Practice Essentials
Thyroid cancers represent approximately 1% of new cancer diagnoses in the United States each year. Thyroid malignancies are divided into papillary carcinomas (80%), follicular carcinomas (10%), medullary thyroid carcinomas (5-10%), anaplastic carcinomas (1-2%), primary thyroid lymphomas (rare), and primary thyroid sarcomas (rare).
Hürthle cell carcinoma is a rare thyroid malignancy that is often considered a variant of follicular carcinoma. Hürthle cell carcinomas account for 2-3% of all thyroid malignancies. They occur more commonly in women than in men and typically manifest in the fifth decade of life. The clinical presentation is similar to that of other thyroid malignancies. See the image below.
A monomorphous cell population of Hürthle cells arranged in loosely cohesive clusters and single cells. The cells are polyhedral and have abundant granular cytoplasm with well-defined cell borders. The nuclei are enlarged and have a central prominent macronucleolus.
For summarized information on staging and treatment, see Thyroid Cancer Staging and Thyroid Cancer Treatment Protocols.
Signs and symptoms of thyroid cancer
Thyroid carcinoma most commonly manifests as a painless, palpable, solitary thyroid nodule. Patients or clinicians discover most of these nodules during routine palpation of the neck.
Signs and symptoms associated with malignancy in thyroid nodules include the following:
Solitary nodules: Most likely to be malignant in patients older than 60 years and in patients younger than 30 years
Increased rate of malignancy in males
Nodular growth
Rapid growth: Ominous sign
Usually painless (nontender to palpation); sudden onset of pain more strongly associated with benign disease (eg, hemorrhage into a benign cyst, subacute viral thyroiditis)
Hard and fixed nodules
Diagnosis of thyroid cancer
The key to the workup of the solitary thyroid nodule is to differentiate malignant from benign disease and, thus, to determine which patients require intervention and which patients may be monitored serially. History taking, physical examination, laboratory evaluation, and fine-needle aspiration biopsy (FNAB) are the mainstays in the evaluation of thyroid nodules. Imaging studies can be adjuncts in select cases.
Examination in patients suspected of thyroid cancer includes the following:
Thorough head and neck examination, including thyroid gland and cervical soft tissues
Indirect laryngoscopy
Firm cervical masses are highly suggestive of regional lymph node metastases. Vocal fold paralysis implies involvement of the recurrent laryngeal nerve.
Procedures
FNAB is the most important diagnostic tool in evaluating thyroid nodules and should be the first intervention. The following are the 4 possible results from this procedure:
Benign disease
Malignant disease
Indeterminate for diagnosis
Nondiagnostic
Up to 50% of repeated biopsies result in a definitive diagnosis. Patients whose findings are indeterminate or nondiagnostic despite repeat biopsy can undergo surgery for lobectomy for tissue diagnosis. Nondiagnostic cases can also be monitored clinically, and radioiodine scans can be useful for determining the functional status of the nodule, because most hyperfunctioning nodules are benign.
Laboratory testing
The following laboratory studies may be used to assess patients with suspected thyroid cancer:
Serum thyroid-stimulating hormone concentration: Sensitive for hyperthyroidism/hypothyroidism and for evaluation of solitary thyroid nodules
Serum calcitonin/pentagastrin-stimulated calcitonin levels: Elevated levels highly suggestive of medullary thyroid carcinoma
Polymerase chain reaction (PCR) assay for germline mutations in the RET proto-oncogene: For diagnosis of familial medullary thyroid carcinoma
Imaging studies
The following imaging studies may be used to evaluate patients with suspected thyroid cancer:
Neck ultrasonography: Most common modality to evaluate thyroid disease; however, limited usefulness for distinguishing between malignant and benign nodules
Thyroid radioiodine imaging: To determine functional status of a nodule but cannot exclude carcinoma
Neck computed tomography (CT) scanning or magnetic resonance imaging (avoid iodinated contrast agents): To evaluate soft-tissue extension of large or suspicious thyroid masses into the neck, trachea, or esophagus, and to assess metastases to the cervical lymph nodes; no role in routine management of solitary thyroid nodules
A 2015 consensus statement from the American Thyroid Association on preoperative imaging for thyroid cancer surgery stated the following
:
Ultrasonography remains the most important imaging modality in the evaluation of thyroid cancer and should be used routinely to assess the primary tumor and all associated cervical lymph node basins preoperatively
Ultrasonographically guided fine-needle aspiration of suspicious lymph nodes may be useful in guiding the extent of surgery
Cross-sectional imaging (CT scanning with contrast or magnetic resonance imaging [MRI]) may be considered in select circumstances to better characterize tumor invasion and bulky, inferiorly located, or posteriorly located lymph nodes; it may also be used when ultrasonographic expertise is not available
Management of thyroid cancer
Malignant diagnoses require surgical intervention. Papillary thyroid carcinoma and medullary thyroid carcinoma are often positively identified on the basis of FNAB results alone. Cervical metastases discovered preoperatively or intraoperatively should be removed by means of en bloc lymphatic dissection of the respective cervical compartment (selective neck dissection) while sparing the nonlymphatic structures.
Well-differentiated neoplasms
Patients with follicular neoplasm, as determined with FNAB results, should undergo surgery for thyroid lobectomy for tissue diagnosis. The extent of surgical therapy for well-differentiated neoplasms is controversial. Primary treatment for papillary and follicular carcinoma is surgical excision whenever possible. Total thyroidectomy has been the mainstay for treating well-differentiated thyroid carcinoma. Modifications to total thyroidectomy include subtotal thyroidectomy to reduce the risk of recurrent laryngeal nerve injury and hypoparathyroidism.
A 2015 consensus statement from the American Thyroid Association on the management of patients with differentiated thyroid cancer who have recurrent/persistent nodal disease stated the following
:
The appropriate management of patients with nodal metastases may involve compartmental lymph-node dissection, active surveillance, radioactive iodine ablation therapy, external-beam radiation therapy, and/or nonsurgical, image-guided, minimally invasive ablative approaches
Biologic considerations include aggressive histology, extrathyroidal extension of primary tumor, and molecular prognosis for aggressive biology
Surgical/technical considerations include prior recurrences in the same or different compartments
Hürthle cell carcinomas
For patients with Hürthle cell carcinomas based on initial FNAB findings, most surgeons advocate an aggressive approach with lobectomy and isthmectomy, followed by completion thyroidectomy with confirmation on final pathologic result. For tumors larger than 5 cm or for palpable lymphatic metastases, total thyroidectomy (including neck dissection for palpable lymph nodes) is often performed during the initial operation.
Medullary thyroid carcinomas and familialmedullary thyroid carcinomas
Sporadic medullary thyroid carcinomas and familial medullary thyroid carcinomas are treated with total thyroidectomy and lymphatic dissection of the anterior compartment of the neck. If the vasculature of the parathyroid gland is disrupted, autotransplantation of the parathyroid gland into the sternocleidomastoid muscle or the nondominant forearm is performed. In children with multiple endocrine neoplasia (MEN) type 2A and MEN 2B syndromes, prophylactic thyroidectomy and central-compartment lymph-node dissection is performed.
Anaplastic thyroid carcinoma, primary thyroid lymphoma, thyroid sarcoma
Total or subtotal thyroidectomy is performed for anaplastic thyroid carcinoma when the extent of the tumor permits it. Tracheotomy is needed in cases with airway compromise due to tracheal invasion.
Stage IE lymphomas may be treated with total thyroidectomy followed by postoperative radiation therapy. Surgical excision should not be performed if local infiltration into surrounding tissues is evident. Stage IIE lymphomas are treated with combined chemotherapy and radiation therapy. Doxorubicin or CHOP (ie, cyclophosphamide, hydroxydaunomycin, Oncovin [vincristine], prednisone) is the commonly used chemotherapeutic regimen.
The treatment for thyroid sarcomas is total thyroidectomy. Radiation therapy may be used in an adjunctive setting.
Postsurgical management
After total thyroidectomy, patients undergo radioiodine scanning to detect regional or distant metastatic disease, followed by radioablation of any residual disease found. In addition, patients are given thyroid replacement therapy with T4 or triiodothyronine (T3).
In patients with anaplastic thyroid carcinoma, chemotherapy and radiation therapy are typically administered in combination. Postoperative external-beam irradiation is effective in improving local control; this may also be used as primary treatment in unresectable cases. Chemotherapy (most commonly doxorubicin) is added for palliation.