Gerard M. Doherty
Presentation
A 42-year-old woman in good health, whose only medications are oral contraceptives, presents for evaluation of a central neck mass noted on health maintenance examination. Her neck examination shows a firm mass to the right of the larynx that moves up and down with swallowing. She has no palpable lymphadenopathy. She has no family history of thyroid disease and no personal history of radiation exposure.
Differential Diagnosis
A mass in the central neck that moves with swallowing is tethered to the larynx; the most common lesions are of the thyroid gland. Other possibilities include infectious or inflammatory lesions (lymphadenitis, abscess, or sarcoidosis), congenital lesions (thyroglossal duct lesions, branchial cleft cysts, cystic hygroma or laryngocele), or neoplasms of nonthyroid origin (salivary gland, subcutaneous lipoma, sebaceous cyst, carotid body tumor, laryngeal chondroma, soft tissue sarcoma, or metastatic lymphadenopathy). The thyroid lesions can be inflammatory (lymphocytic thyroiditis most common; others include acute thyroiditis, Reidels thyroiditis, or suppurative thyroiditis), benign neoplastic lesions (solitary or multiple adenomas, multinodular hyperplasia), or malignant lesions (papillary, follicular, anaplastic or medullary thyroid cancer, lymphoma or rarely metastatic lesions).
Workup
In this patient, point-of-care ultrasound shows a heterogeneous, mostly hypoechoic, irregularly shaped mass in the right thyroid lobe that measures 34 mm in maximum dimension (Figure 1). The left lobe of the thyroid gland appears normal. Measurement of thyroid function tests shows a normal TSH (thyroid-stimulating hormone) level of 1.37 mIU/L. Because of the suspicious ultrasound appearance, fine needle aspiration cytology under ultrasound guidance is performed and shows papillary thyroid carcinoma.
FIGURE 1 • Thyroid ultrasound demonstrating the suspicious right thyroid lobe mass. A: Transverse view of the thyroid gland. The left lobe (white arrow) appears normal. The right lobe contains a hypoechoic, irregular lesion suspicious for thyroid carcinoma (black arrow). B:Sagittal view of the right thyroid lobe showing the suspicious mass (white arrow) in the lower portion of the right lobe.
Discussion
Thorough initial evaluation includes ultrasound examination of the neck to clarify the physical examination findings. This can help to determine whether the lesion is thyroid in origin and what the characteristics of the thyroid lesion are (solid vs. cystic vs. complex; smooth vs. irregular borders; solitary vs. multiple; hyper-, hypo-, or isoechoic; degree of vascularity; presence or absence of microcalcification; and size). Thyroid nodules can be categorized based on these findings, and the clinical decision of whether to sample the lesion is informed by clinical management guideline. For example, any solid, hypoechoic nodule larger than 10 mm in diameter should be sampled, while mixed solid-cystic lesions without other suspicious findings should only be biopsied if larger than 20 mm.
Assessment of thyroid function is helpful, both to determine the potential need for thyroid hormone supplementation, and to guide the evaluation. Patients with an elevated TSH are more likely to have malignant nodules and may require thyroid hormone supplementation even if the thyroid nodule proves to be benign. Patients with a suppressed TSH may have an overactive thyroid nodule that is extremely unlikely to be malignant. A suppressed TSH in a patient with a thyroid nodule is the only situation currently in which a nuclear thyroid scintiscan is indicated. Other than this relatively uncommon situation, scintiscan is not useful. For these hyperthyroid patients, scintiscan can help to distinguish Grave’s disease with a concomitant (potentially malignant) thyroid nodule from a solitary toxic adenoma (Figure 2).
FIGURE 2 • Nuclear scintiscans are only useful, and are now reserved for, hyperthyroid patients with a thyroid nodule (low TSH). Ultrasound and cytology have replaced the routine use of scintiscan to evaluate thyroid nodules. However, hyperthyroid patients with a solitary thyroid nodule can fit one of two scenarios: Graves disease with a thyroid nodule that can be malignant (A, arrow on the cold right lower pole nodule) or a solitary toxic adenoma with suppression of function in the remainder of the thyroid gland (B, arrow on the hot left lower pole nodule)..
Fine needle aspiration cytology is the gold-standard thyroid nodule assessment. This requires special expertise for interpretation but is very reliable. There are currently six standard categories for reporting of thyroid FNA results: nondiagnostic, benign, follicular lesion of undetermined significance, follicular neoplasm, suspicious for malignancy, and malignant. Nondiagnostic results usually prompt repeat FNA, Benign cytology is followed by interval follow-up evaluation, and suspicious or definitively malignant results are managed by operation. The indeterminate categories can be managed by diagnostic operation, repeat needle aspiration, or follow-up monitoring depending upon the associated characteristics of the patient and the nodule.
Diagnosis and Treatment
Preoperative cervical ultrasound to evaluate the central and lateral cervical lymph node compartments is required prior to operation for thyroid carcinoma. This is necessary in order to identify involved lymph node compartments so that a thorough initial operation can be planned. If there is imageable lymphadenopathy in the lateral compartment, then fine needle aspiration of a lateral neck node with thyroglobulin measurement of the aspirate can determine the presence of metastatic papillary thyroid carcinoma and establish the need for therapeutic neck dissection in that basin. Selective neck dissection based upon the levels of the involved lymph nodes should include any compartment involved (Figure 3).
FIGURE 3 • Lymph node compartments separated into levels and sublevels. Level VI contains the thyroid gland, and the adjacent nodes bordered superiorly by the hyoid bone, inferiorly by the innominate (brachiocephalic) artery, and laterally on each side by the carotid sheaths. The level II, III, and IV nodes are arrayed along the jugular veins on each side, bordered anteromedially by level VI and laterally by the posterior border of the sternocleidomastoid muscle. The level I node compartment includes the submental and submandibular nodes, above the hyoid bone, and anterior to the posterior edge of the submandibular gland. The level V nodes are in the posterior triangle, lateral to the lateral edge of the sternocleidomastoid muscle. (From Cooper DS, Doherty GM, Haugen BR, et al. Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer.[see comment]. Thyroid. 2009;19(11):1167–1214, with permission).
For all but those with the very best prognosis (tumor <10 mm, normal lymph nodes, age < 45 years), patients with papillary thyroid carcinoma should have an initial operation that includes removal of the entire thyroid gland. In addition, any lymph nodes involved by cancer based on preoperative or intraoperative assessment should be removed by complete compartmental dissection. The utility of prophylactic level 6 lymph node dissection for those patients with apparently uninvolved lymph nodes is more controversial, but may provide important prognostic information and potential therapeutic benefit.
In the patient in this scenario, ultrasound of the neck reveals a right level 3 lymph node with suspicious features (Figure 4). Ultrasound-guided needle aspiration of the node shows cells consistent with metastatic papillary thyroid cancer and an aspirate thyroglobulin level of 934 ng/mL. Given these findings, the patient is scheduled for a total thyroidectomy with level 6 lymph node dissection, as well as a right level 2-3-4 lymph node dissection.
FIGURE 4 • Ultrasound examination of the right lateral cervical lymph nodes shows an abnormal right level 3 lymph node in the longitudinal (A) and transverse (B) images. The arrows denote the abnormal lymph node.
Surgical Approach
The extent of the planned operation is dictated by the location of disease. For this patient, with a significant papillary thyroid carcinoma and an involved right lateral neck node metastasis documented, the likelihood of level 6 lymph node involvement is high. The level 6 lymph nodes can be difficult to image by ultrasound when the thyroid gland is in place. The value of total thyroidectomy includes removal of potential multifocal disease in the thyroid gland and preparation for postoperative radioiodine therapy. If a thyroid lobectomy alone is used to manage a thyroid carcinoma, then radioiodine cannot be utilized. Similarly, the value of postoperative surveillance with thyroglobulin levels as a tumor marker is enhanced by total thyroidectomy.
This operation is best done under general anesthesia. Though many thyroid operations can be done using local anesthesia and sedation, the inclusion of central and lateral neck dissection makes this quite difficult. The key steps of the operation are listed in Table 1. Thyroidectomy can be complicated by infection, bleeding, and anesthetic reactions though these are quite unlikely. The more worrisome complications of thyroidectomy are nerve injury and hypoparathyroidism, both because they are more common, and because they can cause permanent functional deficits for the patient.
TABLE 1. Key Technical Steps and Potential Pitfalls for Total Thyroidectomy
The principles of the dissection are as follows:
1. Avoid dividing any structures in the tracheoesophageal groove until the nerve is definitively identified. Small branches of the inferior thyroid artery may seem like they can clearly be safely transected; however, the distortion of tumor, retraction, or previous scar may lead the surgeon to mistakenly divide a branch of the RLN.
2. Identify the ne rve low in the neck, well below the inferior thyroid artery, at the level of the lower pole of the thyroid gland, or below. This allows dissection of the nerve at a site where it is not tethered by its attachments to the larynx or its relation to the inferior thyroid artery.
3. Keep the nerve in view during the subsequent dissection of the thyroid gland from the larynx.
4. Minimize the use of powered dissection posterior to the thyroid gland.
5. Treat each parathyroid gland as though it were the last one.
6. Autograft any parathyroid glands that have questionable viability.
The use of nerve stimulators and laryngeal muscle action potential monitors has been investigated as a tool to try to limit or avoid nerve injuries. The data do not currently support the mandatory use of these devices. However, many experienced surgeons now routinely use a nerve monitoring system intraoperatively.
Management of Complications
Nerve Injury
The main nerves adjacent to the thyroid gland that can be deliberately or inadvertently affected include the recurrent laryngeal nerve immediately adjacent to the thyroid and the external branch of the superior laryngeal nerve. Damage to the RLN causes unilateral paralysis of the muscles that controls the ipsilateral vocal cord. Unilateral RLN injury changes the voice substantially in most patients, and also significantly affects swallowing. Bilateral RLN injury causes paralysis of both cords and usually results in a very limited airway lumen at the cords. These patients usually have a normal-sounding speaking voice, but severe limitations on inhalation velocity because of upper airway obstruction.
RLN paresis is usually temporary, and resolves over days to months. If a unilateral paresis proves to be permanent, then palliation of the cord immobility and voice changes can be achieved with vocal cord injection or laryngoplasty. These procedures stiffen and medialize the paralyzed cord, in order to allow the contralateral cord to appose the paralyzed cord during speech. If both cords are affected, then the palliative procedures are more limited and involve creating an adequate airway for ventilation; improvements in voice quality are not likely, as there is no muscular control of the cord function.
About 10% of patients have some evidence of RLN paresis after thyroidectomy, however, this resolves in most patients. About 1% or fewer patients have permanent nerve injury when total thyroidectomy is performed by experienced surgeons.
The external branch of the superior laryngeal nerve (EBSLN) courses adjacent to the superior pole vessels of the thyroid gland, before separating to penetrate the cricopharyngeus muscle fascia at it superior–posterior aspect. The nerve supplies motor innervation of the inferior constrictor muscles of the larynx. Damage to this nerve changes the ability of the larynx to control high-pressure phonation, such as high-pitched singing or yelling.
To avoid damaging this nerve, the dissection of the upper pole vessels should proceed from a space where the nerve is safely sequestered under the cricopharyngeal fascia, to the superior vessels themselves, thus safely separating the nerve from the tissue to be divided.
Parathyroid Gland Injury
The parathyroid glands are small, delicate structures that share a blood supply with the thyroid gland. Their size and fragility expose them to damage during thyroidectomy. Avoidance of permanent hypoparathyroidism is far more desirable than treatment of it. This can be accomplished by preservation of the parathyroid glands on their native blood supply, or autografting of parathyroid tissue to a muscular bed. If the parathyroid glands cannot be preserved on their native blood supply, then transfer of the gland to a convenient grafting site can maintain function. For normal parathyroid glands, transfer to the sternocleidomastoid muscle provides a convenient vascular bed for autograft. The parathyroid gland must be reduced to pieces that can survive on the diffusion of nutrients temporarily, while neovascular in-growth occurs over several weeks.
The symptoms of hypoparathyroidism are those of severe hypocalcemia. Patients have numbness and tingling in the distal extremities and around the mouth or tongue in the earliest phases. For mild hypocalcemia with tingling, oral calcium supplements (calcium carbonate, 500 to 1,500 mg po, two to four times daily) are often sufficient to resolve the hypocalcemia. If supplementation beyond this level is necessary (as it is for most patients with severe hypocalcemia), then the addition of supplemental vitamin D (calcitriol 0.25 to 1.0 µg daily) increases the gastrointestinal absorption of calcium. Hypocalcemia not controlled by oral supplements, or accompanied by severe symptoms such as muscle cramping, is best managed by intravenous calcium administration. Intravenous calcium gluconate is the only option for intravenous calcium supplementation (calcium chloride should never be used).
Permanent hypoparathyroidism requires lifelong support with calcium supplements and vitamin D analogues. Missing doses of the supplements will usually produce symptoms, of varying severity, and which, while manageable, are often quite bothersome for patients.
In this clinical scenario, under general anesthesia, neck exploration shows a hard mass in the right lobe of the thyroid gland without evident extrathyroidal invasion. There are firm, small lymph nodes in level 6 adjacent to the thyroid gland; these are removed with the surrounding soft tissue. Both lower parathyroid glands are surrounded by abnormal lymph nodes, and so they are removed, minced into small pieces, and reimplanted into the right sternocleidomastoid muscle. The upper parathyroid glands are preserved on the native blood supply. The right level 2-3-4 lymph nodes are dissected free of the jugular vein with careful attention to preservation of the right vagus nerve (cranial nerve X), phrenic nerve, spinal accessory nerve (cranial nerve XI), and hypoglossal nerve. The ansa cervicalis nerve and the omohyoid muscle are divided. At the completion of all dissection, EMG assessment of the bilateral vagus-recurrent laryngeal-vocalis muscle complex shows normal EMG signal with stimulation of the vagus nerve. There is no evidence of lymphatic leak, and no drain is placed.
Adjuvant Therapy
Papillary thyroid cancer typically retains the capability of concentrating iodine. This feature can be exploited by delivering radioactive iodine in doses that will damage the cells, and cause death over a period of several weeks. Iodine is also taken up by salivary gland tissue and gastric mucosa, and is excreted mainly through the kidneys. The radioiodine is most efficiently concentrated in the thyroid tissue when the TSH is elevated, stimulating any remaining normal thyroid cells or thyroid cancer cells, to concentrate the radioiodine. The patient can be prepared with elevated TSH either by removing the thyroid gland and leaving them free of exogenous thyroid hormone, or by administering exogenous recombinant TSH. Either approach appears to be effective in the adjuvant setting. Adjuvant radioiodine is typically reserved for patients with a moderate or high risk of recurrence.
After radioiodine therapy is completed, if indicated, or immediately if exogenous TSH is administered, the patient is treated with exogenous levothyroxine to replace their thyroid function, and to suppress their endogenous TSH. The degree of TSH suppression is determined by the risk of recurrence of the thyroid cancer. Low-risk patients can have the TSH maintained at about the lower limit of normal. Higher-risk patients may have the TSH suppressed further for several years.
In this scenario, the patient’s postoperative recovery is unremarkable, with mild hypocalcemia for 1 week, and normocalcemia by the 2nd week follow-up. The voice is initially scratchy, but this resolves within 5 days. The final pathology shows a 35-mm papillary thyroid carcinoma with tall cell features, confined to the thyroid gland with negative margins. In level 6, 6 of 15 lymph nodes contain papillary thyroid carcinoma. In the level 2-3-4 dissection, 4 of 22 lymph nodes are involved. Because of the lymph node involvement, she subsequently receives 30 mCi of radioiodine under thyrogen stimulation. Her posttreatment radioiodine scan shows some uptake in the central neck consistent with residual thyroid tissue and no evidence of metastases. Her thyroglobulin at that time is <0.5 ng/mL. She will have regular follow-up including physical examination, thyroglobulin measurement, and ultrasound examination of the neck.
TAKE HOME POINTS
· Assessment of a central neck mass likely to originate in the thyroid gland should include ultrasound and possibly fine needle aspiration cytology.
· Papillary thyroid carcinoma has an excellent prognosis; thorough initial treatment including operation limits the long-term likelihood of recurrence and need for repeat therapy.
· Ultrasound evaluation of the lateral neck lymph nodes is important prior to operation in order to define the necessary extent of operation.
· Operation should include total thyroidectomy for most patients and compartmental dissection of any involved lymph node basins.
· Adjuvant radioiodine and TSH suppression with levothyroxine decrease the recurrence rate of papillary thyroid cancer.
· Follow-up management and surveillance algorithms are risk-based, and include monitoring of serum thyroglobulin levels and cervical ultrasound examination.
SELECTED READINGS
Cibas ES, Ali SZ. The Bethesda system for reporting thyroid cytopathology. Thyroid. 2009;19(11):1159–1165.
Cooper DS, Doherty GM, Haugen BR, et al. Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer.[see comment]. Thyroid. 2009;19(11):1167–1214.
Doherty GM. Prophylactic central lymph node dissection: continued controversy.[comment]. Oncology. 2010;23(7):603, 608.
Dralle H, Sekulla C, Lorenz K, et al. Intraoperative monitoring of the recurrent laryngeal nerve in thyroid surgery. World J Surg. 2008;32(7):1358–1366.
Hughes DT, White ML, Miller BS, et al. Influence of prophylactic central lymph node dissection on postoperative thyroglobulin levels and radioiodine treatment in papillary thyroid cancer. Surgery. 2010;148(6):1100–1106; discussion 1006–1107.
Kouvaraki MA, Lee JE, Shapiro SE, et al. Preventable reoperations for persistent and recurrent papillary thyroid carcinoma. Surgery. 2004;136(6):1183–1191.
Kouvaraki MA, Shapiro SE, Fornage BD, et al. Role of preoperative ultrasonography in the surgical management of patients with thyroid cancer. Surgery. 2003;134(6):946–954; discussion 954–945.
Olson JA Jr, DeBenedetti MK, Baumann DS, et al. Parathyroid autotransplantation during thyroidectomy. Results of long-term follow-up.[see comment]. Ann Surg. 1996;223(5):472–478; discussion 478–480.