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Lynch syndrome: clinical, pathological, and genetic insights

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Abstract

Introduction

Lynch syndrome as the most common hereditary colorectal cancer syndrome and the most common cause of hereditary endometrial cancer is characterized by an autosomal dominant inheritance with a penetrance of 85–90%. The molecular genetic underlying mechanism is a mutation in one of the mismatch repair genes.

Methods

In order to identify patients with Lynch syndrome, a nuclear family history should be ascertained and matched with the Amsterdam criteria. A different approach for identification is the adherence to Bethesda criteria and subsequent testing for microsatellite instability. In patients with unstable tumors as an indicator for mismatch repair deficiency, genetic counseling and mutation analysis are warranted. For families fulfilling the Amsterdam criteria, intensified screening is recommended, even if a pathogenic mutation is not identified.

Results

Individuals from families with a proven pathogenic mutation that are tested negative are at normal population risk for cancers and may be dismissed from intensified surveillance. Prophylactic surgery in high-risk individuals without neoplasia is not generally recommended. At the time of a colon primary, however, extended surgery should be discussed in the light of a high rate of metachronous cancers. The worries of impairing functional results have now been evaluated in the light of quality of life in a large international cohort. Interestingly, extended (prophylactic) surgery does not lead to inferior quality of life with equal perioperative risks.

Conclusions

Therefore, taking the risk reduction into account, extended surgery at the time of the first colon primary should at least be discussed, if not recommended. Also, prophylactic hysterectomy and bilateral oophorectomy at the time of a colorectal primary should be recommended if family planning has been completed.

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Conflicts of interest

GM has received a fee as speaker at a Bayer workshop in 2010.

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Authors and Affiliations

  1. Department of Visceral, Thoracic and Vascular Surgery, Philipps University, Marburg, Germany

    Ralph Schneider

  2. Department of General and Visceral Surgery, HELIOS St. Josefs-Hospital, Bochum-Linden, Germany

    Claudia Schneider & Gabriela Möslein

  3. Department of Pathology, University of Heidelberg, Heidelberg, Germany

    Matthias Kloor

  4. Department of Surgery, Caritas Hospital St. Josef, Regensburg, Germany

    Alois Fürst

  5. Department of General and Visceral Surgery, Coloproctology, HELIOS St. Josefs-Hospital, Axstrasse 35, 44879, Bochum, Germany

    Gabriela Möslein

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  1. Ralph Schneider
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  2. Claudia Schneider
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  3. Matthias Kloor
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  4. Alois Fürst
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  5. Gabriela Möslein
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Correspondence to Gabriela Möslein.

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Schneider, R., Schneider, C., Kloor, M. et al. Lynch syndrome: clinical, pathological, and genetic insights. Langenbecks Arch Surg 397, 513–525 (2012). https://doi.org/10.1007/s00423-012-0918-8

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  • DOI: https://doi.org/10.1007/s00423-012-0918-8

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