Thyroid Carcinoma in Birt-Hogg-Dubé Syndrome: Case Series and Review of Literature.

Background

Thyroid cancer (TC) is infrequently encountered in Birt-Hogg-Dubé (BHD) syndrome. We describe three BHD patients with TC and review the relevant literature. Patient Findings: Patient 1, a 55-year-old male with BHD, developed dedifferentiated oncocytic TC with distant metastases, requiring systemic therapy and radiation. Genetic testing revealed pathogenic variants (PVs) in FLCN, DAXX, and TP53. Patient 2, a 51-year-old female, and her 30-year-old daughter (patient 3) were diagnosed with papillary TC and treated with surgery and radioiodine. Tumor testing in patient 3 demonstrated PV in BRAF (V600E). Gene query analysis (n = 2285 patients) identified 2% FLCN PV prevalence in sporadic TCs, but the prevalence increased to 23% in anaplastic TCs. Literature review revealed 15 TC cases in BHD with diverse clinical presentations.

Conclusions

TCs are rare in BHD. FLCN PVs may not be the sole molecular drivers in TCs but may have a substantial role in the development of aggressive TCs.