Der Pathologe

, Volume 31, Issue 6, pp 477–484 | Cite as

Hereditäre Tumoren des Kopf-Hals-Bereichs

  • S. Schwarz-Furlan
  • C. Brase
  • P. Stockmann
  • I. Furlan
  • A. Hartmann
Schwerpunkt

Zusammenfassung

Zu den seltenen erblichen Tumorsyndromen, die sich im Kopf-Hals-Bereich manifestieren, zählen das hereditäre Paragangliom, das Gorlin-Goltz-Syndrom und die Fanconi-Anämie. Beim hereditären Paragangliom treten meist mehrere Tumoren am Glomus caroticum und/oder Glomus jugulotympanicum auf. Die korrespondierenden Gendefekte betreffen den mitochondrialen Succinat-Dehydrogenase-Komplex, der ein autonomes Tumorzellwachstum induziert. Das Gorlin-Goltz-Syndrom ist durch das Auftreten von multiplen Basalzellkarzinomen und keratozystischen odontogenen Tumoren charakterisiert. Die assoziierten Keimbahnmutationen sind im Patched-Gen lokalisiert, das einen Regulator des Zellzyklus darstellt. Bei der Fanconi-Anämie handelt es sich um ein Syndrom chromosomaler Instabilität mit primärem Knochenmarksversagen und sekundärer Entwicklung von Leukämien. Daneben treten Plattenepithelkarzinome im Kopf-Hals-Bereich, im Ösophagus und am äußeren Genitale auf. Es sind bislang 13 unterschiedliche Gendefekte bekannt, die zwei DNA-assoziierte Komplexe, welche die DNA-Reparatur steuern, betreffen.

Schlüsselwörter

Hereditäres Paragangliom Gorlin-Goltz-Syndrom Keratozystischer odontogener Tumor Fanconi-Anämie Kopf-Hals-Tumor 

Abkürzungen

BRCA

Brustkrebsgen

CYLD

Zylindromatose-Gen

FA

Fanconi-Anämie

FAMMM

Familiäres atypisches Melanom auf dem Boden multipler Leberflecken

FANC

Fanconi-Anämie-Gen

GFAP

Gliales fibrilläres saures Protein

HE

Hämatoxylin-Eosin

HNSCC

Plattenepithelkarzinom des Kopf-Hals-Bereichs

JNK

c-Jun N-terminale Kinase

KZOT

Keratozystischer odontogener Tumor

NEMO

NF-κB essenzieller Modulator

NF-1

Neurofibromatose Typ 1

PTCH

Patched-Gen

SDH

Succinat-Dehydrogenase

TGF

Transformierender Wachstumsfaktor

TNF

Tumor-Nekrose-Faktor

TRAF

TNF-Rezeptor-assoziierter Faktor

VHL

Von-Hippel-Lindau

Hereditary head and neck tumors

Abstract

Hereditary paraganglioma, Gorlin-Goltz syndrome and Fanconi anemia are among the rare hereditary tumor syndromes of the head and neck. Patients with hereditary paraganglioma often develop multiple tumors of the glomus caroticum and glomus jugulotympanicum. The corresponding genetic defects of the mitochondrial succinate dehydrogenase complex induce autonomous tumor cell growth. In patients with Gorlin-Goltz syndrome basal cell carcinomas and keratocystic odontogenic tumors usually occur much earlier than in patients with sporadic tumors. The associated germline mutations are located in the patched gene which is a modulator of the cell cycle. Fanconi anemia represents a chromosomal instability syndrome which is characterized by early onset of pancytopenia, i.e. bone marrow failure and subsequent development of acute myeloid leukemia and/or squamous cell carcinomas, especially of the head and neck. A total of 13 different gene clusters have been identified in 2 DNA associated complexes which play an important role in DNA repair mechanisms.

Keywords

Hereditary paraganglioma Gorlin-Goltz syndrome Keratocystic odontogenic tumor Fanconi anemia Head and neck tumor 

Notes

Interessenkonflikt

Der korrespondierende Autor gibt an, dass kein Interessenkonflikt besteht.

Literatur

  1. 1.
    Baysal BE (2002) Hereditary paraganglioma targets diverse paraganglia. J Med Genet 39:617–622CrossRefPubMedGoogle Scholar
  2. 2.
    Schipper J, Boedeker CC, Maier W, Neumann HP (2004) Paragangliomas in the head-/neck region. I: classification and diagnosis. HNO 52:569–574; quiz 575PubMedGoogle Scholar
  3. 3.
    Erickson D, Kudva YC, Ebersold MJ et al (2001) Benign paragangliomas: clinical presentation and treatment outcomes in 236 patients. J Clin Endocrinol Metab 86:5210–5216CrossRefPubMedGoogle Scholar
  4. 4.
    Tischler AS (2008) Pheochromocytoma and extra-adrenal paraganglioma: Updates. Arch Pathol Lab Med 132:1272–1284PubMedGoogle Scholar
  5. 5.
    Griffiths DF, Williams GT, Williams ED (1987) Duodenal carcinoid tumours, phaeochromocytoma and neurofibromatosis: islet cell tumour, phaeochromocytoma and the von Hippel-Lindau complex: two distinctive neuroendocrine syndromes. Q J Med 64:769–782PubMedGoogle Scholar
  6. 6.
    Baysal BE, Ferrell RE, Willett-Brozick JE et al (2000) Mutations in SDHD, a mitochondrial complex II gene, in hereditary paraganglioma. Science 287:848–851CrossRefPubMedGoogle Scholar
  7. 7.
    Baysal BE (2008) Clinical and molecular progress in hereditary paraganglioma. J Med Genet 45:689–694CrossRefPubMedGoogle Scholar
  8. 8.
    Arias-Stella J, Valcarcel J (1976) Chief cell hyperplasia in the human carotid body at high altitudes; physiologic and pathologic significance. Hum Pathol 7:361–373CrossRefPubMedGoogle Scholar
  9. 9.
    Neumann HP, Bausch B, McWhinney SR et al (2002) Germ-line mutations in nonsyndromic pheochromocytoma. N Engl J Med 346:1459–1466CrossRefPubMedGoogle Scholar
  10. 10.
    Boedeker CC, Erlic Z, Richard S et al (2009) Head and neck paragangliomas in von Hippel-Lindau disease and multiple endocrine neoplasia type 2. J Clin Endocrinol Metab 94:1938–1944CrossRefPubMedGoogle Scholar
  11. 11.
    Nederveen FH van, Gaal J, Favier J et al (2009) An immunohistochemical procedure to detect patients with paraganglioma and phaeochromocytoma with germline SDHB, SDHC, or SDHD gene mutations: a retrospective and prospective analysis. Lancet Oncol 10:764–771CrossRefPubMedGoogle Scholar
  12. 12.
    Gorlin RJ, Goltz RW (1960) Multiple nevoid basal-cell epithelioma, jaw cysts and bifid rib. A syndrome. N Engl J Med 262:908–912CrossRefPubMedGoogle Scholar
  13. 13.
    Brannon RB (1976) The odontogenic keratocyst. A clinicopathologic study of 312 cases. Part I. Clinical features. Oral Surg Oral Med Oral Pathol 42:54–72CrossRefPubMedGoogle Scholar
  14. 14.
    Kimonis VE, Goldstein AM, Pastakia B et al (1997) Clinical manifestations in 105 persons with nevoid basal cell carcinoma syndrome. Am J Med Genet 69:299–308CrossRefPubMedGoogle Scholar
  15. 15.
    Gorlin RJ (2004) Nevoid basal cell carcinoma (Gorlin) syndrome. Genet Med 6:530–539CrossRefPubMedGoogle Scholar
  16. 16.
    Lo Muzio L (2008) Nevoid basal cell carcinoma syndrome (Gorlin syndrome). Orphanet J Rare Dis 3:32CrossRefGoogle Scholar
  17. 17.
    Cohen MM Jr (1999) Nevoid basal cell carcinoma syndrome: molecular biology and new hypotheses. Int J Oral Maxillofac Surg 28:216–223CrossRefPubMedGoogle Scholar
  18. 18.
    Boonen SE, Stahl D, Kreiborg S et al (2005) Delineation of an interstitial 9q22 deletion in basal cell nevus syndrome. Am J Med Genet A 132A:324–328CrossRefPubMedGoogle Scholar
  19. 19.
    Lindstrom E, Shimokawa T, Toftgard R, Zaphiropoulos PG (2006) PTCH mutations: distribution and analyses. Hum Mutat 27:215–219CrossRefPubMedGoogle Scholar
  20. 20.
    Barreto DC, Gomez RS, Bale AE et al (2000) PTCH gene mutations in odontogenic keratocysts. J Dent Res 79:1418–1422CrossRefPubMedGoogle Scholar
  21. 21.
    Lee DA, Grossman ME, Schneiderman P, Celebi JT (2005) Genetics of skin appendage neoplasms and related syndromes. J Med Genet 42:811–819CrossRefPubMedGoogle Scholar
  22. 22.
    Young AL, Kellermayer R, Szigeti R et al (2006) CYLD mutations underlie Brooke-Spiegler, familial cylindromatosis, and multiple familial trichoepithelioma syndromes. Clin Genet 70:246–249CrossRefPubMedGoogle Scholar
  23. 23.
    Blake PW, Toro JR (2009) Update of cylindromatosis gene (CYLD) mutations in Brooke-Spiegler syndrome: novel insights into the role of deubiquitination in cell signaling. Hum Mutat 30:1025–1036CrossRefPubMedGoogle Scholar
  24. 24.
    Ferrandiz C, Campo E, Baumann E (1985) Dermal cylindromas (turban tumour) and eccrine spiradenomas in a patient with membranous basal cell adenoma of the parotid gland. J Cutan Pathol 12:72–79CrossRefPubMedGoogle Scholar
  25. 25.
    Jungehulsing M, Wagner M, Damm M (1999) Turban tumour with involvement of the parotid gland. J Laryngol Otol 113:779–783CrossRefPubMedGoogle Scholar
  26. 26.
    Antonescu CR, Terzakis JA (1997) Multiple malignant cylindromas of skin in association with basal cell adenocarcinoma with adenoid cystic features of minor salivary gland. J Cutan Pathol 24:449–453CrossRefPubMedGoogle Scholar
  27. 27.
    D’Andrea AD (2010) Susceptibility pathways in Fanconi’s anemia and breast cancer. N Engl J Med 362:1909–1919CrossRefGoogle Scholar
  28. 28.
    Taniguchi T, D’Andrea AD (2006) Molecular pathogenesis of Fanconi anemia: recent progress. Blood 107:4223–4233CrossRefPubMedGoogle Scholar
  29. 29.
    Jacquemont C, Taniguchi T (2007) The Fanconi anemia pathway and ubiquitin. BMC Biochem 8 (Suppl 1):S10CrossRefPubMedGoogle Scholar
  30. 30.
    Moldovan GL, D’Andrea AD (2009) How the Fanconi anemia pathway guards the genome. Annu Rev Genet 43:223–249CrossRefPubMedGoogle Scholar
  31. 31.
    Schneider-Stock R, Giers A, Motsch C et al (2003) Hereditary p16-Leiden mutation in a patient with multiple head and neck tumors. Am J Hum Genet 72:216–218CrossRefPubMedGoogle Scholar
  32. 32.
    Yarbrough WG, Aprelikova O, Pei H et al (1996) Familial tumor syndrome associated with a germline nonfunctional p16ink4a allele. J Natl Cancer Inst 88:1489–1491CrossRefPubMedGoogle Scholar
  33. 33.
    Suarez C, Rodrigo JP, Ferlito A et al (2006) Tumours of familial origin in the head and neck. Oral Oncol 42:965–978CrossRefPubMedGoogle Scholar
  34. 34.
    Depowski PL, Setzen G, Chui A et al (1999) Familial occurrence of acinic cell carcinoma of the parotid gland. Arch Pathol Lab Med 123:1118–1120PubMedGoogle Scholar
  35. 35.
    Delides A, Velegrakis G, Kontogeorgos G (2005) Familial bilateral acinic cell carcinoma of the parotid synchronous with pituitary adenoma: case report. Head Neck 27:825–828CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • S. Schwarz-Furlan
    • 1
    • 2
  • C. Brase
    • 3
  • P. Stockmann
    • 4
  • I. Furlan
    • 5
  • A. Hartmann
    • 2
  1. 1.Institut für Pathologie KaufbeurenKaufbeurenDeutschland
  2. 2.Pathologisches InstitutUniversitätsklinikum ErlangenErlangenDeutschland
  3. 3.Hals-Nasen-Ohren-KlinikUniversitätsklinikum ErlangenErlangenDeutschland
  4. 4.Klinik für Mund-Kiefer-GesichtschirurgieUniversitätsklinikum ErlangenErlangenDeutschland
  5. 5.Zentrum für Kinder- und Jugendmedizin, Pädiatrische Hämatologie und OnkologieUniversitätsklinikum FreiburgFreiburgDeutschland

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