Medullary thyroid cancer 1

Medullary thyroid cancer

Medullary thyroid cancerClassification and external resources

Micrograph of medullary thyroid carcinoma with amyloid deposition (left of image). Near normal thyroid follicles are also seen (right of image).H&E stain.

ICD-10 C73 [1]

ICD-9 193 [2]

OMIM 155240 [3]

MedlinePlus 000374 [4]

eMedicine med/2272 [5]

MeSH D013964 [6]

Medullary thyroid cancer (MTC) is a form of thyroid carcinoma which originates from the parafollicular cells (Ccells), which produce the hormone calcitonin.[7] Medullary tumors are the third most common of all thyroid cancers.They make up about 3% of all thyroid cancer cases.Approximately 25% of medullary thyroid cancer is genetic in nature, caused by a mutation in the RETproto-oncogene. This form is classified as familial MTC. When MTC occurs by itself it is termed sporadic MTC.When it coexists with tumors of the parathyroid gland and medullary component of the adrenal glands(pheochromocytoma) it is called multiple endocrine neoplasia type 2 (MEN2).It was first characterized in 1959.

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Signs and symptoms

Medullary thyroid carcinoma on ultrasound withtypical small calcifications (arrows)

The major clinical symptom of metastatic medullary thyroid carcinomais diarrhea; occasionally a patient will have flushing episodes. Bothoccur particularly with liver metastasis, and either symptom may be thefirst manifestation of the disease. The flushing that occurs in medullarythyroid carcinoma is indistinguishable from that associated withcarcinoid syndrome. In MTC, the flushing, diarrhea, and itching(pruritis) are all caused by elevated levels of calcitonin gene products(calcitonin or calcitonin gene-related peptide). Alternatively, theflushing and diarrhea observed in carcinoid syndrome is caused byelevated levels of circulating serotonin.

Medullary thyroid carcinoma may also produce a thyroid nodule andenlarged cervical lymph nodes.Sites of spread of medullary thyroid carcinoma include local lymphnodes in the neck, lymph nodes in the central portion of the chest (mediastinum), liver, lung, and bone. Spread toother sites such as skin or brain occurs but is uncommon.

MarkersWhile the increased serum concentration of calcitonin is not harmful, it is useful as a marker which can be tested inblood.A second marker, carcinoembryonic antigen (CEA), also produced by medullary thyroid carcinoma, is released intothe blood and it is useful as a serum or blood tumor marker. In general, measurement of serum CEA is less sensitivethan serum calcitonin for detecting the presence of a tumor, but has less minute to minute variability and is thereforeuseful as an indicator of tumor mass.

GeneticsMutations (DNA changes) in the RET proto-oncogene, located on chromosome 10, lead to the expression of amutated receptor tyrosine kinase protein, termed RET (REarranged during Transfection). RET is involved in theregulation of cell growth and development and its germline mutation is responsible for nearly all cases of hereditaryor familial medullary thyroid carcinoma. Its germline mutation may also be responsible for the development ofhyperparathyroidism and pheochromocytoma. Hereditary medullary thyroid cancer is inherited as an autosomaldominant trait, meaning that each child of an affected parent has a 50/50 probability of inheriting the mutant RETproto-oncogene from the affected parent. DNA analysis makes it possible to identify children who carry the mutantgene; surgical removal of the thyroid in children who carry the mutant gene is curative if the entire thyroid gland isremoved at an early age, before there is spread of the tumor. The parathyroid tumors and pheochromocytomas areremoved when they cause clinical symptomatology. Hereditary medullary thyroid carcinoma or multiple endocrineneoplasia (MEN2) accounts for approximately 25% of all medullary thyroid carcinomas.Seventy-five percent of medullary thyroid carcinoma occurs in individuals without an identifiable family history andis assigned the term "sporadic". Individuals who develop sporadic medullary thyroid carcinoma tend to be older andhave more extensive disease at the time of initial presentation than those with a family history (screening is likely tobe initiated at an early age in the hereditary form). Approximately 25-60% of sporadic medullary thyroid carcinomashave a somatic mutation (one that occurs within a single "parafollicular" cell) of the RET proto-oncogene. Thismutation is presumed to be the initiating event, although there could be other as yet unidentified causes.

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PrognosisDepending on source, the overall 5-year survival rate for medullary thyroid cancer is 80%,83% or 86%,[8] and the10-year survival rate is 75%.[]

By overall cancer staging into stages I to IV, the 5-year survival rate is 100% at stage I, 98% at stage II, 81% at stageIII and 28% at stage IV.[9] The prognosis of MTC is poorer than that of follicular and papillary thyroid cancer whenit has metastasized (spread) beyond the thyroid gland.The prognostic value of measuring calcitonin and carcinoembryonic antigen (CEA) concentrations in the blood wasstudied in 65 MTC patients who had abnormal calcitonin levels after surgery (total thyroidectomy and lymph nodedissection). The prognosis correlated with the rate at which the postoperative calcitonin concentration doubles,termed the calcitonin doubling time (CDT), rather than the pre- or postoperative absolute calcitonin level:• CDT less than 6 months: 3 patients out of 12 (25%) survived 5 years. 1 patient out of 12 (8%) survived 10 years.

All died within 6 months to 13.3 years.• CDT between 6 months and 2 years: 11 patients out of 12 (92%) survived 5 years. 3 patients out of 8 (37%)

survived 10 years. 4 patients out of 12 (25%) survived to the end of the study.• CDT more than 2 years: 41 patients out of 41 (100%) were alive at the end of the study. These included 1

patient whose calcitonin was stable, and 11 patients who had decreasing calcitonin levels.The calcitonin doubling time was a better predictor of MTC survival than CEA but following both tests isrecommended.[10][11]

TreatmentSurgery and radiation therapy have been the major treatments for medullary thyroid carcinoma.

SurgeryExtensive surgery can be effective when the condition is detected early, but a risk for recurrence remains. About halfof patients have metastasis to regional lymph nodes at the time of diagnosis.The European Society of Endocrine Surgeons have published recommendations for the management of thiscondition.[12] The timing of surgery depends on the type of mutation present. For those in the highest risk group,surgery is recommended in the first year of life. In lower risk cases surgery may be delayed up to the age of tenyears, the precise timing depending on the mutation and other factors.

RadiationExternal beam radiotherapy is recommended when there is a high risk of regional recurrence, even after optimumsurgical treatment.Unlike other differentiated thyroid carcinoma, there is no role for radioiodine treatment in medullary-type disease.

Protein kinase inhibitorsClinical trials of protein kinase inhibitors, which block the abnormal kinase proteins involved in the developmentand growth of medullary cancer cells, showed clear evidence of response in 10-30% of patients. In the majority ofresponders there has been less than a 30% decrease in tumor mass, yet the responses have been durable; responseshave been stable for periods exceeding 3 years. The major side effects of this class of drug include hypertension,nausea, diarrhea, some cardiac electrical abnormalities, and thrombotic or bleeding episodes.Vandetanib, trade name Caprelsa, was the first drug (April 2011) to be approved by US Food and DrugAdministration (FDA) for treatment of late-stage (metastatic) medullary thyroid cancer in adult patients who areineligible for surgery.

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Cabozantinib, trade name Cometriq, was granted marketing approval (November 2012) by the U.S. FDA for thisindication.

References[1] http:/ / apps. who. int/ classifications/ icd10/ browse/ 2010/ en#/ C73[2] http:/ / www. icd9data. com/ getICD9Code. ashx?icd9=193[3] http:/ / omim. org/ entry/ 155240[4] http:/ / www. nlm. nih. gov/ medlineplus/ ency/ article/ 000374. htm[5] http:/ / www. emedicine. com/ med/ topic2272. htm[6] http:/ / www. nlm. nih. gov/ cgi/ mesh/ 2014/ MB_cgi?field=uid& term=D013964[7] Hu MI, Vassilopoulou-Sellin R, Lustig R, Lamont JP. "Thyroid and Parathyroid Cancers" (http:/ / www. cancernetwork. com/

cancer-management-11/ chapter05/ article/ 10165/ 1402668) in Pazdur R, Wagman LD, Camphausen KA, Hoskins WJ (Eds) CancerManagement: A Multidisciplinary Approach (http:/ / www. cancernetwork. com/ cancer-management-11/ ). 11 ed. 2008.

[8] National Cancer Institute > Medullary Thyroid Cancer (http:/ / www. cancer. gov/ cancertopics/ pdq/ treatment/ thyroid/ HealthProfessional/page7) Last Modified: 12/22/2010

[9] cancer.org > Thyroid Cancer (http:/ / www. cancer. org/ cancer/ thyroidcancer/ detailedguide/ thyroid-cancer-survival-rates) By the AmericanCancer Society. In turn citing: AJCC Cancer Staging Manual (7th ed).

[10] Thyroid Carcinoma. NCCN guidelines. http:/ / www. nccn. org/ professionals/ physician_gls/ pdf/ thyroid. pdf[11][11] ASCO SEP 3rd edition[12][12] Niederle B, Sebag F, Brauckhoff M (2013) Timing and extent of thyroid surgery for gene carriers of hereditary C cell disease-a consensus

statement of the European Society of Endocrine Surgeons (ESES).Langenbecks Arch Surg

Article Sources and Contributors 5

Article Sources and ContributorsMedullary thyroid cancer  Source: http://en.wikipedia.org/w/index.php?oldid=584490156  Contributors: Andrux, Angelito7, Arcadian, Arnoldberk, Bathosrex, Cortamears, Eleassar,FeatherPluma, Ground Zero, Headbomb, Immunize, J04n, Jmh649, Jwc012, Mikael Häggström, Nephron, Ossip Groth, PKT, R'n'B, Rfgagel, Rhcastilhos, Rich Farmbrough, Rod57, Rosenwig,Rytyho usa, Sanya3, Smartse, Squids and Chips, Urgos, Wouterstomp, 18 anonymous edits

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