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Hereditäres Dickdarmkarzinom

Ein Update zu Genetik und Entitäten aus differenzialdiagnostischer Sicht

Hereditary colorectal cancer

An update on genetics and entities in terms of differential diagnosis

  • Schwerpunkt: Hereditäre Tumorerkrankungen
  • Published:
Der Pathologe Aims and scope Submit manuscript

Zusammenfassung

Der Pathologe kann über die Morphologie wesentlich zum Erkennen hereditärer Ursachen des kolorektalen Karzinoms beitragen. Über die Identifizierung sog. Indexpatienten können präventive Maßnahmen in den betroffenen Familien erfolgen. Die präzise Erfassung der klinischen Präsentation und des histopathologischen Phänotyps können helfen, das Spektrum der zu erwartenden genetischen Veränderungen einzuschränken. Als Neuerungen beim Lynch-Syndrom als Nichtpolyposis-assoziiertes Tumorsyndrom liegt mit EPCAM ein fünfter etablierter Genlocus vor und das neu definierte Lynch-like-Syndrom mit Nachweis somatischer Mismatch-repair(MMR)-Mutationen. Bei den Polyposis-assoziierten Syndromen ist das Spektrum der Polypen, ob serratiert, hamartomatös oder klassisches Adenom, entscheidend. Die resultierende Differenzialdiagnose umfasst u. a. (attenuierte) familiäre Adenomatosis polyposis coli ([a]FAP), MUTYH-assoziierte Polyposis (MAP), Polymerase proofreading-assoziierte Polypose (PPAP), Phosphatase-and-tensin-homolog(PTEN)-Hamartom-Tumorsyndrom (PHTS), Peutz-Jeghers-Syndrom und juvenile Polypose mit jeweils typischem genetischem Hintergrund.

Abstract

The pathologist can contribute to recognizing hereditary causes of colorectal cancer via morphology. By identifying so-called index patients, it is possible to take preventive measures in affected families. The precise definition of the clinical presentation and the histopathological phenotype help to narrow the spectrum of expected genetic alterations. Novelties within Lynch syndrome include the recognition of EPCAM as a fifth gene locus, as well as the newly defined Lynch-like syndrome with evidence of somatic mismatch repair (MMR) mutations. With regard to polyposis-associated syndromes, the spectrum of polyps, whether serrated, hamartomatous or classic adenoma, is of crucial importance. The resulting differential diagnosis includes (attenuated) familial adenomatous polyposis ([a]FAP), MUTYH-associated polyposis (MAP), polymerase proofreading-associated polyposis (PPAP), phosphatase and tensin homolog (PTEN) hamartoma tumor syndrome (PHTS), Peutz-Jeghers syndrome and juvenile polyposis, each with a specific genetic background.

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Abb. 1

Abbreviations

aFAP:

Attenuierte FAP

CAD:

Klassisches Adenom

CED:

Chronisch entzündliche Darmerkrankung

CRC:

Kolorektales Karzinom

DNA:

Desoxyribonukleinsäure

FAP:

Familiäre Adenomatosis polyposis coli

HAM:

Hamartomatöser Polyp

HNPCC:

Hereditäres Nichtpolyposis-Kolonkarzinom

MAP:

MUTYH-assoziierte Polyposis

MMR:

Mismatch-repair-Proteine

MSI:

Mikrosatelitteninstabilität

NSAR:

Nichtsteroidale Antirheumatika

PHTS:

PTEN-Hamartom-Tumorsyndrom

PPAP:

Polymerase proofreading-assoziierte Polypose

SCTAT:

Sex-cord-Tumor mit anulären Tubuli

SSA:

Sessil serratiertes Adenom

TCGA:

The Cancer Genome Atlas

TSA:

Traditionell serratiertes Adenom

WHO:

World Health Organization

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Authors and Affiliations

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

    T. T. Rau & H. Dawson

  2. Pathologisches Institut, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Deutschland

    A. Hartmann

  3. Pathologie Nordhessen, Kassel, Deutschland

    J. Rüschoff

Authors
  1. T. T. Rau
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  2. H. Dawson
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  3. A. Hartmann
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  4. J. Rüschoff
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Correspondence to T. T. Rau.

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Interessenkonflikt

T. T. Rau, H. Dawson, A. Hartmann geben an, dass kein Interessenkonflikt besteht. J. Rüschoff ist Chief Medical Officer und Mitbegründer der Targos GmbH, Kassel, Deutschland.

Dieser Beitrag beinhaltet keine von den Autoren durchgeführten Studien an Menschen oder Tieren.

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Schwerpunktherausgeber

A. Hartmann, Erlangen

S. Lax, Graz

A. Agaimy, Erlangen

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Rau, T.T., Dawson, H., Hartmann, A. et al. Hereditäres Dickdarmkarzinom. Pathologe 38, 156–163 (2017). https://doi.org/10.1007/s00292-017-0294-9

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  • DOI: https://doi.org/10.1007/s00292-017-0294-9

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