it is generally accepted that papillary thyroid carcinoma in children and adolescent population has a different clinical presentation and course than in adults .
initial diagnostic presentation in pediatric patients tends to be in more advanced stage , namely , the larger primary tumor , the higher incidence of primary tumor multicentricity and higher incidence of locoregional metastatic spread .
more specifically , palpable neck lymphonodes are most commonly presenting sites in children ( up to 90% ) .
it is already demonstrated that primary thyroid tumor aggressiveness ( as measured by nuclear atypia , tumor necrosis , and lymphovascular invasion ) correlates with metastatic disease , independently from tumor size .
consequently , histological grade should be set as prognostically important component and included in any classification system of differentiated thyroid cancer .  
despite these aggressive characteristics , specific prognosis in pediatric age is better than in adults . as a consequence , several recommendations have been made that propose less aggressive therapeutic approach ( less than total thyroidectomy and no neck dissection ) .
on the contrary , some researchers advise more aggressive therapy , including total thyroidectomy , neck lymphonode dissection , and postoperative radioiodine ablation [ 46 ] . however , recurrent disease and locoregional spread still present major clinical concern regarding optimal extent of the initial surgical therapy , in pediatric population specifically .
several major studies attempted to evaluate influence of patient and tumor characteristics , as well as treatment factors , but without clear recommendations regarding possible risk factors for developing recurrent disease [ 711 ] .   in this paper , we show our retrospective clinical material in 16 patients up to 18 years of age , who underwent surgical therapy at our institution for diagnosis of thyroid papillary carcinoma .
the aim of the presentation is to give insight into clinical and selected pathological characteristics ( tumor size and aggressiveness , multicentricity , and locoregional spread ) of the disease in pediatric age , assess their role in cancer risk , and identify possible critical parameters for developing metastatic disease .
this study is a retrospective analysis of data from 16 pediatric patients with papillary thyroid cancer , ages from 1018 .
all patients were operated upon at the department of ent  head and neck surgery , university hospital  sisters of charity  , zagreb , croatia during the 28-year period ( 19802008 ) .
all patients underwent total thyroidectomy with or without neck dissection ( paratracheal or some type of lateral neck dissection ) .
's neck dissection classification data from consensus statement on the classification and terminology of neck dissection .
medical data were collected from patient documentation ( intraoperative reports , recurrences , fnab results , and additional thyroid diagnosis ) and final pathology reports , as well as from the hospital registry for thyroid diseases were reviewed .
postoperatively , we followed diagnostic and therapeutic guidelines for differentiated thyroid cancer , issued by croatian thyroid society ; postoperative diagnostic scintigraphy was performed with 13  mci i. high - risk patients were put to 100200  mci i ablation without l - t4 .
posttherapeutic whole body scintigraphy was performed 58 days after i. six to twelve months later , the patients were followed up with the exploration of neck ultrasound , ft4 , tsh , tg , and tga ( without l - t4 ) measurements and afterwards yearly .  
all patients were assigned to groups for variables of age ( 18 and comparison group > 18 years ) , gender , size ( diameter ) and pathological parameters of primary tumor aggressiveness , multicentricity , type of neck dissection performed , and presence of locoregional metastatic foci in neck .
grading of pathological aggressiveness , multicentricity , and locoregional spread is demonstrated in table 2 .
we applied statistical analysis of differences with  test and model of multivariate logistic regression for risk factors for metastatic locoregional spread .
from the total of 699 cases with papillary thyroid cancers of all ages , 16 patients ( 2.3% ) with age up to 18 years fulfilled inclusion criteria , 13 females , and 3 males .
the average age at the moment of diagnosis was 16 , with a range of 10 to 18 years .
majority of patients presented with palpable thyroid mass , 12/16 or 75% , and palpable neck node in 8/16 , or 50% .
there were only 4 microcarcinoma cases ( 25% ) , which is in sharp contrast to older population ( 45% microcarcinoma ) .
distribution of parameters of pathological aggressiveness , multicentricity , neck dissection , and metastatic spread and comparison by age group ( 18 and > 18 years ) are shown in table 3 .
results showed that 60% of pediatric tumors were aggressive , according to our chosen criteria .
forty percent of tumors were multicentric , with foci in both lobes twice as often as in the single lobe ( 13% versus 27% ) .
there were 77% positive metastatic tumors : paratracheal metastases in 23% and lateral neck metastases in 54% .
overall , no age differences were found for pathological aggressiveness ( p = 0.19 ) and multicentricity ( p = 0.89 ) even though younger group had significantly wider aggressiveness ( 34% versus 16% ) .
younger patients had significantly more neck dissections performed ( p = 0.005 ) and more metastatic spread as well ( p = 0.000 ) .
we had two cases of temporary early postoperative hypocalcaemia , which were successfully controlled by calcium carbonate and rocaltrol p. o. there was one case of permanent hypocalcaemia ( recurrent case ) .
there were two cases of disease recurrence , both locoregional : one patient with single neck recurrence ( lateral neck metastatic foci after initial tt and paratracheal nd ) and one patient with two recurrences ( both in lateral neck regions after initial tt and paratracheal nd ) .
both recurrences were detected on follow up by neck palpation and ultrasonography with cytology , and pathologic tg ; both cases were amenable to surgical therapy and were put to further radioiodine treatment .
no patients with n0 neck developed recurrence . in all patients , postoperative and postablative average follow up was at least 5 years , and they were alive and free of disease .
multivariate analysis revealed the presence of multicentric foci in contralateral lobe and higher tumor aggressiveness ( group iii ) to be an independent risk factor for regional metastatic spread ( or 3.119 and 2.591 , resp . ) .
male gender was identified as an additional risk factor ( or 1.919 ) , while older age was associated with lower risk for metastatic development ( or 0.537 ) .
different potential prognostic factors of papillary thyroid cancer have been revealed so far , most importantly patient age , tumor grade , and extension ( extrathyroid invasion , distant metastasis , and less frequently regional ) .
papillary cancer characteristics and behavior in children and adolescent population is subject of several controversies , mainly about the most appropriate surgical therapy , the use of postoperative iodine ablation and tsh suppression , as well as follow - up modalities [ 1 , 13 ] .
it is well demonstrated that clinical course of this disease in children and adolescent population is significantly different : the worse initial clinical presentation in children and , paradoxically , the better disease prognosis than in adult population [ 14 , 15 ] . children tend to present with larger primary tumors , greater incidence of neck lymphonode metastasis , and distant metastasis as well .
possible explanations are more common occurrence of well - differentiated forms of tumor and more effective response to postoperative tsh suppression with thyroid hormone . in our series
most aggressive cases came in the form of a wider tumor aggressiveness , that is , thyroid capsule invasion , penetration of adjacent thyroid tissues , and/or perivascular / perineural spread .
additionally , mean tumor size in younger age group was significantly larger than in adult population .
the role of tumor size was commented recently in the review of sherman , who emphasized that smaller size of thyroid gland in children can lead to earlier thyroid and extrathyroid spread of disease .
papillary thyroid cancer multicentricity is a well - described feature of this tumor , with estimated frequency range from 22% to 49% .
there are major disagreements about the importance of papillary cancer multicentricity ; its etiology and clinical significance are not yet fully understood [ 6 , 1820 ] . as a consequence ,
many authors propose total thyroidectomy as an adequate surgical approach , claiming that more extensive operation decreases the likelihood of recurrence .
thus , multicentricity , when it occurred , was bilateral in more than two - thirds of multicentric cases .
further , on multivariate analysis multicentricity was found to be the most important risk factor for development of metastatic spread ( or 3.119 ) .
interpretations of these findings strongly signify the need for an implementation of more aggressive surgery of the primary tumor , incorporating complete removal of the contralateral thyroid lobe in the same act as thyroidectomy .
locoregional metastatic spread is identified as one of the most important risk factors preceding distant dissemination .
neck metastases occur in 15%60% and with meticulous search can be found in up to 90% of cases [ 22 , 23 ] .
however , even for distant spread , chances of long - term survival are significant , particularly in younger age group .
, there were 77% positive metastatic tumors : paratracheal metastases in 23% , and lateral neck metastases in 54% .
it has been demonstrated that metastatic disease , locoregional and distant , seems to be most important prognostic factor for the good response to therapy .
data from present study clearly demonstrate the significance of detailed preoperative neck examination and careful intraoperative exploration , with special emphasis on lateral neck regions . presently , total or less
commonly subtotal thyroidectomy is considered optimal surgical therapy for papillary thyroid cancer in all preoperatively diagnosed cases [ 18 , 26 ] .
conducted studies showed that more extensive operation ( total thyroidectomy ) usually leads to significant reduction of recurrence [ 9 , 13 , 27 ] . a more conservative surgical approach ( lobectomy )
is advocated by some authors as well , emphasizing less risk of surgical and postoperative morbidity ( temporary or permanent hypoparathyroidism and recurrent laryngeal nerve injury ) [ 11 , 28 , 29 ] .  
thyroid cancer recurrence is more common in extremes of age , most notably in patients less than 20 years of age , as well as older than 60 [ 4 , 30 ] .
generally , studies performed on all age populations revealed higher chances for recurrence in procedures including less than total thyroidectomy . this higher aggressiveness of thyroid cancer demonstrated in younger population does not necessarily bear higher risk for fatal outcome , which is more common in older population [ 14 , 15 ] .
our both recurrence cases had a large primary tumor in the thyroid gland ; one had aggressive characteristics ( thyroid capsule invasion and perivascular , perilymphatic spread ) , and both had initially neck metastatic disease .  
regarding intraoperative and early postoperative complications rate , in our material , we have not found significant differences in perioperative complication rates in children versus older patients , with extent of surgery being the same as for adults .
in recurrent cases , reoperative surgery , which consisted of lateral neck dissection , was performed without any complications . however , in this cohort of patients , we advise that strong emphasis should be put on minimizing morbidity related issues , bearing in mind excellent long - term disease prognosis .   in conclusion , in this study , we investigated parameters of papillary thyroid cancer aggressiveness , multicentricity , and locoregional metastatic spread in children / adolescent population .
overall , papillary thyroid cancer demonstrated aggressiveness in 60% , intraglandular dissemination in 40% , and metastasized locoregionally in 77% of cases . by observing clinicopathological parameters and their distribution across selected groups
multicentric foci in both thyroid lobes and wider tumor aggressiveness were identified as a risk factor for metastatic development .
we support the need for total thyroidectomy and meticulous intraoperative exploration of the thyroid bed and lateral neck , with surgical extirpation of all potential microscopic disease foci . for positive regional metastatic disease , standard paratracheal and/or
modified radical neck dissection is obligatory part of surgery , in the same act as total thyroidectomy , keeping in mind that neck lymphonodes are primary sites of locoregional recurrence . with meticulous attention to technical aspects of surgery
 
 background . 
 thyroid carcinoma is a relatively rare pediatric pathology , comprising around 3% of all childhood tumors . 
 we investigated parameters of tumor aggressiveness , multicentricity , and locoregional metastatic spread patterns in patients up to 18 years of age and made comparison with the older group . 
 all patients were operated upon with total thyroidectomy , with or without lymph - node neck dissection . results . 
 patients with papillary carcinoma present with more advanced stage , larger primary tumor , and more commonly present with palpable thyroid and/or neck node . 
 overall , papillary cancer demonstrated pathological aggressiveness as defined by our criteria in 60% , multicentricity in 40% , and locoregional metastatic foci in 77% of cases . 
 multicentric tumor foci in both thyroid lobes and tumor aggressiveness were identified as a risk factor for metastatic development . 
 conclusion . by observing clinicopathological parameters 
 , we demonstrated that papillary thyroid cancer behaves more aggressively in the younger group . 
 we recommend total thyroidectomy with careful intraoperative exploration of thyroid bed and lateral neck in search for possible metastatic spread . in case of positive findings , 
 it is obligatory to perform a standard neck dissection , keeping in mind that neck lymphonodes are primary site of locoregional recurrence . with meticulous attention to technical aspects of operation 
 , perioperative morbidity should be minimal . 