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 Table of Contents  
Year : 2014  |  Volume : 42  |  Issue : 2  |  Page : 58-63

Sentinel lymph node biopsy using blue dye as guidance for central neck dissection in patients with clinically node-negative papillary thyroid carcinoma

1 Department of Surgery, Faculty of Medicine for Girls, Al-Azhar University, Cairo, Egypt
2 Department of ENT, Faculty of Medicine for Girls, Al-Azhar University, Cairo, Egypt

Date of Submission16-Apr-2014
Date of Acceptance17-Apr-2014
Date of Web Publication31-Jul-2014

Correspondence Address:
El-Sayed Mahmoud Abd-Elwahab
Surgical Department, Faculty of Medicine for Girls, Al-Azhar University, 11759 Cairo
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DOI: 10.4103/1110-1415.137803

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Sentinel lymph node biopsy has recently been used to detect occult lymph node metastases. Occult lymph node metastasis of papillary thyroid carcinoma (PTC) can be detected by sentinel lymph node (SLN) biopsy, but studies in larger patient cohorts undergoing complete central neck dissection are required to assess the diagnostic accuracy of SLN.
Materials and methods
A total of 25 consecutive patients with clinically and ultrasonographically node-negative PTC were enrolled and underwent sentinel lymph node biopsy. After injection of 0.2-0.3 ml methylene blue around the tumor or 0.5-1.0 ml into the thyroid nodule, blue-stained SLNs were collected from the central compartments.
SLNs were identified in 21 of 25 patients (84%); of these, 14 SLNs were positive and seven SLNs were negative by hematoxylin and eosin staining. The false-negative rate was detected in two patients (8%), identified by immunohistochemical staining. The non-SLNs were positive in five patients (20%) from positive SLN patients, and no positive non-SLNs were present in negative SLN patients.
SLN biopsy in patients with PTC without gross clinical or ultrasonographical lymph node involvement was able to detect occult metastasis and may have the potential to select patients who require central neck dissection using methylene blue dye technique in PTC, and it is a safe and technically feasible procedure.

Keywords: Thyroid, cancer, sentinel, Lymph, node

How to cite this article:
Abd-Elwahab ESM, El-hady HA, Khaled OA. Sentinel lymph node biopsy using blue dye as guidance for central neck dissection in patients with clinically node-negative papillary thyroid carcinoma. Tanta Med J 2014;42:58-63

How to cite this URL:
Abd-Elwahab ESM, El-hady HA, Khaled OA. Sentinel lymph node biopsy using blue dye as guidance for central neck dissection in patients with clinically node-negative papillary thyroid carcinoma. Tanta Med J [serial online] 2014 [cited 2020 Dec 2];42:58-63. Available from: http://www.tdj.eg.net/text.asp?2014/42/2/58/137803

  Introduction Top

Nodal metastases are a significant risk factor for survival in patients with papillary thyroid cancer (PTC) [1]. Recent studies have suggested the use of sentinel lymph node (SLN) detection as a less invasive method for studying lymphatic metastatic spread in patients with breast, melanoma, cervical, and thyroid cancers [2]. SLNs are defined as the first lymph nodes that drain primary tumors, and thus reflect the tumor status of the remaining lymph nodes. Sentinel lymph node biopsy (SLNB) has been used in several malignancies such as breast cancer and melanoma, and there have been many attempts to use SLNB to guide neck dissection in PTC [3].

PTC is usually slow growing and has a clinically indolent course. However, regional lymph node metastases are frequent, although the tumors are very small. Occult lymph node metastasis was detected in 27-90% of PTC after surgery [4]. Early studies suggested that occult lymph node metastasis in PTC may result in increased locoregional recurrence, but it does not have a marked impact on overall survival [5].

Small, macroscopic metastatic lymph nodes in the lateral neck that were missed by palpation alone have been detected by high-resolution cervical ultrasonography (US) [6]. However, US has a lower rate of detection of metastatic lymph nodes in the central compartment. Subclinical lymph node metastases can be detected by biopsy of the SLN [7].

Therapeutic central or lateral compartment neck dissection (CCND) should be performed in patients with PTC in whom imaging studies or fine-needle aspiration cytology have clinically demonstrated the presence of cervical lymph node metastasis in the central or lateral compartment. Prophylactic lateral CCND is not generally recommended for PTC that is clinically node negative in the lateral compartment. However, routine prophylactic central CCND remains controversial because of its potential morbidity and unclear benefit. According to the guidelines of the American Thyroid Association, prophylactic CCND may be performed in patients with PTC, especially for advanced T3 and T4 primary tumor [8]. Several authors have claimed that CCND can be performed with low morbidity, but others have demonstrated that CCND is associated with relatively high morbidity such as recurrent laryngeal nerve injury and hypoparathyroidism [9]. Hence, it is important to avoid unnecessary CCND. However, unfortunately, no methods are available for detecting all metastatic lymph nodes preoperatively, and intraoperative inspection and palpation are also unreliable [10].

The aim of this study was to assess the feasibility and clinical efficacy of SLNB in the treatment of clinically node-negative PTC and avoidance of unnecessary lymph node dissection in patients with PTC who do not demonstrate spread to the regional lymph nodes. Therefore, we prospectively assessed the usefulness of SLN biopsy for the detection of central lymph node metastasis in patients with PTC who did not have suspected cervical lymphadenopathy.

  Patients and methods Top

This prospective study included 25 consecutive patients with PTC who underwent SLNB from January 2011 to January 2013. All patients were diagnosed with PTC by preoperative fine-needle aspiration cytology and had no preoperative evidence of cervical lymph node metastasis at physical examination and ultrasound or computed tomography. No patient had a history of thyroid or neck surgery for nonthyroidal head and neck cancers. Patients with large tumors, palpable or US-detected lymph node involvement, and other types of thyroid malignancies were excluded. All patients underwent total thyroidectomy with prophylactic bilateral CCND after SLNB.

We attempted to locate the SLN only in the central compartment and performed prophylactic CCND. We did not attempt to locate the SLN in the lateral compartment because we were not performing prophylactic lateral CCND for clinically and radiologically negative nodes.

Surgical procedure and detection of SLN

Under general anesthesia, a standard, transverse low-collar incision was performed, a subplatysmal skin flap was elevated, and the strap muscles were retracted laterally with minimal dissection to prevent any disruption of lymphatic vessels, and, before mobilization of the gland, 0.2-0.3 ml of methylene blue dye, 1%, was injected peritumorally into the thyroid parenchyma at the 3, 6, 9, and 12 o'clock positions or 0.5-1.0 ml of methylene blue dye, 1%, was injected into the thyroid nodule using a tuberculin syringe. In cases of multiple tumor nodules, the predominant nodule was injected. Within seconds, the blue dye was seen spreading within the ipsilateral thyroid lobe and through lymphatic channels to the central compartment ([Figure 1]a and b). Injection required ˜30 s, and one more minute was permitted to allow lymphatic drainage. About 2 min later, blue-stained lymph nodes were carefully identified in the central compartment by tracing the stained lymphatic vessels.
Figure 1: (a, b) Site of injection of blue dye inside the thyroid nodule and appearance of blue lymphatics.

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Thereafter, total thyroidectomy and bilateral central CCND were successfully carried out in all patients. Lymph nodes that stained blue were defined as SLNs ([Figure 2]a and b). Central compartment lymph nodes that did not stain blue were defined as non-SLNs (NSLNs). The SLN and NSLN samples were sent for permanent section and stained with hematoxylin and eosin in all patients and immunohistochemical staining was performed in negative patients only for detection of false-negative rate (FNR).
Figure 2: (a, b) An identifi ed blue-stained SLN in the central compartment. SLN, sentinel lymph node.

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Patients and tumor characteristics were analyzed, and the locations, numbers, and frequency of detection of SLN were also investigated. FNRs of SLNB were analyzed. Postoperative complications were also evaluated. Vocal cord paralysis was determined by preoperative and postoperative flexible laryngoscopy in all patients. Hypoparathyroidism was defined as any decrease in serum parathyroid hormone level below the normal limit, regardless of hypocalcemic symptoms. Permanent vocal cord palsy and/or hypoparathyroidism were defined as nonrecovery within 6 months.

All patients were followed up regularly by clinical and US examination, whole-body radioiodine scanning, and serum thyroglobulin measurements.

  Results Top

The characteristics of patients and tumor are summarized in [Table 1]. There were a total of 25 patients, of whom 17 were women and eight were men, and their age ranged from 23 to70 years. All tumors were papillary carcinomas, and the tumor size ranged from 0.2 to 1.5 cm; 15 patients had left lobe tumor and 10 patients had right lobe tumor. The SLNs were identified in 21 patients (84%) and identification of SLNs failed in four patients (16%) [Table 2].

The locations of identified SLN are listed in [Table 3]. Of the SLNs detected, 12 patients (48%) were located in the ipsilateral paratracheal) recurrent laryngeal nerve) group, followed by four patients (16%) in the pretracheal group, four patients (16%) in the prelaryngeal group, and one patient (4%) in the contralateral paratracheal group, and no stained lymph node was present in the lateral neck. All patients with contralateral paratracheal SLN also had ipsilateral paratracheal SLN.
Table 1 Patient characteristics and presentations

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Table 2 Results of identifi cation of SLNB in PTC

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Table 3 Location of identifi ed SLNs in the central compartment

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The incidence of positive lymph nodes by hematoxylin and eosin staining was 56%, 14 patients, from successful identified SLNs, whereas the incidence of negative lymph nodes was in seven patients (28%). The FNR was detected in two patients (8%) identified by immunohistochemical staining [Table 4]. The NSLNs were positive in five (20%) positive SLN patients and no positive NSLNs were found in negative SLN patients.
Table 4 Results of successfully identifi ed SLNs by different stains

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Postoperatively, temporary symptomatic hypocalcemia developed in two of 25 patients (8%), and laboratory hypocalcemia developed in four patients (16%); no patient had permanent hypocalcemia. One patient had postoperative temporary paralysis of the unilateral vocal cord, and no permanent paralysis was observed. The wound infection occured in only one patient, and neither mortality nor dye complications were recorded [Table 5].
Table 5 Complications of SLNB in PTC

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  Discussion Top

The SLN is defined as the first lymph node in a regional lymphatic basin that drains a primary tumor. Conceptually, if lymphatic drainage is to occur in a stepwise manner, then the SLN should reflect the pathologic status of the remaining lymph node basin. SLNB, moreover, should beneficially detect early, subclinical metastasis. In the last two decades, SLN biopsy has gained significant consensus as the standard of management for identifying regional lymphatic spread in melanoma [11] and breast cancer [12].

Prophylactic CCND may be unnecessary in clinically node-negative PTC patients. To select candidates for CCND more efficiently, several authors have examined the use of SLNB. A blue dye or radioisotope can be used to detect SLN. SLNB that uses a radioisotope and an intraoperative gamma probe has several advantages [13].

Lymphatic destruction can be avoided because the radioisotope is injected preoperatively. SLN lying outside the central compartment can be located by lymphoscintigraphy, and there is no false-positive staining of the parathyroid gland. Several studies that used radioisotopes and intraoperative gamma probes for SLNB have reported higher detection rates (96-100%) than the blue dye technique, although there was no marked difference in sensitivity and specificity. However, the radioisotope approach is complicated. It involves more time, effort, and cost, and, in addition, radioisotopes are not available in all hospitals [14].

The blue dye method has many advantages. It requires little time, effort, or expenditure. Various blue dyes such as methylene blue, isosulfan blue, and patent blue V can be used. Methylene blue appears to be safer; there are several reports of anaphylaxis with isosulfan blue and patent blue V, but adverse reactions to methylene blue are extremely rare [15]. However, there are also disadvantages to the blue dye technique. It has a lower detection rate, and there can be false-positive staining of adjacent soft tissue, including the parathyroid gland. According to a meta-analysis of SLNB in thyroid cancer, the detection rate of the blue dye technique is 15% lower than that of the radioisotope technique [16].

Haigh and Giuliano [17] reported 33 patients who underwent SLN biopsy using a dye technique. Sentinel nodes were identified in 16/17 patients (94%).

Dixon et al. [18] carried out SLN biopsy on 40 patients. Sentinel node(s) were identified in 10 of 12 patients (83%). The FNR was 20%.

In this study, the detection rate of SLN with methylene blue dye was 84%. This is within the range (83-94%) of prior studies that used the blue dye technique. A possible reason for the lower detection rate of the blue dye technique is disruption of lymphatic vessels from the primary tumor. Most authors injected blue dye peritumorally, before mobilization of the gland. We also injected methylene blue immediately after minimal lateral traction of the strap muscle before mobilization of the gland to minimize disruption of lymphatic vessels.

Noguchi and colleagues performed SLNB only in the central compartment according to the principle that prophylactic lateral CCND is not recommended in clinically node-negative patient with PTC. Some workers have advocated routine prophylactic modified radical neck dissection (MRND) [19]. However, the benefit of MRND in clinically node-negative PTC is unclear, and current guidelines do not recommend prophylactic MRND without evidence of metastasis to the lateral compartment [8].

FNRs among recent reports in which a vital dye technique was used range from 7 to 25%, with a negative predictive value of 37-89% [20]. The FNR is the single most important quality item for the SLN technique. If a negative SLN biopsy could not definitively exclude the presence of positive basin lymph nodes, it adds no further staging information. High numbers of false-negative SLN would render the specific technique unsuitable for routine practice [21]. In the present study, the FNR of the blue dye technique of SLN was 8%.

Lateral neck dissection was not performed in the current study, and therefore SLNs outside the central compartment were not detectable. We realized that a modified lymph node dissection would have been the ideal criterion standard, but we were not able to justify a modified lymph node dissection in patients without gross evidence of lymph node enlargement. During the period of follow-up, none of the patients who had negative SLN showed lateral neck adenopathy.

Prophylactic lateral neck node dissection is not recommended because in patients it is not associated with improved overall survival, and it involves violation of additional planes by a substantially more extensive operation. However, follow-up of thyroid cancer patients by physical examination and ultrasound can identify patients with lateral neck nodal disease that can then be appropriately treated by therapeutic compartmental node dissection [22].

The Arch-Ferrer et al. practice is to perform bilateral central neck dissection for all patients with papillary carcinoma. This adds to the operative time and morbidity. In a clinical setting, when a SLN is detected, examined, and is free from metastases, the patient will not have central neck dissection. He will not need postoperative watchful follow-up for lateral neck nodal metastases [23].

A second potential use of SLN sampling would be to avoid 131 I ablation [23].

It is also doubtful whether prophylactic CCND is necessary in all clinically node-negative PTC because prophylactic CCND is generally recommended for only T3 and T4 advanced primary tumors, according to the American Thyroid Association guidelines. If prophylactic CCND is not recommended and not correlated with recurrence or prognosis in low-risk small PTC, the rationale for SLNB must also be weak [8].

Postoperative complication rate, including recurrent laryngeal nerve injury, hypoparathyroidism, and postoperative hematoma, was not different from previous studies of thyroidectomy. Hence, the addition of SLNB to thyroidectomy looks feasible and safe [24]. In our study postoperatively, temporary symptomatic hypocalcemia developed in two of 25 patients (8%), and laboratory hypocalcemia developed in four patients (16%); no patient had permanent hypocalcemia. One patient had postoperative temporary paralysis of the unilateral vocal cord, and no permanent paralysis was observed. The wound infection occurred in only one patient and mortality was not recorded. These complications were not different from previous studies of thyroidectomy.

Parathyroid glands were not stained by the dye in the current study. It might be that parathyroid glands take the dye only through the venous channels rather than the lymph. Injection strictly to the tumor would therefore avoid this complication.

  Conclusion Top

SLN biopsy in patients with PTC without gross clinical or US lymph node involvement was able to detect occult metastasis and may have the potential to select patients who require central neck dissection, and using methylene blue dye technique in PTC is a safe and technically feasible procedure. However, it is of limited use in the management of clinically node-negative PTC because of the FNR. The role of SLNB has yet to be determined in the thyroid setting, but its accuracy needs further refinement and investigation on larger series of patients before it can be recommended in the routine management of thyroid cancer. We recommended that lateral neck dissection is reserved for clinically or radiologically evident cancer involvement of that compartment, although central neck (level 6) node dissection should be a part of every initial thyroid cancer operation.

  Acknowledgements Top

  References Top

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  [Figure 1], [Figure 2]

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]

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