Researchers reported the rare case of a 70-year-old woman with aggressive calcitonin-negative medullary thyroid carcinoma (MTC), highlighting the difficulty of diagnosing and managing the condition due to its nonsecretory state. The case also underscores the importance of having diagnostic and prognostic guidelines for the disease.

Calcitonin secreted by MTC cells is the gold-standard biomarker for diagnosing and monitoring the disease. However, some cases of MTC can be calcitonin-negative, although this is extremely rare, with just 80 cases reported in the literature.

The case reported here is that of a patient with an aggressive clinical course who presented to the emergency department of Sarawak General Hospital in Kuching, Malaysia, with a 2-day history of painful swallowing, shortness of breath, and loss of voice. Over the next 2 months, her condition worsened, with neck swelling and difficulty swallowing. 

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Physical examination revealed a hard mass in the right anterior area of the neck. A neck computed tomography (CT) scan showed a right thyroid mass with matted cervical lymphadenopathy.

The thyroid mass was biopsied, and malignant cells that were positive for CKAE1/AE3, CD56, synaptophysin, and TTF-1 were identified, suggesting of MTC. However, thyroid function, serum calcium, and carcinoembryonic antigen (CEA) levels were normal, and serum calcitonin was not detected.

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Histopathological examination after tumor debulking and tracheostomy showed a high-grade neuroendocrine tumor, which was negative for calcitonin and leucocyte common antigen. The researchers reported that the patient was diagnosed with calcitonin-negative MTC. She refused further therapy and died soon after. 

The case study was published in the Journal of the ASEAN Federation of Endocrine Societies.

MTC arises from parafollicular cells, or C cells, in the thyroid gland. Malignant C cells usually secrete high levels of calcitonin and CEA.


Loh EW, Tan FHS. A rare case of aggressive calcitonin-negative medullary thyroid carcinoma. J ASEAN Fed Endocr Soc. 2022;37(S2):46.