Eur J Nucl Med Mol Imaging
DOI 10.1007/s00259-013-2476-x
ORIGINAL ARTICLE
SPECT/CT sentinel lymph node identification in papillary
thyroid cancer: lymphatic staging and surgical
management improvement
Amparo Garcia-Burillo & Isabel Roca Bielsa & Oscar Gonzalez & Carles Zafon &
Monica Sabate & Josep Castellvi & Xavier Serres & Carmela Iglesias & Ramon Vilallonga &
Enric Caubet & Jose Manuel Fort & Jordi Mesa & Manuel Armengol & Joan Castell-Conesa
Received: 13 February 2013 / Accepted: 3 June 2013
# Springer-Verlag Berlin Heidelberg 2013
Abstract
Purpose Lymphadenectomy in papillary thyroid carcinoma
(PTC) continues to be controversial. A better staging method
is needed to provide adequate individual surgical treatment.
SPECT/CT lymphoscintigraphy and sentinel lymph node
(SLN) biopsy may improve lymphatic staging and surgical
treatment. Our main objectives were to describe the lymphatic
drainage of PTC using lymphoscintigraphy, to evaluate the
lymphatic spread (comparing SLN and lymphadenectomy re-
sults) and to analyse the impact of SLN identification in surgery.
Methods We prospectively studied 24 consecutive patients
with PTC (19 women; mean age 52.7 years, range 22–81-
years). The day before surgery, lymphoscintigraphy with
ultrasound-guided intratumoral injection (99mTc-nanocolloid,
148 MBq) was performed, obtaining planar and SPECT/CT
images. All patients underwent total thyroidectomy, SLN biop-
sy (hand-held gamma probe) with perioperative analysis, cen-
tral compartment node dissection, or laterocervical lymphade-
nectomy if perioperative stage N1b or positive SLNs in this
lymphatic basin.
Results Lymphoscintigraphy revealed at least one SLN in 19
of 24 patients (79 %) on planar and SPECT/CT images, and in
23 of 24 patients (96 %) during surgery using a hand-held
gamma probe. Lymph node metastases were detected with
classical perioperative techniques (ultrasound guidance and
surgical inspection) in 3 of 24 patients, by perioperative SLN
A. Garcia-Burillo (*) : I. Roca Bielsa : O. Gonzalez : C. Zafon :
M. Sabate : J. Castellvi : X. Serres : C. Iglesias : R. Vilallonga :
E. Caubet : J. M. Fort : J. Mesa : M. Armengol : J. Castell-Conesa
Hospital Universitari Vall d’Hebron, Universitat Autònoma de
Barcelona, Barcelona, Spain
e-mail: ampagarcia@vhebron.net
analysis in 10 of 23, and by definitive histology in 13 of 24.
The false-negative (FN) ratio for SLN was 7.7 % (one patient
with bulky lymph nodes). The FN ratio for perioperative frozen
sections was 15.4 % (two patients, one with micrometastases,
the other with bilateral SLN). Lymphatic drainage was only to
the central compartment in 6 of 24 patients (3 of the 6 with
positive SLNs for metastases), only to the laterocervical basin
in 5 of 24 patients (all unilateral, 2 of 5 positive SLNs) and to
the central and laterocervical compartments in 12 of 24 patients
(6 of 12 and 3 of 12 positive SLNs, respectively).
Conclusion Lymphoscintigraphy reveals the lymph node
drainage in a high proportion of patients. It detects laterocervical
drainage in a significant percentage of patients, allowing the
detection of occult lymph node metastases and improving the
surgical management in PTC.
Keywords Sentinel lymph node . Thyroid cancer . Central
node dissection . Lymphoscintigraphy . SPECT/CT .
99m
Tc-Nanocolloid
Introduction
Papillary thyroid cancer (PTC) represents more than 80 % of
all thyroid malignancies [1]. PTC tends to spread to local
lymph nodes, with the central neck being the most common
compartment involved. The most appropriate strategy for
treatment of patients with PTC is total thyroidectomy togeth-
er with dissection of all clinically apparent metastatic lymph
nodes [2]. However, several studies over recent decades have
shown that occult lymph node metastases may occur in a
significant percentage of patients (up to 90 %) [3]. These
 Eur J Nucl Med Mol Imaging

Table 1 Clinical and pathological characteristics of the 24 patients prophylactic central lymph node dissection be performed in
Characteristic Value all patients (including those without evidence of presurgical
nodal involvement) [4]. Lundgren et al. [5] found that the
Sex, n (%) TNM staging including lymph node and distant metastases is
Female 19 (79) a significant prognostic factor. Nevertheless, the impact of
Male 5 (21) this approach on recurrence and survival is still controversial
Age (years), mean ± SD 52.7 ± 16.6 [6]. Besides, lymph node dissection increases surgical mor-
Tumour size (mm), mean ± SD 16.5 ± 7.2 bidity [7].
Clinical stage Selective sentinel lymph node biopsy (SLNB) has
T stage T1 11 (46) emerged as an effective technique for detecting node metas-
T2 8 (33) tasis in several tumours types, especially breast cancer [8]
T3 5 (21) and melanoma [9]. The sentinel lymph node (SLN) is de-
N stage N0 21 (88 fined as the lymph node that receives drainage from the
N1 3 (13) tumour. The rationale for SLNB is based on the premise that
Tumour location metastasis does not progress randomly, but occurs in a step-
Right lobe 16 (67 wise fashion. Thus, if the SLN is not invaded then there
Left lobe 6 (25) should be no metastasis in more distant lymph nodes. As
Isthmus 2 (8) long ago as 15 years Kelemen et al. [10] proposed the use of
Multifocality SLNB in differentiated thyroid cancer, but the validity of the
No 16 (67) SLNB concept in thyroid malignancies still remains open to
Yes 8 (33) debate. It has been argued that SLNB improves lymph node
staging as well as the selection of patients who would benefit
from compartment-oriented nodal dissection [11]. However,
findings indicate the low accuracy rate of the preoperative some authors have remarked upon the excessive false-
lymph node status. For this reason, it has been proposed that negative (FN) rates among the reports [12].

Fig. 1 Planar and SPECT/CT

images in a patient with only
one SLN in the central
compartment drainage
Eur J Nucl Med Mol Imaging

The objective of the present study was to evaluate the thyroid tumour on the intraoperative/final pathology diagnosis
effectiveness of SLNB for the detection of lymph node (five patients). Table 1 summarizes the characteristics of the 24
metastases in patients with PTC using an isotopic method. remaining patients finally included in the study.

Lymphoscintigraphy and SPECT/CT

Materials and methods
From December 2009 to July 2011, 33 patients with a high
suspicion of PTC were prospectively selected for the study.
Inclusion criteria were PTC on perioperative ultrasonography
and fine-needle aspiration biopsy (FNAB), and no previous
surgical treatment in the cervical area. Nine patients were
excluded because of pregnancy (one patient), patient refusal
(two patients), tracheal invasion (one patient), and nonpapillary
The day before surgery, we performed an ultrasound-guided
intratumoral injection of 99mTc-nanocolloid, using a small
volume (0.1–0.2 ml) in order to avoid a high intratumoral
pressure. The injected activity was calculated to allow the
surgical detection at 24 h (148 MBq 99mTc-nanocolloid).
Planar images of the cervical area (anterior, oblique and
lateral) and SPECT/CT tomographic images (Hawk-eye 4;
General Electric) were obtained 2 to 4 h after the injection.

Fig. 2 Planar and SPECT/CT

images in a patient with
laterocervical and central
compartment drainage.
Quantification of the activity of
the SLN in the images improves
the identification of true SLN
during surgery, avoiding errors
in lymph node removal. Six
SLN were removed during
surgery. One SLN in the central
compartment (420 counts) and
another in the upper
laterocervical basin (555
counts) are triangulated in the
SPECT/CT images
 Eur J Nucl Med Mol Imaging

Table 2 Patient-based results (n = 24): SLN, lymphadenectomy and

FN ratio

Parameter Value

Drainage, n (%) 23 (96)

Number of SLN 78
identified
SLN per patient 3.25
Number of lymph 390
nodes excised
Number of lymph 16.25
nodes excised
per patient
Number of SLN,
n (%)
None 1 (4)
One 3 (12.5)
Fig. 3 Lymphatic drainage per patient: central and laterocervical basin
Two 4 (16.7) distribution with percentage of SLN positivity in each basin. Lymphatic
Three or more 16 (66.7) spread was detected in 13 of the 24 patients
Patients with positive 10 (41.7)
SLNs, n (%)a
Patients with positive SLNsa 13 (54.2)
or lymphadenectomy, n (%) of each SLN was included in the image, so that during surgery
Sensitivity (%) 92
the surgeon had information not only about the number and
Specificity (%) 100
location of the SLNs, but also had data on the relative activity
False-negative in relation
to final diagnosis, n (%)
of each SLN compared with that of the SLN with the highest
activity. Given that the preoperative relative activity between
SLN technique: negative 1 (4)
perioperative frozen sections, different SLNs is approximately maintained at surgery using
negative final pathological the gamma probe, this information allows the surgeon to be
analysis, positive nodes on sure that the correct SLNs and all the SLNs in each lymphatic
lymphadenectomy
basin are excised.
Perioperative analysis 2 (8.3)
(frozen sections): negative
perioperative frozen section, Surgery
positive final pathological
analysis or positive nodes
The surgical procedures were always performed by the same
on lymphadenectomy
team. The procedure was initiated with a total thyroidecto-
a
One patient without SLN detection my. SLNs were then located and removed guided by a hand-
held gamma probe (Europrobe; Eurorad, Chennevieres,
France). SLNs were identified on planar and SPECT/CT
Skin marks were made with permanent ink in the closed skin images, and their relative activities were compared with that
projection of the SLN. of the lymph node with highest uptake. All specimens were
SPECT/CT images were accurately processed and com- immediately sent to the pathology laboratory.
pared to the planar images. Save-screens with the triangula- All patients underwent lymphadenectomy of the central
tion of each SLN were sent to the PACS, allowing visuali- compartment. Lateral compartment dissection was performed
zation of the SLNs in the surgical theatre. All the SLNs were only when the SLN was positive in this area or in those with
identified in the images not only with their location but also perioperative stage N1b. At the end of the procedure, a com-
with their relative activity on the images (Fig. 1). In each plete scan of the operating field was performed using the
lymphatic basin on the images the SLN with the highest activity hand-held gamma probe.
was identified, and all hot lymph nodes with counts >10 % of
this maximum activity were marked (for the surgeon) as Pathological analysis
SLNs (Fig. 1).
If several SLNs were identified, to avoid errors in SLN Perioperative analysis consisted of histological analysis of
removal, the uptake of each SLN was quantified on the frozen sections. The final assessment of all excised speci-
preoperative images (Fig. 2). This technique improved the mens was performed with haematoxylin and eosin staining
identification of true SLN during surgery. The relative activity as well as pan-cytokeratin immunohistochemistry.
Eur J Nucl Med Mol Imaging

Table 3 Lymphatic distribution,

with percentage of positivity in Compartment drainage Patients (n = 24)a SLN
each basin
Total Positive Positive/total

Central 18 (75 %) 8 (44 %) 15/45 (33 %)

Lateral 17 (71 %) 5 (29 %) 8/33 (24 %)

Central only 6 (25 %) 3 (50 %) 4/13 (30.8 %)

Lateral only 5 (21 %) 2 (40 %) 5/14 (35.7 %)
a
One patient without SLN Central and lateral 12 (50 %) 6 (50 %) 14/51 (27.5 %)
detection

Statistical analysis
Data are summarized using the mean ± standard deviation for
continuous variables and proportions for categorical variables.
Tables 3 and 4 show the results of both the patient-based
analysis and SLN-based analysis (in respect of the total num-
bers of SLN excised). Sensitivity, specificity and FN and false-
positive rates were calculated comparing the SLN status to the
final pathology results. A FN result was considered when the
perioperative analysis was negative (SLN not detected or his-
tological frozen section analysis reported as negative) but the
definitive histological result was positive for PTC node in-
volvement. The final SLNB and perioperative analysis were
compared separately against the final diagnosis of the SLNs
and lymphadenectomy.
Results
Lymphoscintigraphy performed the day before surgery was
able to reveal at least one SLN in 19 of 24 patients (79 %) on
planar and SPECT/CT images during the 4 h after injection,
and in 23 of 24 patients (96 %) during surgery using the
hand-held gamma probe. As detailed in Table 2, during the
intraoperative detection, a total of 78 SLNs were found in the
24 patients, with a mean of 3.25 SLNs per patient. One SLN
was excised in 3 patients (12.5 %), two lymph nodes in 4
patients (16.7 %) and three or more SLNs in the remaining
16 patients (66.7 %).
Of the 24 patients, 75 % had SLN in the central compart-
ment, and 71 % in the lateral compartment. Twelve patients
had SLNs in both the central and lateral compartments, six
had SLNs in only the central compartment and five had
SLNs in only the lateral compartment (Fig. 3, Table 3).
Lymph node metastases were detected with classical peri-
operative techniques (ultrasonographic and surgical inspec-
tion) in 3 of the 24 patients. In the perioperative frozen section
study (Tables 2 and 4), SLN metastases were found in 10 of 23
patients (43 %, one patient without SLN detection), corre-
sponding to 22 of 78 SLN (28 %). Thus, in the patient-based
analysis, 44 % and 29 % of the patients had metastatic SLNs
in the central and lateral compartments, respectively (two of
them contralateral to the tumour). In the SLN-based analysis,
33 % and 24 % of the SLNs were metastatic in the central and
lateral compartments, respectively. Five patients with exclu-
sive drainage to the lateral compartment had 35.7 % positive
SLNs.
The final pathological analysis, based on the haematoxylin
and eosin sections and pancytokeratin immunohistochemistry,
was performed on all the SLNs and on all the nodes excised.

Table 4 Perioperative and final

pathological analysis of the SLN Patients Lymph nodes
and lymphadenectomy Positive/totala Positive/total

SLN perioperative frozen section study 10/23 (43 %) 22/78 (28 %)

Lymphadenectomy
Total 13/23 (56.5 %) 64/369 (17 %)
Central compartment 34/265 (13 %)
Lateral compartment (ipsilateral) 29/102 (28 %)
Lateral compartment (contralateral) 1/2 (50 %)
Central compartment only 7 (30.4 %)
Lateral compartment only 2 (8.7 %)
a
Central and lateral compartments 4 (17.4 %)
One patient without SLNs
Table 5 Literature review of SLN procedures in differentiated thyroid cancer

Reference Method Stage (FIGO, No. of Detection No. Positive Patients False- Patients Patients with Performance evaluation
UICC, TNM) patients at surgery of SLNs with negative with ablative
SLNs positive SLNs metastases therapy
SLNs (SLN− or
SLN+)

Total M/F No. % No. % No. % No. % No. % Sensitivity Specificity Accuracy Positive Negative
predictive predictive
value value

[10] BD na 17 3/14 17 100.0 na 12 – na – 0 – na – na na na na na na

[13] BD na 40 na 31 77.5 na 26 – na – 2 – na – na na na na na na
[14] SC na 9 na 8 88.9 na 8 – na – na – na – na na na na na na
[15] SC na 11 na 10 90.9 na na – na – na – 5 38.5 na na na na na na
[16] SC na 6 na na 100.0 na na 66.0 na – na – na – na na na na na na
BD na – na – 100.0 na na 50.0 na – na – na – na na na na na na
GP na – na – 100.0 na na 83.0 na – na – na – na na na na na na
[17] BD na 38 na 27 71.1 na na – 16 59.3 na – 19 70.4 na 84.0 100.0 89.0 na na
[18] BD na 21 na 19 90.5 na 7 – 19 86.4 2 – na – na na na na na na
[19] BD na 22 2/20 20 90.9 na na – na – 2 – 12 60.0 na na na na na na
[20] BD III/IV/VI/VII 29 na 22 75.9 na na – 4 18.2 na – na – na na na na na na
[21] SC na 10 na na 100.0 na na 100.0 na – 1 – na – na na na na na na
[22] BD na 68 na 63 92.6 na 58 92.1 na – 5 – na – na 87.5 100.0 92.1 100.0 8.1
[23] na na 64 na 47 73.4 na 12 – na – 0 – na – na na na na na na
[24] BD na 15 na 10 66.7 8 19 100.0 10 – 1 – na – na 88.0 100.0 90.0 100.0 67.0
[25] BD na 32 na 30 93.8 na na – na – 1 – 14 46.7 na 93.0 na 97.0 na na
SC na 23 na 22 95.7 na na – na – na – na – na 90.0 na 95.0 na na
[26] BD na 9 na 0 0.0 0 0 – 0 – 0 – na – na na na na na na
[27] SC na 41 na 41 100.0 122+ na – 21 51.2 na – 21 51.2 na na na na na na
[28] BD na 40 na 37 92.5 na na – na – 2 – 7 18.9 na 77.7 100.0 95.0 100.0 94.0
[29] BD na 110 na 74 67.3 na 38 51.4 38 51.4 na – na – na na na na na na
[30] BD na 153 na na 107.0 na 13 – 36 – 7 – 7 15.2 na na na na na na
[31] BD na 28 23/5 28 100.0 24 24 100.0 22 78.6 na – 9 32.1 na na na na na na
[32] SC na 64 na 62 96.9 na 62 – na – 7 11.3 12 19.4 na na na na na na
[33] SC T1 (8), T2 (4), 25 8/17 25 100.0 85+ na – na – na – na 48.0 na na na na na na
T3 (9
[34] BD na 25 na 22 88.0 na na – 19 86.4 na – 13 – na na na na na na
[35] SC na 65 na na – na na – na – na – na 52.0 na na na na na na
[12] BD na 98 na 75 76.5 na na – na – na – 15 21.4 na 100.0 86.0 87.0 40.0 100.0
[36] na na 37 na 32 86.5 na na – na – na – 4 33.3 na na na na na na
[37] BD na 54 na 89 91.8 385 19 35.2 na – na – na 21.0 na 79.0 100.0 na na na
Eur J Nucl Med Mol Imaging
Table 5 (continued)

Reference Method Stage (FIGO, No. of Detection No. Positive Patients False- Patients Patients with Performance evaluation
UICC, TNM) patients at surgery of SLNs with negative with ablative
SLNs positive SLNs metastases therapy
SLNs (SLN− or
SLN+)

Total M/F No. % No. % No. % No. % No. % Sensitivity Specificity Accuracy Positive Negative
predictive predictive
Eur J Nucl Med Mol Imaging

value value

SC/BD na 43 na – – – 21 48.8 na – na – na 9.0 na 91.0 100.0 na na na

[38] SC na 23 na na 87.0 na na – na – 2 – 12 – na na na 91.3 100.0 81.8
SC/BD – – – na 100.0 na na – na – – – – – – – – – – –
[39] BD T1 (142), 211 165/ 46 192 91.0 192 71 37.0 47 24.5 na – 26 60.5 na na na na
T2,(35), T3
(32), T4 (2)
na na
[40] SC N0 (18), N1 (2) 20 4/16 20 100.0 62 18 29.0 13 65.0 na – na – – na na na na na
[41] na na 157 na na – na na – na – na – 3 – na na na na na na
[42] BD II (1), III (6). III/ 45 0/45 39 86.7 na na – 21 53.8 7 38.9 7 17.9 na na na 82.1 na 61.1
IV (8), IV (8),
VI(32)
SC/BD na 45 0/45 45 100.0 na na – 24 53.3 3 14.3 na – na na na 93.3 na 85.7
[43] Nanocarbon na 100 na na – 126 na – 77 na na 5.2 na – na 93.3 100.0 97.0 na na
BD na 100 na na – 102 na – 48 na na 9.9 na – na 80.6 100.0 93.0 na na
[44] BD II/III/IV/VI 132 na 132 100.0 1373 1246 90.8 na – 7 na 1079 – na 87.8 na na na na
[45] BD na 114 na 84 73.7 na na – na – na 35.1 24 28.6 na 64.9 100.0 – 100.0 78.3

BD blue dye, SC scintigraphy, na data not available or not mentioned

 Eur J Nucl Med Mol Imaging

Table 6 Meta-analysis review of SLN procedures in differentiated thyroid cancer

Reference Method No. of patients Detection No. of SLNs Positive Patients with positive False-negative Patients with Reports
rate SLNs SLNs SLNs metastases included
at surgery (SLN− or SLN+)

No. % No. % No. % No. % No. %

[46] BD 329 na 83.0 – na – na 87.3 na 12.7 na – 10

SC 128 na 96.0 – na – na 88.7 na 11.3 na – 4
[47] BD na na 83.7 47 na 42.9 na – na 7.7 7 15.0 23
SC na na 98.4 – na – na – na 16.0 – – –
SC/BD na na – – na – na – na 0.0 – – –
[48] BD 891 740 83.1 na na – na – na – na – 18
SC 160 158 98.8 na na – na – na – na – 4
SC/BD 49 48 98.0 na na – na – na – na – 2

BD blue dye, SC scintigraphy, na data not available or not mentioned

Lymphadenectomy was always performed in the central com- Discussion

partment, and in the laterocervical basins only in patients with
perioperative stage N1b (ultrasonography, FNAB) or positive
SLN in the perioperative frozen sections. A total of 369 lymph
nodes were excised. Of these, 265 were from the central
compartment (13 % positive for metastasis), 102 from the
ipsilateral compartment (28 % positive) and 2 from the con-
tralateral compartment (50 % positive). In total, 13 of the 24
patients (54.2 %) were positive for lymph node metastases, 7
only in the central compartment, 2 only in the lateral compart-
ment and the remaining 4 in both compartments.
Of the SLN perioperative frozen section results, three
were FN in relation to the final pathological analysis of each
SLN (Table 2). One patient had negative SLN and bulky
metastatic lymph nodes (larger than 20 mm, positive). This
result of the SLN technique has to be considered FN. Prob-
ably the bulky lymph nodes should have been the SLNs but
they had lost their ability to take up the tracer due to tumour
invasion, and the tracer went to the second echelon lymph
nodes. The second FN result of the SLN technique was in a
patient with micrometastases on definitive histology. The
third FN result of the SLN technique was in a patient with
the tumour located in the isthmus, with multiple bilateral
SLNs. The surgeon performed a radioguided lymphadenec-
tomy, but during surgery only the lymph nodes with higher
activity were considered SLNs. The few SLNs were negative
in the perioperative analysis and the final lymphadenectomy
was positive. This result has to be considered FN for both
surgery and the perioperative frozen section study. In sum-
mary, the overall sensitivity was 77 % and the specificity was
100 %.
Table 5 summarizes sensitivity, specificity, accuracy, and
positive and negative predictive values for our series and
compares our results with those reported previously. Meta-
analyses are summarized in Table 6.
Cervical nodal metastasis in PTC is a common occurrence,
with the central neck being the most common compartment
involved. In patients with preoperative or intraoperative evi-
dence of nodal metastasis, total thyroidectomy with “thera-
peutic” cervical lymph node dissection is indicated [2]. How-
ever, in those patients without evidence of lymph node in-
volvement, “prophylactic” central neck dissection remains a
controversial topic [5]. It has been argued that the sensitivity
of perioperative diagnostic techniques is very low. Cervical
ultrasonography has a lower rate of detection of metastatic
lymph nodes in the central compartment. Furthermore, retro-
spective studies have shown that regional lymph node metas-
tases are associated with tumour recurrence. However, there is
a lack of definitive evidence that prophylactic node dissection
improves cancer outcome. Moreover, lymph node dissection
is associated with higher complications rates, including per-
manent hypoparathyroidism and vocal cord paresis, when
compared to total thyroidectomy alone.
Several surgical strategies for detecting subclinical node
metastases have been proposed. One of these is selective
SLNB. The SLN is defined as the lymph node that receives
drainage from the tumour. As long ago as 15 years Kelemen
et al. [10] proposed the use of SLNB in differentiated thyroid
cancer. Since then, several authors have reported that its use is
feasible and safe [32, 39]. However, the validity of the SLNB
concept in thyroid malignancies remains open to debate. One
of the debatable issues is the considerable variation in the rate
of detection of SLN. Two general methods have been
employed: the blue dye technique and the radioisotope tech-
nique. A meta-analysis carried out in 2008 concluded that
studies using the latter method yielded an approximately
13 % higher SLN detection rate than those using the former
[46]. Some authors have used a combination of both methods
Eur J Nucl Med Mol Imaging
and have reported better results [42]. The most recent meta-
analysis published in 2011 [47] showed that the detection rates
for the blue dye, radioisotope and combined techniques were
83.7 %, 98.4 % and 96 %, respectively. In the current study,
using a radiotracer (99mTc-colloid), we detected the SLN in 23
of 24 patients (96 %). This is concordant with other results [32].
With this method, our results showed a sensitivity of 77 %, a
specificity of 100 % and an accuracy of 87 %. Although high,
our sensitivity rate is somewhat lower than the average rates
reported in the literature, both for the all-methods sensitivity
rate (85.5 %) and for the only-lymphoscintigraphy method
(91.5 %). However, our specificity rate equals that of the
combined lymphoscintigraphy/blue dye method (100 %).
In the SLNB technique, a FN result was considered when the
perioperative analysis was negative but the definitive histologi-
cal result was positive for PTC node involvement. Our FN rate
was 23 %. The FN rates of the studies that used SLN detection
by blue dye or by combination of lymphoscintigraphy and blue
dye are similar (20.7 % and 14.3 %, respectively). According to
the literature, the most important item for validating SLNs is the
FN rate [12]. Certainly, a high FN rate renders any specific
technique unsuitable for routine practice [46]. The FN rate is
related to several aspects. In the current series there were three
FN results. The first was attributed to lymph node micrometas
tases. The main limitation of perioperative frozen section meth-
od is in detecting micrometastases. Probably, as in other cancer
types, the addition of molecular biology methodology to a
standard detection method should improve the accuracy of the
intraoperative assessment of the SLNs in thyroid carcinoma [49,
50]. The second FN results was in a patient with a bulky nodal
disease. It has been reported that in patients with bulky meta-
static lymph nodes the normal path of lymphatic drainage can be
blocked by tumour-laden lymphatics [13, 51]. Finally, the third
FN result in the current series was in a patient with a tumour
located in the isthmus and with bilateral lymphatic drainage. All
three cases suggest that SLN may be less feasible in some
special clinical situations. Therefore, in order to validate the
technique, these conditions should be clearly defined.
Although this was a small series, it is worth noting that in
the presurgical study, only three patients were staged as
lymph node positive (N1), whereas after SLNB the figure
increased to ten in the intraoperatively frozen analysis and to
13 in the final pathological examination. Thus, the metastasis
rate was 54 % in a series of patients in which the presurgical
rate was over 12 %. Hence, the rate of node involvement in
patients with no clinically suspected lymph node metastases
is very high, as has been found in other studies [52, 53].
More recently, Lee et al. have found that SLNB is a useful
method for detecting not only central but also occult lateral
neck lymph node metastases [54].
In conclusion, SLN detected by a radioisotope method is a
valuable technique that permits the detection of occult lymph
node metastases in the cervical region in patients with PTC.
Compared to preoperative ultrasonographic and clinical
staging, SLNB upstages a significant number of patients
initially N0 (12.5 % compared to 46 %). Previously accepted
surgery included systematic central compartment lymphad-
enectomy and only lateral compartment lymphadenectomy
in those with preoperative evidence of lymphatic spread in
these basins. SLNB should lead to the avoidance of central
compartment lymphadenectomy in 50 % of patients. Regard-
ing lateral compartment drainage, in 71 % of the patients
SLN were removed from these basins. The most relevant
change in clinical management was lateral compartment
lymphadenectomy during initial surgery in 21 % of patients.
Acknowledgments This work was supported by grant FIS PI09/
90440 from the Health Research Fund of the Spanish “Instituto de
Salud Carlos III”.
Conflicts of interest None.
References
1. Hundahl S, Fleming I, Fremgen A, Menck H. A National Center
Data Base report on 53,856 cases of thyroid carcinoma treated in
the U.S., 1985–1995. Cancer. 1998;83:2638–48.
2. American Thyroid Association (ATA) Guidelines Taskforce on
Thyroid Nodules and Differentiated Thyroid Cancer; Cooper D,
Doherty G, Haugen B, Kloos RT, Lee SL, Mandel SJ, et al. Revised
American Thyroid Association management guidelines for patients
with thyroid nodules and differentiated thyroid cancer. Thyroid.
2009;19:1167–214.
3. Dralle H, Machens A. Surgical approaches in thyroid cancer and
lymph-node metastases. Best Pract Res Clin Endocrinol Metab.
2008;22:971–87.
4. Carling T, Long 3rd WD, Udelsman R. Controversy surrounding
the role for routine central lymph node dissection for differentiated
thyroid cancer. Curr Opin Oncol. 2010;22:30–4.
5. Lundgren CI, Hall P, Dickman PW, Zedenius J. Clinically significant
prognostic factors for differentiated thyroid carcinoma: a population-
based, nested case-control study. Cancer. 2006;106(3):524–31.
6. Mazzaferri E, Doherty G, Steward D. The pros and cons of pro-
phylactic central compartment lymph node dissection for papillary
thyroid carcinoma. Thyroid. 2009;19:683–9.
7. Sakorafas G, Sampanis D, Safioleas M. Cervical lymph node dissec-
tion in papillary thyroid cancer: current trends, persisting controver-
sies, and unclarified uncertainties. Surg Oncol. 2010;19:e58–70.
8. Cheng G, Kurita S, Torigian D, Alavi A. Current status of sentinel
lymph-node biopsy in patients with breast cancer. Eur J Nucl Med
Mol Imaging. 2011;38:562–75.
9. Prieto V. Sentinel lymph nodes in cutaneous melanoma. Clin Lab
Med. 2011;31:301–10.
10. Kelemen P, Van Herle A, Giuliano A. Sentinel lymphadenectomy
in thyroid malignant neoplasms. Arch Surg. 1998;133:288–92.
11. Rubello D, Pelizzo M, Al-Nahhas A, Salvatori M, O'Doherty MJ,
Giuliano AE, et al. The role of sentinel lymph node biopsy in
patients with differentiated thyroid carcinoma. Eur J Surg Oncol.
2006;32:917–21.
12. Anand S, Gologan O, Rochon L, Tamilia M, How J, Hier MP, et al.
The role of sentinel lymph node biopsy in differentiated thyroid
carcinoma. Arch Otolaryngol Head Neck Surg. 2009;135:1199–
204.

13. Dixon E, McKinnon J, Pasieka J. Feasibility of sentinel lymph node
biopsy and lymphatic mapping in nodular thyroid neoplasms.
World J Surg. 2000;24:1396–401.
14. Rettenbacher L, Sungler P, Gmeiner D, Kässmann H, Galvan G.
Detecting the sentinel lymph node in patients with differentiated
thyroid carcinoma. Eur J Nucl Med. 2000;27:1399–401.
15. Sahin M, Yapici O, Dervisoglu A, Basoglu T, Canbaz F, Albayrak
S, et al. Evaluation of lymphatic drainage of cold thyroid nodules
with intratumoral injection of Tc-99m nanocolloid. Clin Nucl Med.
2001;26:602–5.
16. Catarci M, Zaraca F, Angeloni R, Mancini B, de Filippo MG, Massa
R, et al. Preoperative lymphoscintigraphy and sentinel lymph node
biopsy in papillary thyroid cancer. A pilot study. J Surg Oncol.
2001;77:21–4.
17. Tsugawa K, Noguchi M, Miwa K, Bando E, Yokoyama K,
Nakajima K, et al. Dye- and gamma probe-guided sentinel lymph
node biopsy in breast cancer patients: using patent blue dye and
technetium-99m-labeled human serum albumin. Breast Cancer.
2000;7:87–94.
18. Fukui Y, Yamakawa T, Taniki T, Numoto S, Miki H, Monden Y.
Sentinel lymph node biopsy in patients with papillary thyroid
carcinoma. Cancer. 2001;92:2868–74.
19. Arch J, Velasquez D, Fajardo R, Gamboa A, Herrera M. Accuracy
of sentinel lymph node in papillary thyroid carcinoma. Surgery.
2001;130(6):907–13.
20. Pellizo M, Boschi I, Toniato A, Bernante P, Piotto A, Rinaldo A,
et al. The sentinel node procedure with Patent Blue V dye in the
surgical treatment of papillary thyroid carcinoma. Acta
Otolaryngol. 2001;121(3):421–4.
21. Stoeckli S, Pfaltz Steiner H, Schmid S. Sentinel lymph node biopsy
in thyroid tumors: a pilot study. Eur Arch Otorhinolaryngol.
2003;260:364–8.
22. Takami H, Sasaki K, Ikeda Y, Tajima G, Kameyama K. Detection of
sentinel lymph nodes in patients with papillary thyroid cancer.
Asian J Surg. 2003;26:145–8.
23. Dzodic R, Markovic I, Inic M, Jokic N, Zegarac M, Djurisic I, et al.
Identification of sentinel lymph in thyroid carcinoma. Acta Chir
Iugosl. 2003;50:103–6.
24. Chow T, Lim B, Kwok S. Sentinel lymph node dissection in
papillary thyroid carcinoma. ANZ J Surg. 2004;74:10–2.
25. Nakano S, Uenosono Y, Ehi K, Arigami T, Higashi Y, Maeda T,
et al. Lymph node mapping for detection of sentinel nodes in
patients with papillary thyroid cancer. Gan To Kagaku Ryoho.
2004;31:801–4.
26. Peparini N, Maturo A, Di Matteo F, Tartaglia F, Marchesi M,
Campana E. Blue-dye sentinel node mapping in thyroid carcinoma:
debatable results of feasibility. Acta Chir Bel. 2006;32:523–7.
27. Pellizo M, Merante I, Toniato A, Piotto A, Bernante P, Paggetta C,
et al. Sentinel node mapping and biopsy in thyroid cancer: a
surgical perspective. Biomed Pharmacother. 2006;60(8):4405–8.
28. Dzodic R, Markovic I, Inic M, Jokic N, Djurisic I, Zegarac M, et al.
Sentinel lymph node biopsy may be used to support the decision to
perform modified radical neck dissection in differentiated thyroid
carcinoma. World J Surg. 2006;30(5):841–6.
29. Pellizo M, Merante I, Piotto A, Bernante P, Pagetta C, Rubello D,
et al. Sentinel lymph node procedure in thyroid carcinoma patients.
Our experience. Minerva Chir. 2006;61(1):25–9.
30. Rubello D, Nanni C, Merante I, Toniato A, Piotto A, Rampin A, et al.
Sentinel lymph node (SLN) procedure with patent V blue dye in 153
patients with papillary thyroid carcinoma (PTC): is it an accurate
staging method? J Exp Clin Cancer Res. 2006;25(4):483–6.
31. Nenkov R, Radev R, Madzhov R, Krasnaliev I. Sentinel lymph node
biopsy in patients with papillary thyroid carcinoma. Khirurgiia (Sofiia).
2006;(6):55–6.
32. Carcoforo P, Feggi L, Transforini G, Lanzara S, Sortini D, Zulian V,
et al. Use of preoperative lymphoscintigraphy and intraoperative
Eur J Nucl Med Mol Imaging
gamma-probe detection for identification of the sentinel lymph
node in patients with papillary thyroid carcinoma. Eur J Surg
Oncol. 2007;33(9):1075–80.
33. Pellizo M, Rubello D, Boschin I, Piotto A, Paggetta C, Toniato A,
et al. Contribution of SLN investigation with 99mTc-nanocolloid in
clinical staging of thyroid cancer: technical feasibility. Eur J Nucl
Med Mol Imaging. 2007;34(6):934–8.
34. Wang J, Deng X, Jin X, Zhang C, Zhou J, Zhou Q, et al. Surgical
exploration of the sentinel lymph nodes in the papillary thyroid
carcinoma. Rev Laryngol Otol Rhinol (Bord). 2008;129(4-5):285–
7.
35. Boschin I, Toniato A, Piotto A, Ide E, Casara D, Guolo A, et al.
99Tc nanocolloid sentinel node procedure in thyroid carcinoma.
Langenbecks Arch Surg. 2008;393(5):705–8.
36. Takeyama H, Tabei I, Uchida K, Morikawa T. Sentinel node biopsy for
follicular tumours of the thyroid gland. Br J Surg. 2009;96(5):490–5.
37. Lee S, Choi J, Lim H, Kim W, Choe J, Lee J, et al. Sentinel lymph
node biopsy in papillary thyroid cancer: comparison study of blue
dye method and combined radioisotope and blue dye method in
papillary thyroid cancer. Eur J Surg Oncol. 2009;35(9):974–9.
38. Zhang B, Yan D, Liu L, Niu L, An C, Zhang Z, et al. Sentinel lymph
node biopsy in papillary thyroid cancer. Zhonghua Zhong Liu Za
Zhi. 2010;32(10):782–5.
39. Cunningham D, Yao K, Turner R, Singer F, Van Herle A, Giuliano A.
Sentinel lymph node biopsy for papillary thyroid cancer: 12 years of
experience at a single institution. Ann Surg Oncol. 2010;17(11):2070–
5.
40. Sabaté-Fernández M, Roca I, Kisiel N, Garcia-Burillo A, Porta F,
Gonzalez O, et al. Usefulness of selective sentinel lymph node
biopsy in the diagnosis of extension of papillary thyroid cancer.
Annual Congress of the EANM 2011. October 2011, Birmingham.
Eur J Nucl Med Mol Imaging. 2011;38 Suppl 2:OP305.
41. Amir A, Payne R, Richardson K, Hier M, Mlynarek A, Caglar D.
Sentinel lymph node biopsy in thyroid cancer: it can work but there
are pitfalls. Otolaryngol Head Neck Surg. 2011;145(5):723–6.
42. Huang O, Wo W, Wang O, You J, Huang D, Hu X, et al. Sentinel
lymph node biopsy is unsuitable for routine practice in younger
female patients with unilateral low-risk papillary thyroid carcino-
ma. BMC Cancer. 2011;11:386.
43. Hao R, Chen J, Zhao L, Liu C, Wang O, Huang G, et al. Sentinel
lymph node biopsy using carbon nanoparticles for Chinese patients
with papillary thyroid microcarcinomas. Eur J Surg Oncol.
2012;38(8):718–24.
44. Li X, Ma H, Tian X, Jin X. Elective neck dissection in papillary
thyroid carcinoma patients. Acta Chir Belg. 2012;112(1):44–50.
45. Ji Y, Lee K, Park Y, Hong S, Paik S, Tae K. Clinical efficacy of
sentinel lymph node biopsy using methylene blue dye in clinically
node-negative papillary thyroid carcinoma. Ann Surg Oncol.
2012;19(6):1868–73.
46. Rajmakers PG, Paul MA, Lips P. Sentinel node detection in
patients with thyroid carcinoma: a meta-analysis. Word J Surg.
2008;32:1961–7.
47. Balasubramanian S, Harrison B. Systematic review and meta-
analysis of sentinel node biopsy in thyroid cancer. Br J Surg.
2011;98(3):334–44.
48. Kaczka K, Celnik A, Luks B, Jasion J, Pomorski L. Sentinel lymph
node biopsy techniques in thyroid pathologies – a meta-analysis.
Endokrynol Pol. 2012;63(3):222–31.
49. Blumencranz P, Pieretti M, Allen K, Blumencranz L. Molecular
analysis of breast sentinel lymph nodes. Surg Oncol Clin N Am.
2011;20:467–85.
50. Cserni G. Intraoperative analysis of sentinel lymph nodes in breast
cancer by one-step nucleic acid amplification. J Clin Pathol.
2012;65:193–9.
51. Mijovic T, Richardson K, Payne RJ, How J. Sentinel lymph node
biopsy in well differentiated thyroid cancer. In: Fahey T, editor.
Eur J Nucl Med Mol Imaging
Updates in the understanding and management of thyroid cancer.
Rijeka: InTech; 2012. p. 217–234.
52. Pelizzo M, Toniato A, Sorgato N, Losi A, Torresan F, Merante BI.
99Tc nanocolloid sentinel node procedure in papillary thyroid
carcinoma: our mono-institutional experience on a large series of
patients. Acta Otorhinolaryngol Ital. 2009;29:321–5.
53. Roh J, Park C. Sentinel lymph node biopsy as guidance for central
neck dissection in patients with papillary thyroid carcinoma. Cancer.
2008;113:1527–31.
54. Lee S, Kim S, Hur S, Choe J, Kim J, Kim J. The efficacy of lateral neck
sentinel lymph node biopsy in papillary thyroid carcinoma. World J
Surg. 2011;35:2675–82.