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Proceedings of the 2023 North American Society of Head and Neck Pathology Companion Meeting, New Orleans, LA, March 12, 2023: Navigating New Developments in High Grade Sinonasal Neuroendocrine and Neuroectodermal Neoplasms

  • Proceeding of the North American Society of Head and Neck Pathology Companion Meeting, March 12, 2023, New Orleans, LA
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Abstract

Although the definitions of sinonasal neuroendocrine and neuroectodermal neoplasms did not change substantially in the 5th edition WHO Classification of Head and Neck Tumours, the diagnosis of olfactory neuroblastoma (ONB), small cell neuroendocrine carcinoma, and large cell neuroendocrine carcinoma remains quite challenging in practice. Ambiguities surrounding the amount of keratin expression allowable in ONB and the amount of neuroendocrine differentiation seen in sinonasal undifferentiated carcinoma (SNUC) lead to significant diagnostic discrepancies at the high grade end of this tumor spectrum. Furthermore, a group of problematic neuroepithelial tumors that show overlapping features of ONB and neuroendocrine carcinoma have never been recognized in formal classification schemes. Since publication of the 5th edition WHO, two new tumor entities have been proposed that help resolve these problems. Olfactory carcinoma is defined by high grade keratin-positive neuroectodermal cells with frequent intermixed glands and shows recurrent Wnt pathway, ARID1A, and RUNX1 alterations. IDH2-mutant sinonasal carcinoma is a molecularly-defined category that encompasses tumors with undifferentiated (SNUC), large cell neuroendocrine, and neuroepithelial phenotypes. This review will provide a practical overview of these emerging entities and their application to diagnostic challenges in the post-WHO sinonasal neuroendocrine and neuroectodermal tumor classification.

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References

  1. Thompson LDR, Bishop JA (2022) Update from the 5th edition of the world health organization classification of head and neck tumors: nasal cavity, paranasal sinuses and skull Base. Head Neck Pathol 16:1–18

    Article  PubMed  PubMed Central  Google Scholar 

  2. Bell D, Classe M, Perez-Ordonez B et al (2022) Olfactory neuroblastoma. In: WHO Classification of Tumours Editorial Board, ed. WHO Classification of Head and Neck Tumours. Lyon, France: International Agency for Research on Cancer

  3. Mete O, Wenig BM (2022) Update from the 5th edition of the world health organization classification of head and neck tumors: overview of the 2022 WHO classification of head and neck neuroendocrine neoplasms. Head Neck Pathol 16:123–142

    Article  PubMed  PubMed Central  Google Scholar 

  4. Rooper LM, Classe M, Nose V et al (2022) Small cell neuroendocrine carcinoma. In: WHO Classification of Tumours Editorial Board, ed. WHO Classification of Head and Neck Tumours. Lyon, France: International Agency for Research on Cancer

  5. Rooper LM, Classe M, Nose V et al (2022) Large cell neuroendocrine carcinoma. In: WHO Classification of Tumours Editorial Board, ed. WHO Classification of Head and Neck Tumours. Lyon, France: International Agency for Research on Cancer

  6. Choi KY, Amit M, Tam S et al (2021) Clinical implication of diagnostic and histopathologic discrepancies in sinonasal malignancies. Laryngoscope 131:E1468–E1475

    Article  CAS  PubMed  Google Scholar 

  7. Turri-Zanoni M, Maragliano R, Battaglia P et al (2017) The clinicopathological spectrum of olfactory neuroblastoma and sinonasal neuroendocrine neoplasms: refinements in diagnostic criteria and impact of multimodal treatments on survival. Oral Oncol 74:21–29

    Article  PubMed  Google Scholar 

  8. Zunitch MJ, Fisch AS, Lin B et al (2023) Molecular evidence for olfactory neuroblastoma as a tumor of malignant globose basal cells. Mod Pathol 35(6):100122

    Article  Google Scholar 

  9. Holbrook EH, Wu E, Curry WT et al (2011) Immunohistochemical characterization of human olfactory tissue. Laryngoscope 121:1687–1701

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Rooper LM, Bishop JA, Westra WH (2018) INSM1 is a sensitive and specific marker of neuroendocrine differentiation in head and neck tumors. Am J Surg Pathol 42:665–671

    Article  PubMed  Google Scholar 

  11. Wooff JC, Weinreb I, Perez-Ordonez B et al (2011) Calretinin staining facilitates differentiation of olfactory neuroblastoma from other small round blue cell tumors in the sinonasal tract. Am J Surg Pathol 35:1786–1793

    Article  PubMed  Google Scholar 

  12. Gay LM, Kim S, Fedorchak K et al (2017) Comprehensive genomic profiling of Esthesioneuroblastoma reveals additional treatment options. Oncologist 22:834–842

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Kaur RP, Izumchenko E, Blakaj DM et al (2021) The genomics and epigenetics of olfactory neuroblastoma: a systematic review. Laryngoscope Investig Otolaryngol 6:721–728

    Article  PubMed  PubMed Central  Google Scholar 

  14. de la Lazo L, McHugh JB, Cani AK et al (2017) Comprehensive molecular profiling of olfactory neuroblastoma identifies potentially targetable FGFR3 amplifications. Mol Cancer Res 15:1551–1557

    Article  Google Scholar 

  15. Topcagic J, Feldman R, Ghazalpour A et al (2018) Comprehensive molecular profiling of advanced/metastatic olfactory neuroblastomas. PLoS ONE 13:e0191244

    Article  PubMed  PubMed Central  Google Scholar 

  16. Gallia GL, Zhang M, Ning Y et al (2018) Genomic analysis identifies frequent deletions of dystrophin in olfactory neuroblastoma. Nat Commun 9:5410

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Bell D, Saade R, Roberts D et al (2015) Prognostic utility of hyams histological grading and kadish-morita staging systems for esthesioneuroblastoma outcomes. Head Neck Pathol 9:51–59

    Article  PubMed  Google Scholar 

  18. Morita A, Ebersold MJ, Olsen KD et al (1993) Esthesioneuroblastoma: prognosis and management. Neurosurgery 32:706–714 (discussion 714–705)

    Article  CAS  PubMed  Google Scholar 

  19. Kaur G, Kane AJ, Sughrue ME et al (2013) The prognostic implications of hyam’s subtype for patients with kadish stage C esthesioneuroblastoma. J Clin Neurosci 20:281–286

    Article  PubMed  Google Scholar 

  20. Malouf GG, Casiraghi O, Deutsch E et al (2013) Low- and high-grade esthesioneuroblastomas display a distinct natural history and outcome. Eur J Cancer 49:1324–1334

    Article  PubMed  Google Scholar 

  21. Van Gompel JJ, Giannini C, Olsen KD et al (2012) Long-term outcome of esthesioneuroblastoma: hyams grade predicts patient survival. J Neurol Surg B Skull Base 73:331–336

    Article  PubMed  PubMed Central  Google Scholar 

  22. Kadish S, Goodman M, Wang CC (1976) Olfactory neuroblastoma: a clinical analysis of 17 cases. Cancer 37:1571–1576

    Article  CAS  PubMed  Google Scholar 

  23. Bell D (2018) Sinonasal neuroendocrine neoplasms: current challenges and advances in diagnosis and treatment, with a focus on olfactory neuroblastoma. Head Neck Pathol 12:22–30

    Article  PubMed  PubMed Central  Google Scholar 

  24. Bell D, Hanna EY, Weber RS et al (2016) Neuroendocrine neoplasms of the sinonasal region. Head Neck 38(Suppl 1):E2259–2266

    Article  PubMed  Google Scholar 

  25. Mitchell EH, Diaz A, Yilmaz T et al (2012) Multimodality treatment for sinonasal neuroendocrine carcinoma. Head Neck 34:1372–1376

    Article  PubMed  Google Scholar 

  26. Perez-Ordonez B, Caruana SM, Huvos AG et al (1998) Small cell neuroendocrine carcinoma of the nasal cavity and paranasal sinuses. Hum Pathol 29:826–832

    Article  CAS  PubMed  Google Scholar 

  27. Dogan S, Vasudevaraja V, Xu B et al (2019) DNA methylation-based classification of sinonasal undifferentiated carcinoma. Mod Pathol 32:1447–1459

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Bishop JA, Guo TW, Smith DF et al (2013) Human papillomavirus-related carcinomas of the sinonasal tract. Am J Surg Pathol 37:185–192

    Article  PubMed  PubMed Central  Google Scholar 

  29. Kuan EC, Alonso JE, Tajudeen BA et al (2017) Small cell carcinoma of the head and neck: a comparative study by primary site based on population data. Laryngoscope 127:1785–1790

    Article  PubMed  Google Scholar 

  30. Rivero A, Liang J (2016) Sinonasal small cell neuroendocrine carcinoma: a systematic review of 80 patients. Int Forum Allergy Rhinol 6:744–751

    Article  PubMed  Google Scholar 

  31. van der Laan TP, Bij HP, van Hemel BM et al (2013) The importance of multimodality therapy in the treatment of sinonasal neuroendocrine carcinoma. Eur Arch Otorhinolaryngol 270:2565–2568

    Article  PubMed  Google Scholar 

  32. van der Laan TP, Iepsma R, Witjes MJ et al (2016) Meta-analysis of 701 published cases of sinonasal neuroendocrine carcinoma: the importance of differentiation grade in determining treatment strategy. Oral Oncol 63:1–9

    Article  PubMed  Google Scholar 

  33. Thompson ED, Stelow EB, Mills SE et al (2016) Large cell neuroendocrine carcinoma of the Head and Neck: a clinicopathologic series of 10 cases with an emphasis on HPV Status. Am J Surg Pathol 40:471–478

    Article  PubMed  PubMed Central  Google Scholar 

  34. Argani P, Perez-Ordonez B, Xiao H et al (1998) Olfactory neuroblastoma is not related to the ewing family of tumors: absence of EWS/FLI1 gene fusion and MIC2 expression. Am J Surg Pathol 22:391–398

    Article  CAS  PubMed  Google Scholar 

  35. Axe S, Kuhajda FP (1987) Esthesioneuroblastoma: intermediate filaments, neuroendocrine, and tissue-specific antigens. Am J Clin Pathol 88:139–145

    Article  CAS  PubMed  Google Scholar 

  36. Frierson HF Jr, Ross GW, Mills SE et al (1990) Olfactory neuroblastoma: additional immunohistochemical characterization. Am J Clin Pathol 94:547–553

    Article  PubMed  Google Scholar 

  37. Fukushima S, Sugita Y, Niino D et al (2012) Clincopathological analysis of olfactory neuroblastoma. Brain Tumor Pathol 29:207–215

    Article  CAS  PubMed  Google Scholar 

  38. Hirose T, Scheithauer BW, Lopes MB et al (1995) Olfactory neuroblastoma. An immunohistochemical, ultrastructural, and flow cytometric study. Cancer 76:4–19

    Article  CAS  PubMed  Google Scholar 

  39. Taxy JB, Bharani NK, Mills SE et al (1986) The spectrum of olfactory neural tumors: a light-microscopic immunohistochemical and ultrastructural analysis. Am J Surg Pathol 10:687–695

    Article  CAS  PubMed  Google Scholar 

  40. Wick MR, Stanley SJ, Swanson PE (1988) Immunohistochemical diagnosis of sinonasal melanoma, carcinoma, and neuroblastoma with monoclonal antibodies HMB-45 and anti-synaptophysin. Arch Pathol Lab Med 112:616–620

    CAS  PubMed  Google Scholar 

  41. Capper D, Engel NW, Stichel D et al (2018) DNA methylation-based reclassification of olfactory neuroblastoma. Acta Neuropathol 136:255–271

    Article  CAS  Google Scholar 

  42. Classe M, Yao H, Mouawad R et al (2018) Integrated multi-omic analysis of esthesioneuroblastomas identifies two subgroups linked to cell ontogeny. Cell Rep 25:811–821

    Article  CAS  PubMed  Google Scholar 

  43. Gloss S, Jurmeister P, Thieme A et al (2021) IDH2 R172 mutations across poorly differentiated Sinonasal tract malignancies: forty molecularly homogenous and histologically variable cases with favorable outcome. Am J Surg Pathol 45:1190–1204

    Article  PubMed  PubMed Central  Google Scholar 

  44. Faragalla H, Weinreb I (2009) Olfactory neuroblastoma: a review and update. Adv Anat Pathol 16:322–331

    Article  CAS  PubMed  Google Scholar 

  45. Shah K, Perez-Ordonez B (2016) Neuroendocrine neoplasms of the sinonasal Tract: neuroendocrine carcinomas and olfactory neuroblastoma. Head Neck Pathol 10:85–94

    Article  PubMed  PubMed Central  Google Scholar 

  46. Jo VY, Agaimy A, Franchi A et al (2022) Sinonasal undifferentiated carcinoma. In: WHO Classification of Tumours Editorial Board, ed. WHO Classification of Head and Neck Tumours. Lyon, France: International Agency for Research on Cancer

  47. Frierson HF Jr, Mills SE, Fechner RE et al (1986) Sinonasal undifferentiated carcinoma. an aggressive neoplasm derived from schneiderian epithelium and distinct from olfactory neuroblastoma. Am J Surg Pathol 10:771–779

    Article  PubMed  Google Scholar 

  48. Mills SE (2002) Neuroectodermal neoplasms of the head and neck with emphasis on neuroendocrine carcinomas. Mod Pathol 15:264–278

    Article  PubMed  Google Scholar 

  49. Charles NC, Petris CK, Kim ET (2016) Aggressive esthesioneuroblastoma with divergent differentiation: a taxonomic dilemma. Orbit 35:357–359

    Article  PubMed  Google Scholar 

  50. Meyer C, Hamersley ERS, Manosalva RE et al (2017) Olfactory neuroblastoma with divergent differentiation: an unusual histologic finding in a rare tumor. Head Neck Pathol 11:531–536

    Article  PubMed  PubMed Central  Google Scholar 

  51. Miura K, Mineta H, Yokota N et al (2001) Olfactory neuroblastoma with epithelial and endocrine differentiation transformed into ganglioneuroma after chemoradiotherapy. Pathol Int 51:942–947

    Article  CAS  PubMed  Google Scholar 

  52. Attwood JE, Jeyaretna DS, Sheerin F et al (2020) Mixed olfactory neuroblastoma and adenocarcinoma with in situ neuroendocrine hyperplasia. Head Neck Pathol 14:792–798

    Article  PubMed  Google Scholar 

  53. Gandhoke CS, Dewan A, Gupta D et al (2017) A rare case report of mixed olfactory neuroblastoma: carcinoma with review of literature. Surg Neurol Int 8:83

    Article  PubMed  PubMed Central  Google Scholar 

  54. Miller DC, Goodman ML, Pilch BZ et al (1984) Mixed olfactory neuroblastoma and carcinoma. A report of two cases. Cancer 54:2019–2028

    Article  CAS  PubMed  Google Scholar 

  55. Seethala RR, Wenig BM, Barnes EL et al (2007) Olfactory neuroblastoma with divergent differentiation: from ganglioneuroblastoma to carcinoma. Mod Pathol 20:229A

    Google Scholar 

  56. Stelow EB, Mills SE, Jo VY et al (2010) Adenocarcinoma of the upper aerodigestive tract. Adv Anat Pathol 17:262–269

    Article  PubMed  Google Scholar 

  57. Hassoun J, Gambarelli D, Grisoli F et al (1981) Esthesioneuroepithelioma, a true neurosensorial tumor. Light- and electron-microscopic study of a case with endocranial extension. Acta Neuropathol 55:77–80

    Article  CAS  PubMed  Google Scholar 

  58. Sugita Y, Kusano K, Tokunaga O et al (2006) Olfactory neuroepithelioma: an immunohistochemical and ultrastructural study. Neuropathology 26:400–408

    Article  PubMed  Google Scholar 

  59. Takahashi H, Ohara S, Yamada M et al (1987) Esthesioneuroepithelioma: a tumor of true olfactory epithelium origin. An ultrastructural and immunohistochemical study. Acta Neuropathol 75:147–155

    Article  CAS  PubMed  Google Scholar 

  60. Utsuki S, Kawano N, Oka H et al (2000) Olfactory neuroepithelioma arising from the olfactory placode. Clin Neuropathol 19:7–12

    CAS  PubMed  Google Scholar 

  61. Wenig BM (2015) Olfactory carcinoma. Atlas of head and neck pathology. Elsevier, Cambridge, pp 155–156

    Google Scholar 

  62. Rooper LM, Bishop JA, Faquin WC et al (2022) Sinonasal tumors with neuroepithelial differentiation (olfactory carcinoma): delineation of their pathologic and clinical features with insights into their relationship to olfactory neuroblastoma and sinonasal carcinoma. Am J Surg Pathol 46:1025–1035

    Article  PubMed  Google Scholar 

  63. Rooper LM, Gagan J, Nishino M et al (2022) USCAP 2022 abstracts: head and neck pathology (800–850). Mod Pathol 35:960–1015

    Article  Google Scholar 

  64. Rooper LM, Agaimy A, Gagan J et al (2022) Comprehensive molecular profiling of sinonasal teratocarcinosarcoma highlights recurrent SMARCA4 inactivation and CTNNB1 mutations. Am J Surg Pathol 47:224–233. https://doi.org/10.1097/PAS.0000000000001976

    Article  PubMed  Google Scholar 

  65. Rooper LM, Uddin N, Gagan J et al (2020) Recurrent loss of SMARCA4 in sinonasal teratocarcinosarcoma. Am J Surg Pathol 44:1331–1339

    Article  PubMed  Google Scholar 

  66. Jurmeister P, Gloss S, Roller R et al (2022) DNA methylation-based classification of sinonasal tumors. Nat Commun 13:7148

    Article  PubMed  PubMed Central  Google Scholar 

  67. Dogan S, Chute DJ, Xu B et al (2017) Frequent IDH2 R172 mutations in undifferentiated and poorly-differentiated sinonasal carcinomas. J Pathol 242:400–408

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Jo VY, Chau NG, Hornick JL et al (2017) Recurrent IDH2 R172X mutations in sinonasal undifferentiated carcinoma. Mod Pathol 30:650–659

    Article  CAS  PubMed  Google Scholar 

  69. Dogan S, Frosina D, Geronimo JA et al (2020) Molecular epidemiology of IDH2 hotspot mutations in cancer and immunohistochemical detection of R172K, R172G, and R172M variants. Hum Pathol 106:45–53

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Mito JK, Bishop JA, Sadow PM et al (2018) Immunohistochemical detection and molecular characterization of IDH-mutant sinonasal undifferentiated carcinomas. Am J Surg Pathol 42:1067–1075

    Article  PubMed  Google Scholar 

  71. Stevens TM, Rooper LM, Bacchi CE et al (2022) Teratocarcinosarcoma-like and adamantinoma-like head and neck neoplasms harboring NAB2::STAT6: unusual variants of solitary fibrous tumor or novel tumor entities? Head Neck Pathol 16(3):746–754

    Article  PubMed  PubMed Central  Google Scholar 

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  1. Department of Pathology, The Johns Hopkins University School of Medicine, 401 N. Broadway, Weinberg 2242, Baltimore, MD, 21231, USA

    Lisa M. Rooper

  2. Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Lisa M. Rooper

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LMR performed literature review and prepared the manuscript. All authors read and approved the final paper.

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Correspondence to Lisa M. Rooper.

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Rooper, L.M. Proceedings of the 2023 North American Society of Head and Neck Pathology Companion Meeting, New Orleans, LA, March 12, 2023: Navigating New Developments in High Grade Sinonasal Neuroendocrine and Neuroectodermal Neoplasms. Head and Neck Pathol 17, 299–312 (2023). https://doi.org/10.1007/s12105-023-01548-8

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