!DOCTYPE html PUBLIC “-//W3C//DTD XHTML 1.1//EN” “http://www.w3.org/TR/xhtml11/DTD/xhtml11.dtd”>
|
I. THYROID CARCINOMA
A. Definition. Thyroid cancer consists of a group of neoplasms including differentiated (papillary, follicular, Hurthle cell, and follicular variant of papillary); medullary (sporadic and hereditary); poorly differentiated, anaplastic; and lymphoma. The most common site of spread of thyroid cancer is the cervical nodes, with the central nodal compartment affected most often.
B. Epidemiology. In 2013, there were 60,220 new cases of thyroid cancer in US, with a disproportionate number of females and patients under the age of 55. Studies from Asia reveal that thyroid cancer has become the most commonly diagnosed cancer in women. It is estimated that by 2014, thyroid cancer in females will outnumber that in males by 4:1. Despite the rising incidence of thyroid cancer, prognosis remains favorable, reflecting the indolent nature of the disease. The majority of thyroid cancer (90%) is well-differentiated thyroid carcinoma of papillary, follicular, or Hurthle cell pathology. Ten-year survival rates for patients with these subtypes are 93%, 85%, and 76%, respectively.
1. Differentiated. Subtypes include papillary, follicular, Hurthle cell, and poorly differentiated. Papillary carcinoma is the most common, accounting for 85%, and commonly metastasizes to the lymph nodes. In contrast, follicular carcinomas are more prone to systemic metastases.
2. Poorly differentiated. These tend to be more aggressive, more often are not iodine avid, and have a poorer prognosis.
3. Anaplastic. These carcinomas are almost never curable. Management includes surgical excision, if possible, and experimental protocols or palliative radiation. Survival is usually measured in weeks to months.
4. Medullary thyroid carcinomas (MTC). These can present as either sporadic tumors (75%) or as part of the multiple endocrine neoplasia syndromes (MEN2A and MEN 2B-25%). Sporadic and hereditary MTCs have similar clinical courses, but sporadic lesions often present later in life with neck masses largely due to lack of screening, almost always have lymph node metastases, and require extensive lymph node dissections. Hereditary MTCs are often detected as a result of familial screening, which allows for earlier detection and performance of preventative thyroidectomy in presymptomatic gene carriers.
a. MEN2A and MEN2B. The hallmark of these syndromes is MTC, which may be bilateral and multifocal. The MEN2A syndrome is characterized by MTC (100% penetrance), hyperparathyroidism (<25% penetrance), pheochromocytoma (<40% penetrance), and Hirschsprung’s disease (<3%). The MEN2B syndrome is characterized by MTC (100% penetrance), pheochromocytoma (50% penetrance), megacolon (100% penetrance), and by characteristic facial and skeletal features (“marfanoid habitus”). The MEN2 syndromes are caused by germline gain of function mutations in the RET proto-oncogene. There are strong genotype–phenotype correlations. For example, Hirschsprung’s disease is only associated with mutations in codon 609, 611, 618, and 620, while MEN2B is usually associated with codon 918 mutation. Patients with inherited RET proto-oncogene mutations identified by genetic screening should have prophylactic thyroidectomy. Patients with established MTC should be treated with surgery after screening for pheochromocytoma preoperatively. Patients with metastatic MTC are also candidates for therapy with tyrosine kinase inhibitors. Controversy exists over the appropriate age for prophylactic thyroidectomy, extent of lymph node dissection based on calcitonin level, and timing of systemic therapy in metastatic disease.
C. Presentation
1. Subjective. Patients with thyroid cancer of any type usually present with a thyroid or nodal mass in the neck, which may be associated with hoarseness, dysphagia, or difficulty breathing.
2. Objective. The physical exam reveals a mass in the thyroid that moves up and down with swallowing, but which may be fixed in position if there is significant local invasion. Cervical lymphadenopathy may be present. Frequently, there is an appreciable hoarse quality to the voice.
D. Diagnosis. Generally made by fine-needle aspiration cytology.
E. Workup
1. Laboratory assessment. Specific diagnostic labs include thyroid function tests, thyroglobulin, and calcitonin levels. The tumor markers thyroglobulin levels and antithyroglobulin antibodies are used to follow patients after treatment for differentiated thyroid cancer. Following treatment, thyroglobulin is measured either with or without TSH level modulation (achieved either by thyroid hormone withdrawal or administration of recombinant thyroglobulin [ThyrogenTM]). Calcitonin levels are followed in patients with MTC, and are used preoperatively to help determine the extent of node dissection, and postoperatively to screen for disease persistence, recurrence, and progression.
2. Imaging. Ultrasound will demonstrate the intrathyroidal tumor mass and adjacent lymph nodes. Computed tomography of the neck, chest, and abdomen may be helpful to distinguish pulmonary and mediastinal disease spread. Features of metastatic nodes in the neck include presence of calcifications; wide but short, rounded lesions; and obliteration of the fatty hilum. The only current recommended role for FDG/PET imaging is in patients with differentiated carcinoma with elevated thyroglobulin levels postoperatively and negative iodine imaging. In medullary carcinoma, computed tomography is highly favored over PET.
3. Endoscopy. Laryngoscopy should be performed on all patients with hoarseness as this may reveal a vocal cord paralysis. If tracheal or esophageal invasion is suspected, bronchoscopy and/or endoscopy is warranted.
F. Pathology. Routine light microscopy of the tissue specimen after staining with hematoxylin and eosin may identify the main cytologic subclasses of thyroid cancers. Special stains for calcitonin or immunoglobulin markers may be necessary if medullary carcinoma or lymphoma is suspected. Genetic mutations identified by molecular testing of tissue and aspirates, including BRAF, RAS, PAX8-PPAR gamma, and RET-PTC rearrangements, have been associated with differentiated thyroid cancer, though controversy exists over their utility in guiding surgical therapy.
G. Treatment. Surgical resection is usually the treatment modality of choice for thyroid cancer confined to the neck, though the extent of dissection and the adjuvant therapies vary by disease subtype.
1. Surgery. For differentiated thyroid cancer, total thyroidectomy is indicated for tumors >4 cm in diameter or tumors less than 4 cm with risk factors including age >45 years, cervical lymph node metastases, poorly differentiated histology, or extrathyroidal extension. There is controversy regarding whether or not to do prophylactic central lymph node dissection. However, the subcategory of minimally invasive follicular carcinoma generally follows an indolent course and can be treated adequately with lobectomy. For MTC, total thyroidectomy is generally recommended, and preoperative imaging and calcitonin levels should determine the extent of lymph node dissection. For anaplastic thyroid cancers, there is controversy as to whether or not surgery is ever indicated. The role of surgery for lymphoma is usually limited to tissue diagnosis only or in settings of airway compromise.
2. Radioactive iodine (RAI). Thyroid tissue selectively takes up iodine and is the primary location of its use in the body. Therefore, targeted radioactive therapy is possible. RAI is typically recommended for primary tumors >4 cm, gross extrathyroidal extension, or elevated postoperative unstimulated thyroglobulin levels (>5 to 10 ng/mL). RAI may selectively be applied for primary tumors measuring 1 to 4 cm, high-risk histology, lymphovascular invasion, cervical lymph node disease, macroscopic multifocality, or postoperative unstimulated thyroglobulin levels <5 to 10 ng/mL. RAI is not typically indicated for small, intrathyroidal, unifocal lesions, or undetectable postoperative unstimulated thyroglobulin. Additionally, RAI is not indicated in the setting of gross residual disease. Exact timing of adjuvant RAI is institution specific.
3. External beam radiation therapy. The role for this therapy in thyroid cancer is limited to tumors of the anaplastic subtype. This can be either adjuvant or palliative in nature.
4. Hormonal therapy.
Related posts:
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
