The diagnostic puzzle of thyroid paraganglioma: when the usual suspects fail—a case report

Summary Background Thyroid paraganglioma (TPGL) is an exceptionally rare neuroendocrine tumor, with fewer than 75 cases reported. Its clinical and imaging features often resemble those of medullary thyroid cancer, making diagnosis challenging. Accurate identification is essential for appropriate surgical management and genetic counselling. Case presentation A 63-year-old woman with atrial fibrillation was incidentally found to have a right thyroid nodule in carotid ultrasound. High-resolution ultrasonography showed a solid, hypoechoic EU-TIRADS 4 lesion; fine-needle aspiration was inconclusive. The patient underwent right lobectomy with isthmectomy. Histology revealed a well-circumscribed intrathyroidal mass composed of epithelioid cells in a nested (zellballen) pattern and delicate vascular stroma. Immunohistochemistry was positive for synaptophysin, neuron-specific enolase, CD56, and S‑100, but negative for TTF‑1, calcitonin, parathyroid hormone (PTH), and cytokeratin, confirming thyroid paraganglioma. Clinical discussion Thyroid paraganglioma usually arises from inferior laryngeal paraganglia and is often discovered incidentally. Its features overlap with those of other thyroid neoplasms, requiring immunohistochemical confirmation to avoid misdiagnosis. Functional catecholamine secretion is rare and was absent in this case. About 25% of paragangliomas are linked to hereditary syndromes such as SDHB mutations, warranting genetic assessment. Surgical excision is the treatment of choice, while long-term surveillance is recommended due to uncertain biological behavior. Conclusion Thyroid paraganglioma is a rare entity that should be considered in intrathyroidal neuroendocrine tumors. Diagnosis depends on histopathology and immunohistochemistry, and surgical removal is typically curative.