar
  121. 121.
    Scheithauer BW, Rodriguez FJ, Spinner RJ, Dyck PJ, Salem A, Edelman FL, Amrami KK, Fu YS (2008) Glomus tumor and glomangioma of the nerve. Report of two cases. J Neurosurg 108:348–356PubMedCrossRefGoogle Scholar
  122. 122.
    Scheithauer BW, Erdogan S, Rodriguez FJ, Burger PC, Woodruff JM, Kros JM, Gokden M, Spinner RJ (2009) Malignant peripheral nerve sheath tumors of cranial nerves and intracranial contents: a clinicopathologic study of 17 cases. Am J Surg Pathol 33:325–338PubMedCrossRefGoogle Scholar
  123. 123.
    Scheithauer BW, Amrami KK, Folpe AL, Silva AI, Edgar MA, Woodruff JM, Levi AD, Spinner RJ (2011) Synovial sarcoma of nerve. Hum Pathol 42:568–577PubMedCrossRefGoogle Scholar
  124. 124.
    Shelekhova KV, Danilova AB, Michal M, Kazakov DV (2008) Hybrid neurofibroma-perineurioma: an additional example of an extradigital tumor. Ann Diagn Pathol 12:233–234PubMedCrossRefGoogle Scholar
  125. 125.
    Shiurba RA, Eng LF, Urich H (1984) The structure of pseudomeissnerian corpuscles. An immunohistochemical study. Acta Neuropathol 63:174–176PubMedCrossRefGoogle Scholar
  126. 126.
    Slomiany MG, Dai L, Bomar PA, Knackstedt TJ, Kranc DA, Tolliver L, Maria BL, Toole BP (2009) Abrogating drug resistance in malignant peripheral nerve sheath tumors by disrupting hyaluronan-CD44 interactions with small hyaluronan oligosaccharides. Cancer Res 69:4992–4998PubMedCrossRefGoogle Scholar
  127. 127.
    Smith TW, Bhawan J (1980) Tactile-like structures in neurofibromas. An ultrastructural study. Acta Neuropathol 50:233–236PubMedCrossRefGoogle Scholar
  128. 128.
    Spinner RJ, Scheithauer BW, Perry A, Amrami KK, Emnett R, Gutmann DH (2007) Colocalized cellular schwannoma and plexiform neurofibroma in the absence of neurofibromatosis. Case report. J Neurosurg 107:435–439PubMedCrossRefGoogle Scholar
  129. 129.
    Spinner RJ, Scheithauer BW, Amrami KK, Wenger DE, Hebert-Blouin MN (2012) Adipose lesions of nerve: the need for a modified classification. J Neurosurg 116:418–431Google Scholar
  130. 130.
    Swanson PE, Stanley MW, Scheithauer BW, Wick MR (1988) Primary cutaneous leiomyosarcoma. A histological and immunohistochemical study of 9 cases, with ultrastructural correlation. J Cutan Pathol 15:129–141PubMedCrossRefGoogle Scholar
  131. 131.
    Terry J, Saito T, Subramanian S, Ruttan C, Antonescu CR, Goldblum JR, Downs-Kelly E, Corless CL, Rubin BP, van de Rijn M, Ladanyi M, Nielsen TO (2007) TLE1 as a diagnostic immunohistochemical marker for synovial sarcoma emerging from gene expression profiling studies. Am J Surg Pathol 31:240–246PubMedCrossRefGoogle Scholar
  132. 132.
    Tozbikian G, Shen R, Suster S (2008) Signet ring cell gastric schwannoma: report of a new distinctive morphological variant. Ann Diagn Pathol 12:146–152PubMedCrossRefGoogle Scholar
  133. 133.
    Trassard M, Le Doussal V, Bui BN, Coindre JM (1996) Angiosarcoma arising in a solitary schwannoma (neurilemoma) of the sciatic nerve. Am J Surg Pathol 20:1412–1417PubMedCrossRefGoogle Scholar
  134. 134.
    Trojani M, Contesso G, Coindre JM, Rouesse J, Bui NB, de Mascarel A, Goussot JF, David M, Bonichon F, Lagarde C (1984) Soft-tissue sarcomas of adults; study of pathological prognostic variables and definition of a histopathological grading system. Int J Cancer 33:37–42PubMedCrossRefGoogle Scholar
  135. 135.
    Tsang WY, Chan JK, Chow LT, Tse CC (1992) Perineurioma: an uncommon soft tissue neoplasm distinct from localized hypertrophic neuropathy and neurofibroma. Am J Surg Pathol 16:756–763PubMedCrossRefGoogle Scholar
  136. 136.
    Turc-Carel C, Dal Cin P, Limon J, Rao U, Li FP, Corson JM, Zimmerman R, Parry DM, Cowan JM, Sandberg AA (1987) Involvement of chromosome X in primary cytogenetic change in human neoplasia: nonrandom translocation in synovial sarcoma. Proc Natl Acad Sci USA 84:1981–1985PubMedCrossRefGoogle Scholar
  137. 137.
    Voltaggio L, Murray R, Lasota J, Miettinen M (2011) Gastric schwannoma: a clinicopathologic study of 51 cases and critical review of the literature. Hum Pathol [Epub ahead of print]Google Scholar
  138. 138.
    Watabe K, Kumanishi T, Ikuta F, Oyake Y (1983) Tactile-like corpuscles in neurofibromas: immunohistochemical demonstration of S-100 protein. Acta Neuropathol 61:173–177PubMedCrossRefGoogle Scholar
  139. 139.
    Weinreb I, Bray P, Ghazarian D (2007) Plexiform intraneural granular cell tumour of a digital cutaneous sensory nerve. J Clin Pathol 60:725–726PubMedCrossRefGoogle Scholar
  140. 140.
    Weiss SW, Langloss JM, Enzinger FM (1983) Value of S-100 protein in the diagnosis of soft tissue tumors with particular reference to benign and malignant Schwann cell tumors. Lab Invest 49:299–308PubMedGoogle Scholar
  141. 141.
    Weiss SW, Nickoloff BJ (1993) CD-34 is expressed by a distinctive cell population in peripheral nerve, nerve sheath tumors, and related lesions. Am J Surg Pathol 17:1039–1045PubMedCrossRefGoogle Scholar
  142. 142.
    Weiss SW, Goldblum JR (eds) (2007) Enzinger and Weiss’s Soft Tissue Tumors, 5th edn. Mosby Elsevier, PhiladelphiaGoogle Scholar
  143. 143.
    West RB, Corless CL, Chen X, Rubin BP, Subramanian S, Montgomery K, Zhu S, Ball CA, Nielsen TO, Patel R, Goldblum JR, Brown PO, Heinrich MC, van de Rijn M (2004) The novel marker, DOG1, is expressed ubiquitously in gastrointestinal stromal tumors irrespective of KIT or PDGFRA mutation status. Am J Pathol 165:107–113PubMedCrossRefGoogle Scholar
  144. 144.
    White W, Shiu MH, Rosenblum MK, Erlandson RA, Woodruff JM (1990) Cellular schwannoma. A clinicopathologic study of 57 patients and 58 tumors. Cancer 66:1266–1275PubMedCrossRefGoogle Scholar
  145. 145.
    Wick MR, Swanson PE, Scheithauer BW, Manivel JC (1987) Malignant peripheral nerve sheath tumor. An immunohistochemical study of 62 cases. Am J Clin Pathol 87:425–433PubMedGoogle Scholar
  146. 146.
    Woodruff JM, Marshall ML, Godwin TA, Funkhouser JW, Thompson NJ, Erlandson RA (1983) Plexiform (multinodular) schwannoma. A tumor simulating the plexiform neurofibroma. Am J Surg Pathol 7:691–697PubMedCrossRefGoogle Scholar
  147. 147.
    Woodruff JM, Christensen WN (1993) Glandular peripheral nerve sheath tumors. Cancer 72:3618–3628PubMedCrossRefGoogle Scholar
  148. 148.
    Woodruff JM, Perino G (1994) Non-germ-cell or teratomatous malignant tumors showing additional rhabdomyoblastic differentiation, with emphasis on the malignant Triton tumor. Semin Diagn Pathol 11:69–81PubMedGoogle Scholar
  149. 149.
    Woodruff JM, Selig AM, Crowley K, Allen PW (1994) Schwannoma (neurilemoma) with malignant transformation. A rare, distinctive peripheral nerve tumor. Am J Surg Pathol 18:882–895PubMedCrossRefGoogle Scholar
  150. 150.
    Woodruff JM (1999) Pathology of tumors of the peripheral nerve sheath in type 1 neurofibromatosis. Am J Med Genet 89:23–30PubMedCrossRefGoogle Scholar
  151. 151.
    Woodruff JM, Scheithauer BW, Kurtkaya-Yapicier O, Raffel C, Amr SS, LaQuaglia MP, Antonescu CR (2003) Congenital and childhood plexiform (multinodular) cellular schwannoma: a troublesome mimic of malignant peripheral nerve sheath tumor. Am J Surg Pathol 27:1321–1329PubMedCrossRefGoogle Scholar
  152. 152.
    Wu J, Williams JP, Rizvi TA, Kordich JJ, Witte D, Meijer D, Stemmer-Rachamimov AO, Cancelas JA, Ratner N (2008) Plexiform and dermal neurofibromas and pigmentation are caused by Nf1 loss in desert hedgehog-expressing cells. Cancer Cell 13:105–116PubMedCrossRefGoogle Scholar
  153. 153.
    Yeh I, McCalmont TH (2011) Distinguishing neurofibroma from desmoplastic melanoma: the value of the CD34 fingerprint. J Cutan Pathol 38:625–630PubMedCrossRefGoogle Scholar
  154. 154.
    Yu J, Deshmukh H, Payton JE, Dunham C, Scheithauer BW, Tihan T, Prayson RA, Guha A, Bridge JA, Ferner RE, Lindberg GM, Gutmann RJ, Emnett RJ, Salavaggione L, Gutmann DH, Nagarajan R, Watson MA, Perry A (2011) Array-based comparative genomic hybridization identifies CDK4 and FOXM1 alterations as independent predictors of survival in malignant peripheral nerve sheath tumor. Clin Cancer Res 17:1924–1934PubMedCrossRefGoogle Scholar
  155. 155.
    Zamecnik M, Mukensnabl P, Sokol L, Michal M (2004) Perineurial cells and nerve axons in gastrointestinal schwannomas: a similarity with neurofibromas. An immunohistochemical study of eight cases. Cesk Patol 40:150–153PubMedGoogle Scholar
  156. 156.
    Zheng H, Chang L, Patel N, Yang J, Lowe L, Burns DK, Zhu Y (2008) Induction of abnormal proliferation by nonmyelinating Schwann cells triggers neurofibroma formation. Cancer Cell 13:117–128PubMedCrossRefGoogle Scholar
  157. 157.
    Zhou H, Coffin CM, Perkins SL, Tripp SR, Liew M, Viskochil DH (2003) Malignant peripheral nerve sheath tumor: a comparison of grade, immunophenotype, and cell cycle/growth activation marker expression in sporadic and neurofibromatosis 1-related lesions. Am J Surg Pathol 27:1337–1345PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Fausto J. Rodriguez
    • 1
    Email author
  • Andrew L. Folpe
    • 2
  • Caterina Giannini
    • 2
  • Arie Perry
    • 3
  1. 1.Division of Neuropathology, Department of PathologyJohns Hopkins UniversityBaltimoreUSA
  2. 2.Division of Anatomic PathologyMayo ClinicRochesterUSA
  3. 3.Division of NeuropathologyUniversity of California San FranciscoSan FranciscoUSA

Personalised recommendations