SAT562 Metastatic Oncocytic (Formerly Hürthle Cell) Thyroid Carcinoma in a Patient With Birt-Hogg-Dubé Syndrome

Disclosure: S. Vaid: None. R. Klein: None. P. Veeraraghavan: None. D.M. Blakaj: None. A. Agrawal: None. J. Sipos: None. S.I. Sherman: None. J. Klubo-Gwiezdzinska: None. S. Gubbi: None. Introduction: Birt-Hogg-Dubé syndrome (BHD) is a rare, autosomal dominant disorder due to a germline loss-of-function mutation in the folliculin (FLCN) gene. Clinical manifestations include pulmonary cysts, renal cell carcinoma, and skin tumors, while tumors of other sites such as thyroid are uncommon. Here, we report an extremely rare case of oncocytic thyroid carcinoma (OTC) in a patient with BHD. Clinical case: A 55-year-old male with BHD noted a lump in his neck which was identified as a 3 cm right thyroid nodule on sonogram. Medical history only included BHD, which was diagnosed based on the presence of pulmonary cysts and two family members with BHD. No family members had thyroid tumors, and the patient denied any history of radiation exposure. Fine needle aspiration biopsy was indeterminate (Bethesda III). A total thyroidectomy and central lymph node (LN) dissection was performed as LN metastases were identified on intraoperative frozen section. Histopathology revealed 3 foci of OTC, largest being 3.8 cm, with extrathyroidal extension into fibroadipose tissue, 3/31 LN metastases with the largest deposit of 0.5 cm without extranodal extension. A 156.6 mCi dose of I-131 radioiodine (RAI) was administered. No uptake was noted on the post-therapy scan. Four months later, new right lateral cervical lymphadenopathy was noted on computed tomogram (CT). A right lateral selective neck dissection was performed, which identified 3/28 metastatic LNs without extranodal extension. Next generation gene sequencing testing of the metastatic tumor revealed the pathogenic FLCN (H429fs*27) variant, along with TP53 (R248Q), and DAXX (L666fs*29) pathogenic variants. Over the next 20 months, serum thyroglobulin increased from 1.8 ng/ml to 121 ng/mL (normal: 1.6 - 59.9 ng/mL). Several sub-centimeter lung nodules and new right cervical lymphadenopathy were noted on CT, and these lesions demonstrated increased uptake on fluorodeoxyglucose positron emission tomography (PET/CT) and on Ga-68 DOTATATE PET/CT scans. Due to close proximity to the right internal jugular vein, the cervical lymphadenopathy was deemed to be inoperable. Stereotactic radiation was administered to the neck, which resulted in substantial shrinkage of the neck metastases. The patient continues to be on active surveillance, with tyrosine kinase inhibitors or peptide receptor radionuclide therapy being potential future systemic therapy options in case of disease progression. Conclusion: Thyroid tumors have been occasionally reported in BHD. While most of them are papillary or follicular tumors, only one case of OTC in BHD has been previously reported in the literature [1]. This report underscores the importance of screening for thyroid neoplasms in patients with BHD. Reference: 1. Panagiotidis et al. World J Nucl Med. 2018;17(2):123-125 Presentation Date: Saturday, June 17, 2023