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noma Patients with MEN 2B have activating mutations in exon 16 of the ret oncogene These germline mutations can be detected by DNA analysis of peripheral WBCs, allowing identification of gene carriers within the family When a family with MEN 2A or familial medullary thyroid carcinoma does not have an identifiable ret oncogene mutation, gene carriers may still be identified using family linkage analysis Somatic mutations of the ret oncogene can be identified in the tumors of 30% of patients with sporadic (nonfamilial) medullary thyroid carcinoma (See Multiple Endocrine Neoplasia) Medullary thyroid carcinoma represents about 3% of thyroid cancers About one-third of cases are sporadic, onethird are familial, and one-third are associated with MEN type 2 Therefore, discovery of a medullary thyroid carcinoma makes genetic analysis mandatory, as noted above If a gene defect is discovered, related family members must have genetic screening for that specific gene defect Even when no gene defect is detectable, family members should have regular thyroid surveillance Medullary thyroid carcinoma arises from parafollicular thyroid cells that can secrete calcitonin, prostaglandins, serotonin, ACTH, corticotropin-releasing hormone (CRH), and other peptides These peptides can cause symptoms and can be used as tumor markers Early local metastases are usually present, usually to adjacent muscle and trachea as well as to local and mediastinal lymph nodes Eventually, late metastases may appear in the bones, lungs, adrenals, or liver Metastases to the neck may be detected by ultrasound Metastases are best detected using 18 FDG-PET whole-body scanning Medullary thyroid carcinoma does not concentrate iodine Anaplastic thyroid carcinoma is caused by certain gene mutations, including inactivating mutations of the p53 tumor suppressor gene, as described above for papillary and follicular thyroid carcinomas Anaplastic thyroid carcinoma represents about 2% of thyroid cancers It usually presents in an older patient as a rapidly enlarging mass in a multinodular goiter It is the most aggressive thyroid carcinoma and metastasizes early to surrounding nodes and distant sites Local pressure symptoms include dysphagia or vocal cord paralysis This tumor does not concentrate iodine Other thyroid malignancies together represent about 3% of thyroid cancers Lymphoma of the thyroid is more common in older women It usually presents as a rapidly enlarging, painful mass arising out of a multinodular or diffuse goiter affected by autoimmune thyroiditis, with which it may be confused microscopically About 20% of cases have concomitant hypothyroidism Thyroid lymphomas are most commonly B cell lymphomas (50%) or mucosa-associated lymphoid tissue (MALT; 23%); other types include follicular, small lymphocytic, and Burkitt s lymphoma and Hodgkin s disease Thyroidectomy is rarely required Metastatic cancers may sometimes involve the thyroid, particularly bronchogenic, breast, and renal carcinomas and malignant melanoma
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Thyroid carcinoma usually presents as a palpable, firm, nontender nodule in the thyroid Most thyroid carcinomas are
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1 Ultrasound of the neck Ultrasound of the neck should be performed routinely on all patients with thyroid cancer for the initial diagnosis and for follow-up Ultrasound is useful in determining the size and location of the malignancy as well as the location of any neck metastases 2 Radioactive iodine scanning RAI (131I or 123I) thyroid and whole-body scanning is used after thyroidectomy for surveillance as described below, supplanting its previous use to determine whether a nodule was cold as a sign of malignancy 3 CT scanning CT scanning may demonstrate metastases and is particularly useful for localizing and monitoring lung metastases However, CT scanning is less sensitive than ultrasound for detecting metastases within the neck Iodinated contrast should never be given prior to RAI scanning or RAI therapy, since the large amounts of iodine in contrast media competitively inhibit the uptake of RAI by the thyroid, greatly reducing the effectiveness of subsequent RAI scanning and therapy Medullary carcinoma in the thyroid, nodes, and liver may calcify, but lung metastases rarely do so 4 MRI MRI is particularly useful for imaging bone metastases 5 PET scanning PET scanning is particularly useful for detecting thyroid cancer metastases that do not have sufficient iodine uptake to be visible on RAI scans 18FDG-PET/CT fusion scanning is particularly sensitive and allows tumor volumetric determinations The sensitivity of 18FDG-PET scanning for differentiated thyroid cancer is enhanced if the patient is hypothyroid or receiving thyrotropin, which increases the metabolic activity of differentiated thyroid cancer Disadvantages of PET scanning include its lack of specificity for thyroid cancer as well as its expense and lack of availability in many locations 18FDG-PET scanning has prognostic implications, since differentiated thyroid cancer metastases with low standard uptake value scores are associated with a better prognosis
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asymptomatic, but large thyroid cancers can cause neck discomfort, dysphagia, or hoarseness (due to pressure on the recurrent laryngeal nerve) About 3% of thyroid malignancies present with a metastasis, usually to local lymph nodes but sometimes to distant sites such as bone or lung Metastatic functioning differentiated thyroid carcinoma can sometimes secrete enough thyroid hormone to produce thyrotoxicosis Medullary thyroid carcinoma frequently causes flushing and persistent diarrhea (30%), which may be the initial clinical feature Patients with metastases often experience fatigue as well as other symptoms Cushing s syndrome develops in about 5% of patients from secretion of ACTH or CRH Signs of pressure or invasion of surrounding tissues are present in anaplastic or large tumors; recurrent laryngeal nerve palsy can occur
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