April 2011, Vol 18, No. 2 Cancer Control 83

From the Department of Surgery at the University of Michigan, Ann Arbor, Michigan. Dr Hughes is now with Montefi ore Medical Center/Albert Einstein College of Medicine, Bronx, NY.

Submitted February 24, 2010; accepted April 16, 2010.

Address correspondence to David T. Hughes, MD, Montefi ore Medical Center/Albert Einstein College of Medicine, 1400 Bainbridge Avenue, Bronx, NY 10467. E-mail: dhughes@montefi ore.org

No signifi cant relationship exists between the authors and the com-panies/organizations whose products or services may be referenced in this article.

IntroductionPapillary thyroid cancer is the most common form of differentiated thyroid cancer, comprising approximately 90% of the 44,670 estimated new cases of thyroid cancer in the United States in 2010.1 The established primary treat-ment of papillary thyroid cancer per American Thyroid Association (ATA) guidelines is total thyroidectomy for all tumors larger than 1 cm, while thyroid lobectomy is suffi cient for tumors smaller than 1 cm.2 The ATA consensus statement also recommends therapeutic central neck dissection in patients with clinically involved nodes and prophylactic central neck dissection in ad-vanced primary tumors (T3 or T4) without evidence of

Central neck lymph node dissection

is an important component in the

treatment of papillary thyroid cancer.

Rebecca Kinkead. Nadav and Sara (detail), 2009. Oil and alkyd on canvas, 45� × 37�.

Central Neck Dissection for Papillary Thyroid CancerDavid T. Hughes, MD, and Gerard M. Doherty, MD

Background: Central compartment lymph node dissection is a common adjunct to thyroidectomy in the treatment of papillary thyroid cancer. The indications, surgical technique, potential benefi ts, and operative risks of this procedure should be clearly defi ned in order to provide optimal care to these patients.Methods: A systematic review of the literature and an analysis of evidence-based recommendations were performed regarding central neck node dissection for patients with papillary thyroid carcinoma.Results: Cervical nodal metastasis in papillary thyroid cancer is a common occurrence. The presence of metastasis is associated with increased recurrence rates and may decrease survival. Detection of central and lateral neck nodal metastasis preoperatively with clinical examination and cervical ultrasound is important in determining the appropriate initial surgical management. Level VI neck dissection and central neck dissection are terms often used interchangeably to describe surgical excision of all lymph nodes from the hyoid bone to the sternal notch between the carotid arteries, but the addition of the superior mediastinal lymph nodes in compartment VII should be included in the central neck dissection. Due to improved recurrence rates and survival, therapeutic central neck dissection is recommended for all patients with nodal involvement detected pre- or intraoperatively. Prophylactic central neck dissection in patients without detectable nodal disease remains a controversial topic due to a lack of defi nitive evidence of improved recurrence rates or survival and the possibility of higher complication rates compared to total thyroidectomy alone. Reoperative central nodal dissection can be a challenging procedure with increased complication rates but with good outcomes in experienced centers.Conclusions: Central neck lymph node dissection plays an important role in the appropriate treatment of papillary thyroid cancer at initial presentation and in cases of recurrent disease. Surgeons caring for this group of patients should have familiarity and skill with this procedure.

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nodal involvement.2 Radioactive iodine ablation plays an important role in adjuvant treatment following thyroid-ectomy for some subgroups of patients based on risk of recurrence.2 This treatment algorithm achieves extremely low death rates; however, the rates for cervical lymph node metastasis and recurrence remain signifi cant. De-spite the ATA recommendations, there is controversy re-garding the ideal surgical management of the central neck lymph nodes in patients with papillary thyroid cancer.

Nodal Metastasis in Papillary Thyroid CancerIncidence and RelevancePapillary thyroid cancer and the follicular variant of papillary thyroid cancer have a propensity for cervical lymphatic spread that occurs in 20% to 50% of patients on standard review of surgical pathologic specimens and in 90% of those examined for micrometastases.3,4 The spread of tumors cells occurs in a predictable pattern that initiates in the perithyroidal lymph nodes of the central neck and progresses to the lymph nodes of the lateral cervical compartments and the superior medias-tinum.5,6 “Skip” metastases to the lateral compartment

without central neck nodal involvement are rare but do occur.5,6 Patients with nodal metastasis have higher rates of persistent and recurrent disease during postop-erative surveillance.6 The impact of nodal metastasis on overall survival remains debatable; several studies have demonstrated no difference in mortality, while two large population-based studies have shown increased mortal-ity in patients with regional lymph node metastasis.7-11

Detection of Nodal MetastasisThe initial approach to a patient with a thyroid nodule should include a detailed examination of the thyroid and the cervical lymph node compartments. The clas-sifi cation system of cervical lymph node compartments is well defi ned and is important not only in identifying the location of pathologic lymph nodes, but also in plan-ning surgical treatment as outlined and illustrated in the recent ATA guidelines for management of thyroid cancer (Fig 1).2,12,13 Patients with papillary thyroid cancer oc-casionally present on initial assessment with palpable cervical lymphadenopathy, which is most often located in the central neck or levels III and IV of the lateral neck, usually in conjunction with an ipsilateral thyroid nodule.

Cervical ultrasound, often performed as an offi ce-based examination, is the primary imaging modality for the initial assessment as well as the postoperative sur-veillance of patients with papillary thyroid cancer. High-resolution ultrasonography can detect cervical nodal metastasis in 14% to 20% of papillary thyroid cancer patients and can detect pathologic nodes as small as 2 to 3 mm without the risks associated with radiation exposure.14,15 Ultrasound is also easily repeatable and has been shown to change the surgical procedure per-formed in 39% of thyroid cancer patients.14,15 A dedicated cervical ultrasound to include nodal levels II–VI should be performed, ideally by a dedicated clinician such as the thyroid endocrinologist, the operating surgeon, or a radiologist with particular interest, to detect nonpalpable lymph node metastases in patients undergoing surgical evaluation for any thyroid nodule (Fig 2). The sensitivity

Fig 1. — Lymph node compartments of the neck. Level VI and VII are included in central neck dissection, while lateral neck dissection typically includes levels II–V for treatment of papillary thyroid cancer. From Ameri-can Thyroid Association Surgery Working Group, American Association of Endocrine Surgeons, American Academy of Otolaryngology-Head and Neck Surgery, et al. Consensus statement on the terminology and classifi cation of central neck dissection for thyroid cancer. Thyroid. 2009;19(11):1153-1158. Courtesy of Mary Ann Liebert, Inc.

Fig 2. — Ultrasonic appearance of level III lymph node with papillary thyroid cancer metastasis using 12.5 MHz linear transducer. Note the irregular border of the lymph node and the lack of the normal hyperechoic hilar line.

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of cervical ultrasound to detect pathologic lymph nodes in papillary thyroid cancer patients is higher in the lateral neck (94%) than in the central neck (53% to 55%), and this disparity may be considered as additional support for prophylactic central neck dissection.16 Pathologic lymph node metastasis detected on ultrasound can be confi rmed with ultrasound-guided fi ne needle aspiration. In patients with suspected mediastinal disease or with bulky cervical lymphadenopathy, cross-sectional imaging with CT should be considered as it can aid in the plan-ning of nodal dissection and often identifi es pathologic level VI and VII lymph nodes within the superior medi-astinum that are not detected on cervical ultrasound or physical examination.

Operative Considerations for Central Neck Lymph Node DissectionTechniqueCervical nodal dissection for papillary thyroid cancer should include a systematic or en bloc nodal basin dissec-tion rather than a selective or “berry picking” dissection due to higher rates of persistent and recurrent disease with the later approach.17 The ATA consensus statement12 regarding the terminology and classifi cation of the central neck defi nes the central compartment nodal dissection as all perithyroidal and paratracheal soft tissue and lymph nodes with borders extending superiorly to the hyoid bone, inferiorly to the innominate artery, and laterally to the common carotid arteries and is well described and illustrated by Grodski et al18 (Fig 3). The inclusion of the level VII nodes in the superior mediastinum with

the central neck dissection should be noted as this is often a site of persistent disease following central neck dissection. Moo et al19 compared ipsilateral vs bilateral central neck dissection for papillary thyroid cancer and concluded that an ipsilateral dissection was suffi cient in tumors less than 1 cm, while tumors larger than 1 cm required bilateral central neck dissection based on the high incidence of contralateral central neck disease in a retrospective analysis of the pattern of nodal metastases in surgical specimens. Some additional studies demonstrat-ed that ipsilateral central neck dissection was adequate for tumors larger than 1 cm.20 If lateral cervical metastases are present in levels II–V, a bilateral central nodal dissec-tion should be included with the modifi ed radical neck dissection to remove the presumed central neck nodal disease based on described patterns of nodal spread.21

ComplicationsComplications of central neck dissection include injury to the recurrent laryngeal nerve or the external branch of the superior laryngeal nerve, which occurs in 1% to 2% of patients based on several studies.20,22-25 Small retro-spective studies have shown that the addition of central compartment lymphadenectomy to total thyroidectomy for thyroid cancer has not increased nerve injury rates in experienced hands.20,22,23,26 In cases of reoperative central lymph node dissection after either previous thyroidectomy or central node dissection, reports have noted increased nerve injury rates ranging from 1% to 12%.24,25,27-29 Temporary hypoparathyroidism following central neck dissection occurs in 14% to 40% of cases depending on the defi nition of hypoparathyroidism used in the study.20,22,23,30-33 The higher incidence of tempo-rary hypoparathyroidism is likely due to the increased incidence of parathyroid reimplantation and inadvertent inclusion of parathyroid glands in the nodal dissection. Reports are mixed regarding the risk of permanent hypo-parathyroidism. A meta-analysis of retrospective studies reported a 1.2% incidence as defi ned by the requirement for calcium supplements greater than 6 to 12 months postoperatively; however, none showed a statistically signifi cant difference in total thyroidectomy with or with-out central neck dissection.34

Situational ConsiderationsTherapeutic Central Neck DissectionPathologic lymph node involvement noted on preopera-tive clinical or imaging assessment is a well-established indication for therapeutic lymph node dissection.2 A careful search for the presence of pathologic central com-partment lymph nodes with both physical examination and cervical ultrasound is critical during preoperative assessment. The presence of pathologic level VI lymph nodes should prompt detailed physical and ultrasonic examination of the lateral cervical nodal chains for ad-ditional evidence of metastasis. Suspicion of lymph node

Fig 3. — Right-level VI lymph node dissection including all perithyroidal and paratracheal soft tissue and lymph nodes. Judicious use of parathyroid reimplantation should be utilized with regard to the lower parathyroid glands. From Grodski S, Cornford L, Sywak M, et al. Routine level VI lymph node dissection for papillary thyroid cancer: surgical technique. ANZ J Surg. 2007;77(4):203-208. Reprinted with permission of John Wiley and Sons, Inc.

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involvement can be confi rmed with fi ne needle aspira-tion biopsy. The surgical technique for therapeutic nodal dissection should include both the ipsilateral and the contralateral central compartments. The lymph node dissection specimen should be excised en bloc during thyroidectomy. Any incidental note of suspicious nodes in the lateral neck should prompt biopsy and frozen sec-tion analysis for confi rmation of cancer involvement. If cancer is present in any lateral neck nodes, the dissection should be extended to an ipsilateral modifi ed radical neck dissection to include levels II–V.35-37 Liberal application of parathyroid reimplantation during central neck dis-section should be employed to prevent postoperative hypoparathyroidism.20

There are several goals in the use of nodal dissection for clinically evident locoregional lymph node metastasis in papillary thyroid cancer. The primary intent is loco-regional control of disease, given the correlation of nodal metastasis with signifi cant increases in persistent and recurrent disease.6,8,38,39 Several studies have demon-strated decreased recurrence rates and improved sur-vival when the burden of cervical disease is removed via therapeutic neck dissection.15,33,40 In patients with known distant metastatic disease, the debulking of cervical dis-ease for palliative purposes is benefi cial in preventing local complications.

Prophylactic Central Neck DissectionProphylactic or routine central neck dissection for pa-tients with papillary thyroid carcinoma is defi ned as complete excision of the level VI and VII lymph nodes in patients with no evidence of nodal involvement after preoperative clinical and imaging evaluation. The role of prophylactic central neck dissection remains a conten-tious issue regarding its benefi ts and risks, and several reports have reviewed this subject.41-43 Several single-institution retrospective cohort studies on total thyroid-ectomy alone vs with prophylactic neck dissection, as well as a meta-analysis of these studies, have reported mixed results.20,22,23,30,31,34

Proponents of prophylactic central neck dissection at the time of initial thyroidectomy cite the high inci-dence of cervical lymph node metastasis and the associ-ated increase in recurrence rates with the possibility of decreased survival. The low sensitivity of preoperative ultrasound evaluation and intraoperative assessment to accurately detect lymph node involvement is also used as rationale for routine central neck dissection.15,38,44 The addition of central neck dissection to initial total thyroidectomy can provide valuable staging informa-tion and has been shown to upstage approximately a third of patients older than 45 years of age to stage III disease in two retrospective reviews.45,46 This upstag-ing has important implications for further treatment as those with nodal metastasis are likely to receive higher doses of I131 ablation treatment, while those with small,

noninvasive tumors without nodal disease can forgo I131 ablation. The evidence to support prophylactic dissec-tion due to decreased recurrence rates and improved survival is sparse and is primarily composed of a pro-spective population-based study from Sweden.47 This study demonstrated that the rate of death due to thyroid cancer, which ranged from 8.4% to 11.1%, was reduced to 1.6% in patients who underwent central neck dissection compared to contemporary controls. However, several retrospective cohort studies have shown no difference or only a slight improvement in recurrence or survival rates.36,48-50 While an additional benefi t of reduced post-operative thyroglobulin levels after central neck dissec-tion was demonstrated by Sywak et al,20 a recent study at our institution showed no difference in thyroglobulin levels between total thyroidectomy or total thyroidec-tomy with central neck dissection.46 In patients with known distant metastasis without evidence of cervical nodal involvement, a prophylactic neck dissection to include both the central neck and the ipsilateral lateral neck has been recommended by some due to the high rates of nodal involvement in this group of patients on histological analysis.51 Overall, the addition of prophylac-tic central neck dissection appears to provide important staging information that can affect radioactive iodine ablative treatment, but the evidence regarding recurrence and survival benefi ts remains limited and confl icted.

The arguments against prophylactic central lymph node dissection at the time of initial thyroidectomy for papillary cancer focus on the unproven benefi t and the possibility of increased complications. The relevance of subclinical cervical lymph node metastasis on rates of recurrence and survival has been questioned by some ret-rospective studies.50 Additionally, there is a lack of proven benefi t in outcomes after prophylactic central node dis-section. The possibility of increased complication rates with central neck dissection has been addressed, although again by only small retrospective cohort studies.20-23,26,31,52 Higher rates of temporary hypoparathyroidism with cen-tral neck dissection seem consistent between these stud-ies, while the rates of permanent hypoparathyroidism and nerve injury rates are statistically similar compared with total thyroidectomy alone.34,42 The debate on the role of routine central neck dissection in the treatment of papillary thyroid carcinoma is likely to continue until a large randomized trial with long-term follow-up can be completed.

Reoperative Central Neck DissectionReoperative central neck dissection is defi ned as removal of all remaining soft tissue in the level VI and VII compart-ments in a patient who has undergone previous thyroid-ectomy or central lymph node dissection. This is often indicated for patients with papillary thyroid cancer who are noted to have central neck lymph node involvement on surveillance examination or imaging studies after com-

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pletion of radioactive iodine ablation therapy. The goal of reoperative neck dissection is the removal of all persistent or recurrent cervical disease. It is important to closely evaluate patients for the presence of additional pathologic lymphadenopathy in the lateral neck and superior medi-astinum. Combining imaging modalities with cervical ultrasound and cross-sectional imaging with CT or PET/CT can help to guide operative planning and to determine the necessary extent of nodal dissection. Ultrasound and physical examination will often miss pathologic lymph-adenopathy in the superior mediastinum, which can be detected with cross-sectional imaging and can usually be removed via a cervical incision with caudal extension of the central compartment lymphadenectomy (Fig 4). Preoperative laryngoscopy should be performed before all reoperative procedures to determine the presence of recurrent laryngeal nerve injury, which can affect the approach to reoperative nodal dissection. Several studies have demonstrated increased risk of complications with reoperative central neck dissection, with nerve injury rates of 1% to 12% and permanent hypoparathyroidism rates of 0 to 3.5%.24,25,27-29 Given the challenging nature of reoperative neck dissection, consideration of recurrent laryngeal nerve monitoring and special care to preserve the parathyroid vascular pedicles originating from the inferior thyroidal arteries are important.

ConclusionsCentral neck dissection is the most common neck dis-section completed for patients with papillary thyroid cancer and can be performed safely and effectively with low complication rates by experienced surgeons. Thera-peutic central neck dissection is recommended for all patients with clinically evident disease. Prophylactic central neck dissection should be considered in order to provide more accurate staging in high-risk patients. However, conclusive data are lacking regarding its infl u-ence on recurrence, survival, and complication rates.

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Fig 4. — CT imaging demonstrating a superior mediastinal lymph node involved with recurrent papillary thyroid carcinoma (arrow). This was re-moved via a cervical incision during reoperative central neck dissection and was positive for metastatic papillary thyroid cancer.

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