Early Bilateral Thyroid Metastasis from Clear Cell Renal Cell Carcinoma with Co-occurring VHL and TP53 Mutations: A Case Report

Introduction

Clear cell renal cell carcinoma (ccRCC) is a recognized source of thyroid metastases, typically presenting after a prolonged disease-free interval following nephrectomy. Early thyroid involvement is unusual and can be diagnostically challenging because metastatic ccRCC may mimic benign thyroid disease or a primary thyroid neoplasm. We report an uncommon case of early, sequential bilateral thyroid metastasis from ccRCC associated with co-occurring VHL and TP53 mutations.

Case Presentation

A 65-year-old man initially presented with hematuria and anemia and was diagnosed with grade 3 ccRCC. He underwent right radical nephrectomy and adrenalectomy. Pathologic staging was pT3aN0M0 with negative surgical margins, and postoperative imaging showed no residual or metastatic disease. Approximately three years later, thyroid ultrasound performed for thyroid enlargement demonstrated heterogeneous echotexture and patchy hypoechogenicity initially interpreted as possible thyroiditis. Subsequent evaluation led to right hemithyroidectomy. Histopathologic examination demonstrated metastatic ccRCC involving the thyroid. Immunohistochemistry showed tumor cells negative for TTF-1 and thyroglobulin and positive for CAIX, supporting renal origin. Molecular profiling identified co-occurring VHL and TP53 mutations. Approximately 12 months after the initial thyroid surgery, surveillance identified a new metastatic lesion in the contralateral thyroid lobe, and the patient was evaluated for completion thyroidectomy.

Discussion

This case is distinguished by the unusually short interval between nephrectomy and thyroid metastasis, followed by rapid sequential involvement of the contralateral thyroid lobe. Thyroid metastases from RCC can resemble thyroiditis or primary thyroid neoplasms radiologically and cytologically, emphasizing the importance of considering metastatic disease in patients with a history of RCC. Immunohistochemistry was essential in establishing the diagnosis. VHL alterations are characteristic of ccRCC, whereas TP53 mutations are considerably less common. The coexistence of these alterations in a tumor demonstrating early and recurrent metastatic behavior raises the possibility that the molecular profile may reflect biologically aggressive disease, although a causal relationship cannot be established from a single case.

Conclusion

Thyroid metastasis should remain in the differential diagnosis of new thyroid abnormalities in patients with a history of ccRCC, even when imaging suggests benign thyroid disease and the interval from nephrectomy is relatively short. This case highlights an unusual pattern of early, sequential bilateral thyroid metastasis and demonstrates the diagnostic value of immunohistochemistry and molecular characterization. Recognition of atypical metastatic patterns may facilitate earlier diagnosis and inform multidisciplinary surveillance and management.