|Papillary thyroid carcinoma; Lymph node; Metastasis;
Pattern; Predictive factors
|Thyroid carcinoma is the most common endocrine neoplasm,
corresponding to 95.0% of them, and they make up 2.0% of all malignant
tumors. Thyroid carcinoma exhibits a high index of dissemination
to the cervical lymph nodes . Neck ultrasound identifies lymph
node metastases in 20-30% of cases, especially in the areas closest to
the thyroid gland, where their frequency is higher. However, those
percentages correspond to fewer than half of the patients with lymph
node metastasis . Although the presence of neck metastases increases
the rate of local recurrence, the risks of elective lymph node dissection
should be assessed relative to its potential benefits, such as reduction
of the number of reoperations. Thus, the indication for elective lymph
node dissection is controversial for individuals with noclinically
manifest metastases in the neck (N0) . Although reduced patient
survival has been reported in cases with patent neck metastasis,
objections have been raised as to the methods applied by those studies
[4-6]. The aim of the present study was to investigate the clinical and
anatomo pathological variables associated with greater risk of cervical
lymph node dissemination, as well as the characteristics and pattern of
dissemination of metastases in individuals with PTC.
|Case Series and Methods
|This was a retrospective study of 203 individuals with PTC subjected
to surgery from 2005 to 2013. From that initial sample, 95 volunteers
were excluded because lymph node dissection was not performed, three
were excluded because they exhibited other concomitant head and neck
malignant neoplasms, and four were excluded because they exhibited
histological variants other than the classical and/or follicular ones.
Therefore, the final sample comprised 101 individuals with histological
diagnosis of classical PTC or its follicular variant, whose surgery was
performed by the same surgeon at the Clinical Hospital of Federal
University of Minas Gerais (Universidade Federal de Minas Gerais –
UFMG) and Benjamin Guimarães Foundation/Baleia Hospital, Belo
Horizonte, MG, Brazil. Eighty-two (81.2%) were female and 19 (18.8%) were male, and the average age of the sample was 42 years (range 10–
75 years). The participants were subjected to central compartment
lymphadenectomy, i.e., bilateral dissection of levels VI and VII. In the
cases with suspected lateral lymph nodes, lateral neck compartmental
lymphadenectomy (levels II to V) was also performed (Figure 1).
Figure 1 – Neck-lymphatic drainage levels Adapted from Porcaro-
Salles et al. . The non-parametric chi-squared test of independence
was used in the analysis of the categorical variables of interest. In the
case of variables represented by fewerthan five individuals, Fisher’s
exact test was used. Student’s t-test was used to compare continuous
variables, such as lymph node size and number of dissected lymph
nodes. Multivariate analysis was performed by means of binary logistic
regression, including the variables that exhibited p-values lower than
0.05 on univariate analysis. The significance level was established
as 5% in all the tests. Analyses were performed using IBM-SPSS® v.
20. The study was approved by the research ethics committees of the
|Among the 101 individuals assessed, 51 (50.5%) exhibited neck
metastasis: 32/51 (62.7%) in the central compartment only and
19/51 (37.3%) in the central andlateral compartments. In no case
were the metastases contralateral to a unilateralprimary tumor. Four
cases of bilateral central compartment metastases occurred, all in individuals with multicentric disease affecting both thyroid lobes. The
average number of dissected lymph nodes per patient was 7.8 ± 4.7
in group N0 (without metastasis) and 20.3 ± 16.3 in group N+ (with
metastasis). In the latter, the average number of lymph nodes dissected
exclusively in the central compartment was 12.8 ± 9.1. Comparison
of the number of lymph nodes dissected in the central compartment
between individuals from groups N+ and N0 revealed a significantly
larger number in group N+ (p = 0.01). The lymph node size varied
from 0.1 to 4.0 cm. The average lymph node size was 1.32 ± 0.9 cm
in group N+ and 1.15 ± 0.4 cm in group N0 (p = 0.34). Univariate
analysis found that angiolymphatic infiltration, multicentric disease,
extra thyroid extension, tumor diameter (≥ 1.0 cm), and age (< 45
years) were associated with the occurrence of neck metastasis (p < 0.05)
(Table 1). In contrast, gender and follicular variant were not associated
with neck-lymphatic dissemination (Table 1). Univariate analysis
comparing the groups with (N+) and without neck metastasis (N0).
Multivariate analysis showed that the individuals with multicentric
tumors or angiolymphatic invasion had increased risk of necklymphatic
dissemination (respectively, p = 0.014, odds ratio (OR) =
4.113; p = 0.003, OR = 5.997). Tumors with diameter ≥ 1.0 cm had
increased risk of neck-lymphatic dissemination (p = 0.043, OR = 3.098).
The risk of neck metastasis of individuals with extra thyroid extension
of the tumor or age < 45 years was not different from that of the other
individuals (p > 0.05 for both) (Table 2). Multivariate analysis assessing
the risk of neck metastasis (OR: odds ratio; CI: confidence interval).
|All the individuals included in the present study were subjected to
cervicallymph node dissection, and the presence of micrometastases was
established basedon histological examination. Whenever suspicious
lateral lymph nodes were found,lateral compartment neck dissection
was systematically associated with centralcompartment dissection. The
fact that all the surgical procedures were performed bythe same surgeon
reduced the bias associated with the surgical technique used. Neck
metastases were found in 51/101 (50.5%) participants, in 19 (37.3%)
ofwhom the lateral compartment was also affected, agreeing with other
authors’ reports. No participant exhibited metastases contralateral
to the primary tumor, which is also asomewhat rare finding in other
studies (9.8–18.9%) [8-10]. The patients with neck metastasis had more
dissected lymph nodes than theones without metastasis (p = 0.01), but
the lymph node size did not differ betweengroups (p = 0.34). Therefore,
it was not possible to identify suspicious lymph nodesbased on their
size exclusively (p = 0.34). Macdonald et al.  compared the sizes
ofmetastatic and non-metastatic lymph nodes, and although the ones larger than 1.0 cm were associated with higher risk of malignancy, a
substantial fraction of theindividuals they assessed had metastasis in
smaller lymph nodes. Unfortunately, it is a retrospective study did not
have access to the size of all dissected lymph nodes, only the size of the
largest surgical specimen. Thus, exclusive resection of enlarged lymph
nodes in the transoperative period is not reliable for diagnosing and
treating neck metastases. All metastatic lymph nodes were ipsilateral
to the primary tumor. Therefore, ipsilateral central compartment
dissection might suffice to remove most metastatic lymph nodes, except
in case of multicentric tumors. The index of metastases in patients with
tumor size smaller than 1 cm tumor was 28.1%. Indeed, some authors
[12,13] recommend ipsilateral central lymphadenectomy as routine in
N0 tumors, as, in theory, the risk of surgical complications is reduced,
without posing a threat to theaccuracy of the procedure.
|All the instances of lateral neck metastasis were systematically
associated with the presence of metastatic lymph nodes in the central
compartment. This finding gives further support to the routine
practice of central compartment dissection of the neck whenever the
lateral compartment lymph nodes are dissected. Younger patients are
usually given a better prognosis based on systems such as TNM 
or MACIS . Even so, the incidence of neck metastasis is higher
in young patients, particularly in children, compared to older ones
[16,17], regardless of prognosis. In the present series, the incidence
of neck metastasis was higher in the patients <45 years old compared
to the older ones (p = 0.045). This risk could not be quantified on
multivariate analysis (p = 0.081). Angiolymphatic invasion was
associated with a higher incidence of neck metastasis. However, its identification is performed only on histopathological examination
of the surgical specimen, and thus, it might bear implications for the
adjuvant treatment of disease. As concerns the histological subtypes,
there was no statistically significant difference between neck-lymphatic
dissemination in classical PTC and the follicular variant, in agreement
with previous findings .
|The participants younger than 45 years and those with multicentric
tumors ≥ 1.0 cm in diameter exhibited a higher incidence of central
neck metastasis (p < 0.05).
|It is worth noting that both of these variables can be identified
before surgery. Extra thyroid extension is a weak prognostic factor in
PTC relative to the risk of local recurrence, and by itself, it indicates
at least stage T3 in the TNM staging system. In addition, some studies
have found that patient survival was shorter when the tumor extended
beyond the thyroid capsule. In the present study, although univariate
analysis showed that the participants with extra thyroid extension had
a greater incidence of neck metastasis (p = 0.005), the corresponding
risk could not be quantified on multivariate analysis. The impact of
microscopic neck metastasis and elective cervical lymph node dissection is uncertain . Some authors suggest performing
elective cervical lymph node dissection ipsilateral to the tumor to
remove most of the probably affected lymph nodes with less risk of
surgical complications [12,13,19]. The results of the present study
lend further support to that suggestion, as no instance of metastasis
contralateral to the primary tumor occurred. In conclusion, the factors
predictive of neck lymph node metastasis were age <45 years, tumor
diameter ≥ 1.0 cm, multicentric disease, extra thyroid extension and
angiolymphatic invasion. The neck metastases were all ipsilateral to
the primary tumor. Lymph node size was not a reliable predictor of
the presence or absence of metastasis, indicating that histopathological
examination of the surgical specimen is necessary to establish a
diagnosis of metastatic disease.
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