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Update from the 5th Edition of the World Health Organization Classification of Head and Neck Tumors: The Neck and Lymph Nodes, Metastasis, and Melanocytic Tumors

  • Update from the 5th Edition of the World Health Organization Classification of Head and Neck Tumors
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Abstract

The changes made in the fifth edition of the WHO Classification of Head and Neck Tumors demonstrate the recent diagnostic, histopathological, and molecular advances in the field, and this updated information will hopefully lead to improved and standardized tumor subtyping. This review summarizes the changes related tumors and tumor-like lesions of the neck and lymph nodes (Chapter 11), metastasis to the head and neck region (Chapter 15), and melanocytic tumors (Chapter 10).

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References

  1. Robbins KT, Clayman G, Levine PA, Medina J, Sessions R, Shaha A, et al. Neck dissection classification update: revisions proposed by the American Head and Neck Society and the American Academy of Otolaryngology-Head and Neck Surgery. Arch Otolaryngol Head Neck Surg. 2002;128(7):751–8.

    Article  PubMed  Google Scholar 

  2. de Visscher JG, van der Wal KG, de Vogel P. The plunging ranula. Pathogenesis, diagnosis and management. J Craniomaxillofac Surg. 1989;17(4):182–5.

    Article  PubMed  Google Scholar 

  3. Jain P. Plunging ranulas and prevalence of the “tail sign” in 126 consecutive cases. J Ultrasound Med. 2020;39(2):273–8.

    Article  PubMed  Google Scholar 

  4. Zhao YF, Jia Y, Chen XM, Zhang WF. Clinical review of 580 ranulas. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2004;98(3):281–7.

    Article  PubMed  Google Scholar 

  5. Acierno SP, Waldhausen JH. Congenital cervical cysts, sinuses and fistulae. Otolaryngol Clin N Am. 2007;40(1):161–76, vii–viii.

  6. Goldenberg D, Begum S, Westra WH, Khan Z, Sciubba J, Pai SI, et al. Cystic lymph node metastasis in patients with head and neck cancer: An HPV-associated phenomenon. Head Neck. 2008;30(7):898–903.

    Article  PubMed  Google Scholar 

  7. Pai RK, Erickson J, Pourmand N, Kong CS. p16(INK4A) immunohistochemical staining may be helpful in distinguishing branchial cleft cysts from cystic squamous cell carcinomas originating in the oropharynx. Cancer. 2009;117(2):108–19.

    CAS  PubMed  Google Scholar 

  8. Cao D, Begum S, Ali SZ, Westra WH. Expression of p16 in benign and malignant cystic squamous lesions of the neck. Hum Pathol. 2010;41(4):535–9.

    Article  CAS  PubMed  Google Scholar 

  9. Bishop JA, Westra WH. Ciliated HPV-related carcinoma: a well-differentiated form of head and neck carcinoma that can be mistaken for a benign cyst. Am J Surg Pathol. 2015;39(11):1591–5.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Sivars L, Landin D, Rizzo M, Haeggblom L, Bersani C, Munck-Wikland E, et al. Human papillomavirus (HPV) is absent in branchial cleft cysts of the neck distinguishing them from HPV positive cystic metastasis. Acta Otolaryngol. 2018;138(9):855–8.

    Article  CAS  PubMed  Google Scholar 

  11. Lewis JS Jr, Beadle B, Bishop JA, Chernock RD, Colasacco C, Lacchetti C, et al. Human papillomavirus testing in head and neck carcinomas: guideline from the College of American Pathologists. Arch Pathol Lab Med. 2018;142(5):559–97.

    Article  PubMed  Google Scholar 

  12. Bradley PT, Bradley PJ. Branchial cleft cyst carcinoma: fact or fiction? Curr Opin Otolaryngol Head Neck Surg. 2013;21(2):118–23.

    Article  PubMed  Google Scholar 

  13. Chadburn A, Abdul-Nabi AM, Teruya BS, Lo AA. Lymphoid proliferations associated with human immunodeficiency virus infection. Arch Pathol Lab Med. 2013;137(3):360–70.

    Article  CAS  PubMed  Google Scholar 

  14. Chadburn A, Metroka C, Mouradian J. Progressive lymph node histology and its prognostic value in patients with acquired immunodeficiency syndrome and AIDS-related complex. Hum Pathol. 1989;20(6):579–87.

    Article  CAS  PubMed  Google Scholar 

  15. Ioachim HL, Ryan JR, Blaugrund SM. Salivary gland lymph nodes. The site of lymphadenopathies and lymphomas associated with human immunodeficiency virus infection. Arch Pathol Lab Med. 1988;112(12):1224–8.

    CAS  PubMed  Google Scholar 

  16. Labouyrie E, Merlio JP, Beylot-Barry M, Delord B, Vergier B, Brossard G, et al. Human immunodeficiency virus type 1 replication within cystic lymphoepithelial lesion of the salivary gland. Am J Clin Pathol. 1993;100(1):41–6.

    Article  CAS  PubMed  Google Scholar 

  17. Ryan JR, Ioachim HL, Marmer J, Loubeau JM. Acquired immune deficiency syndrome--related lymphadenopathies presenting in the salivary gland lymph nodes. Arch Otolaryngol (Chicago, IL: 1960). 1985;111(8):554–6.

  18. Hernandez-Prera JC. Sialadenitis of the major salivary glands: a tumor-like lesion of various etiologies and morphological appearances. AJSP Rev Rep. 2020;25:255–64.

    Google Scholar 

  19. Allard RH. The thyroglossal cyst. Head Neck Surg. 1982;5(2):134–46.

    Article  CAS  PubMed  Google Scholar 

  20. Thompson LD, Herrera HB, Lau SK. A clinicopathologic series of 685 thyroglossal duct remnant cysts. Head Neck Pathol. 2016;10(4):465–74.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Rohof D, Honings J, Theunisse HJ, Schutte HW, van den Hoogen FJ, van den Broek GB, et al. Recurrences after thyroglossal duct cyst surgery: results in 207 consecutive cases and review of the literature. Head Neck. 2015;37(12):1699–704.

    Article  PubMed  Google Scholar 

  22. Pryor SG, Lewis JE, Weaver AL, Orvidas LJ. Pediatric dermoid cysts of the head and neck. Otolaryngol Head Neck Surg. 2005;132(6):938–42.

    Article  PubMed  Google Scholar 

  23. Orozco-Covarrubias L, Lara-Carpio R, Saez-De-Ocariz M, Duran-McKinster C, Palacios-Lopez C, Ruiz-Maldonado R. Dermoid cysts: a report of 75 pediatric patients. Pediatr Dermatol. 2013;30(6):706–11.

    Article  PubMed  Google Scholar 

  24. Hanikeri M, Waterhouse N, Kirkpatrick N, Peterson D, Macleod I. The management of midline transcranial nasal dermoid sinus cysts. Br J Plast Surg. 2005;58(8):1043–50.

    Article  CAS  PubMed  Google Scholar 

  25. Palaskar SJ, Garde J, Bartake A, Narang B. Teratoid cyst of the oral cavity: a rare entity. J Oral Maxillofac Pathol. 2014;18(3):469–71.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Smith PS, McClure J. Unusual subcutaneous mixed tumour exhibiting adipose, fibroblastic, and epithelial components. J Clin Pathol. 1982;35(10):1074–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Rosai J, Limas C, Husband EM. Ectopic hamartomatous thymoma. A distinctive benign lesion of lower neck. Am J Surg Pathol. 1984;8(7):501–13.

    Article  CAS  PubMed  Google Scholar 

  28. Fetsch JF, Laskin WB, Michal M, Remotti F, Heffner D, Ellis G, et al. Ectopic hamartomatous thymoma: a clinicopathologic and immunohistochemical analysis of 21 cases with data supporting reclassification as a branchial anlage mixed tumor. Am J Surg Pathol. 2004;28(10):1360–70.

    Article  PubMed  Google Scholar 

  29. Weissferdt A, Kalhor N, Petersson F, Moran CA. Ectopic hamartomatous thymoma—new insights into a challenging entity: a clinicopathologic and immunohistochemical study of 9 cases. Am J Surg Pathol. 2016;40(11):1571–6.

    Article  PubMed  Google Scholar 

  30. Sato K, Thompson LDR, Miyai K, Kono T, Tsuda H. Ectopic hamartomatous thymoma: a review of the literature with report of new cases and proposal of a new name: biphenotypic branchioma. Head Neck Pathol. 2018;12(2):202–9.

    Article  PubMed  Google Scholar 

  31. Kazakov DV, Mukensnabl P, Hes O, Michal M. ‘Ectopic’ ectopic hamartomatous thymoma. Histopathology. 2004;45(2):202–4.

    Article  CAS  PubMed  Google Scholar 

  32. Liang PI, Li CF, Sato Y, Lee VK, Bahrami A, Chuang SS. Ectopic hamartomatous thymoma is distinct from lipomatous pleomorphic adenoma in lacking PLAG1 aberration. Histopathology. 2013;62(3):518–22.

    Article  PubMed  Google Scholar 

  33. Saeed IT, Fletcher CD. Ectopic hamartomatous thymoma containing myoid cells. Histopathology. 1990;17(6):572–4.

    Article  CAS  PubMed  Google Scholar 

  34. Thompson LDR, Gagan J, Washington A, Miller RT, Bishop JA. Biphenotypic branchioma: a better name than ectopic hamartomatous thymoma for a neoplasm with HRAS mutation. Head Neck Pathol. 2020;14(4):884–8.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Hui M, Uppin SG, Paul TR, Jena S, Patil RS, Ranganath R. Need for re-classifying the rare condition of ectopic hamartomatous thymoma based on tumor analysis. Arch Otorhinolaryngol Head Neck Surg (AOHNS). 2020;4(3):1.

    Google Scholar 

  36. Weinreb I, O’Malley F, Ghazarian D. Ectopic hamartomatous thymoma: a case demonstrating skin adnexal differentiation with positivity for epithelial membrane antigen, androgen receptors, and BRST-2 by immunohistochemistry. Hum Pathol. 2007;38(7):1092–5.

    Article  CAS  PubMed  Google Scholar 

  37. Michal M, Neubauer L. Carcinoma arising in ectopic hamartomatous thymoma. A previously unpublished occurrence. Report of two cases. Zentralbl Pathol. 1993;139(4–5):381–6.

    CAS  PubMed  Google Scholar 

  38. Thompson LDR, Herrera HB, Lau SK. Thyroglossal duct cyst carcinomas: a clinicopathologic series of 22 cases with staging recommendations. Head Neck Pathol. 2017;11(2):175–85.

    Article  PubMed  Google Scholar 

  39. Pradhan R, Agarwal A, Lombardi CP, Raffaelli M. Applied embryology of the thyroid and parathyroid glands. In Surgery of the Thyroid and Parathyroid Glands. Elsevier; 2021. p. 15–25.e4.

  40. Rayess HM, Monk I, Svider PF, Gupta A, Raza SN, Lin HS. Thyroglossal duct cyst carcinoma: a systematic review of clinical features and outcomes. Otolaryngol Head Neck Surg. 2017;156(5):794–802.

    Article  PubMed  Google Scholar 

  41. Rossi ED, Martini M, Straccia P, Cocomazzi A, Pennacchia I, Revelli L, et al. Thyroglossal duct cyst cancer most likely arises from a thyroid gland remnant. Virchows Arch. 2014;465(1):67–72.

    Article  PubMed  Google Scholar 

  42. Stein T, Murugan P, Li F, El Hag MI. Can medullary thyroid carcinoma arise in thyroglossal duct cysts? A search for parafollicular C-cells in 41 resected cases. Head Neck Pathol. 2018;12(1):71–4.

    Article  PubMed  Google Scholar 

  43. Som P, Miletich I. The embryology of the salivary glands: an update. Neurographics. 2015;5(4):167–77.

    Article  Google Scholar 

  44. Kurian EM, Miller R, McLean-Holden AL, Oliai BR, Bishop JA. Low molecular weight cytokeratin immunostaining for extrafollicular reticulum cells is an effective means of separating salivary gland tumor-associated lymphoid proliferation from true lymph node involvement. Head Neck Pathol. 2020;14(3):593–7.

    Article  PubMed  Google Scholar 

  45. Ferlito A, Bertino G, Rinaldo A, Mannarà GM, Devaney KO. A review of heterotopia and associated salivary gland neoplasms of the head and neck. J Laryngol Otol. 1999;113(4):299–303.

    Article  CAS  PubMed  Google Scholar 

  46. Daniel E, McGuirt WF Sr. Neck masses secondary to heterotopic salivary gland tissue: a 25-year experience. Am J Otolaryngol. 2005;26(2):96–100.

    Article  PubMed  Google Scholar 

  47. Rooper LM, Thompson LDR, Gagan J, Oliai BR, Weinreb I, Bishop JA. Salivary intraductal carcinoma arising within intraparotid lymph node: a report of 4 cases with identification of a novel STRN-ALK fusion. Head Neck Pathol. 2021;15(1):179–85.

    Article  PubMed  Google Scholar 

  48. Civantos FJ, Vermorken JB, Shah JP, Rinaldo A, Suárez C, Kowalski LP, et al. Metastatic squamous cell carcinoma to the cervical lymph nodes from an unknown primary cancer: management in the HPV era. Front Oncol. 2020;10:593164.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Grau C, Johansen LV, Jakobsen J, Geertsen P, Andersen E, Jensen BB. Cervical lymph node metastases from unknown primary tumours. Results from a national survey by the Danish Society for Head and Neck Oncology. Radiother Oncol. 2000;55(2):121–9.

    Article  CAS  PubMed  Google Scholar 

  50. Miller FR, Karnad AB, Eng T, Hussey DH, Stan McGuff H, Otto RA. Management of the unknown primary carcinoma: long-term follow-up on a negative PET scan and negative panendoscopy. Head Neck. 2008;30(1):28–34.

    Article  PubMed  Google Scholar 

  51. Fakhry C, Lacchetti C, Rooper LM, Jordan RC, Rischin D, Sturgis EM, et al. Human papillomavirus testing in head and neck carcinomas: ASCO Clinical Practice Guideline Endorsement of the College of American Pathologists Guideline. J Clin Oncol. 2018;36(31):3152–61.

    Article  PubMed  Google Scholar 

  52. Nakao K, Yuge T, Mochiki M, Nibu K, Sugasawa M. Detection of Epstein-Barr virus in metastatic lymph nodes of patients with nasopharyngeal carcinoma and a primary unknown carcinoma. Arch Otolaryngol Head Neck Surg. 2003;129(3):338–40.

    Article  PubMed  Google Scholar 

  53. Singhi AD, Stelow EB, Mills SE, Westra WH. Lymphoepithelial-like carcinoma of the oropharynx: a morphologic variant of HPV-related head and neck carcinoma. Am J Surg Pathol. 2010;34(6):800–5.

    Article  PubMed  Google Scholar 

  54. Fujimoto M, Matsuzaki I, Takahashi Y, Iwahashi Y, Warigaya K, Kojima F, et al. High-risk human papillomavirus E6/E7 mRNA is rarely detected in nonanogenital cutaneous squamous cell carcinoma: an RNA in situ hybridization-based tissue microarray study. Am J Dermatopathol. 2019;41(3):205–10.

    Article  PubMed  Google Scholar 

  55. Brash DE. UV signature mutations. Photochem Photobiol. 2015;91(1):15–26.

    Article  CAS  PubMed  Google Scholar 

  56. Mueller SA, Gauthier MA, Ashford B, Gupta R, Gayevskiy V, Ch’ng S, et al. Mutational patterns in metastatic cutaneous squamous cell carcinoma. J Invest Dermatol. 2019;139(7):1449–58.e1.

  57. Donizy P, Wróblewska JP, Dias-Santagata D, Woznica K, Biecek P, Mochel MC, et al. Merkel cell carcinoma of unknown primary: immunohistochemical and molecular analyses reveal distinct UV-signature/MCPyV-negative and high immunogenicity/MCPyV-positive profiles. Cancers (Basel). 2021;13(7):1621.

    Article  CAS  Google Scholar 

  58. Rindi G, Klimstra DS, Abedi-Ardekani B, Asa SL, Bosman FT, Brambilla E, et al. A common classification framework for neuroendocrine neoplasms: an International Agency for Research on Cancer (IARC) and World Health Organization (WHO) expert consensus proposal. Mod Pathol. 2018;31(12):1770–86.

    Article  PubMed  PubMed Central  Google Scholar 

  59. Bishop JA, Westra WH. Human papillomavirus-related small cell carcinoma of the oropharynx. Am J Surg Pathol. 2011;35(11):1679–84.

    Article  PubMed  PubMed Central  Google Scholar 

  60. Michal M, Skálová A, Simpson RH, Raslan WF, Curík R, Leivo I, et al. Cribriform adenocarcinoma of the tongue: a hitherto unrecognized type of adenocarcinoma characteristically occurring in the tongue. Histopathology. 1999;35(6):495–501.

    Article  CAS  PubMed  Google Scholar 

  61. Batson OV. THE FUNCTION OF THE VERTEBRAL VEINS AND THEIR ROLE IN THE SPREAD OF METASTASES. Ann Surg. 1940;112(1):138–49.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Morgenstern L. The Virchow–Troisier node: a historical note. Am J Surg. 1979;138(5):703.

    Article  CAS  PubMed  Google Scholar 

  63. 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(5):594–611.

    Article  PubMed  Google Scholar 

  64. Prasad ML, Jungbluth AA, Iversen K, Huvos AG, Busam KJ. Expression of melanocytic differentiation markers in malignant melanomas of the oral and sinonasal mucosa. Am J Surg Pathol. 2001;25(6):782–7.

    Article  CAS  PubMed  Google Scholar 

  65. Xu X, Palsgrove D, Kurian E, Yan S, Oliai BR, Bishop JA. Variable expression of S100 protein in sinonasal malignant mucosal melanoma: a potential diagnostic pitfall. Head Neck Pathol. 2020;14(4):929–35.

    Article  PubMed  PubMed Central  Google Scholar 

  66. Nassar KW, Tan AC. The mutational landscape of mucosal melanoma. Semin Cancer Biol. 2020;61:139–48.

    Article  CAS  PubMed  Google Scholar 

  67. Hintzsche JD, Gorden NT, Amato CM, Kim J, Wuensch KE, Robinson SE, et al. Whole-exome sequencing identifies recurrent SF3B1 R625 mutation and comutation of NF1 and KIT in mucosal melanoma. Melanoma Res. 2017;27(3):189–99.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Zhou Z, Gong Q, Wang Y, Li M, Wang L, Ding H, et al. The biological function and clinical significance of SF3B1 mutations in cancer. Biomark Res. 2020;8(1):38.

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

The author would like to give special thanks to Jill Gregory, CMI, (Icahn School of Medicine at Mount Sinai) and Annikka Weissferdt, MD (Department of Pathology, MD Anderson Cancer Center, Houston, TX) for providing Figs. 1 and 4, respectively.

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Hernandez-Prera, J.C. Update from the 5th Edition of the World Health Organization Classification of Head and Neck Tumors: The Neck and Lymph Nodes, Metastasis, and Melanocytic Tumors. Head and Neck Pathol 16, 110–122 (2022). https://doi.org/10.1007/s12105-022-01433-w

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