Medullary thyroid cancer pathophysiology

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Medullary thyroid cancer Microchapters


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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ammu Susheela, M.D. [2]


Development of medullary thyroid cancer is the result of genetic mutation of RET proto-oncogene. On gross pathology, well-circumscribed, gray, white, or yellow-colored masses are characteristic findings of medullary thyroid cancer. On microscopic histopathological analysis, polygonal to the spindle to small cells, interstitial edema, and vascular hyalinized stroma are characteristic findings of medullary thyroid cancer.



Associated Conditions

Gross Pathology

  • Medullary thyroid cancer is usually a well circumscribed, gray, white, or yellow colored mass which is gritty to firm in consistency.[9]

Microscopic Pathology

  • On microscopic histopathological analysis, presence of amyloid is a characteristic finding of medullary thyroid cancer.[10][11]
  • Other microscopic features associated with the diagnosis of medullary thyroid cancer include:
    • The majority of tumor cells are epithelioid, but spindle cells may be found as well.
    • The nuclei demonstrate the characteristic granular appearance known as salt-and-pepper.
    • The cytoplasm of tumor cells contains perinuclear calcitonin-containing azurophilic granules that are best seen in samples stained with the May–Grünwald–Giemsa stain.
Medullary thyroid cancer Image Image
  • Medullary thyroid carcinoma
H&E stain, low power. Contributed in wikimedia.commons
H&E stain, high power. Contributed in wikimedia.commons
  • Medullary thyroid cancer amyloid
H&E stain, medium power. Contributed in wikimedia.commons
H&E stain, high power. Contributed in wikimedia.commons
  • Thyroid MedullaryCarcinoma Comedonecrosis
H&E stain, medium power. Contributed in wikimedia.commons
H&E stain, high power. Contributed in wikimedia.commons
  • Medullary thyroid carcinoma spindle cell
H&E stain, low power. Contributed in wikimedia.commons
H&E stain, medium power. Contributed in wikimedia.commons
  • Medullary thyroid carcinoma spindle cell
H&E stain, low power. Contributed in wikimedia.commons
H&E stain, high power. Contributed in wikimedia.commons
  • For more images of medullary thyroid cancer please click here



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  2. Wells, Samuel A.; Asa, Sylvia L.; Dralle, Henning; Elisei, Rossella; Evans, Douglas B.; Gagel, Robert F.; Lee, Nancy; Machens, Andreas; Moley, Jeffrey F.; Pacini, Furio; Raue, Friedhelm; Frank-Raue, Karin; Robinson, Bruce; Rosenthal, M. Sara; Santoro, Massimo; Schlumberger, Martin; Shah, Manisha; Waguespack, Steven G. (2015). "Revised American Thyroid Association Guidelines for the Management of Medullary Thyroid Carcinoma". Thyroid. 25 (6): 567–610. doi:10.1089/thy.2014.0335. ISSN 1050-7256.
  3. Gertner ME, Kebebew E (August 2004). "Multiple endocrine neoplasia type 2". Curr Treat Options Oncol. 5 (4): 315–25. PMID 15233908.
  4. Wells SA, Asa SL, Dralle H, Elisei R, Evans DB, Gagel RF, Lee N, Machens A, Moley JF, Pacini F, Raue F, Frank-Raue K, Robinson B, Rosenthal MS, Santoro M, Schlumberger M, Shah M, Waguespack SG (June 2015). "Revised American Thyroid Association guidelines for the management of medullary thyroid carcinoma". Thyroid. 25 (6): 567–610. doi:10.1089/thy.2014.0335. PMC 4490627. PMID 25810047.
  5. Berndt I, Reuter M, Saller B, Frank-Raue K, Groth P, Grussendorf M, Raue F, Ritter MM, Höppner W (March 1998). "A new hot spot for mutations in the ret protooncogene causing familial medullary thyroid carcinoma and multiple endocrine neoplasia type 2A". J. Clin. Endocrinol. Metab. 83 (3): 770–4. doi:10.1210/jcem.83.3.4619. PMID 9506724.
  6. Ercolino, Tonino; Lai, Roberta; Giachè, Valentino; Melchionda, Salvatore; Carella, Massimo; Delitala, Alessandro; Mannelli, Massimo; Fanciulli, Giuseppe (2014). "Patient affected by neurofibromatosis type 1 and thyroid C-cell hyperplasia harboring pathogenic germ-line mutations in both NF1 and RET genes". Gene. 536 (2): 332–335. doi:10.1016/j.gene.2013.12.003. ISSN 0378-1119.
  7. Koch, Christian A; Brouwers, Frederieke M; Vortmeyer, Alexander O; Tannapfel, Andrea; Libutti, Steven K; Zhuang, Zhengping; Pacak, Karel; Neumann, Hartmut PH; Paschke, Ralf (2006). "Somatic VHLgene alterations in MEN2-associated medullary thyroid carcinoma". BMC Cancer. 6 (1). doi:10.1186/1471-2407-6-131. ISSN 1471-2407.
  8. Raue, Friedhelm; Frank-Raue, Karin (2015). "Epidemiology and Clinical Presentation of Medullary Thyroid Carcinoma". 204: 61–90. doi:10.1007/978-3-319-22542-5_3. ISSN 0080-0015.
  9. Husain, Nuzhat; Shukla, Saumya; Awasthi, NamrataP (2014). "Papillary variant of medullary carcinoma thyroid". Indian Journal of Pathology and Microbiology. 57 (1): 151. doi:10.4103/0377-4929.130933. ISSN 0377-4929.
  10. 10.0 10.1 Nelkin BD, de Bustros AC, Mabry M, Baylin SB (June 1989). "The molecular biology of medullary thyroid carcinoma. A model for cancer development and progression". JAMA. 261 (21): 3130–5. PMID 2654432.
  11. Valenta, Lubomir J.; Michel-Bechet, Marc; Mattson, Joan C.; Singer, Frederick R. (1977). "Microfollicular thyroid carcinoma with amyloid rich stroma, resembling the medullary carcinoma of the thyroid (MCT)". Cancer. 39 (4): 1573–1586. doi:10.1002/1097-0142(197704)39:4<1573::AID-CNCR2820390433>3.0.CO;2-A. ISSN 0008-543X.
  12. Nakazawa, Tadao; Cameselle-Teijeiro, José; Vinagre, João; Soares, Paula; Rousseau, Emmanuel; Eloy, Catarina; Sobrinho-Simões, Manuel (2014). "C-Cell-Derived Calcitonin-Free Neuroendocrine Carcinoma of the Thyroid". International Journal of Surgical Pathology. 22 (6): 530–535. doi:10.1177/1066896914525228. ISSN 1066-8969.
  13. Mendelsohn, Geoffrey; Wells, Samuel A.; Baylin, Stephen B. (1984). "Relationship of tissue carcinoembryonic antigen and calcitonin to tumor virulence in medullary thyroid carcinoma. An immunohistochemical study in early, localized, and virulent disseminated stages of disease". Cancer. 54 (4): 657–662. doi:10.1002/1097-0142(1984)54:4<657::AID-CNCR2820540412>3.0.CO;2-V. ISSN 0008-543X.

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