Barbara Zarebczan
Herbert Chen
Presentation
A 27-year-old female presents to her primary care physician with a complaint of an enlarging neck mass. She first noticed this mass 2 months ago and comes in concerned because it has grown considerably larger. She denies having dyspnea, difficulty speaking, and dysphagia. She has no known medical problems and is currently not on any medications. She is adopted and does not know her family history. On physical examination, her vital signs are normal. She has a palpable, nontender neck mass, approximately 3 cm in diameter, to the left of midline just below the cricothyroid cartilage. No other masses are palpable, and the remainder of her exam is within normal limits.
Differential Diagnosis
A nontender neck mass has a wide differential that can be divided into three categories: neoplasms, congenital lesions, and inflammatory masses. Neoplasms presenting as a neck mass can be benign, such as lipomas and benign thyroid nodules, but in an adult, a neck mass should be considered a malignancy until proven otherwise. Some of the most common malignancies of the neck include thyroid cancers, laryngeal carcinomas, and lymphomas. Congenital masses can present at any age and include thyroglossal duct cysts and branchial cleft cysts, which usually become apparent when they become infected. Other congenital neck lesions include lymphangiomas, dermoid cysts, and thymic cysts. Enlarged lymph nodes resulting from a viral or bacterial illness are the most common inflammatory masses encountered.
Workup
The patient undergoes further evaluation of her neck mass with an ultrasound that demonstrates a 3-cm nodule in the left lobe (Figure 1) and suspicious lymph nodes in the central neck and near the left carotid artery. At this time, a fine needle aspiration (FNA) is performed and returns as being suspicious for medullary thyroid cancer.
FIGURE 1 • Ultrasound demonstrating a 3-cm, hypoechoic left thyroid nodule.
The patient undergoes laboratory testing, which demonstrate an elevated serum calcitonin of 9,091 pg/mL (normal <5 pg/mL), an elevated carcinoembryonic antigen (CEA) level of 320 ng/L (normal <2.5 ng/mL), and a normal calcium of 9.3 mg/dL. The patient also undergoes RET gene testing, which comes back positive for a germline mutation. Given this finding, the patient undergoes additional testing to evaluate for tumors associated with MEN-2. Her parathyroid hormone, plasma normetanephrine, and plasma and urinary metanephrine levels are all normal.
Given the findings of suspicious lymph nodes on her ultrasound as well as her highly elevated calcitonin level, the patient undergoes a metastatic workup. Neck CT demonstrates the previously seen nodule and enlarged lymph nodes (Figure 2A,B). A CT scan of her chest and abdomen demonstrates no metastatic disease.
FIGURE 2 • A: CT of the neck with a cross-sectional image demonstrating a large, left thyroid nodule and left lateral lymph nodes. B: Coronal views of the same CT redemon-strating the thyroid nodule and lymph nodes surrounding the left internal jugular vein and the carotid artery.
Diagnosis and Treatment
Medullary thyroid cancer (MTC) represents 3% to 10% of all thyroid cancers. Similar to other thyroid cancers, many MTCs present as thyroid nodules, which should be evaluated with an ultrasound and FNA biopsy (Figure 3).
FIGURE 3 • Chart explains the workup of a patient with suspected medullary thyroid cancer, beginning with an ultrasound and FNA, followed by measurement of calcitonin and CEA levels. Operative management is based on the extent of nodal and metastatic disease.
MTCs arise from the parafollicular C cells of the thyroid, which produce calcitonin, a neuroendocrine tumor marker that is helpful in diagnosing the disease, as well as identifying recurrence. Approximately 50% of MTCs can also secrete CEA, which should also be obtained during preoperative evaluation. If the patient has evidence of lymph node metastases or a calcitonin level >400 pg/mL, a metastatic workup including CT scans of the neck, chest, and abdomen should be performed.
The majority of MTCs occur sporadically, but up to 20% are due to germ-line mutations in the RET protooncogene. Hereditary MTCs occur in multiple endocrine neoplasia (MEN) syndrome 2A and 2B and in familial MTC. According to the American Thyroid Association guidelines, all patients diagnosed with MTC should undergo RET gene testing. Screening for hyperparathyroidism and pheochromocytoma should also be performed, as a pheochromocytoma needs to be resected prior to thyroid resection.
The mainstay of treatment for MTC remains surgery. For patients with no evidence of lymph node and distant metastases, a total thyroidectomy and prophylactic central neck (level VI) dissection are recommended by most surgeons. For those patients with lymph node metastases limited to the central neck compartment, a total thyroidectomy and central neck dissection are performed. Patients with suspected metastases to the lateral neck compartments should undergo a total thyroidectomy and central neck dissection, as well as a modified lateral neck (levels II, III, IV, V) dissection.
Surgical Approach
A total thyroidectomy begins with a transverse incision made just below the cricoid cartilage, ideally in an existing neck crease (Table 1). In order to facilitate a modified radical neck dissection, this incision may be extended laterally or a hockey-stick incision may be made to allow for wider exposure. The total thyroidectomy should be completed in the usual manner with care taken to avoid injury to the recurrent laryngeal nerves and parathyroid glands.
TABLE 1. Key Technical Steps and Potential Pitfalls to Total Thyroidectomy with Central Neck Dissection and Modified Lateral Neck Dissection
Once the thyroid has been removed, attention can be turned to completing the central neck dissection. The recurrent laryngeal nerves are dissected out and all the fatty tissue between the carotid sheaths from the hyoid bone superiorly to the brachiocephalic vessels inferiorly, including the thymus, is removed.
The lateral neck dissection is then begun by dissecting the anterior triangle, containing level II, III, and IV lymph nodes. The submandibular gland is retracted superiorly, and the inferior margins of the digastric and omohyoid muscles are skeletonized defining the superior aspect of dissection. The internal jugular vein is exposed and the lateral branches are ligated or sealed, defining the medial border of dissection. The sternocleidomastoid muscle can then be retracted laterally and the tissue on its posterior surface can be dissected, with care taken to identify and preserve the spinal accessory nerve. Attention can then be turned to dissection of the posterior triangle, containing level V lymph nodes. Once the spinal accessory nerve has been identified, the posterior border of the sternocleidomastoid muscle can then be skeletonized down to the trapezius muscle, defining the lateral border of dissection. The dissection proceeds down to the clavicle, which defines the inferior border of resection. Once the fatty tissue containing the lateral neck lymph nodes has been dissected free from all adjacent structures, it can be removed en bloc.
After the lymph node tissue has been removed, if required, a drain can be placed in the lateral neck. The medial aspect of the sternocleidomastoid muscle is then reapproximated to the lateral border of the sternothyroid muscle with interrupted sutures. The platysma is reapproximated in the same manner. Finally, the skin is closed with a running subcuticular stitch.
Special Intraoperative Considerations
Due to the extent of the lymph node dissection, care should be taken to identify the thoracic duct as it enters the neck on the left. Most commonly, the thoracic duct empties into the left subclavian vein at its junction with the left internal jugular vein. Surgeons should be aware of aberrant ductal anatomy, with patients having a right thoracic duct, draining into the right subclavian vein. If the thoracic duct is inadvertently injured and a chyle leak is identified intraoperatively, it should be ligated with either nonabsorbable sutures and/or hemoclips.
Postoperative Management
In the immediate postoperative period, a surgeon should be aware of potential complications associated with total thyroidectomy and neck dissection. One of these complications is that of a hematoma, which could result in tracheal compression and respiratory distress. In the event of a hematoma causing tracheal compression, the incision should be opened immediately at the bedside, followed by reoperation to evaluate for the cause of bleeding.
As mentioned in the potential intraoperative pitfalls, inadvertent injury to the recurrent laryngeal does occur and if bilateral will lead to immediate respiratory distress upon extubation requiring an emergent tracheostomy. Unilateral injury of the nerve results in hoarseness and requires evaluation and treatment by an otolaryngologist.
Transient hypoparathyroidism, due to injury or removal of one or more parathyroid glands, is another complication of thyroidectomy and neck dissection, which requires short-term calcium supplementation. Rarely, this becomes permanent requiring, lifelong vitamin D and calcium supplementation.
Another complication of total thyroidectomy and neck dissection is that of a chyle leak, identified as a milky, white discharge high in triglycerides. Initially, this is managed by placing the patient on a fat-free diet, antibiotics, and application of a pressure dressing. If the chyle leak does not resolve, surgical exploration with ligation of the thoracic duct or application of a biologic sealant may be necessary.
Patients suffering from medullary thyroid cancer will also require long-term surveillance consisting of measurements of calcitonin and/or CEA levels every 6 months for 1 year and then annually thereafter. If the patient were to have an elevation in calcitonin and/or CEA levels, an ultrasound of the neck should be performed to evaluate for recurrent local disease.
Case Conclusion
The patient undergoes a successful total thyroidectomy with central and modified left lateral neck dissection. She is discharged on postoperative day 1 on thyroid hormone replacement. At 6 months, her calcitonin level is 3 pg/mL and her CEA is 0.5 ng/mL. At her 1-year visit, her calcitonin and her CEA levels are unchanged.
TAKE HOME POINTS
· 75% of medullary thyroid cancers are sporadic, and 25% are inherited in syndromes such as familial medullary thyroid cancer, MEN 2A, and MEN 2B.
· Tumors secrete calcitonin, CEA, serotonin, ACTH, calcitonin gene-related peptide (CGRP).
· Tumor is of C cell origin, so radioactive iodine therapy is ineffective.
· If patients are RET mutation carriers, prophylactic total thyroidectomy is recommended based on the specific mutation and level of risk for developing MTC during childhood, with level 3 needing surgery within the first 6 months of life, level 2 by age 5, and level 1 between ages 5 and 10.
· If patients have pheochromocytoma, it is operated on first to avoid hypertensive crisis.
· Surgical treatment includes total thyroidectomy and central neck dissection; if lateral neck lymph nodes are involved, perform modified lateral neck dissection.
· Long-term surveillance includes measurement of calcitonin and CEA.
SUGGESTED READINGS
American Thyroid Association Guidelines Task Force; Kloos R, Eng C, Evans D, et al. Medullary thyroid cancer: management guidelines of the American Thyroid Association. Thyroid. 2009;19:565–612.
Duh Q-Y, Clark OH, Kebebew E. Atlas of Endocrine Surgical Techniques. Philadelphia, PA: Saunders Elsevier, 2010.
Lal G, Clark OH. In F. Brunicardi, ed. Schwartz’s Manual of Surgery. New York, NY: McGraw-Hill, 2006:943–988.
Pinchot S, Chen H, Sippel R. Incisions and exposure of the neck for thyroidectomy and parathyroidectomy. Operat Tech Gen Surg. 2008;10:63–76.
Shaha A. Complications of neck dissection for thyroid cancer. Ann Surg Oncol. 2008;15:397–399.
Sippel R, Kunnimalaiyaan M, Chen H. Current management of medullary thyroid cancer. Oncologist. 2008;13:539–547.