Medullary thyroid cancer (MTC) accounts for around 5% of all thyroid cancers. The prognosis of the cancer upon presentation is poor; about 90% of patients with a tumor size greater than 4 cm in diameter have metastasis to both central and latero-cervical lymph nodes.
One of the characteristic features of MTC is abnormally high levels of calcitonin. Calcitonin levels are not just useful for diagnosing MTC; they hold prognostic value as well. Patients with calcitonin levels of more than 500 pg/mL prior to surgery are unlikely to experience a meaningful reduction in their calcitonin levels post-surgery.
In Cureus, Pishdad and colleagues presented the case study of a patient with a benign MTC.
A 62-year-old woman presented with a 2-year history of a “lump” sensation in the neck. She did not demonstrate any neck pain, dysphagia, or symptoms of hypo/hyperthyroidism.
The Steps to Diagnosing MTC
A physical neck examination revealed a 4 cm thyroid nodule on the right side of the neck, which moved easily upon swallowing. No cervical lymphadenopathy was detected.
An ultrasound of the neck was conducted, revealing a right-sided hypoechoic nodule measuring 4.12 cm x 1.84 cm. Thyroid function tests were normal but calcitonin levels were highly elevated, at 8754.0 pg/mL. Carcinoembryonic antigen (CEA) levels were also elevated, at 29.0 ng/mL.
Read more about medullary thyroid carcinoma epidemiology
A fine-needle aspiration was performed, and the cytology demonstrated a monomorphic population of multitudinous spindle cells with very few neoplastic cells present. The neoplastic cells stained focally for Chromogranin A. These findings were highly suggestive of MTC.
Genetic studies were performed with the following results:
- Positive for Harvey rat sarcoma viral oncogene homolog (HRAS) mutation
- Negative for rearranged during transfection (RET) mutation
- Negative for paired box 8/peroxisome proliferator-activated receptor gamma (PAX8/PPARG)
- Negative for neuroblastoma RAS viral oncogene homolog (NRAS)
- Negative for Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation.
A whole-body CT scan revealed no evidence of metastasis. The patient’s physicians decided to perform a total thyroidectomy.
Post-surgery, the patient was started on levothyroxine to ensure thyroid-stimulating hormone (TSH) levels were maintained at normal levels. At 12 months of follow-up, the patient’s calcitonin levels had come down to 3 ng/mL and her CEA levels had been reduced to 1.5 ng/mL.
Management of Benign MTC
In this study, the patient’s MTC diagnosis was first suspected upon cytology findings. The lump in the neck itself was insufficient for a definite diagnosis of MTC to be made.
“The discovery of MTC necessitates further investigations for evaluation of the disease extent, screening for pheochromocytoma and hyperparathyroidism, as well as genetic mutation analysis to determine whether MTC is sporadic or hereditary,” the research team wrote.
In addition to determining the possible cause of MTC, it is also vital to determine if the cancer has metastasized. MTC usually metastasizes to the lymph nodes, lungs, liver, skin, and bones. The presence of metastasis naturally means that the cancer is at an advanced stage and physicians should then come up with a suitable management strategy accordingly. According to the American Thyroid Association, palliative therapy should be considered should the patient be found to have advanced MTC.
As mentioned earlier, calcitonin levels have diagnostic and prognostic value in MTC. The American Thyroid Association Guidelines state, “In studies evaluating serum levels of calcitonin and procalcitonin in patients with MTC, calcitonin was found to have equal or superior diagnostic accuracy.” The patient’s extremely high calcitonin levels, matched with her cytology results, confirmed the diagnosis of MTC.
Read more about medullary thyroid carcinoma treatment
In this case, the patient’s treatment was rather straightforward; a total thyroidectomy combined with levothyroxine managed to reduce her calcitonin and CEA levels to normal. In Cancers, Marotta and colleagues wrote that although “thyroid nodules are detected in up to 60% of people by ultrasound examination, most of them are benign nodules requiring only follow up.”
The Role of Genetic Testing
The testing performed in this case for various RAS mutations is significant because the presence of RAS mutations was once considered an important prognostic marker, in that it poses a risk for the evolution from adenoma to carcinoma.
However, “it is clear now that the impact of RAS mutations on thyroid cells, normal and transformed, and the impact on the clinical behavior of thyroid neoplasms must not . . . be considered by itself but rather together with other genetic abnormalities in a more complex contest,” Marotta et al wrote.
One of the key takeaways from this case study is that genetic studies are important to determine the exact type of cancer under investigation. In this study, the genetic tests carried out complemented other investigations in helping physicians arrive at a correct diagnosis.
“This case highlights the need for comprehensive research studies on genomic profiling in MTC to better understand the relationship of different genomic mutations with prognosis and outcome,” the researchers concluded.
Marotta V, Bifulco M, Vitale M. Significance of RAS mutations in thyroid benign nodules and non-medullary thyroid cancer. Cancers (Basel). 2021;13(15):3785. doi:10.3390/cancers13153785
Pishdad R, Vahidi Rad M, Cespedes L. A benign medullary thyroid cancer. Cureus. 2022;14(1):e21038. doi:10.7759/cureus.21038
Wells SA Jr, Asa SL, Dralle H, et al. Revised American Thyroid Association guidelines for the management of medullary thyroid carcinoma. Thyroid. 2015;25(6):567-610. doi:10.1089/thy.2014.0335