Der Chirurg

, 79:1017

Hereditäre Schilddrüsenkarzinome

Leitthema

Zusammenfassung

Hereditäre Schilddrüsenkarzinome werden in ca. 5% der differenzierten (DTC) und 25% der medullären Schilddrüsenkarzinome nachgewiesen. Sie kommen sowohl als Organkrebs innerhalb eines Tumorsyndroms vor (z. B. differenzierte Karzinome bei FAP-Gardner-Syndrom, medulläre Karzinome beim MEN2-Syndrom), aber auch als alleiniger familiärer Organtumor. Unabhängig von der Manifestationsform treten hereditäre Schilddrüsenkarzinome häufig bei jüngeren Patienten und multifokal auf. Das Resektionsausmaß muss aufgrund der vorliegenden Keimbahnmutationen grundsätzlich in der Entfernung der gesamten Schilddrüse bestehen. Teilentfernungen der Schilddrüse, wie sie für frühe Tumorstadien der sporadischen Tumoren ausreichend sein können, sind daher unabhängig vom Tumorstadium beim hereditären Schilddrüsenkrebs nicht indiziert.

Bei den meisten hereditären differenzierten Schilddrüsenkarzinomen ist die genetische Disposition unbekannt. Somit sind ein molekulargenetisches Screening und eine DNA-basierte prophylaktische Chirurgie nicht möglich. Auch bei den syndromal assoziierten DTC (FAP-Gardner-Syndrom, Cowden-Syndrom etc.) ist eine prophylaktische Chirurgie nicht begründet, da deren Prognose sich nicht von der sporadischer DTC unterscheidet.

Beim hereditären medullären Karzinom ist die genetische Ursache der Punktmutationen im RET-Protoonkogen seit 15 Jahren bekannt. Es werden jedoch stets neue krankheitsauslösende Mutationen des RET-Protoonkogens berichtet, so dass eine abschließende Wertung aller bestehenden Mutationen derzeit nicht möglich ist. Grundsätzlich besteht eine Genotyp-Phänotyp-Korrelation mit mutationsspezifischen Risikogruppen (Risikogruppe 1–3), die eine mutationsorientierte prophylaktische Thyreoidektomie möglich machen. Aufgrund der erheblichen Variationen innerhalb der einzelnen Risikogruppen ist jedoch ein streng mutationsspezifisches Vorgehen hinsichtlich Operationszeitpunkt und -ausmaß (ohne oder mit Lymphknotendissektion) nicht möglich, so dass einem kombiniert molekulargenetisch-biochemischen Konzept unter gleichzeitiger Berücksichtigung der Ergebnisse des Pentagastrinstimulationstestes der Vorzug zu geben ist.

Schlüsselwörter

Hereditäres Schilddrüsenkarzinom Differenziertes Schilddrüsenkarzinom Medulläres Schilddrüsenkarzinom Prophylaktische Thyreoidektomie 

Hereditary thyroid cancer

Abstract

Hereditary thyroid carcinomas are present in about 5% of differentiated (DTC) and 25% of medullary thyroid carcinomas (MTC). They are part of a multiorgan tumour syndrome (e. g. FAP Gardner’s syndrome with DTC and MEN 2 syndrome with MTC) or confined to the thyroid gland. Hereditary thyroid carcinomas typically show multifocal growth and occur in young patients. Due to germ cell mutations as the underlying cause of disease, partial thyroidectomies that may be justified in early sporadic carcinomas are not indicated in this type of tumours. In the case of hereditary DTC, the genetic basis of the disease has been demonstrated only in syndromatic tumour variants. In most nonsyndromatic cases, specific genetic alterations have not yet been identified. In both types of hereditary DTC, prophylactic thyroidectomy is not warranted due to the favourable prognosis of tumours that do not differ from sporadic ones. Point mutations of the RET proto-oncogene have been known for 15 years to be the genetic basis of hereditary MTC. Recently several new mutations were discovered; however, final conclusions regarding their clinical significance are not possible at present. Basically it has been shown that the clinical aggressivity of tumour development follows a genotype-phenotype correlation (risk groups 1–3). However, in mutations of all risk classes there exists a wide spectrum of different stages of hereditary C-cell disease in individual risk groups. Regarding time and extent of prophylactic thyroidectomy (without or with lymph node dissection) a combined molecular-biochemical concept including the use of pentagastrin-stimulated calcitonin values is therefore recommended.

Keywords

Hereditary thyroid carcinoma Differentiated thyroid carcinoma Medullary thyroid carcinoma Prophylactic thyroidectomy 

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Copyright information

© Springer Medizin Verlag 2008

Authors and Affiliations

  1. 1.Universitätsklinik für Allgemein-, Viszeral- und GefäßchirurgieUniversitätsklinikum Halle, Medizinische Fakultät der Martin-Luther-Universität Halle-Wittenberg, Halle (Saale)HalleDeutschland

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