Neuroectodermal and Melanocytic Tumors

  • Alessandro FranchiEmail author


The group of neuroectodermal and melanocytic tumors includes three malignant tumor types: sinonasal melanoma, olfactory neuroblastoma, and Ewing sarcoma. These tumors are often difficult to characterize, due to the overlap of their histologic features and immunohistochemical profiles with other entities. Olfactory neuroblastoma is a unique tumor type that characteristically originates in the superior nasal cavity, involving the cribriform plate of the ethmoid sinus, part of the superior turbinate (concha), or the superior half of the nasal septum. The prognosis depends on the stage, which is assigned according to the Kadish system, and on histologic grading, which is assigned according to the Hyams criteria.


Melanoma Olfactory neuroblastoma Ewing sarcoma 


  1. 1.
    Cove H. Melanosis, melanocytic hyperplasia, and primary malignant melanoma of the nasal cavity. Cancer. 1979;44:1424–33.PubMedCrossRefPubMedCentralGoogle Scholar
  2. 2.
    Hofbauer GF, Böni R, Simmen D, Mihic D, Nestle FO, Burg G, Dummer R. Histological, immunological and molecular features of a nasal mucosa primary melanoma associated with nasal melanosis. Melanoma Res. 2002;12:77–82.PubMedCrossRefPubMedCentralGoogle Scholar
  3. 3.
    Clifton N, Harrison L, Bradley PJ, Jones NS. Malignant melanoma of nasal cavity and paranasal sinuses: report of 24 patients and literature review. J Laryngol Otol. 2011;125:479–85.PubMedCrossRefPubMedCentralGoogle Scholar
  4. 4.
    Thompson LD, Wieneke JA, Miettinen M. Sinonasal tract and nasopharyngeal melanomas: a clinicopathologic study of 115 cases with a proposed staging system. Am J Surg Pathol. 2003;27:594–611.PubMedCrossRefPubMedCentralGoogle Scholar
  5. 5.
    Takeshita H, Miwa T, Furukawa M. Osteocartilaginous differentiation of mucosal melanoma in the sinonasal cavity. Ann Otol Rhinol Laryngol. 2002;111:1112–5.PubMedCrossRefPubMedCentralGoogle Scholar
  6. 6.
    Lee H, Torres FX, McLean SA, Chen R, Lee MW. Immunophenotypic heterogeneity of primary sinonasal melanoma with aberrant expression of neuroendocrine markers and calponin. Appl Immunohistochem Mol Morphol. 2011;19:48–53.PubMedCrossRefPubMedCentralGoogle Scholar
  7. 7.
    Safadi RA, Bader DH, Abdullah NY, Sughhayer MA. Immunohistochemical expression of keratins 6, 7, 8, 14, 16, 18, 19, and MNF-116 pancytokeratin in primary and metastatic melanoma of the head and neck. Oral Surg Oral Med Oral Pathol Oral Radiol. 2016;121:510–9.PubMedCrossRefPubMedCentralGoogle Scholar
  8. 8.
    Smith SM, Schmitt AC, Carrau RL, Iwenofu OH. Primary sinonasal mucosal melanoma with aberrant diffuse and strong desmin reactivity: a potential diagnostic pitfall! Head Neck Pathol. 2015;9:165–71.PubMedCrossRefPubMedCentralGoogle Scholar
  9. 9.
    Zebary A, Jangard M, Omholt K, Ragnarsson-Olding B, Hansson J. KIT, NRAS and BRAF mutations in sinonasal mucosal melanoma: a study of 56 cases. Br J Cancer. 2013;109:559–64.PubMedPubMedCentralCrossRefGoogle Scholar
  10. 10.
    Wroblewska JP, Mull J, Wu CL, et al. SF3B1, NRAS, KIT, and BRAF mutation; CD117 and cMYC expression; and tumoral pigmentation in Sinonasal melanomas: an analysis with newly found molecular alterations and some population-based molecular differences. Am J Surg Pathol. 2019;43:168–77.PubMedCrossRefGoogle Scholar
  11. 11.
    Cosgarea I, Ugurel S, Sucker A, et al. Targeted next generation sequencing of mucosal melanomas identifies frequent NF1 and RAS mutations. Oncotarget. 2017;8:40683–92.PubMedPubMedCentralCrossRefGoogle Scholar
  12. 12.
    Hintzsche JD, Gorden NT, Amato CM, et al. Whole-exome sequencing identifies recurrent SF3B1 R625 mutation and comutation of NF1 and KIT in mucosal melanoma. Melanoma Res. 2017;27:189–99.PubMedPubMedCentralCrossRefGoogle Scholar
  13. 13.
    Amit M, Tam S, Abdelmeguid AS, et al. Mutation status among patients with sinonasal mucosal melanoma and its impact on survival. Br J Cancer. 2017;116:1564–71.PubMedPubMedCentralCrossRefGoogle Scholar
  14. 14.
    Turri-Zanoni M, Medicina D, Lombardi D, et al. Sinonasal mucosal melanoma: molecular profile and therapeutic implications from a series of 32 cases. Head Neck. 2012;35(8):1066–77.PubMedCrossRefPubMedCentralGoogle Scholar
  15. 15.
    Franchi A, Alos L, Gale N, et al. Expression of p16 in sinonasal malignant melanoma. Virchows Arch. 2006;449:667–72.PubMedCrossRefPubMedCentralGoogle Scholar
  16. 16.
    Kardon DE, Thompson LD. Sinonasal mucosal malignant melanoma: report of an unusual case mimicking schwannoma. Ann Diagn Pathol. 2000;4:303–7.PubMedCrossRefPubMedCentralGoogle Scholar
  17. 17.
    Moreno MA, Roberts DB, Kupferman ME, et al. Mucosal melanoma of the nose and paranasal sinuses, a contemporary experience from the M. D. Anderson Cancer Center. Cancer. 2010;116:2215–23.PubMedPubMedCentralGoogle Scholar
  18. 18.
    Prasad ML. Update on pigmented lesions of the sinonasal tract. Head Neck Pathol. 2007;1:50–4.PubMedPubMedCentralCrossRefGoogle Scholar
  19. 19.
    Khan MN, Kanumuri VV, Raikundalia MD, et al. Sinonasal melanoma: survival and prognostic implications based on site of involvement. Int Forum Allergy Rhinol. 2014;4:151–5.PubMedCrossRefPubMedCentralGoogle Scholar
  20. 20.
    Trapp TK, Fu YS, Calcaterra TC. Melanoma of the nasal and paranasal sinus mucosa. Arch Otolaryngol Head Neck Surg. 1987;113:1086–9.PubMedCrossRefPubMedCentralGoogle Scholar
  21. 21.
    Theilgaard SA, Buchwald C, Ingeholm P, et al. Esthesioneuroblastoma: a Danish demographic study of 40 patients registered between 1978 and 2000. Acta Otolaryngol. 2003;123:433–9.PubMedCrossRefPubMedCentralGoogle Scholar
  22. 22.
    Turner JH, Reh DD. Incidence and survival in patients with sinonasal cancer: a historical analysis of population based data. Head Neck. 2012;34:877–85.PubMedCrossRefPubMedCentralGoogle Scholar
  23. 23.
    Jethanamest D, Morris LG, Sikora AG, Kutler DI. Esthesioneuroblastoma: a population-based analysis of survival and prognostic factors. Arch Otolaryngol Head Neck Surg. 2007;133:276–80.PubMedCrossRefPubMedCentralGoogle Scholar
  24. 24.
    Kunc M, Gabrych A, Czapiewski P, Sworczak K. Paraneoplastic syndromes in olfactory neuroblastoma. Contemp Oncol (Pozn). 2015;19:6–16.Google Scholar
  25. 25.
    Ng HK, Poon WS, Poon CY, South JR. Intracranial olfactory neuroblastoma mimicking carcinoma: report of two cases. Histopathology. 1988;12:393–403.PubMedCrossRefPubMedCentralGoogle Scholar
  26. 26.
    Banerjee AK, Sharma BS, Vashista RK, Kak VK. Intracranial olfactory neuroblastoma: evidence for olfactory epithelial origin. J Clin Pathol. 1992;45:299–302.PubMedPubMedCentralCrossRefGoogle Scholar
  27. 27.
    Curtis JL, Rubinstein LJ. Pigmented olfactory neuroblastoma: a new example of melanotic neuroepithelial neoplasm. Cancer. 1982;49:2136–43.PubMedCrossRefPubMedCentralGoogle Scholar
  28. 28.
    Bishop JA, Thompson LD, Cardesa A, et al. Rhabdomyoblastic differentiation in head and neck malignancies other than rhabdomyosarcoma. Head Neck Pathol. 2015;9:507–18.PubMedPubMedCentralCrossRefGoogle Scholar
  29. 29.
    Meyer C, Hamersley ERS, Manosalva RE, Torske K, McIntyre N, Mitchell A. Olfactory neuroblastoma with divergent differentiation: an unusual histologic finding in a rare tumor. Head Neck Pathol. 2017;11:531–6.PubMedPubMedCentralCrossRefGoogle Scholar
  30. 30.
    Hyams VJ, Batsakis JG, Michaels L. Tumors of the upper respiratory tract and ear. Armed forces Institute of Pathology Fascicles, 2nd series. Washington: American Registry of Pathology Press; 1988.Google Scholar
  31. 31.
    Tajudeen BA, Arshi A, Suh JD, St John M, Wang MB. Importance of tumor grade in esthesioneuroblastoma survival. A population-based analysis. JAMA Otolaryngol Head Neck Surg. 2014;140:1124–9.PubMedCrossRefPubMedCentralGoogle Scholar
  32. 32.
    Hirose T, Scheithauer BW, Lopes MB, Gerber HA, Altermatt HJ, Harner SG, VandenBerg SR. Olfactory neuroblastoma. An immunohistochemical, ultrastructural, and flow cytometric study. Cancer. 1995;76:4–19.PubMedCrossRefPubMedCentralGoogle Scholar
  33. 33.
    Frierson HF Jr, Ross GW, Mills SE, Frankfurter A. Olfactory neuroblastoma. Additional immunohistochemical characterization. Am J Clin Pathol. 1990;94:547–53.PubMedCrossRefPubMedCentralGoogle Scholar
  34. 34.
    Wooff JC, Weinreb I, Perez-Ordonez B, Magee JF, Bullock MJ. Calretinin staining facilitates differentiation of olfactory neuroblastoma from other small round blue cell tumors in the sinonasal tract. Am J Surg Pathol. 2011;35:1786–93.PubMedCrossRefPubMedCentralGoogle Scholar
  35. 35.
    Taggart MW, Hanna EY, Gidley P, Weber RS, Bell D. Achaete-scute homolog 1 expression closely correlates with endocrine phenotype and degree of differentiation in sinonasal neuroendocrine tumors. Ann Diagn Pathol. 2015;19:154–6.PubMedCrossRefPubMedCentralGoogle Scholar
  36. 36.
    Min KW. Usefulness of electron microscopy in the diagnosis of “small” round cell tumors of the sinonasal region. Ultrastruct Pathol. 1995;19:347–63.PubMedCrossRefGoogle Scholar
  37. 37.
    López-Hernández A, Vivanco B, Franchi A, et al. Genetic profiling of poorly differentiated sinonasal tumours. Sci Rep. 2018;8:3998.PubMedPubMedCentralCrossRefGoogle Scholar
  38. 38.
    Guled M, Myllykangas S, Frierson HF Jr, et al. Array comparative genomic hybridization analysis of olfactory neuroblastoma. Mod Pathol. 2008;21:770–8.PubMedCrossRefGoogle Scholar
  39. 39.
    Lazo de la Vega L, McHugh JB, Cani AK, et al. Comprehensive molecular profiling of olfactory neuroblastoma identifies potentially targetable FGFR3 amplifications. Mol Cancer Res. 2017;15:1551–7.PubMedCrossRefGoogle Scholar
  40. 40.
    Gay LM, Kim S, Fedorchak K, et al. Comprehensive genomic profiling of esthesioneuroblastoma reveals additional treatment options. Oncologist. 2017;22:834–42.PubMedPubMedCentralCrossRefGoogle Scholar
  41. 41.
    Papadaki H, Kounelis S, Kapadia SB, Bakker A, Swalsky PA, Finkelstein SD. Relationship of p53 gene alterations with tumor progression and recurrence in olfactory neuroblastoma. Am J Surg Pathol. 1996;20:715–21.PubMedCrossRefPubMedCentralGoogle Scholar
  42. 42.
    Weiss GJ, Liang WS, Izatt T, et al. Paired tumor and normal whole genome sequencing of metastatic olfactory neuroblastoma. PLoS One. 2012;7:e37029.PubMedPubMedCentralCrossRefGoogle Scholar
  43. 43.
    Cohen ZR, Marmor E, Fuller GN, DeMonte F. Misdiagnosis of olfactory neuroblastoma. Neurosurg Focus. 2002;12:e3.PubMedCrossRefPubMedCentralGoogle Scholar
  44. 44.
    Franchi A, Palomba A, Cardesa A. Current diagnostic strategies for undifferentiated tumours of the nasal cavities and paranasal sinuses. Histopathology. 2011;59:1034–45.PubMedCrossRefPubMedCentralGoogle Scholar
  45. 45.
    Thompson LD. Olfactory neuroblastoma. Head Neck Pathol. 2009;3:252–9.PubMedPubMedCentralCrossRefGoogle Scholar
  46. 46.
    Turri-Zanoni M, Maragliano R, Battaglia P, et al. The clinicopathological spectrum of olfactory neuroblastoma and sinonasal neuroendocrine neoplasms: refinements in diagnostic criteria and impact of multimodal treatments on survival. Oral Oncol. 2017;74:21.PubMedCrossRefPubMedCentralGoogle Scholar
  47. 47.
    Dulguerov P, Allal AS, Calcaterra TC. Esthesioneuroblastoma: a meta-analysis and review. Lancet Oncol. 2001;2:683–90.PubMedCrossRefPubMedCentralGoogle Scholar
  48. 48.
    Platek ME, Merzianu M, Mashtare TL, et al. Improved survival following surgery and radiation therapy for olfactory neuroblastoma: analysis of the SEER database. Radiat Oncol. 2011;6:41.PubMedPubMedCentralCrossRefGoogle Scholar
  49. 49.
    Yin ZZ, Gao L, Luo JW, et al. Long-term outcomes of patients with esthesioneuroblastomas: a cohort from a single institution. Oral Oncol. 2016;53:48–53.PubMedCrossRefPubMedCentralGoogle Scholar
  50. 50.
    Harvey RJ, Nalavenkata S, Sacks R, et al. Survival outcomes for stage-matched endoscopic and open resection of olfactory neuroblastoma. Head Neck. 2017;39:2425–32.PubMedCrossRefPubMedCentralGoogle Scholar
  51. 51.
    Su SY, Bell D, Ferrarotto R, et al. Outcomes for olfactory neuroblastoma treated with induction chemotherapy. Head Neck. 2017;39:1671–9.PubMedCrossRefPubMedCentralGoogle Scholar
  52. 52.
    Bell D, Saade R, Roberts D, Ow TJ, Kupferman M, Demonte F, et al. Prognostic utility of Hyams histological grading and Kadish-Morita staging systems for esthesioneuroblastoma outcomes. Head Neck Pathol. 2015;9:51–9.PubMedCrossRefPubMedCentralGoogle Scholar
  53. 53.
    Banuchi VE, Dooley L, Lee NY, et al. Patterns of regional and distant metastasis in esthesioneuroblastoma. Laryngoscope. 2016;126:1556–61.PubMedPubMedCentralCrossRefGoogle Scholar
  54. 54.
    Eden BV, Debo RF, Larner JM, et al. Esthesioneuroblastoma. Long term outcome and patterns of failure. The University of Virginia experience. Cancer. 1994;73:2556–62.PubMedCrossRefPubMedCentralGoogle Scholar
  55. 55.
    Kadish S, Goodman M, Wang CC. Olfactory neuroblastoma. A clinical analysis of 17 cases. Cancer. 1976;37:1571–6.PubMedCrossRefPubMedCentralGoogle Scholar
  56. 56.
    Morita A, Ebersold MJ, Olsen KD, Foote RL, Lewis JE, Quast LM. Esthesioneuroblastoma: prognosis and management. Neurosurgery. 1993;32:706-15.CrossRefGoogle Scholar
  57. 57.
    Cotterill SJ, Ahrens S, Paulussen M, Jurgens HF, Voute PA, Gadner H, Craft AW. Prognostic factors in Ewing’s tumor of bone: analysis of 975 patients from the European Intergroup Cooperative Ewing’s Sarcoma study group. J Clin Oncol. 2000;18:3108–14.PubMedCrossRefPubMedCentralGoogle Scholar
  58. 58.
    Allam A, El-Husseiny G, Khafaga Y, et al. Ewing’s sarcoma of the head and neck: a retrospective analysis of 24 cases. Sarcoma. 1999;3:11–5.PubMedPubMedCentralCrossRefGoogle Scholar
  59. 59.
    Hafezi S, Seethala RR, Stelow EB, et al. Ewing’s family of tumors of the sinonasal tract and maxillary bone. Head Neck Pathol. 2011;5:8–16.PubMedCrossRefPubMedCentralGoogle Scholar
  60. 60.
    Bishop JA, Alaggio R, Zhang L, Seethala RR, Antonescu CR. Adamantinoma-like Ewing family tumors of the head and neck: a pitfall in the differential diagnosis of basaloid and myoepithelial carcinomas. Am J Surg Pathol. 2015;39:1267–74.PubMedPubMedCentralCrossRefGoogle Scholar

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© Springer Nature Switzerland AG 2020

Authors and Affiliations

  1. 1.Department of Translational Research and of New Technologies in Medicine and SurgeryUniversity of PisaPisaItaly

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