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Gering differenzierte Schilddrüsenkarzinome

Eine unterdiagnostizierte Entität

Poorly differentiated thyroid carcinoma

An underdiagnosed entity. German version

  • Schwerpunkt: Endokrine/Neuroendokrine Pathologie
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Zusammenfassung

Gering differenzierte Schilddrüsenkarzinome (PDTC) stellen einen seltenen Subtyp des Schilddrüsenkarzinoms dar, welcher biologisch zwischen den gut differenzierten Schilddrüsenkarzinomen (papilläre und follikuläre Schilddrüsenkarzinome) auf der einen Seite und den anaplastischen Schilddrüsenkarzinomen auf der anderen Seite angesiedelt ist.

Die Diagnose des konventionellen wie des onkozytären PDTC ist schwierig und wird in der täglichen Routine oft verpasst. Derzeit werden diese Tumoren nach Kriterien der aktuelle WHO-Klassifikation diagnostiziert, welche in einer Konsensustagung 2006 in Turin erarbeitet wurden. Selbst ein kleiner Anteil eines PDTC von nur 10 % innerhalb eines Schilddrüsenkarzinoms beeinflusst die Prognose nachhaltig und die onkozytäre Variante hat einen nochmals ungünstigeren Verlauf. Immunhistochemische Analysen sind meist nicht hilfreich und werden genutzt, um ein medulläres Schilddrüsenkarzinom mittels Calcitonin auszuschließen oder die Follikelepithelzelle als Ursprungszelle mittels Thyreoglobulin nachzuweisen.

Auf molekularer Ebene gibt es eine große Überlappung unterschiedlicher Mutationen in den verschiedenen Schilddrüsenkarzinomen wie BRAF, RAS, CTNNB1 oder TP53 welche sich durch das Konzept der schrittweisen Dedifferenzierung gut erklären lassen. Entsprechend existiert nach wie vor kein eigenständiges, für die Diagnostik einsetzbares molekulares Profil.

PDTC haben ein distinktes miRNA-Profil im Vergleich zu anderen Schilddrüsenkarzinomen. Das durchschnittliche rezidivfreie Überleben liegt unter einem Jahr und etwa 50 % der Patienten versterben an ihrem Tumor. Thyrosinkinaseinhibitoren eröffnen gemeinsam mit einer leistungsstarken molekularen Diagnostik neue Therapiechancen in diesen schwer zu therapierenden Karzinomen.

Abstract

Poorly differentiated thyroid carcinomas (PDTCs) are a rare subtype of thyroid carcinomas that are biologically situated between well-differentiated papillary/follicular thyroid carcinomas and anaplastic thyroid carcinomas (ATCs).

The diagnosis of conventional as well as oncocytic poorly differentiated thyroid carcinoma is difficult and often missed in daily routine. The current WHO criteria to allow the diagnosis of PDTCs are based on the results of a consensus meeting held in Turin in 2006. Even a minor poorly differentiated component of only 10% of a given carcinoma significantly affects patient prognosis and the oncocytic subtype may even have a worse outcome. Immunohistochemistry is not much help and is mostly used to exclude a medullary thyroid carcinoma with calcitonin and to establish a follicular cell of origin via thyroglobulin staining.

Due to the concept of stepwise dedifferentiation, there is a vast overlap of different molecular alterations like BRAF, RAS, CTNNB1, TP53 and others between different thyroid carcinoma subtypes. A distinctive molecular tumor profile is therefore currently not available.

PDTCs have a unique miRNA signature, which separates them from other thyroid carcinomas.The average relapse free survival is less than one year and about 50% of patients die of the disease. Modern tyrosine kinase inhibitors offer in conjunction with powerful molecular diagnostic new chances in these difficult to treat carcinomas.

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Authors and Affiliations

  1. Institut für Pathologie, Universität Bern, Murtenstraße 31, 3008, Bern, Schweiz

    M. S. Dettmer,  A. Schmitt &  A. Perren

  2. Institut für Pathologie, Stadtspital Triemli, Birmensdorferstraße 497, 8063, Zürich, Schweiz

    P. Komminoth

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M. S. Dettmer, A. Schmitt, P. Komminoth und A. Perren geben an, dass kein Interessenkonflikt besteht.

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K. W. Schmid, Essen

H. A. Baba, Essen

H.-U. Schildhaus, Essen

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Dettmer, M.S., Schmitt, A., Komminoth, P. et al. Gering differenzierte Schilddrüsenkarzinome. Pathologe 40, 227–234 (2019). https://doi.org/10.1007/s00292-019-0613-4

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