Diagnostic Approach and Management of Lynch Syndrome (Hereditary Nonpolyposis Colorectal Carcinoma): A Guide for Clinicians

Authors

  • Dr. Yvonne M.C. Hendriks MD, PhD,

    1. Hendriks is Specialist Registrar in Clinical Genetics, Center of Human and Clinical Genetics, Leiden University Medical Center, Leiden, the Netherlands
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  • Dr. Andrea E. de Jong MD,

    1. de Jong is Specialist Registrar in Gastroenterology, Netherlands Foundation of the Detection of Hereditary Tumours, Leiden, the Netherlands
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  • Prof. Hans Morreau MD, PhD,

    1. Morreau is Pathologist, Department of Pathology, Leiden University Medical Center, Leiden, the Netherlands
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  • Dr. Carli M.J. Tops PhD,

    1. Tops is Molecular Geneticist, Center of Human and Clinical Genetics, Leiden University Medical Center, Leiden, the Netherlands
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  • Dr. Hans F. Vasen MD, PhD,

    1. Vasen is Director of the Netherlands Foundation of the Detection of Hereditary Tumours, and Internist, Department of Gastroenterology, Leiden University Medical Center, Leiden, the Netherlands
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  • Dr. Juul Th. Wijnen PhD,

    1. Wijnen is Molecular Geneticist, Center of Human and Clinical Genetics, Leiden University Medical Center, Leiden, the Netherlands
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  • Prof. Martijn H. Breuning MD, PhD,

    1. Breuning is Clinical Geneticist and Head of the Center of Human and Clinical Genetics, Center of Human and Clinical Genetics, Leiden University Medical Center, Leiden, the Netherlands
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  • Dr. Annette H.J.T. Bröcker-Vriends MD, PhD

    1. Bröcker-Vriends is Clinical Geneticist, Center of Human and Clinical Genetics, Leiden University Medical Center, Leiden, the Netherlands
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Abstract

The patient with a family history for colorectal carcinoma constitutes a complicated diagnostic challenge involving many clinicians. The diagnostic workup of familial colorectal cancer is an elaborate and time consuming process in which the family and several medical specialists closely collaborate. However, establishing a diagnosis can be very rewarding. If a mutation is detected in the family, a satisfactory explanation can be provided for an accumulation of tumors at young age, and often of untimely death. Appropriate presymptomatic testing can be offered to reduce mortality among at-risk family members, and relatives not at risk can avoid uncertainty and needlessly intensive surveillance.

We show the differential diagnostic considerations when an individual with a family history of colorectal carcinoma is encountered, with emphasis on Lynch syndrome (Hereditary Nonpolyposis Colorectal Carcinoma [HNPCC]). Practical recommendations for laboratory workup of suspected Lynch syndrome, including analysis of tumor tissue by microsatellite instability analysis and immunohistochemistry, and germline DNA analysis are given. Furthermore, the clinical management after a molecular diagnosis has been made is described. The diagnostic scheme presented here allows efficient and effective analysis of colorectal carcinoma cases with (suspected) Lynch syndrome, making optimal use of currently available technology.

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