Daniel Bengtsson1,2, Patrick Joost3, Christos Aravidis4, Marie Askmalm Stenmark5,6,7, Ann-Sofie Backman8,9, Beatrice Melin10, Jenny von Salomé11,12, Theofanis Zagoras13, Samuel Gebre-Medhin7,12, Pia Burman14. 1. Department of Clinical and Experimental Medicine, Linköping University, 58183 Linköping, Sweden. 2. Department of Internal Medicine, Kalmar County Hospital, 39185 Kalmar, Sweden. 3. Department of Oncology and Pathology, Institute of Clinical Sciences, Lund University, 22184 Lund, Sweden. 4. Department of Immunology, Genetics and Pathology, Uppsala University, 75185 Uppsala, Sweden. 5. Division of Clinical Genetics, Department of Clinical and Experimental Medicine, Linköping University, 58185 Linköping, Sweden. 6. Department of Clinical Genetics, Office for Medical Services, 22184 Lund, Sweden. 7. Division of Clinical Genetics, Department of Laboratory Medicine, Lund University, 22184 Lund, Sweden. 8. Centrum for Digestive Diseases, Karolinska University Hospital, Solna, 17176 Stockholm, Sweden. 9. Institution of Medicine, Karolinska Institutet, Solna, 17176 Stockholm, Sweden. 10. Department of Radiation Sciences, Oncology, Umeå University, 90187 Umeå, Sweden. 11. Department of Molecular Medicine and Surgery, Karolinska Institutet, Solna, 17176 Stockholm, Sweden. 12. Department of Clinical Genetics, Karolinska University Hospital, Solna, 17176 Stockholm, Sweden. 13. Department of Clinical Pathology and Genetics, Sahlgrenska University Hospital, 41345 Gothenburg, Sweden. 14. Department of Endocrinology, Skåne University Hospital, Malmö, University of Lund, 20502 Malmö, Sweden.
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.
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.
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