6918 A Unique Case of Oncocytic Thyroid Cancer with an NBN Gene Pathogenic Variant
Authors: Grover Ashna , Jhawar Sakshi , Shekhar Skand , Avadhanula Shirisha A , Al-Naqeeb Ghadah , Thota Geethika , Veeraraghavan Padmasree , Cochran Craig , Kao-Hsieh Marie Y , Gharib Ahmed , Escorcia Freddy E , Del Rivero Jaydira , Klubo-Gwiezdzinska Joanna , Gubbi Sriram 
Published: October 2024

Disclosure: A. Grover: None. S. Jhawar: None. S. Shekhar: None. S.A. Avadhanula: None. G. Al-Naqeeb: None. G. Thota: None. P. Veeraraghavan: None. C. Cochran: None. M.Y. Kao-Hsieh: None. A. Gharib: None. F.E. Escorcia: None. J. Del Rivero: None. J. Klubo-Gwiezdzinska: None. S. Gubbi: None.

Introduction: Oncocytic thyroid carcinoma (OTC), previously known as “Hürthle cell” carcinoma, makes up less than 5% of all thyroid cancers. OTCs are often aggressive with a high risk of metastasis, and a poorer prognosis compared to other forms of differentiated thyroid carcinoma (DTC). Molecular drivers of OTC include pathogenic variants (PVs) in NRAS, DAXX, CDKN1A, the mitochondrial genome and chromosomal alterations. PVs in the NBN gene in OTC have not been previously reported. Case: A 53-year-old male was noted to have a thyroid nodule on a routine physical examination. Patient denied any hyper/hypothyroid or compressive symptoms, and family history was unremarkable. Cytopathologic analysis of the fine needle aspiration biopsy of the nodule was consistent with a thyroid follicular neoplasm (Bethesda IV). A total thyroidectomy with central compartment neck dissection was performed. Histopathologic examination demonstrated a 7 cm x 4 cm x 4 cm OTC with capsular and lymphovascular invasion, but without extra-thyroidal extension or lymph node metastasis (pT3aN0Mx). Subsequently, adjuvant radioiodine (RAI) I131 therapy with 165 mCi was administered and post-therapy scan revealed neck uptake. One-year post-therapy RAI diagnostic scan was negative. Three years following the initial thyroid surgery, elevated serum thyroglobulin (Tg) levels were noted. A computed tomogram of the chest revealed multiple bilateral lung nodules. Further imaging ruled out involvement of other distant sites. A diagnostic lower lung wedge resection demonstrated metastatic OTC. The tumor stained positive for CK7, PAX8, TG, TTF-1 and negative for CK20 on immunohistochemistry. Next-generation sequencing of the tumor tissue (Oncomine Comprehensive Assay v3) revealed a PV in the NBN gene (c.2166_2167delGCinsAT; p.Trp722Ter). A year later, the serum Tg levels continued to rise, and the lung nodules had increased in size. Due to disease progression, lenvatinib was initiated. A [F18]-fluorodeoxyglucose positron emission tomography performed one year later demonstrated persistent pulmonary tumor burden with new osseous metastasis in the right scapula, left acetabulum, and the sternum. Zoledronic acid was initiated for the treatment of the skeletal metastases, and palliative external beam radiation (2000 cGy in 5 fractions) was administered to the sternal lesion to alleviate the bone pain. Conclusion: The NBN gene encodes for the protein nibrin, a member of the MRE11/RAD50 complex that is involved in DNA repair. PVs in NBN are commonly identified in non-thyroidal malignancies such as breast and lung carcinomas. While NBN PVs are rarely reported in DTCs, as per our knowledge, this is the first described case of OTC with a PV in NBN as the molecular driver, manifesting with an aggressive disease course. Identification of this novel PV therefore adds to the current knowledge of the molecular landscape of OTC.

Presentation: 6/3/2024