Medullary Thyroid Carcinoma (MTC)


Medullary thyroid carcinoma (MTC) is a calcitonin-secreting neuroendocrine tumor arising from C cells of the thyroid gland.1,2 MTC is a rare tumor, with an approximate incidence of less than 0.5 per 100,000 population,1,2 and it accounts for fewer than 10% of all malignant thyroid tumors.3 MTC usually presents at an advanced stage with spread to the lymphatics.4 The 10-year disease-specific survival rates vary from 75% to 82% in population-based cohorts.1,5 Operative resection is the mainstay of curative treatment.6 The American Thyroid Association guidelines recommend total thyroidectomy including central lymph node dissection as the basic method of surgical treatment for patients with a preoperative diagnosis of MTC. Ipsilateral and/or contralateral lateral lymph node dissections may be done according to the clinical findings, ultrasonographic features, and levels of calcitonin.6

When internal organs are involved, advanced MTC can lead to complications related to the secretion of hormones, lymph node metastasis, and distant metastasis. 

Patients with advanced MTC may present with frequent episodes of diarrhea due to highly elevated calcitonin levels. Diarrhea is the most striking hormone-mediated clinical feature of MTC, whereas flushing is rare, although it may occur. Occasionally, ectopic secretion of adrenocorticotropic hormone (ACTH) may lead to Cushing syndrome.7

Lymph Node Metastasis

Many sporadic and hereditary cases of MTC are not detectable on genetic or biochemical screening. Patients may present with a palpable neck mass. Cervical lymph node metastases have been observed in 25% to 63% of such cases.8 Metastases are seen in the central compartment of the neck in the perithyroidal, paratracheal (level VI), and upper mediastinal (level VII) nodes. The lymph nodes of the central compartment are located between the carotid arteries from the hyoid bone to the innominate vein. Bilateral spread is usually seen within this compartment. Spread to the lymphatics develops in the lateral neck compartment. The middle and lower jugular nodes (levels III and IV) are commonly involved. The high jugular (level II) and posterior triangle (level V) nodes are less frequently involved.9,10 

Distant Metastasis

Distant metastasis is noted in up to 10% of patients with MTC.11,12 MTC metastasizes through the lymphatic and blood vessels, extends to the cervical and mediastinal lymph nodes, and secondarily involves the liver, lungs, and bones. In a subset of patients with advanced disease, symptoms of obstruction and dysphagia may develop because of aggressive local growth.12 Patients with distant metastasis may also have symptoms of diarrhea and flushing because of elevated levels of calcitonin in the blood. Carcinoembryonic antigen (CEA) is also an important marker during follow-up, and measurement of the CEA level is very useful in patients with moderate calcitonin production.12

Postoperative Complications

The benefits of surgical treatment must always be weighed against the risks and potential complications of surgery during a determination of the best possible treatment option for a patient. Thyroid surgery-specific complications (hypoparathyroidism and recurrent laryngeal nerve [RLN] palsy) were observed postoperatively in 12.3% of patients with all types of thyroid cancer in a population-based study.13 Another study indicated that the incidence of complications is usually related to the extent of dissection of the central lymph nodes (level VI) and the surgeon’s level of expertise. The rates of postoperative complications can be minimized if total thyroidectomy is performed with an accurate technique.14 

Hypoparathyroidism

Hypoparathyroidism is the most common complication following thyroid surgery and is significant because permanent hypoparathyroidism is linked to high rates of morbidity and mortality and to a reduced quality of life.2,15 The incidence of transient hypoparathyroidism has been observed to vary from 0.3% to 49%, and that of permanent hypoparathyroidism from 0% to 13%.16

Recurrent Laryngeal Nerve Palsy

The incidence of RLN palsy has been estimated to be from 0% to 5%.16 RLN palsy has detrimental effects on quality of life. The various causes of transient RLN palsy are excessive nerve skeletonization, axonal damage due to enormous strain, “a frigore” or “a calore” paralysis, thermic lesions resulting from electrocoagulation, viral neuritis, and orotracheal intubation paralysis.17 Logopedic rehabilitation must be initiated as soon as possible in patients with vocal cord palsy. Patients with an injured RLN are treated with voice therapy; laryngeal reinnervation procedures; injection laryngoplasty with the use of materials like gel foam, fat, and collagen; arytenoid adduction; or medialization laryngoplasty with expanded polytetrafluoroethylene (E-PTTE, Gore-Tex).18 Although insertion of an electrode into the endotracheal tube for intraoperative RLN monitoring has been proposed, it tends not to reduce the incidence of RLN palsy.18 

Bleeding and Other Complications

Hematoma is a fatal complication of thyroidectomy. The acute respiratory embarrassment caused by hematoma formation is fatal if the hematoma is not immediately removed surgically. Thus, thorough hemostasis done with the utmost care is necessary during thyroid surgery.19 Other common postoperative complications, such as postoperative fever, infection, and cardiopulmonary and thromboembolic events, have also been reported.13 

References

  1. Opsahl EM, Akslen LA, Schlichting E, et al. Trends in diagnostics, surgical treatment, and prognostic factors for outcomes in medullary thyroid carcinoma in Norway: a nationwide population-based study. Eur Thyroid J. 2019;8(1):31-40. doi:10.1159/000493977
  2. van Beek DJ, Almquist M, Bergenfelz AO, Musholt TJ, Nordenström E,  on behalf of the EUROCRINE® Council. Complications after medullary thyroid carcinoma surgery: multicentre study of the SQRTPA and EUROCRINE® databases [published online October 14, 2020]. Br J Surg. doi:10.1002/bjs.12055
  3. Wells SA Jr, Franz C. Medullary carcinoma of the thyroid gland. World J Surg. 2000;24(8):952-956. doi:10.1007/s002680010166
  4. Machens A, Hauptmann S, Dralle H. Prediction of lateral lymph node metastases in medullary thyroid cancer. Br J Surg. 2008;95(5):586-591. doi:10.1002/bjs.6075
  5. Mathiesen JS, Kroustrup JP, Vestergaard P, et al. Survival and long-term biochemical cure in medullary thyroid carcinoma in Denmark 1997-2014: a nationwide study. Thyroid. 2019;29(3):368-377. doi:10.1089/thy.2018.0564
  6. 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
  7. Raue F, Frank-Raue K. Epidemiology and clinical presentation of medullary thyroid carcinoma. Recent Results Cancer Res. 2015;204:61-90. doi:10.1007/978-3-319-22542-5_3
  8. Rougier P, Parmentier C, Laplanche A, et al. Medullary thyroid carcinoma: prognostic factors and treatment. Int J Radiat Oncol Biol Phys. 1983;9(2):161-169. doi:10.1016/0360-3016(83)90093-7
  9. Moley JF, DeBenedetti MK. Patterns of nodal metastases in palpable medullary thyroid carcinoma: recommendations for extent of node dissection. Ann Surg. 1999;229(6):880-888. doi:10.1097/00000658-199906000-00016
  10. Shah JP. Cervical lymph node metastases–diagnostic, therapeutic, and prognostic implications. Oncology (Williston Park). 1990;4(10):61-69; discussion 72, 76.
  11. Kanteti AP, Atiya S, Hein A, Cox JL, Martinez Duarte E. Medullary thyroid carcinoma presenting as metastatic disease to the breast. Case Rep Pathol. 2020 May 22;2020:6138409. doi:10.1155/2020/6138409
  12. WHO classification of tumours of endocrine organs. In: Lloyd RV, Osamura RY, Kloppel G, Rosai J, eds. WHO Classification of Tumours, 4th ed, vol 10. Lyon, France: International Agency for Research on Cancer (IARC); 2017.
  13. Papaleontiou M, Hughes DT, Guo C, Banerjee M, Haymart MR. Population-based assessment of complications following surgery for thyroid cancer. J Clin Endocrinol Metab. 2017;102(7):2543-2551. doi:10.1210/jc.2017-00255
  14. Toniato A, Boschin IM, Piotto A, et al. Complications in thyroid surgery for carcinoma: one institution’s surgical experience. World J Surg. 2008;32(4):572-575. doi:10.1007/s00268-007-9362-2
  15. Bergenfelz A, Nordenström E, Almquist M. Morbidity in patients with permanent hypoparathyroidism after total thyroidectomy. Surgery. 2020;167(1):124-128. doi:10.1016/j.surg.2019.06.056
  16. Woodson G. Pathophysiology of recurrent laryngeal nerve injury. In: Randolph G, ed. Surgery of the Thyroid and Parathyroid Glands, 3rd ed. Philadelphia, PA: Elsevier; 2020:404-409.
  17. Rosato L, Avenia N, Bernante P, et al. Complications of thyroid surgery: analysis of a multicentric study on 14,934 patients operated on in Italy over 5 years. World J Surg. 2004;28(3):271-276. doi:10.1007/s00268-003-6903-1
  18. Lee YS, Nam KH, Chung WY, Chang HS, Park CS. Postoperative complications of thyroid cancer in a single center experience. J Korean Med Sci. 2010;25(4):541-545. doi:10.3346/jkms.2010.25.4.541
  19. Reeve T, Thompson NW. Complications of thyroid surgery: how to avoid them, how to manage them, and observations on their possible effect on the whole patient. World J Surg. 2000;24(8):971-975. doi:10.1007/s002680010160

Reviewed by Debjyoti Talukdar, MD, on 7/1/2021.