A very rare case of “triple-negative” tumor markers calcitonin, carcinoembryonic antigen (CEA), and chromogranin A in medullary thyroid carcinoma (MTC) was recently identified in a case report and published in Archives of Medical Science.

“Compared with other thyroid malignancies, MTC exhibits distinctive histopathological features, and the most important immunohistochemical markers are [calcitonin] and CEA; in fact, in the absence of [calcitonin] expression, the diagnosis of MTC should be questioned,” Martínex-Montoro et al explained.

The case describes a 44-year-old female who presented with neck swelling for 3 months. Regarding past medical and family history, she only admitted to having arterial hypertension treated with a daily dose of 50 mg of atenolol. During the physical examination, findings included a 30 mm x 20 mm thyroideal nodule in the left lobule of tender consistency that moved synchronically to swallowing.

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Plasma levels of thyroid-stimulating hormone, thyroid hormones, and thyroid peroxidase antibody were inside the normal range. A neck ultrasound revealed a 30 mm x 12 mm x 17 mm nodule with well-defined walls and a homogeneous hypoechoic solid pattern, with peripheral and central vascularization. Histologic analysis of cytology taken by fine-needle aspiration reported an important number of single-follicular cells with 3D groups overlapping follicular cells, classifying them into a Bethesda category 4.

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Given the inconclusive findings, the healthcare team performed a diagnostic left hemithyroidectomy. The anatomopathological characteristics of the resected tissue were compatible with MTC. Tumor markers such as cytokeratins, chromogranin A, neuron-specific enolase, and synaptophysin showcased strong diffuse staining, but amyloid material, present in 60% of MTC tumors, was absent in this case.

Moreover, calcitonin, CEA chromogranin A, thyroglobulin, and 5-hydroxyindoleacetic acid plasma levels were normal at <2 pg/ml, 0.22 ng/ml, 6.2 ng/ml,12 ng/ml, and 3.56 mg/day, respectively. At 2 months postsurgery, the patient underwent a completion thyroidectomy. Consistent follow-up neck, thoracic and abdominal computed tomographies, neck ultrasounds, and blood work, including CEA levels, have consistently reported no signs of local recurrence or invasive disease during 13 years.

“Some authors have argued that the absence of [calcitonin] secretion implies poor differentiation of the tumor, which may be a sign of adverse prognosis, especially among tumors with [calcitonin]-negative [immunohistochemistry], although recent studies have shown a very variable prognosis,” the authors said.

“Our case expressed a low Ki67 proliferation index, and there was no evidence of regional or distant disease postoperatively.” Finally, there are no specific guidelines on the surveillance of this disease, possibly due to its rarity. In this publication, continued monitoring with computed tomography, ultrasound, and blood tests proved to be useful and accurate.


Martínez-Montoro J I, Gómez-Pérez A M, Gallego E, et al. “Triple-negative” non-secretory medullary thyroid cancer: uncommon pathological findings in a rare disease. Arch Med Sci. Published online April 20, 2022. doi:10.5114/aoms/147431