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ORIGINAL ARTICLE
Year : 2016  |  Volume : 12  |  Issue : 2  |  Page : 1006-1009

The significance of enlarged cervical lymph nodes in diagnosing thyroid cancer


Department of Surgery, Division of Endocrine and Oncological Surgery, School of Medicine, Tulane University, New Orleans, LA, USA

Date of Web Publication25-Jul-2016

Correspondence Address:
Emad Kandil
Department of Surgery, Division of Endocrine and Oncological Surgery, School of Medicine, Tulane University, New Orleans, LA
USA
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-1482.171360

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 > Abstract 


Introduction: We aim to investigate the significance of enlarged cervical lymph nodes (ECLN) identified by initial surgeon-performed ultrasound (US) as a tool for determining the risk of malignancy in the patients presenting with suspicious thyroid nodules.
Methods: Radiological and surgical reports were retrospectively reviewed for the patients with suspicious thyroid nodules who underwent thyroidectomy and preoperative comprehensive neck US. Ultrasonographic features of the identified cervical lymph nodes were correlated with the final pathology report. Patients with malignancy other than papillary thyroid cancer (PTC) were excluded.
Results: The study consisted of 440 patients. On final pathology, PTC was found in 142 patients (32.3%), the remaining 298 (67.7%) exhibited benign findings. ECLN (>1 cm) were found in 66 (46.5%) patient with PTC compared to only 53 (17.8%) patients with benign nodules (P < 0.001). Of the 119 patients with ECLN, 54.6% had benign appearing ECLN with no suspicious features, 26.1% had one suspicious feature, and 19.3% had more than one suspicious features. Benign appearing ECLN had a positive predictive value (PPV) of 41.54%, negative predictive value (NPV) of 59.02%, sensitivity of 51.92%, and specificity of 48.65% in predicting malignancy as opposed to the absence of ECLN. While as opposed to benign looking ECLN, ECLN with only one suspicious feature had a PPV of 70.97%, NPV of 50.00%, sensitivity of 33.33%, and specificity of 83.02%, and ECLN with two or more suspicious feature had a PPV of 73.91%, NPV of 48.96%, sensitivity of 25.76%, and specificity of 88.68%.
Conclusion: ECLN are associated with an increased likelihood of thyroid malignancy in the patients undergoing evaluation of a suspicious nodule. The risk of malignancy in thyroid nodules increases with the presence of suspicious ultrasonographic features on cervical lymph nodes.

Keywords: Enlarged cervical lymph nodes, papillary thyroid cancer, papillary thyroid carcinoma, thyroid, thyroid nodule, thyroid surgery, ultrasound


How to cite this article:
Mohamed HE, Mohamed SE, Anwar MA, Al-Qurayshi Z, Sholl A, Thethi T, Khan A, Aslam R, Kandil E. The significance of enlarged cervical lymph nodes in diagnosing thyroid cancer. J Can Res Ther 2016;12:1006-9

How to cite this URL:
Mohamed HE, Mohamed SE, Anwar MA, Al-Qurayshi Z, Sholl A, Thethi T, Khan A, Aslam R, Kandil E. The significance of enlarged cervical lymph nodes in diagnosing thyroid cancer. J Can Res Ther [serial online] 2016 [cited 2019 May 19];12:1006-9. Available from: http://www.cancerjournal.net/text.asp?2016/12/2/1006/171360




 > Introduction Top


Nodular disease of the thyroid gland is becoming increasingly prevalent. This is largely attributed to the increased detection of nodules by the routine implication of ultrasonography in clinical practice and the population being evaluated. The clinical importance of thyroid nodules rests with the need to exclude nodules that may harbor thyroid malignancy; which occurs in 5–15% depending on age, sex, radiation exposure history, and other factors.[1],[2] In the United States, thyroid cancer shows the fastest rising incidence among all major human cancers, with estimated new cases exceeding 56,460 in 2012; taking the lives of 1780 patients.[3]

The evaluation of malignant sonographic features of thyroid nodules can help to predict malignancy in thyroid nodules.[4],[5],[6],[7] When malignancy is documented from cytological assessment of a thyroid nodule, the American Thyroid Association (ATA) guidelines recommend a comprehensive neck ultrasound (US) be performed with the US guided fine-needle aspiration (FNA) of any suspicious cervical lymph nodes to confirm the metastases.[8] However, the ATA guidelines do not expand the indications of comprehensive neck US to examine the cervical compartment in patients with suspicious thyroid nodules.

Ideally, increasing the diagnostic and predictive value for thyroid cancer via a preoperative comprehensive neck US could help in accurately predicting malignancy in these nodules with suspicious features and help preoperatively to shape an appropriate surgical plan. A recent study by Hands et al.[9] showed a correlation between the presence of benign enlarged cervical lymph nodes (ECLN), found on preoperative neck US, and the risk of papillary thyroid cancer (PTC) in thyroid nodules. However, they did not investigate the correlation between the identification of suspicious ultrasonographic features in ECLN and prediction of malignancy in thyroid nodules. We aim to study if ECLN with benign or suspicious features identified on the preoperative US can predict the diagnosis of thyroid cancer in the patients with suspicious thyroid nodules.


 > Methods Top


This is a retrospective review of a cohort of the patients with thyroid nodules who were referred to a single surgeon for the surgical intervention between 2009 and 2013 at a North American Tertiary Care Center. This retrospective study was performed under the Institutional Review Board approval. Each patient underwent a comprehensive neck US by a single endocrine surgeon as part of a routine preoperative workup. The patients were placed in the supine position with a pillow underneath the upper back for maximal neck extension. Multiple sonographic images of the central, lateral, and posterior compartments of the neck were taken using a 15 MHz linear transducer. Size, shape, nodal architecture, echogenicity, and vascularity were recorded. FNA was done if warranted only for suspicious lymph nodes per the recent ATA guidelines.[8]

Each patient's demographics, US reports, and surgical pathologies were reviewed. Patients were divided into two groups according to the final surgical pathology; one group included patients with benign thyroid pathology and the other group included patients with a final surgical pathology of PTC. Patients were further classified according to the presence or absence of ECLN. An ECLN was defined as a lymph node greater than 1cm in greatest dimension.

We used the current ATA guideline's definition for suspicious cervical lymph nodes, which include features such as increased vascularity, round shape, and loss of fatty hilum.[8]

Patients with surgical pathology confirming evidence of follicular, medullary, lymphoma, and anaplastic carcinomas were not included to keep the study limited to the association with PTC and ECLN. In addition, we excluded the patients with microscopic PTC and the patients who had prior neck surgery.

Statistical analysis

Postpositive test probabilities of having thyroid cancer were calculated by multiplying the pretest probability with positive likelihood (LH +) ratio. Fagan nomogram was used to illustrate the change in cancer probabilities by US findings.[10] Posttest probabilities were compared to the pretest probability (as a reference group) using Binomial exact tests to identify the presence of a significant increase or decrease in cancer probabilities based on the US findings. All statistical procedures were performed using SAS software, version 9.2 for Windows (SAS Institute Inc., Cary, NC, USA).


 > Results Top


Of a total of 615 patients, 440 consecutive patients met inclusion criteria. The average age of the patients was 49.0 ± 13.6 years, with the majority of the patients being female (84.8%). Final thyroid pathology showed PTC in 142 (32.3%) patients along with 298 (67.7%) patients with benign thyroid pathology. Overall, ECLN were found in 119 (27.1%) patients. Of the patients with PTC on final surgical pathology, 66 (46.5%) had ECLN on ultrasonography. However, of the patients with a benign final surgical pathology, 53 (17.8%) patients had ECLN on ultrasonography (P < 0.001). Patients with enlarged benign appearing lymph nodes did not undergo FNA biopsy as they did not meet the criteria for biopsy set per ATA guidelines, whereas the patients with ECLN with one or more suspicious features did undergo FNA biopsy.

The average size of preoperative ECLN that were associated with PTC had 1.2 ± 0.83 cm at the largest dimension, which was not comparable to ECLN associated with the benign nodules with a mean of 0.67 ± 0.48 cm (P < 0.0001).

Of the patients with ECLN, 31 patients (26.05%) had one suspicious feature, 23 patients (19.33%) had two or more suspicious feature, and 65 patients (54.62%) had no suspicious features. All 54 patients having ECLN with suspicious features underwent US guided FNA biopsy. Of these 54 patients, 39 (72.2%) had positive cytopathological findings confirming metastasis, warranting comprehensive compartmental lymph node dissection. Of these 39 patients, 22 (56.41%) had ECLN with one suspicious feature on preoperative comprehensive neck US, while 17 (43.6%) patients had two or more suspicious feature.

Of the 298 patients with benign surgical pathology, 145 (48.8%) underwent surgery for an enlarging suspicious thyroid nodule, 96 (32.3%) underwent surgery due to a large goiter with compressive symptoms, 40 (13.5%) underwent surgery for a suspicious follicular neoplasm, and 16 patients (5.4%) underwent surgery due to Graves' disease.

ECLN with benign or suspicious features was prognostic in predicting PTC in thyroid nodules. ECLN with no suspicious features had a PPV of 41.54%, a NPV of 59.02%, a sensitivity of 51.92%, and a specificity of 48.65% for PTC as opposed to the absence of ECLN (P < 0.07). Additional suspicious features can increase the accuracy in predicting PTC in thyroid nodules. As opposed to benign looking ECLN, ECLN with only one suspicious feature had a PPV of 70.97%, a NPV of 59.02%, a sensitivity of 33.33%, and a specificity of 83.02% (P < 0.001). Furthermore, ECLNs with two or more suspicious feature had a PPV of 73.91%, an NPV of 48.96%, a sensitivity of 25.76%, and a specificity of 88.68% (P < 0.001) [Figure 1].
Figure 1: Positive predictive value and negative predictive value in predicting thyroid malignancy in thyroid nodules for enlarged cervical lymph nodes with benign or suspicious features. (ECLN: Enlarged cervical lymph nodes; PPV: Positive predictive value; NPV: Negative predictive value)

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The presence of ECLN is associated with increased diagnostic accuracy of PTC in patients with suspicious thyroid nodules. However, suspicious features of these ECLN can increase this accuracy. All ECLN had a pretest probability of 32% (the probability of cancer before US examination). ECLN with no suspicious features had a posttest possibility of 48.18% and a LH ratio of 1.0 (P = 0.9587), while ECLN with one suspicious feature had a posttest possibility of 48.33% and a LH ratio of 1.96 (P < 0.001). ECLN with more than one suspicious feature had a posttest possibility of 52.02% and a LH ratio of 2.28 (P < 0.001) [Figure 2].
Figure 2: Fagan nomogram of the pretest and posttest probabilities of cancer according to the presence or absence of suspicious features. The presence of enlarged cervical lymph nodes increases the likelihood of papillary thyroid cancer in suspicious thyroid nodules. The presence of suspicious features in enlarged cervical lymph nodes further increases this likelihood. (ECLN: Enlarged cervical lymph nodes)

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 > Discussion Top


Cervical lymph nodes are a common area for malignant thyroid cells to metastasize via lymphatic drainage in upto 60% of cases.[11] Furthermore, ECLN is easy to assess during the ultrasonographic evaluation of suspicious thyroid nodules. It is imperative to preoperatively differentiate between benign and malignant ECLN to determine if a biopsy is needed to rule out metastatic disease.

Our data showed ECLN seen on neck US increased the specificity for discovering thyroid malignancy in ultrasonographically suspicious thyroid nodules. In addition, the presence of suspicious characteristics in ECLN increased this specificity further. Scanning for ECLN with suspicious characteristics can be done easily during a US guided FNA biopsy of a suspicious thyroid nodule. The evaluation takes little extra time and can provide vital additional information, helping the surgeon plan the optimal surgical approach.

The NPV of benign appearing ECLN was 59.02%, with a specificity of 48.65%. This helps in validating our hypothesis that ECLN can assist in ruling out PTC. The absence of ECLN on the preoperative US can give useful information to a surgeon in the preoperative decision making. In contrast, situations with multiple thyroid nodules with the presence of ECLN can add to the suspicion of a possible malignancy in one of these thyroid nodules. This could direct surgeons to biopsy more suspicious nodule due to a higher chance of malignancy. Future prospective studies should be considered to study the biopsy results of these benign ECLN that do not meet criteria for FNA under current ATA guidelines. No current data in the literature indicates if these benign ECLN truly harbor metastatic disease.

Our study is similar to a recent study by Hands et al.[9] in which they investigated the correlation between benign ECLN and predicting thyroid malignancy in thyroid nodules. Our results differ from that of Hands et al. in respect to specificity (48.65% vs. 90%) and NPV (59.02% vs. 80%) in the patients with benign ECLN. Additionally, Hands et al. did not evaluate the patients with suspicious lymph nodes. In our study, we are showing that additional suspicious features of ECLN would increase the specificity in diagnosing PTC in thyroid nodules. Our data shows that one suspicious feature would increase the specificity to 83.02% and having more than one suspicious feature increases the specificity to 88.68%.


 > Limitations Top


This study is limited in the sense that it is a retrospective review of patients presenting to a single surgeon. It was difficult to determine if a better diagnosis of thyroid cancer can be made solely based on the presence of ECLN, with or without suspicious features. It would be ethically conflicting to perform this study disregarding other variables such as thyroid nodule features and patient demographics. A prospective study could more accurately determine a relationship between ECLN and malignancy in thyroid nodules.


 > Conclusion Top


The presence of ECLN increased predictive value in diagnosing PTC and in suspicious thyroid nodules. The presence of suspicious features in these ECLN can increase this predictive value. In addition to the information obtained from FNA biopsy done on the suspicious thyroid nodules, the presence of ECLN on preoperative neck US can provide valuable information to assist a surgeon in deciding the best surgical treatment for the patients with suspicious thyroid nodules. We believe this study will encourage further research investigating the association between ECLN and papillary thyroid cancer.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
 > References Top

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Mandel SJ. A 64-year-old woman with a thyroid nodule. JAMA 2004;292:2632-42.  Back to cited text no. 1
    
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Hegedüs L. Clinical practice. The thyroid nodule. N Engl J Med 2004;351:1764-71.  Back to cited text no. 2
    
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Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012. CA Cancer J Clin 2012;62:10-29.  Back to cited text no. 3
    
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Koike E, Noguchi S, Yamashita H, Murakami T, Ohshima A, Kawamoto H, et al. Ultrasonographic characteristics of thyroid nodules: Prediction of malignancy. Arch Surg 2001;136:334-7.  Back to cited text no. 4
    
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Papini E, Guglielmi R, Bianchini A, Crescenzi A, Taccogna S, Nardi F, et al. Risk of malignancy in nonpalpable thyroid nodules: Predictive value of ultrasound and color-Doppler features. J Clin Endocrinol Metab 2002;87:1941-6.  Back to cited text no. 5
    
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Cappelli C, Pirola I, Cumetti D, Micheletti L, Tironi A, Gandossi E, et al. Is the anteroposterior and transverse diameter ratio of nonpalpable thyroid nodules a sonographic criteria for recommending fine-needle aspiration cytology? Clin Endocrinol (Oxf) 2005;63:689-93.  Back to cited text no. 6
    
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Moon WJ, Jung SL, Lee JH, Na DG, Baek JH, Lee YH, et al. Benign and malignant thyroid nodules: US differentiation – Multicenter retrospective study. Radiology 2008;247:762-70.  Back to cited text no. 7
    
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American Thyroid Association (ATA) Guidelines Taskforce on Thyroid Nodules and Differentiated Thyroid Cancer, Cooper DS, Doherty GM, Haugen BR, Kloos RT, Lee SL, et al. Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid 2009;19:1167-214.  Back to cited text no. 8
    
9.
Hands KE, Cervera A, Fowler LJ. Enlarged benign-appearing cervical lymph nodes by ultrasonography are associated with increased likelihood of cancer somewhere within the thyroid in patients undergoing thyroid nodule evaluation. Thyroid 2010;20:857-62.  Back to cited text no. 9
    
10.
Fagan TJ. Letter: Nomogram for Bayes theorem. N Engl J Med 1975;293:257.  Back to cited text no. 10
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11.
Pereira JA, Jimeno J, Miquel J, Iglesias M, Munné A, Sancho JJ, et al. Nodal yield, morbidity, and recurrence after central neck dissection for papillary thyroid carcinoma. Surgery 2005;138:1095-100.  Back to cited text no. 11
    


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