Risk factors for cervical lymph node metastasis in ...

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Feb 24, 2016 - metastasis were size, multifocality, capsular invasion, and lymphovascular invasion. With regard to the risk of developing lymph node ...
Published on Ear, Nose & Throat Journal (http://www.entjournal.com) Home > Risk factors for cervical lymph node metastasis in papillary thyroid microcarcinoma: A metaanalysis

Risk factors for cervical lymph node metastasis in papillary thyroid microcarcinoma: A meta-analysis | Reprints February 24, 2016 by Nopawan Vorasubin, MD; Chau Nguyen, MD, FACS; Marilene Wang, MD

Abstract A number of studies of predictive factors for lymph node metastasis in papillary thyroid microcarcinoma have been published. We conducted a systematic meta-analysis of some of these studies, and we present our findings herein. We searched the PubMed database and found 13 eligible studies and case series of papillary thyroid microcarcinoma that were published in the English-language literature from January 2001 through December 2012, and we analyzed their findings. The most commonly investigated tumor characteristics associated with lymph node metastasis were size, multifocality, capsular invasion, and lymphovascular invasion. With regard to the risk of developing lymph node metastasis, patients with larger tumors had a 1.93 greater chance (95% confidence interval [CI]: 1.36 to 2.73, p < 0.001), those with multifocal tumors had a 3.03 greater chance (95% CI: 2.05 to 4.47; p < 0.001), those with capsular invasion had a 4.13 greater chance (95% CI: 2.40 to 7.10; p < 0.001), and those with lymphovascular invasion had a 2.76 greater chance (95% CI: 1.50 to 5.07; p = 0.005). We conclude that patients with larger and/or multifocal papillary thyroid microcarcinomas and tumors associated with capsular or lymphovascular invasion have a significantly greater risk of developing lymph node metastasis.

Introduction Papillary thyroid microcarcinoma is a subtype of papillary thyroid carcinoma that includes tumors smaller than 10 mm. These microtumors account for 30% of all cases of papillary thyroid carcinoma.1 The optimal treatment for papillary thyroid microcarcinoma continues to be a topic of

debate in the literature, and a number of approaches have been proposed, ranging from observation to the same type of aggressive treatment undertaken for larger papillary thyroid carcinomas, including total thyroidectomy with radioactive iodine ablation.1-4 The biologic behavior of papillary thyroid microcarcinoma has yet to be fully defined, with some populations apparently presenting with more aggressive features than others. Furthermore, a small number of patients with papillary thyroid microcarcinoma present with clinical lymph node metastasis. Although factors predictive of lymph node metastasis have been identified for papillary thyroid carcinoma, no such systematic study has been conducted for papillary thyroid microcarcinoma. The reported incidence of lymph node metastasis in papillary thyroid carcinoma has ranged widelyfrom 20 to 90%.1 While it has been well established that lymph node metastasis is a significant risk factor for locoregional recurrence, its impact on survival has yet to be elucidated.1,3 Arguments have been made in favor of performing prophylactic neck dissection of the central compartment.5-7 According to these arguments: 

there is an increased risk to the recurrent laryngeal nerve during revision surgery should a lymph node metastasis occur later;



the incision for a total thyroidectomy does not need to be modified to include central neck dissection;



preoperative ultrasonography has been shown to yield low sensitivity in detecting lymph node metastasis in the central compartment; and



patients older than 45 years are less sensitive to radioactive iodine, therefore residual neck disease would not respond to this adjuvant therapy.

Authors who prefer to forgo prophylactic neck dissection argue that the paucity of information regarding the relationship between lymph node metastasis and survival is not worth the increased risk of neck dissection.7,8 These risks include postoperative vocal fold paralysis and hypoparathyroidism. Currently, the American Thyroid Association guidelines recommend inclusion of neck dissection for papillary thyroid carcinoma only in the setting of clinically evident lymph node metastasis.9 However, given that potentially 90% of patients with papillary thyroid microcarcinoma will have a lymph node metastasis at their initial presentation, with as many as 30% lacking clinical signs on physical examination or imaging, it is evident that a significant proportion of cases would be missed if prophylactic neck dissection were not performed.1,7 In this article, we aim to identify factors in papillary thyroid microcarcinoma that would predict the development of lymph node metastasis. Identification of such factors could allow for more precise stratification of patients into high- and low-risk groups, which would potentially enable an individually tailored approach to treatment.

Materials and methods We conducted a PubMed search for studies and series that specifically investigated factors associated with lymph node metastasis in patients with papillary thyroid microcarcinoma. Our selection was limited to retrospective reviews that included sufficient data and that were published in English from January 2001 through December 2012. We systematically reviewed these articles to identify clinical and pathologic factors associated with the presence of lymph node metastasis. We narrowed our search to include tumor characteristics that had been reviewed in more than half of the articles that we considered. We then conducted a meta-analysis of articles that addressed these selected characteristics using an odds ratio (OR) of lymph node metastasis to determine effect sizes. Heterogeneity was assessed using the Cochran Q test and I2 index with p < 0.1 and I2 > 25% as evidence of considerable heterogeneity. A random-effects model was used whenever there was evidence of significant heterogeneity, while a fixed-effects model was used in cases in which there was no significant heterogeneity.

Results Thirteen articles, which included a total of 3,929 patients, met our inclusion criteria.1-8,10-14 The central compartment was the predominant site of lymph node metastasis in 6 studies and the lateral compartment in 5; the compartment was not specified in the other 2 studies. Regardless of the site, the incidence of lymph node metastasis ranged from 3.1 to 64%. Among the 13 articles, a total of nine factors were evaluated for their association with lymph node metastasis: sex, age, tumor size, multifocality, thyroid capsular invasion, lymphovascular invasion, extrathyroidal extension, nonincidental diagnosis, and the location of the primary tumor (table 1).

Table 1. Clinicopathologic characteristics associated with lymph node metastasis (LNM) in patients with papillary thyroid microcarcinoma Author

Site of LNM

Incidence of LNM (%)

Factors investigated for association with LNM

Sex*

Age†

Size‡

MF

CI LVI ETE NID

Lo c

X

X

X

* Five studies (indicated by +) found that male sex was a risk factor. † Three studies (+) found that age 5 mm, 2 studies (ˆ) used a threshold of 6 mm, and 1 study (#) used 5 mm, 2 used a threshold of ≤6 or >6 mm, and 1 used