SUN-386 - Thyroidentity Theft: Metastatic Renal Cell Carcinoma Masquerading as Primary Thyroid Malignancy

Introduction: Metastatic cancers to the thyroid are a rare clinical occurrence that are found in 0.07% of FNA cytology results and account for up to 2.1% of all thyroid malignancies (1). Discovery of previously undiagnosed clear cell renal cell carcinoma (ccRCC) during the evaluation of incidentally discovered thyroid nodules occurs in only 0.02% of thyroid biopsies or resections that yield a malignant diagnosis (1). High clinical suspicion is key, as up to 36% of metastatic cancers are misinterpreted as primary thyroid carcinomas (1). Immunohistochemistry (IHC) staining for specific markers is crucial for accurate diagnosis.

Case Presentation: A 78-year-old male with a history of Graves’ disease in remission following methimazole treatment was incidentally found to have a 3.2 x 2 x 2.1 cm left thyroid nodule on CT neck imaging. Dedicated thyroid ultrasound showed a 2.3 cm left TIRADS-5 nodule without regional lymphadenopathy, which on fine needle aspiration (FNA) biopsy, revealed atypia of unknown significance. Molecular testing via Afirma reported the nodule as “suspicious”- conferring an estimated 50% risk of malignancy- but was negative for mutations including BRAF and RET. Repeat FNA biopsy demonstrated IHC features suggestive of papillary thyroid carcinoma (PTC): staining weakly positive for Thyroglobulin (TG) but negative for Calcitonin. The patient underwent total thyroidectomy due to concerns for possible PTC and persistence of Graves’ antibodies raising the risk of future recurrence. Interestingly, the final pathology demonstrated a well-defined metastatic clear cell carcinoma within the left thyroid lobe. IHC staining was positive for PAX8, CD10, and Vimentin, and was negative for TTF1 and TG, consistent with metastatic ccRCC. Subsequent CT Chest, Abdomen, & Pelvis identified a 9 cm right renal mass and a 1.9 cm right adrenal indeterminate nodule (negative evaluation for pheochromocytoma). The patient underwent right radical nephrectomy with right adrenalectomy and paracaval lymph node dissection, demonstrating oligometastatic (OM) ccRCC to only the thyroid with no further evidence of metastatic disease.

Conclusion: This case highlights the significance of IHC staining when differentiating primary thyroid malignancy from metastatic ccRCC: while both display PAX8 positivity, TTF1 and TG staining is specific for differentiated thyroid cancers. Even without a known primary malignancy, clinicians should maintain a high degree of suspicion for metastatic disease when thyroid-specific IHC staining is absent as thyroid nodules may be the index presentation. Though OM ccRCC to the thyroid has a poor prognosis (5-year disease-free survival of 58%), long-term cure is possible with successful surgical resection.
1. Ghossein CA, Khimraj A, Dogan S, Xu B. Metastasis to the thyroid gland: a single-institution 16-year experience. Histopathology. 2021 Mar;78(4):508-519.

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