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.
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