A rare case of medullary thyroid carcinoma (MTC) and paraganglioma exhibits that tumor-to-tumor metastasis (TTM) is a possible occurrence, according to a study recently published in the Tohoku Journal of Experimental Medicine.

“Careful follow-up should be considered in cases with high carcinoembryonic antigen (CEA) and calcitonin levels, even if it has been long since the first MTC operation,” the authors wrote.

This case report and literature review aim to document a remarkable case of TTM in a 36-year-old female with multiple endocrine neoplasia type 2B (MEN 2B). The study, published recently, sheds light on the unusual phenomenon where primary tumor cells metastasize to other tumors in the body.

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The patient first received the diagnosis of MEN 2B at 24 years of age. She underwent total thyroidectomy at 15 years of age for MTC and bilateral adrenalectomy for pheochromocytomas at 29 years of age.

At 36 years of age, follow-up imaging revealed a retroperitoneal tumor of 30 mm adjacent to the left kidney and a 16 mm liver tumor in segment 6. Surgeons promptly resected both tumors for further examination.

Histological examination of the retroperitoneal tumor unveiled the classic Zellballen pattern, indicating a paraganglioma recurrence. However, pathologists discovered a white nodule positive for CEA and weakly positive for calcitonin inside the paraganglioma. These features led to diagnosing of a metastatic MTC with high malignant potential. Additionally, the liver lesion was confirmed as metastasis of MTC.

This is the first reported instance of TTM where MTC metastasized to a paraganglioma in a MEN 2B patient. While there have been previous instances of TTM involving thyroid carcinomas, MTC had not previously been documented as a donor tumor.

“In cases that reported MTC recurrence to occur 15 years or decades after thyroidectomy, although there were no evident lesions on imaging, the calcitonin levels remained high,” the authors noted.

The patient’s aggressive form of MTC posed a significant challenge, as it rapidly spread to regional lymph nodes and distant organs, including the liver, bone, and lungs. Regular follow-up with computed tomography (CT) and monitoring of CEA and calcitonin levels revealed high tumor marker levels during periods of MTC recurrence, indicating the importance of vigilant surveillance in such cases.

Stringent diagnostic criteria for TTM were met in this case, including confirmation of true metastasis, more than 1 primary tumor, and exclusion of contiguous growth or lymphatic spread. Donor tumors in TTM typically display more aggressive characteristics than recipient tumors, making this particular case all the more remarkable, the researchers concluded.


Takido N, Saito R, Okada K, et al. Tumor-to-tumor metastasis of medullary thyroid carcinoma to paraganglioma in a multiple endocrine neoplasia type 2B patient: a case report and literature review. Tohoku J Exp Med. Published online July 20, 2023. doi:/10.1620/tjem.2023.J058