Sentinel lymph node biopsy:Is it a reliable indicator of lateral nodal involvement in papillary thyroid carcinoma?

Sentinel lymph node biopsy:Is it a reliable indicator of lateral nodal involvement in papillary thyroid carcinoma?

Gamal Saleh, MD; Mostafa El-Sayed,MD; Hussein Al-Gohry,MD Department of General Surgery Benha University Hospitals, Egypt.

Abstract

Aim: Is to evaluate  the role of sentinel  lymph node biopsy (SLNB) in diagnosis of lateral nodal involvement in NO papillary thyroid cancer patients.

Methods: 20 patients were included in this study; total thyroidectomy  with dissection of the central neck compartment was done in all patients. 0.5 ml of 2% methylene blue dye was injected into the primary tumour; blue stained SLN in lateral neck was identified and examined by frozen

section. If any of the SLNs were positive on the frozen section, selective neck dissection (levels

II-IV) was performed during same operation. In false-negative cases of SLNs reoperation was

carried out after 1 week.

Results: There were 6.7%false-negative rate; 100% specificity; 80% sensitivity, 93% negative predictive value;  100% positive predictive value, with 94.7% overall accuracy. Postoperative transient recurrent laryngeal nerve palsy occurred in 2 patients; but none of the patients had permanent  nerve palsy. One patient required calcium supplement on discharge; however, no patient developed permanent hypocalcaemia.

Conclusion: SLNB is an easy and accurate method for assisting the diagnosis of metastasis in the lateral neck compartment, and it could reduce the risk of complications of thyroid surgery. We recommend  this technique  to support  the decision to perform selective neck dissection in NO papillary thyroid cancer patients.

Key words: Papillary thyroid cancer, sentinel lymph node, lateral neck compartment.

Introduction:

Management of occult lymphatic  disease in   papillary thyroid cancer (PTC) is controversial. While  occult  regional  lymph node involvement  ranges from 25% to 90% and  is associated with  increased tumor recurrence, there is no evidence that removal of these nodes confers a survival advantage.l-5

American Thyroid Association 2006 guidelines,6 specify that the primary disease and involved lymph nodes should be removed and, additionally, that the operation should facilitate radioactive iodine  administration, permit accurate surveillance, and minimize the risk of disease recurrence. To these ends, they recommend the  following steps: (a) preoperative neck ultrasound; (b) either near­ total or total thyroidectomy; (c) routine central compartment neck dissection; and (d) lateral

neck compartment lymph node dissection for either clinical or image-identified lymph node metastasis.

The extent  of lateral  neck  dissection for fine-needle aspiration-confirmed disease in the lateral  neck remains a controversial and hot topic for debate)-12

Intra-operative lymphatic mapping with sentinel lymph node biopsy (the first lymph node  draining into  a lymphatic basin)  has become a revolutionary concept in the management of solid malignancies and can be adopted also in thyroid carcinoma, especially in  patients NO at  clinical and  ultrasound examinations as an alternative to elective lymph node dissection.13-15

In the case of positive sentinel lymph node (SLN) findings, it seems wise to extend lymph node  dissection to  the level  to  which  the

positive node belongs, which may even be the laterocervical comparbnent. This helps to avoid a high incidence  of node recurrence  and the risks  of  prophylactic node  dissection or reoperation.I6,17

The aim of this non-randomized, prospective study is to evaluate the role of sentinel lymph node biopsy  (SLNB)  in diagnosis of lateral nodal  involvement in NO papillary thyroid cancer patients.

Patients and methods:

From June 2008 to May 2011, 20 patients, diagnosed as having PTC without lymph node metastasis based on finding from preoperative ultrasonography and fine needle  aspiration, were included in this study. Patients with locally invasive tumours, distant metastases, and previous head and neck surgery were excluded off the study.

With Ethics Committee approval, all patients

were informed and consented before surgery after explanation & discussion of the procedure and possible surgical options.

Surgical technique:

A standard collar incision was  made approximately 2 finger-breadths above the sternal notch. After dissection of  the subplatysmal flap, the infrahyoid muscles were divided in the midline and separated laterally from the thyroid gland and before mobilization of the gland; 0.5 m1of2% methylene blue dye was injected into the primary tumor with a 25- gauge  needle, taking  care  not  to stain  the surrounding tissue.

Immediately after the lobe was stained, the plane between the sternocleidomastoid muscle and the strap muscles was opened by dissecting the entire medial border of  the sternocleidomastoid muscle, which was retracted  laterally throughout the dissection. The omohyoid muscle was identified, encircled, dissected superiorly and laterally, thereby exposing the internal jugular vein and common carotid  artery  looking for the  blue-stained lymphatic vessels  and  lymph  nodes  in the

jugulo-carotid chain and recognized as SLNs. If there were no stained nodes, the closest node to the  blue-stained lymphatic vessels  was considered to be the SLN.

The dissected nodes  were  examined by frozen section histopathological examination. Meanwhile, total thyroidectomy with dissection of the central neck compartment and clearance of pretracheal and  paratracheal nodes  was routinely performed. Prior to  total thyroidectomy, all parathyroid glands  were preserved and both recurrent laryngeal nerves were identified and followed  to the entrance into the larynx.

If any of the SLNs were positive  on the frozen section, selective neck dissection (levels II-IV)  was performed  in the same operation via a vertical extension of the incision superiorly along  the anterior  border  of the sternocleidomastoid muscle, Figure(l-8).

All   thyroid glands and   lymph  node

specimens were  sent  for  paraffin section examination.   In false-negative cases of SLNs (negative findings on  frozen-section examination but positive  on paraffin section examination), selective  neck dissection  was performed as a reoperative procedure after 1 week.

Postoperative complications including affection  of vocal cord mobility, hoarseness of  voice,  appearance of  manifestations of hypoparathyroidism in the form of tingling sensation around the lips or infingertips, muscle cramps, carpopedal  spasms and the need for supplemental calcium treatment were recorded.

The  validity of  the  test  was  estimated regarding  the identification rate, sensitivity, specificity, positive predictive value, negative predictive value, and accuracy.

Statistical analysis:

The  collected data  were  tabulated and analyzed using t-test  and Z-test.  Statistical analysis was conducted using  the SPSS (Version 16) for Windows statistical package. Values ofP <0.05 were considered significant

Figure{l): Level designations of lymph node groups in the neckJ8

Figure(2): Elevation of subplatysmal flap and cutting of the cervical fascia in the midline.

Figure(3): Exposure of thyroid  gland  (T).

.\

-    . '

Figure(4): Injection of methylene blue before mobilization of the gland.

Figure(5): Blue staining of thyroid gland after methylene blue injection.

Figure(6): Cutting of the fascia (arrow) along the medial border of sternocleidomastoid muscle (S).

Figure(7): Isolation of omohyoid muscle (0) after dissection between sternocleidomastoid muscle (S) and strap muscles.

Figure(8): Identification of blue-stained sentinel lymph node (arrow).S indicates sternocleidomastoid muscle; 0 (omohyoid muscle); I (internal jugular vein).

Results:

The study comprised 20 patients; 14 (70%)

females  and 6 (30%) males,  with mean age

46.9±12.7 years;  range  26-65 years. The median tumour size was 1.6cm. 7 patients had tumours less than 1cm in diameter, 9 patients had tumours measuring 1-2cm and 4 patients had tumours measuring 2-3cm indiameter. Of

20 patients, thyroid tumours were solitary in

16 cases while multifocality was found in 4 cases. Of16 cases with solitary thyroid tumour, the tumour was found in one lobe in 15 cases while in one case the tumor was found in the isthmus, Table(l).

Identification and biopsy of blue-stained SLN inthe jugula-carotid chain was successful in 19 out of 20 cases while in one patient no lymphatic channels were  visualized and he was excluded off the study.The identification rate of SLN was 95%.The median number of SNLs per draining area was 2 (mean 3.05). Frozen section examination of SLNS revealed

metastasis in 4 cases for whom selective neck dissection was  performed during  the  first operation. Paraffin section examination of the excised specimen showed metastasis in 5 cases including the 4 positive casesby frozen section examination. For the 5th case selective  neck dissection was performed after  one  week.

Regarding the validity of the test, we found

a false-negative rate of 6.7% (1out of 15).The specificity of  the  method was  100%, the sensitivity  was 80%, the negative predictive value was 93% (14 out of 15), and the positive predictive value was 100% (4 out of 4), while overall accuracy was 94.7% (18 out of 19), Table(l).

Postoperative transient recurrent laryngeal

nerve palsy occurred in 2 patients; but none of the patients had permanent nerve palsy.One patient required calcium supplement on discharge; however, no  patient developed permanent  hypocalcaemia,  Table(3).

Table(l): Characteristics of the patients.

---C-h-a-ra-c-t-er-is-t-ic-s------------N-o-.----

Gender (female :male)                    14:6

Tumor size (mm)

<10                                     7

10-20                                  9

20-30                                   4

Localization

Table(2): Validity of the method.

Table (3): Complications among the study group.

Discussion:

Papillary thyroid  carcinoma is the most common thyroid malignancy, accounting for

80%  of all  thyroid cancers.19  It has  been

reported that 70% to 90% of patients with PTC had no evidence oflymph node metastasis but had micrometastases in adjacent lymph nodes.20-22 Therefore, at the time of initial treatment for PTC, patients may already have regional lymph node metastasis, and a treatment policy  should  be  established accordingly.

There are  two  representative regional compartments of lymph nodes to which PTC frequently metastasize. One  is the  central compartment, and  the  other  is the  lateral compartment. Goropoulos et al.,23 and Greene et al.,24 believed that metastases first involve the nodes in the central compartment and then the lateral compartment of the neck. However, skip metastasis leaping the central lymph node compartment  has been reported in PTC.25-28

Moreover in a large  series by Ito and Miyauchi,29 they demonstrated that of 694 papillary carcinoma patients who underwent dissection  not only of level VI but also level II-IV, 11% were level VI-negative and level

11-IV-positive and 15% were level VI-positive but level II-IV-negative. This finding strongly suggests that PTC  initially metastasizes to either level VI    or level II-IV with similar incidences.

Gimm et  aJ.27  and   Machens et  ai.,5

demonstrated that the central compartment  is the most commonly involved with metastases. However, central  node  metastasis is more difficult to be detected by ultrasound than lateral node  metastasis, probably due  to disturbance from the air-filled trachea and from the thyroid  itself.30 Since this compartment can be dissected through the same wound as thyroidectomy, and re-operation is very hazardous in recurrence with increased risk of permanent hypoparathyroidism and recurrent laryngeal nerve injury, these nodes have been routinely dissected by most endocrine surgeons according to the American Thyroid Association

guidelines.1

Since wound extension  and a wide range of  tissue  peeling leading to postoperative discomfort in  the  neck  and  shoulder are unavoidable in the dissection of the lateral nodes, routine prophylactic  modified radical

lateral  neck  dissection for patients without preoperatively positive nodes in the lateral compartment is  not  usually performed in Europe and the United States. Most Western guidelines agree on performing therapeutic dissection only  when  metastatic cervical lymphadenopathy is evident.31 However, some reports have  referred to the  usefulness of prophylactic lymph  node  dissection under specific  conditions.13 In  Japan, several institutions have been performing prophylactic modified radical lateral neck dissection for all patients with PTC due to the high prevalence of pathological lymph node metastasis.30 Also, Machens  et al.26 claimed  that patients  with tumours more than 1em represent candidates for prophylactic lateral neck dissection. The argument supporting prophylactic lymph node dissection is  that  locoregional recurrence

''which increase the psychological and financial burdens on  the  patient" and  even  distant metastasis  can be prevented. Conversely  Ito et al.,32 reported  that prophylactic modified radical neck  dissection does  not  improve disease-free survival.

So far the most useful tool for detecting

metastatic lateral nodes is ultrasonography  as it shows a very high positive predictive value and  specificity, even  greater than  90%. However, it often misses small metastases with many false negatives; low negative predictive value and  low  sensitivity  (21.6%).29,33

Radioactive iodine ablation following total thyroidectomy in  patients with well­ differentiated thyroid cancer has been shown retrospectively to decrease  the incidence of regional recurrence.34,35 This benefit is believed to be secondary  to the destruction of occult micrometastases in clinically negative nodes. Since not all patients with well-differentiated thyroid cancer have lymph node involvement, not  all patients would benefit from postoperative radioactive iodine ablation, which may account for the discrepancy in the literature as to the benefit of 1311 ablation.36 There is therefore a reasonable rationale for exploring the use of SLNB for thyroid  malignancy to identify those who harbor occult lymph node metastases  in the lateral compartment. Thus help selection of patients who would benefit from,  a more  extensive procedure through modified radical  neck   dissection,  and

postoperative radioactive iodine  ablation. Moreover, Toniato14  reported that  SLN procedure may be considered a criterion to select patients in view of ablative 131I therapy; indeed, patients  classified  NO after the SLN technique  could avoid ablative 131I therapy, while N1 patients should have 1311 therapy.

In the current study, we used 0.5 ml of 2% methylene blue dye for intraoperative lymphatic mapping in 20 cases ofPTC. There were 95% identification rate; 100%  specificity; 80% sensitivity; 93% negative predictive value;

100% positive predictive  value, with 94.7%

overall  accuracy. However,  the accuracy  of detection of SLN  in the  central neck compartment was not evaluated as total thyroidectomy with central compartment dissection was  routinely performed in all patients of the study. These results go in hand with that reported by Bae et al.,13 who reported

88.9% diagnostic accuracy and the sensitivity and specificity were  83.3% and  100%, respectively.The positive predictive value and negative predictive value were 100% and 75%, respectively. Also Wiseman et  aJ.37 summarized the results of several studies and found that the  average rate of  SLN identification was 91% (66o/o-100%) and when identified, the SLN accurately  predicted  the disease status  of the  neck  in most patients (80o/o--100%). Moreover, Catry et al.,38 reported that false negative rate for SLN detection  is the single most important quality item for the SLN technique.In the current study we reported false-negative rate of6.7%. This is better than

12.5%  and 22% reported  by Takami et al.,4 and Roh and Park39 respectively.

In our study, there was no meaningful time loss consumed for identification of SLN. This agreed with other studies.13,37,40 All patients in the current study had smooth postoperative course with no permanent recurrent laryngeal nerve injury or permanent hypoparathyroidism. This  coincides with  that reported by other series.13,40-42 This could be attributed  to the use  of  methylene blue  which  stained the majority of nodes in the  central neck compartment facilitating their  removal  and also simplified discrimination fromparathyroid glands.

It could be concluded that SLNB is an easy and accurate method for assisting the diagnosis

of metastasis in the lateral neck compartment, and it could reduce the risk of complications of  thyroid surgery. We  recommend this technique to support the decision to perform selective neck dissection in NO papillary thyroid cancer patients.

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