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Update from the 5th Edition of the World Health Organization Classification of Head and Neck Tumors: Familial Tumor Syndromes

  • UPDATE FROM THE 5TH EDITION OF THE WORLD HEALTH ORGANIZATION CLASSIFICATION OF HEAD AND NECK TUMORS
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Abstract

The initiative of the 5th edition of the WHO classification of the Head and Neck Tumours establishing a new section dedicated to familial/heritable tumor syndromes with tumors and lesions in the head and neck region was much needed to better understand the tumours, diseases, and associated syndromes, as well as establish recommendations for monitoring and treating these patients. (WHO Classification of Tumours Editorial Board. Head and Neck tumours. Lyon (France): International Agency for Research on Cancer; 2022. https://publications.iarc.fr/). Within the newly established chapter on genetic tumor syndromes, we have described the main manifestations on the head and neck region in 15 syndromes. This review highlights the important findings within these syndromes, especially on the update on syndromes with tumors involving the head and neck region, as Gorlin syndrome/nevoid basal cell carcinoma syndrome associated with odontogenic keratocysts; Brooke-Spiegler syndrome/familial cylindromatosis and the associated membranous-type salivary gland basal cell adenoma, PTEN hamartoma tumor syndrome/Cowden syndrome with associated facial skin and mucosal lesions and characteristic multinodular thyroid lesions, Von Hippel Lindau syndrome and the associated middle ear endolymphatic sac tumor, as well as the fascinating genetic aspects of the diverse Head and Neck Paragangliomas. We will also discuss hyperparathyroidism-jaw tumor syndrome is characterized by parathyroid tumors in association with fibro-osseous jaw tumors, as well as head and neck desmoid tumors associated with familial adenomatous polyposis with Gardner syndrome variant familial, multicentric head and neck squamous cell carcinoma, tuberous sclerosis and neurofibromatosis type 1-associated head and neck lesions.

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References

  1. Howell JB, Caro MR. The basal-cell nevus: its relationship to multiple cutaneous cancers and associated anomalies of development. AMA Arch Dermatol. 1959;79(1):67–77 (discussion 77-80).

    CAS  Google Scholar 

  2. Gorlin RJ, Goltz RW. Multiple nevoid basal-cell epithelioma, jaw cysts and bifid rib. A syndrome. N Engl J Med. 1960;262:908–12.

    CAS  PubMed  Google Scholar 

  3. Evans DG, et al. Complications of the naevoid basal cell carcinoma syndrome: results of a population based study. J Med Genet. 1993;30(6):460–4.

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Bresler SC, Padwa BL, Granter SR. Nevoid basal cell carcinoma syndrome (Gorlin Syndrome). Head Neck Pathol. 2016;10(2):119–24.

    PubMed  PubMed Central  Google Scholar 

  5. Stojanov IJ, et al. Biallelic PTCH1 inactivation is a dominant genomic change in sporadic keratocystic odontogenic tumors. Am J Surg Pathol. 2020;44(4):553–60.

    PubMed  PubMed Central  Google Scholar 

  6. Foulkes WD, et al. Cancer surveillance in Gorlin syndrome and Rhabdoid tumor predisposition syndrome. Clin Cancer Res. 2017;23(12):e62–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Karhade DS, Afshar S, Padwa BL. What is the prevalence of undiagnosed nevoid basal cell carcinoma syndrome in children with an odontogenic keratocyst? J Oral Maxillofac Surg. 2019;77(7):1389–91.

    PubMed  Google Scholar 

  8. Li TJ. The odontogenic keratocyst: a cyst, or a cystic neoplasm? J Dent Res. 2011;90(2):133–42.

    CAS  PubMed  Google Scholar 

  9. Qu J, et al. PTCH1 alterations are frequent but other genetic alterations are rare in sporadic odontogenic keratocysts. Oral Dis. 2019;25(6):1600–7.

    PubMed  Google Scholar 

  10. Robinson RA. Basal cell adenoma and basal cell adenocarcinoma. Surg Pathol Clin. 2021;14(1):25–42.

    PubMed  Google Scholar 

  11. Rito M, et al. Frequent and differential mutations of the CYLD gene in basal cell salivary neoplasms: linkage to tumor development and progression. Mod Pathol. 2018;31(7):1064–72.

    CAS  PubMed  Google Scholar 

  12. Nagao T, et al. Carcinoma in basal cell adenoma of the parotid gland. Pathol Res Pract. 1997;193(3):171–8.

    CAS  PubMed  Google Scholar 

  13. Nose V. Genodermatosis affecting the skin and mucosa of the head and neck: clinicopathologic, genetic, and molecular aspect–PTEN-hamartoma tumor syndrome/cowden syndrome. Head Neck Pathol. 2016;10(2):131–8.

    PubMed  PubMed Central  Google Scholar 

  14. Laury AR, et al. Thyroid pathology in PTEN-hamartoma tumor syndrome: characteristic findings of a distinct entity. Thyroid. 2011;21(2):135–44.

    PubMed  Google Scholar 

  15. Bausch B, et al. Characterization of endolymphatic sac tumors and von Hippel-Lindau disease in the International Endolymphatic Sac Tumor Registry. Head Neck. 2016;38(Suppl 1):E673–9.

    PubMed  Google Scholar 

  16. Codreanu CM, et al. Endolymphatic sac tumors in von Hippel-Lindau disease: report of three cases. Otol Neurotol. 2010;31(4):660–4.

    PubMed  Google Scholar 

  17. Codreanu C, Tran Ba Huy P. Isolate vertigo crisis revealing an endolymphatic sac tumor. Rom J Morphol Embryol. 2010;51(2):387–9.

    CAS  PubMed  Google Scholar 

  18. Wick CC, et al. Endolymphatic sac tumors. Otolaryngol Clin North Am. 2015;48(2):317–30.

    PubMed  Google Scholar 

  19. Vortmeyer AO, et al. Nervous system involvement in von Hippel-Lindau disease: pathology and mechanisms. Acta Neuropathol. 2013;125(3):333–50.

    PubMed  Google Scholar 

  20. Wanebo JE, et al. The natural history of hemangioblastomas of the central nervous system in patients with von Hippel-Lindau disease. J Neurosurg. 2003;98(1):82–94.

    PubMed  Google Scholar 

  21. Binderup MLM, et al. Retinal hemangioblastoma: prevalence, incidence and frequency of underlying von Hippel-Lindau disease. Br J Ophthalmol. 2018;102(7):942–7.

    PubMed  Google Scholar 

  22. Ruppert MD, et al. Ocular manifestations of von Hippel-Lindau disease. Cureus. 2019;11(8):e5319.

    PubMed  PubMed Central  Google Scholar 

  23. Reich M, et al. Genotype-phenotype correlation in von Hippel-Lindau disease. Acta Ophthalmol. 2021. https://doi.org/10.1111/aos.14843.

    Article  PubMed  Google Scholar 

  24. Heffner DK. Low-grade adenocarcinoma of probable endolymphatic sac origin A clinicopathologic study of 20 cases. Cancer. 1989;64(11):2292–302.

    CAS  PubMed  Google Scholar 

  25. el-Naggar AK, et al. Tumors of the middle ear and endolymphatic sac. Pathol Annu. 1994;29(Pt 2):199–231.

    PubMed  Google Scholar 

  26. Bisceglia M, D’Angelo VA, Wenig BM. Endolymphatic sac papillary tumor (Heffner tumor). Adv Anat Pathol. 2006;13(3):131–8.

    PubMed  Google Scholar 

  27. Skalova A, et al. Endolymphatic sac tumor (aggressive papillary tumor of middle ear and temporal bone): report of two cases with analysis of the VHL gene. Pathol Res Pract. 2008;204(8):599–606.

    CAS  PubMed  Google Scholar 

  28. Michaels L. Origin of endolymphatic sac tumor. Head Neck Pathol. 2007;1(2):104–11.

    PubMed  PubMed Central  Google Scholar 

  29. Bell D, et al. Endolymphatic sac tumor (aggressive papillary tumor of middle ear and temporal bone): sine qua non radiology-pathology and the University of Texas MD Anderson Cancer Center experience. Ann Diagn Pathol. 2011;15(2):117–23.

    PubMed  Google Scholar 

  30. Thompson LDR, et al. CAIX and pax-8 commonly immunoreactive in endolymphatic sac tumors: a clinicopathologic study of 26 cases with differential considerations for metastatic renal cell carcinoma in von hippel-lindau patients. Head Neck Pathol. 2019;13(3):355–63.

    PubMed  Google Scholar 

  31. Smith JD, et al. Head and neck paragangliomas: a two-decade institutional experience and algorithm for management. Laryngoscope Investig Otolaryngol. 2017;2(6):380–9.

    PubMed  PubMed Central  Google Scholar 

  32. Kriegsmann K, et al. Insulinoma-associated protein 1 (INSM1) in thoracic tumors is less sensitive but more specific compared with synaptophysin, chromogranin A, and CD56. Appl Immunohistochem Mol Morphol. 2020;28(3):237–42.

    CAS  PubMed  Google Scholar 

  33. Juhlin CC, Zedenius J, Hoog A. Clinical routine application of the second-generation neuroendocrine markers ISL1, INSM1, and secretagogin in neuroendocrine neoplasia: staining outcomes and potential clues for determining tumor origin. Endocr Pathol. 2020;31(4):401–10.

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Pinato DJ, et al. Immunohistochemical markers of the hypoxic response can identify malignancy in phaeochromocytomas and paragangliomas and optimize the detection of tumours with VHL germline mutations. Br J Cancer. 2013;108(2):429–37.

    CAS  PubMed  Google Scholar 

  35. Favier J, et al. Carbonic anhydrase 9 immunohistochemistry as a tool to predict or validate germline and somatic VHL mutations in pheochromocytoma and paraganglioma-a retrospective and prospective study. Mod Pathol. 2020;33(1):57–64.

    CAS  PubMed  Google Scholar 

  36. Kimura N, et al. Familial cervical paragangliomas with lymph node metastasis expressing somatostatin receptor type 2A. Endocr Pathol. 2010;21(2):139–43.

    PubMed  Google Scholar 

  37. Amar L, et al. International consensus on initial screening and follow-up of asymptomatic SDHx mutation carriers. Nat Rev Endocrinol. 2021;17(7):435–44.

    CAS  PubMed  PubMed Central  Google Scholar 

  38. McCrary HC, et al. Characterization of malignant head and neck paragangliomas at a single institution across multiple decades. JAMA Otolaryngol Head Neck Surg. 2019;145(7):641–6.

    PubMed  PubMed Central  Google Scholar 

  39. Bouaoun L, et al. TP53 variations in human cancers: new lessons from the IARC TP53 database and genomics data. Hum Mutat. 2016;37(9):865–76.

    CAS  PubMed  Google Scholar 

  40. Prime SS, et al. A review of inherited cancer syndromes and their relevance to oral squamous cell carcinoma. Oral Oncol. 2001;37(1):1–16.

    CAS  PubMed  Google Scholar 

  41. Scheckenbach K, et al. Squamous cell carcinomas of the head and neck in Fanconi anemia: risk, prevention, therapy, and the need for guidelines. Klin Padiatr. 2012;224(3):132–8.

    CAS  PubMed  Google Scholar 

  42. Saito Y, et al. Risk factors for the development of desmoid tumor after colectomy in patients with familial adenomatous polyposis: multicenter retrospective cohort study in Japan. Ann Surg Oncol. 2016;23(Suppl 4):559–65.

    PubMed  Google Scholar 

  43. Lee BD, et al. A case report of Gardner syndrome with hereditary widespread osteomatous jaw lesions. Oral Surg Oral Med Oral Pathol Oral Radiol Endodontol. 2009;107(3):e68-72.

    Google Scholar 

  44. Nah KS. Osteomas of the craniofacial region. Imaging Sci Dent. 2011;41(3):107–13.

    PubMed  PubMed Central  Google Scholar 

  45. Boyraz B, et al. Cribriform-morular thyroid carcinoma is a distinct thyroid malignancy of uncertain cytogenesis. Endocr Pathol. 2021;32(3):327–35.

    CAS  PubMed  Google Scholar 

  46. Carpenter TO, et al. Case 32–2021: a 14-year-old girl with swelling of the jaw and hypercalcemia. N Engl J Med. 2021;385(17):1604–13.

    PubMed  Google Scholar 

  47. Nguyen QD, DarConte MD, Hebert AA. The cutaneous manifestations of tuberous sclerosis complex. Am J Med Genet C Semin Med Genet. 2018;178(3):321–5.

    PubMed  Google Scholar 

  48. Bree AF, Shah MR, for the BCNS Colloquium Group. Consensus statement from the first international colloquium on basal cell nevus syndrome (BCNS). Am J Med Genet Part A. 2011;155:2091–7.

    Google Scholar 

  49. Pilarski R, Burt R, Kohlman W, et al. Cowden syndrome and the PTEN hamartoma tumor syndrome: systematic review and revised diagnostic criteria. J Natl Cancer Inst. 2013;105(21):1607–16.

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA

    Vania Nosé

  2. MD Anderson Cancer Center, Houston, TX, USA

    Alexander J. Lazar

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  1. Vania Nosé
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  2. Alexander J. Lazar
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Correspondence to Vania Nosé.

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All authors have contributed to this work and both authors declare they have no conflict of interest as it relates to this study.

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All evaluations performed in this analysis do not involve any individual patient’s data, but was still performed in accordance with the ethical standards of the institutional review board. The opinions or assertions contained herein are the private views of the authors.

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Nosé, V., Lazar, A.J. Update from the 5th Edition of the World Health Organization Classification of Head and Neck Tumors: Familial Tumor Syndromes. Head and Neck Pathol 16, 143–157 (2022). https://doi.org/10.1007/s12105-022-01414-z

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