Introduction
Lynch syndrome (LS) is an autosomal dominant genetic disease associated with germ-line mutations of genes involved in mismatch repair (MLH1, MSH2, MSH6 and PMS2) and the EPCAM gene. LS patients are at increased risk for colorectal cancer and other malignancies (especially endometrial, ovarian, and gastric cancer). There are few reported cases of thyroid cancer in patients suffering from LS.
Aims & Methods
To systematically investigate the presence of thyroid nodules in LS patients, to assess their cytologic classes and to explore its association with genetic features of the disease. A retrospective and descriptive analysis was conducted to include all LS patients followed at CEMAD (Centro Malattie Apparato Digerente) of Fondazione Policlinico Universitario A. Gemelli IRCCS. For each patient, characteristics of LS disease and previous history of thyroid disease were evaluated. Majority of patients underwent thyroid ultrasound (US) and nodule cytology was performed when needed. Gene mutations were reviewed for each patient with thyroid nodules and previous history of thyroid disease.
Results
A total of 139 LS patients, 52 males and 87 females, were included in the study. 103 patients (74%) underwent thyroid ultrasound examination, and 7 patients (5%) had a previous history of thyroid disease (cancer or multinodular goitre). For these two groups, mean age was 51.9 years. 29 patients (21%) did not already perform US at the time of analysis. Thyroid nodules were found in 62 patients (60%) who underwent US and 9 of them (14%) had suspicious features of malignancy inducing fine-needle aspiration biopsy. Cytologic analysis classified 7 of 9 cases (78%) as TIR2 and 2 (22%) as TIR3a. Between patients with nodular thyroid disease (single nodule, multinodular goitre and cancer), most of them (25 patients, 36% of total) were carriers of MSH6 mutation, while 22 (32%), 17 (24%) and 5 (7%) had MSH2, MLH1 and PMS2 mutations, respectively.
Conclusion
A high prevalence of thyroid nodules is found in patients with Lynch Syndrome, especially in MSH6 carrier patients. Performing at least one thyroid ultrasound examination is suggested for detection of nodular thyroid disease in LS patients. Systematic investigations are needed to estimate their prevalence, features, and risk of malignant transformation.
References
NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) Genetic/Familial High-Risk Assessment: Colorectal Version 2.2023 — October 30, 2023
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