eMedicine Specialties > Oncology > Carcinomas of Endocrine Organs

Thyroid, Medullary Carcinoma: Differential Diagnoses & Workup

Author: Anastasios K Konstantakos, MD, Clinical Associate Surgeon, Department of Cardiovascular Surgery, Billings Clinic, Billings, Montana
Contributor Information and Disclosures

Updated: Sep 29, 2009

Differential Diagnoses

Carcinoid Tumor, Intestinal
Thyroid Lymphoma
De Quervain Thyroiditis
Thyroid Nodule
Goiter
Thyroid, Anaplastic Carcinoma
Goiter, Toxic Nodular
Thyroid, Follicular Carcinoma
Graves Disease
Thyroid, Medullary Carcinoma
Hyperthyroidism
Thyroid, Papillary Carcinoma
Multiple Endocrine Neoplasia, Type 2

Other Problems to Be Considered

VIPomas

Workup

Laboratory Studies

  • According to the American Thyroid Association, preoperative laboratory testing in patients with possible medullary thyroid carcinoma (MTC) has 3 purposes1 :
    • Predict the extent of metastatic disease; this will determine the extent of preoperative imaging and may alter the surgical approach
    • In patients with MEN 2, identify primary hyperparathyroidism and/or pheochromocytoma —comorbid conditions that alter the surgical approach and surgical priorities.
    • Identify RET mutation carriers so that testing of appropriate family members can allow for early diagnosis and treatment of affected individuals.
  • Obtain serum calcitonin levels. Calcitonin is the principal biochemical marker in MTC; it is used for detection, staging, postoperative management, and prognosis.1 The higher that the calcitonin levels are above normal, the greater the likelihood of MTC; basal levels of >100 pg/mL have been found to have 100% positive predictive value for MTC.1,4 Very rarely, patients with clinically apparent MTC may not have elevated calcitonin levels.
    • Machens et al found that in RET carriers who are at risk for MTC but have not yet undergone treatment, calcitonin levels can be used to determine the need for lymph node dissection.5 In their study of 308 RET carriers, all patients with node-positive MTC had elevated basal calcitonin levels (91.4 pg/mL or higher); no patients with normal pretherapy calcitonin levels had lymph node metastasis. These researchers suggest that unless clinical evidence indicates a need for it, RET carriers with normal pretherapeutic basal calcitonin levels may forgo lymph node dissection.
  • Traditionally, a pentagastrin-induced rise in calcitonin secretion has been used to diagnose MTC; however, pentagastrin is not available in the United States and many other countries, and DNA testing for RET has replaced this diagnostic method in familial cases.
  • Consider a 24-hour urinalysis for catecholamine metabolites (eg, vanillylmandelic acid [VMA], metanephrine) to rule out concomitant pheochromocytoma in patients with MEN type 2A or 2B. Pheochromocytoma must be treated before MTC.1
  • Obtain screening for the development of familial MTC in family members of patients with a history of MTC or MEN 2A or 2B.
  • Screen all family members for missense mutation in RET in leukocytes.
  • Finding a RET mutation in an asymptomatic family member should lead to discussion and pursuit of a prophylactic total thyroidectomy (see Treatment).

Imaging Studies

  • Patients in whom medullary thyroid carcinoma (MTC) is diagnosed or suspected on the basis of fine needle aspiration findings or calcitonin levels should undergo preoperative ultrasonography to detect lymph node metastases. The study should be performed by an experienced operator and should include the superior mediastinum and the central and lateral neck compartments.1
  • Patients with regional lymph node involvement or calcitonin levels >400 pg/mL should undergo preoperative CT scanning of the chest and neck, as well as 3-phase, contrast-enhanced, multidetector liver CT or contrast-enhanced MRI to detect metastatic disease.1

Procedures

  • Fine-needle aspiration yields cytologic information, allowing diagnosis of MTC.6

Histologic Findings

Grossly, medullary thyroid carcinoma (MTC) resembles a well-circumscribed off-white nodule with a rough texture. Microscopically, it contains nests of round or ovoid cells. A fibrovascular stroma is usually intercalated between cells. Sometimes, amyloid material, consisting of calcitonin prohormone, may occur in the MTC stroma. Perhaps most importantly, immunohistochemical diagnosis of MTC can be made by demonstrating calcitonin using radioactive calcitonin antiserum against MTC cells.

Staging

A 2009 article argued that using the 1997 TNM staging criteria is more accurate for medullary thyroid carcinoma than the 2002 criteria in terms of assessing prognosis. Under the 2002 criteria, a significantly higher percentage of patients were classified as having stage IV disease. The authors indicated that elevated calcitonin that remains stable often does not indicate a poor outcome, and patients with lymph node metastases but no distant disease would be better classified as having stage III cancer.7

More on Thyroid, Medullary Carcinoma

Overview: Thyroid, Medullary Carcinoma
Differential Diagnoses & Workup: Thyroid, Medullary Carcinoma
Treatment & Medication: Thyroid, Medullary Carcinoma
Follow-up: Thyroid, Medullary Carcinoma
References
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References

  1. [Guideline] Kloos RT, Eng C, Evans DB, Francis GL, Gagel RF, Gharib H, et al. Medullary thyroid cancer: management guidelines of the American Thyroid Association. Thyroid. Jun 2009;19(6):565-612. [Medline]. [Full Text].

  2. Hundahl SA, Cady B, Cunningham MP, Mazzaferri E, McKee RF, Rosai J, et al. Initial results from a prospective cohort study of 5583 cases of thyroid carcinoma treated in the united states during 1996. U.S. and German Thyroid Cancer Study Group. An American College of Surgeons Commission on Cancer Patient Care Evaluation study. Cancer. Jul 1 2000;89(1):202-17. [Medline].

  3. Kebebew E, Greenspan FS, Clark OH, et al. Extent of disease and practice patterns for medullary thyroid cancer. J Am Coll Surg. Jun 2005;200(6):890-6. [Medline].

  4. Costante G, Meringolo D, Durante C, Bianchi D, Nocera M, Tumino S, et al. Predictive value of serum calcitonin levels for preoperative diagnosis of medullary thyroid carcinoma in a cohort of 5817 consecutive patients with thyroid nodules. J Clin Endocrinol Metab. Feb 2007;92(2):450-5. [Medline]. [Full Text].

  5. Machens A, Lorenz K, Dralle H. Individualization of lymph node dissection in RET (rearranged during transfection) carriers at risk for medullary thyroid cancer: value of pretherapeutic calcitonin levels. Ann Surg. Aug 2009;250(2):305-10. [Medline].

  6. Chang TC, Wu SL, Hsiao YL. Medullary thyroid carcinoma: pitfalls in diagnosis by fine needle aspiration cytology and relationship of cytomorphology to RET proto-oncogene mutations. Acta Cytol. Sep-Oct 2005;49(5):477-82. [Medline].

  7. Boostrom SY, Grant CS, Thompson GB, Farley DR, Richards ML, Hoskin TL, et al. Need for a revised staging consensus in medullary thyroid carcinoma. Arch Surg. Jul 2009;144(7):663-9. [Medline].

  8. Ye L, Santarpia L, Gagel RF. Targeted Therapy for Endocrine Cancer: The Medullary Thyroid Carcinoma Paradigm. Endocr Pract. Jun 22 2009;1-24. [Medline].

  9. Ducic Y, Oxford L. Transcervical elective superior mediastinal dissection for thyroid carcinoma. Am J Otolaryngol. Jul-Aug 2009;30(4):221-4. [Medline].

  10. Sherman SI. Advances in chemotherapy of differentiated epithelial and medullary thyroid cancers. J Clin Endocrinol Metab. May 2009;94(5):1493-9. [Medline].

  11. Schlumberger MJ, Elisei R, Bastholt L, Wirth LJ, Martins RG, Locati LD, et al. Phase II study of safety and efficacy of motesanib in patients with progressive or symptomatic, advanced or metastatic medullary thyroid cancer. J Clin Oncol. Aug 10 2009;27(23):3794-801. [Medline].

  12. Laure Giraudet A, Al Ghulzan A, Aupérin A, Leboulleux S, Chehboun A, Troalen F, et al. Progression of medullary thyroid carcinoma: assessment with calcitonin and carcinoembryonic antigen doubling times. Eur J Endocrinol. Feb 2008;158(2):239-46. [Medline]. [Full Text].

  13. Carlomagno F, Santoro M. Identification of RET kinase inhibitors as potential new treatment for sporadic and inherited thyroid cancer. J Chemother. Nov 2004;16 Suppl 4:49-51. [Medline].

  14. Chi DD, Moley JF. Medullary thyroid carcinoma: genetic advances, treatment recommendations, and the approach to the patient with persistent hypercalcitoninemia. Surg Oncol Clin N Am. Oct 1998;7(4):681-706. [Medline].

  15. Evans DB, Fleming JB, Lee JE, et al. The surgical treatment of medullary thyroid carcinoma. Semin Surg Oncol. 1999;16:50-63. [Medline].

  16. Fitze G. Management of patients with hereditary medullary thyroid carcinoma. Eur J Pediatr Surg. Dec 2004;14(6):375-83. [Medline].

  17. Gibelin H, Essique D, Jones C, et al. Increased calcitonin level in thyroid nodules without medullary carcinoma. Br J Surg. May 2005;92(5):574-8. [Medline].

  18. Hyer SL, Newbold K, Harmer C. Familial medullary thyroid cancer: clinical aspects and prognosis. Eur J Surg Oncol. May 2005;31(4):415-9. [Medline].

  19. Quayle FJ, Moley JF. Medullary thyroid carcinoma: including MEN 2A and MEN 2B syndromes. J Surg Oncol. Mar 1 2005;89(3):122-9. [Medline].

  20. Rosenthal MS, Pierce HH. Inherited medullary thyroid cancer and the duty to warn: revisiting Pate v. Threlkel in light of HIPAA. Thyroid. Feb 2005;15(2):140-5. [Medline].

  21. Shaha AR. Management of the neck in thyroid cancer. Otolaryngol Clin North Am. 1998;31:823-31.

  22. Udelsman R, Lakatos E, Ladenson P. Optimal surgery for papillary thyroid carcinoma. World J Surg. 1996;20:88-93. [Medline].

  23. You YN, Lakhani V, Wells SA Jr, Moley JF. Medullary thyroid cancer. Surg Oncol Clin N Am. Jul 2006;15(3):639-60. [Medline].

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Further Reading

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Keywords

medullary thyroid carcinoma, MTC, thyroid cancer, thyroid cancer symptoms, thyroid cancer diagnosis, thyroid cancer treatment, thyroid tumor, multiple endocrine neoplasia, MEN, thyroidectomy, hypothyroidism

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Contributor Information and Disclosures

Author

Anastasios K Konstantakos, MD, Clinical Associate Surgeon, Department of Cardiovascular Surgery, Billings Clinic, Billings, Montana
Disclosure: Nothing to disclose.

Medical Editor

Lodovico Balducci, MD, Professor of Oncology and Medicine, University of South Florida College of Medicine; Division Chief, Senior Adult Oncology Program, H Lee Moffitt Cancer Center and Research Institute
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

CME Editor

Rajalaxmi McKenna, MD, FACP, Southwest Medical Consultants, SC, Department of Medicine, Good Samaritan Hospital, Advocate Health Systems
Rajalaxmi McKenna, MD, FACP is a member of the following medical societies: American Society of Clinical Oncology, American Society of Hematology, and International Society on Thrombosis and Haemostasis
Disclosure: Nothing to disclose.

 
 
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