Corticotroph Pituitary Carcinoma in a Patient With Lynch Syndrome (LS) and Pituitary Tumors in a Nationwide LS Cohort

Research output: Contribution to journalArticle

Abstract

Context: Lynch syndrome (LS) is a cancer-predisposing syndrome caused by germline mutations in genes involved in DNA mismatch repair (MMR). Patients are at high risk for several types of cancer, but pituitary tumors have not previously been reported.

Case: A 51-year-old man with LS (MSH2 mutation) and a history of colon carcinoma presented with severe Cushing disease and a locally aggressive pituitary tumor. The tumor harbored a mutation consistent with the patient's germline mutation and displayed defect MMR function. Sixteen months later, the tumor had developed into a carcinoma with widespread liver metastases. The patient prompted us to perform a nationwide study in LS.

Nationwide Study: A diagnosis consistent with a pituitary tumor was sought for in the Swedish National Patient Registry. In 910 patients with LS, representing all known cases in Sweden, another two clinically relevant pituitary tumors were found: an invasive nonsecreting macroadenoma and a microprolactinoma (i.e., in total three tumors vs. one expected).

Conclusion: Germline mutations in MMR genes may contribute to the development and/or the clinical course of pituitary tumors. Because tumors with MMR mutations are susceptible to treatment with immune checkpoint inhibitors, we suggest to actively ask for a family history of LS in the workup of patients with aggressive pituitary tumors.

Details

Authors
  • Daniel Bengtsson
  • Patrick Joost
  • Christos Aravidis
  • Marie Askmalm Stenmark
  • Ann Sofie Backman
  • Beatrice Melin
  • Jenny von Salomé
  • Theofanis Zagoras
  • Samuel Gebre-Medhin
  • Pia Burman
Organisations
External organisations
  • Linköping University
  • Kalmar County Hospital
  • Uppsala University
  • Karolinska Institute
  • Umeå University
  • Karolinska University Hospital
  • Sahlgrenska University Hospital
  • Skåne University Hospital
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cancer and Oncology
Original languageEnglish
Pages (from-to)3928-3932
Number of pages5
JournalThe Journal of clinical endocrinology and metabolism
Volume102
Issue number11
StatePublished - 2017 Nov 1
Peer-reviewedYes