This cohort study aims to determine the prevalence and risk factors for multifocal disease in pediatric patients with papillary thyroid carcinoma.
Key Points
Question
What are the prevalence and risk factors for multifocality in pediatric papillary thyroid carcinoma (PTC)?
Findings
This cohort study of 212 pediatric patients with PTC found a prevalence of 46% for multifocal disease, including 34% for bilateral multifocal disease. Age and advanced T and N stages were associated with multifocal as well as bilateral multifocal disease.
Meaning
Risk factors such as age, advanced T and N stages, and the high prevalence of multifocal disease should be considered when weighing the risks and benefits of surgical management options in pediatric patients with PTC.
Abstract
Importance
Current guidelines recommend total thyroidectomy for the majority of pediatric thyroid cancer owing to an increased prevalence of multifocality. However, there is a paucity of information on the exact prevalence and risk factors for multifocal disease—knowledge that is critical to improving pediatric thyroid cancer management and outcomes.
Objective
To determine the prevalence and risk factors for multifocal disease in pediatric patients with papillary thyroid carcinoma (PTC).
Design, Setting, and Participants
This multicenter retrospective cohort study included patients 18 years or younger who underwent thyroidectomy for PTC from 2010 to 2020 at 3 tertiary pediatric hospitals and 2 tertiary adult and pediatric hospitals in the US.
Main Outcomes and Measures
Demographic and clinical variables, including age, family history of thyroid cancer, autoimmune thyroiditis, prior radiation exposure, cancer predisposition syndrome, tumor size, tumor and nodal stage, PTC pathologic variant, and preoperative imaging, were assessed for association with presence of any multifocal, unilateral multifocal, and bilateral multifocal disease using multiple logistic regression analyses. Least absolute shrinkage and selection operator analysis was performed to develop a model of variables that may predict multifocal disease.
Results
Of 212 patients, the mean age was 14.1 years, with 23 patients 10 years or younger; 173 (82%) patients were female. Any multifocal disease was present in 98 (46%) patients, with bilateral multifocal disease in 73 (34%). Bilateral multifocal disease was more accurately predicted on preoperative imaging than unilateral multifocal disease (48 of 73 [66%] patients vs 9 of 25 [36%] patients). Being 10 years or younger, T3 tumor stage, and N1b nodal stage were identified as predictors for multifocal and bilateral multifocal disease.
Conclusions and Relevance
This large, multicenter cohort study demonstrated a high prevalence of multifocal disease in pediatric patients with PTC. Additionally, several potential predictors of multifocal disease, including age and advanced T and N stages, were identified. These risk factors and the high prevalence of multifocal disease should be considered when weighing the risks and benefits of surgical management options in pediatric patients with PTC.
Introduction
Thyroid cancer is the most common endocrine cancer in children, with accelerating incidence over the past 2 decades.1,2 Similar to thyroid cancer in adults, approximately 90% of pediatric thyroid cancer is composed of papillary thyroid carcinoma (PTC), while follicular thyroid carcinoma and medullary thyroid carcinoma account for the remaining 10% of cases.3 However, pediatric PTC in particular frequently presents with more advanced disease and higher rates of recurrence and persistent disease than in adults.3,4 Rates of extracapsular extension have been reported in up to 50% of children vs 30% of adults, regional nodal involvement in up to 80% vs 50%, and distant metastasis in up to 30% vs 5%.4,5
Multifocal disease has been found in up to 65% of pediatric patients with thyroid cancer compared with approximately 38% of adults with thyroid cancer.4,6 Associations between multifocal disease and higher risk of recurrence and persistent disease in children have been suggested in some studies.7,8 Current guidelines and consensus statements recommend total thyroidectomy in nearly all pediatric patients with PTC, largely driven by the increased prevalence of multifocality and associated risk of recurrence and persistent disease.3,9 When compared with lobectomy, total thyroidectomy has been shown in some studies to lower the risk of recurrence and persistent disease from 35% to 6% in pediatric patients.10 Total thyroidectomy additionally facilitates use of radioactive iodine therapy and serum thyroglobulin levels for surveillance postoperatively.4
Total thyroidectomy is not without considerable operative risks, which are increased in children compared with adults.3 Hypoparathyroidism has been reported in up to 15% of pediatric patients and recurrent laryngeal nerve injury in up to 6%.3 Long-term consequences such as need for lifetime thyroid hormone replacement have potentially greater effects on young patients as well. Meanwhile, the long-term prognosis in pediatric thyroid cancer remains excellent despite its more aggressive presentation and the effect of multifocal as well as bilateral multifocal disease on overall survival outcomes in children being debated.11,12,13 Hence, it remains unclear if total thyroidectomy is warranted for the majority of pediatric patients with PTC, or if de-escalation of guideline recommendations and more limited surgery is potentially indicated in some patients.
Currently, there is a lack of data to predict which children may be candidates for more limited surgery. Studies assessing risk factors for multifocal disease in pediatric patients thus far have been limited to small, single-center experiences. Larger tumor size, extrathyroidal extension, lymph nodal involvement, lymphovascular invasion, extranodal extension, and the diffuse sclerosing pathologic variant of PTC have been suggested as potential predictors of multifocality in pediatric thyroid cancer. However, the data are conflicting.14,15,16 This cohort study represents, to our knowledge, the first large, multicenter study to explore predictors of multifocality in pediatric thyroid cancer.
Methods
Study Design
This was a multicenter, retrospective cohort study of patients 18 years or younger with a diagnosis of PTC who underwent thyroid surgery from 2010 to 2020 at the Ann & Robert H. Lurie Children’s Hospital of Chicago, Children’s Hospital of Philadelphia, Oregon Health & Science University, Texas Children’s Hospital, and The University of Texas MD Anderson Cancer Center. Institutional review board approval was obtained at all 5 centers contributing to this study. Data were obtained from databases approved by each institution’s institutional review board for outcomes research; therefore, consent from each patient was not required.
Participants
Patients were included in this study if they were 18 years or younger, had a pathologic diagnosis of PTC, and underwent primary surgical management, including lobectomy or total thyroidectomy. The electronic medical record for each patient was reviewed for demographic and clinical data. Patients with incomplete demographic or clinical data were excluded. Demographic variables included age and sex. Clinical variables consisted of known risk factors for thyroid cancer, including history of radiation exposure, autoimmune thyroiditis, or cancer predisposing syndrome, and family history of thyroid cancer, as well as multifocality prediction on preoperative imaging. Pathologic description included PTC pathologic variants; tumor size; American Joint Committee on Cancer, 7th edition, TNM staging system; and presence of unilateral multifocal or bilateral multifocal disease. Autoimmune thyroiditis was defined as Hashimoto thyroiditis or Graves disease diagnosed on history or pathology. Thyroid cancer predisposing syndromes included Cowden, DiGeorge, familial adenomatous polyposis, and Li-Fraumeni syndromes. Pathologic variants of PTC were categorized as classic, follicular, diffuse sclerosing, or other. Rare pathologic variants in the study population, including cribriform-morular, oncocytic, solid, tall cell, or mixed, were categorized as other.
Statistical Analysis
Descriptive statistical analysis was performed using Excel, version 16.35 (Microsoft Corporation). Multiple logistic regression analysis was performed to identify demographic and clinical variables independently associated with all multifocal disease, unilateral multifocal disease, and bilateral multifocal disease. Odds ratios (ORs) were calculated for each variable based on regression coefficients, and 95% CIs around the OR are reported. Least absolute shrinkage and selection operator (LASSO) regression analysis was also performed to identify variables that best predict multifocal disease. LASSO, an extended form of multiple regression, is a penalized regression analysis that involves selecting for a reduced set of variables that are more strongly associated with the response variable and shrinking the regression coefficients of less important variables to zero to effectively exclude them from the final predictive model. This helps to minimize prediction error and increase the interpretability of the model.17 Larger coefficients represent stronger associations in LASSO analysis, while negative coefficients represent negative associations. Multiple logistic regression and LASSO analyses were both performed using RStudio, version 1.2.1335 (RStudio Inc).
Results
A total of 212 patients 18 years or younger who underwent thyroidectomy for a diagnosis of PTC from 2010 through 2020 were identified across the 5 study sites. The demographics and clinical characteristics of the study population are summarized in Table 1. The mean age was 14.1 years, with 23 patients 10 years or younger. There was a female preponderance (n = 173 [82%]), 25 (12%) patients reported a family history of thyroid cancer, and 67 (32%) reported a history of autoimmune thyroiditis.
Table 1. Cohort Demographic and Clinical Characteristics (N = 212).
| Characteristic | No. (%) |
|---|---|
| Age at diagnosis, y | |
| ≤10 | 23 (11) |
| >10 | 189 (89) |
| Sex | |
| Female | 173 (82) |
| Male | 39 (18) |
| Family history of thyroid cancer | 25 (12) |
| Autoimmune thyroiditisa | 67 (32) |
| Prior radiation exposure | 11 (5) |
| Thyroid cancer predisposing syndromeb | 8 (4) |
| PTC Variant | |
| Classic | 147 (69) |
| Follicular | 31 (15) |
| Diffuse sclerosing | 16 (8) |
| Otherc | 18 (8) |
| T staged | |
| T1 | 84 (40) |
| T2 | 43 (20) |
| T3 | 74 (35) |
| T4 | 11 (5) |
| N stage | |
| N0 | 58 (27) |
| N1a | 60 (28) |
| N1b ipsilateral | 36 (17) |
| N1b bilateral | 58 (27) |
| M stage | |
| M0 | 186 (88) |
| M1 | 26 (12) |
| Tumor size, cm | |
| ≤1.0 | 40% (19) |
| 1.1-2.0 | 70 (33) |
| 2.1-4.0 | 67 (32) |
| >4.0 | 35 (17) |
| Any multifocal disease predicted on preoperative imaging | 60 (28) |
| Pathology results positive for multifocal disease | 57 (95) |
| Pathology results negative for multifocal disease | 3 (5) |
| Any multifocal disease | 98 (46) |
| Unilateral multifocal disease | 25 (12) |
| Unilateral multifocal disease predicted on preoperative imaging | 9 (36) |
| Bilateral multifocal disease | 73 (34) |
| Bilateral multifocal disease predicted on preoperative imaging | 48 (66) |
Abbreviation: PTC, papillary thyroid carcinoma.
Autoimmune thyroid disease was defined as Hashimoto thyroiditis or Graves disease diagnosed on history or pathology.
Thyroid cancer predisposing syndromes include Cowden, DiGeorge, familial adenomatous polyposis, Li-Fraumeni, and multiple endocrine neoplasia type 2A and 2B syndromes.
Other PTC variants include cribriform-morular, oncocytic, solid, tall cell, and mixed.
Staging according to the American Joint Committee on Cancer, 7th edition.
On pathologic analysis, 147 (69%) patients were diagnosed with the classic variant of PTC, 31 (15%) with the follicular variant, and 16 (8%) with the diffuse sclerosing variant. Eighteen (8%) patients had other rare variants, including cribriform-morular, oncocytic, solid, tall cell, or mixed.
The majority of patients presented with localized disease, including 84 (40%) with stage T1 disease, 43 (20%) with T2, 74 (35%) with T3, and 11 (5%) with T4. In terms of nodal stage, 58 (27%) patients had N0 disease, 60 (28%) had N1a disease, 36 (17%) had ipsilateral N1b disease, and 58 (27%) had bilateral N1b disease. Distant metastasis was present in 26 (12%) patients. The maximum tumor dimension was 1.0 cm or smaller in 40 (19%) patients, 1.1 to 2.0 cm in 70 (33%) patients, 2.1 to 4.0 cm in 67 (32%) patients, and larger than 4.0 cm in 35 (17%) patients.
Multifocal disease (unilateral or bilateral) was found on final pathology in 98 (46%) patients, with unilateral multifocal disease in 25 (12%) patients and bilateral multifocal disease in 73 (34%) patients. Any multifocal disease was predicted on preoperative imaging in 60 (28%) patients, of which 3 were false positives. Only 9 of 25 (36%) patients with unilateral multifocal disease and 48 of 73 (66%) patients with bilateral multifocal disease had been predicted to have multifocal disease on preoperative imaging.
LASSO analysis found being 10 years or younger, T3 tumor stage, bilateral N1b nodal stage, and presence of distant metastasis to be potential predictors of multifocal disease overall as well as bilateral multifocal disease (Tables 2 and 3). Smaller tumor size was identified as a potential negative predictor of any multifocal disease (Tables 2 and 3). On multiple logistic regression analysis, the only variable with a statistically significant association with multifocal disease was bilateral N1b disease with an OR of 4.70 (95% CI, 1.47-16.39) for any multifocal disease and an OR of 5.38 (95% CI, 1.67-18.44) for bilateral multifocal disease (Tables 2 and 3). Neither LASSO nor multiple logistic regression analysis identified any predictive variables for unilateral multifocal disease.
Table 2. Predictors of Any Multifocal Disease in Patients With PTC.
| Characteristic | Multiple logistic regression, odds ratio (95% CI) | LASSO coefficient |
|---|---|---|
| Age, y | ||
| ≤10 | 2.95 (0.99-9.47) | 0.22 |
| >10 | 1 [Reference] | Reference |
| Sex | ||
| Female | 1 [Reference] | Reference |
| Male | 1.00 (0.44-2.26) | NI |
| Family history of thyroid cancer | 0.98 (0.36-2.57) | NI |
| Autoimmune thyroiditisa | 1.07 (0.54-2.13) | NI |
| Prior radiation exposure | 0.76 (0.16-3.38) | NI |
| Thyroid cancer predisposing syndromeb | 0.45 (0.05-2.73) | NI |
| Pathologic variant | ||
| Classic | 1 [Reference] | Reference |
| Follicular | 0.43 (0.15-1.13) | NI |
| Diffuse sclerosing | 1.90 (0.47-9.71) | NI |
| Otherc | 2.36 (0.73-8.20) | 0.47 |
| T staged | ||
| T1 | 1 [Reference] | Reference |
| T2 | 0.94 (0.26-3.33) | NI |
| T3 | 2.19 (0.77-6.35) | 0.93 |
| T4 | 0.93 (0.14-6.20) | NI |
| N stage | ||
| N0 | 1 [Reference] | Reference |
| N1a | 1.08 (0.47-2.54) | NI |
| N1b ipsilateral | 1.43 (0.59-3.49) | NI |
| N1b bilateral | 4.70 (1.47-16.39) | 0.40 |
| M stage | ||
| M0 | 1 [Reference] | Reference |
| M1 | 1.03 (0.32-3.29) | 0.14 |
| Tumor size, cm | ||
| ≤1 | 1.10 (0.27-4.58) | −0.14 |
| 1.1-2 | 1.23 (0.38-4.07) | NI |
| 2.1-4 | 1.19 (0.38-3.82) | NI |
| >4 | 1 [Reference] | Reference |
Abbreviations: LASSO, least absolute shrinkage and selection operator; NI, not included in final LASSO model; PTC, papillary thyroid carcinoma.
Autoimmune thyroid disease was defined as Hashimoto thyroiditis or Graves disease diagnosed on history or pathology.
Thyroid cancer predisposing syndromes include Cowden, DiGeorge, familial adenomatous polyposis, Li-Fraumeni, and multiple endocrine neoplasia type 2A and 2B syndromes.
Other PTC variants include cribriform-morular, oncocytic, solid, tall cell, and mixed.
Staging according to the American Joint Committee on Cancer, 7th edition.
Table 3. Predictors of Bilateral Multifocal Disease in Patients With PTC.
| Characteristic | Multiple logistic regression, odds ratio (95% CI) | LASSO coefficient |
|---|---|---|
| Age, y | ||
| ≤10 | 1.88 (0.61-5.73) | 0.29 |
| >10 | 1 [Reference] | Reference |
| Sex | ||
| Female | 1 [Reference] | Reference |
| Male | 1.52 (0.65-3.53) | 0.21 |
| Family history of thyroid cancer | 0.78 (0.23-2.27) | NI |
| Autoimmune thyroiditisa | 1.25 (0.59-2.64) | NI |
| Prior radiation exposure | 1.42 (0.31-6.05) | NI |
| Thyroid cancer predisposing syndromeb | 1.21 (0.14-7.18) | NI |
| Pathologic variant | ||
| Classic | 1 [Reference] | Reference |
| Follicular | 0.58 (0.18-1.63) | NI |
| Diffuse sclerosing | 1.88 (0.50-8.10) | NI |
| Otherc | 1.55 (0.47-5.03) | 0.20 |
| T staged | ||
| T1 | 1 [Reference] | Reference |
| T2 | 0.93 (0.23-3.59) | NI |
| T3 | 2.31 (0.75-7.01) | 0.80 |
| T4 | 1.34 (0.19-8.84) | NI |
| N stage | ||
| N0 | 1 [Reference] | Reference |
| N1a | 1.53 (0.60-4.04) | NI |
| N1b ipsilateral | 1.35 (0.50-3.68) | NI |
| N1b bilateral | 5.38 (1.67-18.44) | 1.12 |
| M stage | ||
| M0 | 1 [Reference] | Reference |
| M1 | 0.87 (0.27-2.73) | 0.14 |
| Tumor size, cm | ||
| ≤1 | 0.83 (0.19-3.62) | −0.04 |
| 1.1-2 | 0.68 (0.21-2.21) | NI |
| 2.1-4 | 0.87 (0.28-2.69) | NI |
| >4 | 1 [Reference] | Reference |
Abbreviations: LASSO, least absolute shrinkage and selection operator; NI, not included in final LASSO model; PTC, papillary thyroid carcinoma.
Autoimmune thyroid disease was defined as Hashimoto thyroiditis or Graves disease diagnosed on history or pathology.
Thyroid cancer predisposing syndromes include Cowden, DiGeorge, familial adenomatous polyposis, Li-Fraumeni, and multiple endocrine neoplasia type 2A and 2B syndromes.
Other PTC variants include cribriform-morular, oncocytic, solid, tall cell, and mixed.
Staging according to the American Joint Committee on Cancer, 7th edition.
Discussion
This study represents, to our knowledge, the first large, multicenter study to assess the prevalence and predictors of multifocal disease in pediatric patients with thyroid cancer. The prevalence of any multifocal disease and bilateral multifocal disease in this study population was consistent with reported rates in the pediatric literature up to 65% and 30%, respectively.3,4,6,16,18 In this study, the rate of detection of multifocal disease on preoperative imaging was lower than what has previously been reported in the literature.19 This finding may be because of variability in sensitivity of ultrasonography detection between multiple institutions and highlights the challenges of accurate preoperative detection of multifocal disease. High-quality ultrasonography evaluation is important if multifocal disease is to be used as a preoperative criterion for determining extent of surgery.
In keeping with the known association between lymph nodal involvement and multifocal disease, the current study found important associations between N1b nodal status and any multifocal and bilateral multifocal disease on multiple logistic regression analysis.18,20 Specifically, bilateral lateral neck involvement was strongly predictive for both any multifocal and bilateral multifocal disease, while ipsilateral lateral neck involvement alone was not shown to be a predictor. This finding suggests that further granularity in nodal status with the inclusion of laterality is a potentially important consideration in pediatric PTC staging.
Although statistical inference cannot be drawn from LASSO analysis, it offers a theoretically more accurate alternative to multiple logistic regression analysis for identification of variables with the strongest association with the response variable by shrinking and eliminating more weakly associated variables. The current study demonstrates this potential because LASSO analysis identified several additional variables, including being 10 years or younger, T3 tumor stage, N1b nodal stage, and presence of distant metastasis, as potential predictors of any multifocal and bilateral multifocal disease compared with multiple logistic regression analysis. These findings are consistent with previously reported associations between young age, large tumor size, extrathyroidal extension, lymph nodal involvement, and multifocal disease in patients with pediatric thyroid cancer.16,21,22 While T3 tumor stage, N1b nodal stage, or presence of distant metastasis are potential predictors of multifocal disease, the risk of multifocal disease in such advanced-stage disease is likely irrelevant because total thyroidectomy would be required. In contrast, though multiple logistic regression analysis did not show a statistically significant association between age and multifocal disease, LASSO analysis did identify being 10 years or younger as a predictor of multifocal disease. Further large, multicenter studies are therefore needed to determine if age can be used as a criterion for more limited surgery in pediatric PTC.
In adults, total thyroidectomy was historically recommended in nearly all thyroid cancers larger than 1 cm based on studies demonstrating superior disease-free and overall survival; however, lobectomy in selected thyroid tumors up to 4 cm has become common practice after more recent studies showed similar outcomes when compared with total thyroidectomy.23 Yet, the optimal surgical management of pediatric thyroid cancer remains controversial. Current evidence suggests pediatric thyroid cancer is a distinct entity biologically and clinically from adult thyroid cancer. Molecular testing studies in pediatric patients with thyroid cancer have demonstrated a higher frequency of oncogenic fusions, including RET and NTRK1/3 fusions, and lower frequency of oncogenic point mutations such as the BRAF V600E variant in pediatric patients with thyroid cancer compared with adults.24,25 Histologic studies have found the diffuse sclerosing variant to be more common in pediatric PTC.24
Current guidelines and consensus statements recommend total thyroidectomy in the majority of pediatric thyroid cancers based on studies reporting higher rates of multifocal and bilateral multifocal disease in children and superior disease-free survival for total thyroidectomy compared with lobectomy.3,9,10,26,27,28 Preoperative knowledge of the presence of unilateral or bilateral multifocal disease is most relevant for decision-making in management of pediatric PTC given the rarity of multifocality in follicular thyroid carcinoma and the aggressiveness of medullary thyroid carcinoma, for which total thyroidectomy is uniformly performed. Still, the long-term overall survival benefit of total thyroidectomy in PTC remains unclear.19,22,29,30 Furthermore, these benefits must be weighed against the considerable risks of complications in total thyroidectomy, including hypoparathyroidism and recurrent laryngeal nerve injury.
A number of recent studies have revisited the association between multifocal disease and persistent and recurrent disease when considering the potential role of lobectomy in pediatric PTC.19,22,31 This renewed interest is largely based on studies in adults that have shown that the presence of multifocal disease does not meaningfully affect disease-free or overall survival in patients with PTC.6 In children, Chen et al22 found no difference in disease-free survival for total thyroidectomy compared with lobectomy in a series of 90 patients with PTC and multifocal disease. Bilateral multifocal disease represents a notable subset of multifocal disease with potential effect on survival in thyroid cancer. However, the adult literature is conflicting, and no pediatric studies assessing this association have been published to date.13,32 Using a combination of risk criteria including tumor size, pathologic features, extracapsular extension, lymph nodal involvement, and distant metastasis, Kluijfhout et al19 determined that up to 53% of pediatric patients with differentiated thyroid carcinoma may be eligible for lobectomy without a negative influence on survival.
Despite the increasing incidence of pediatric thyroid cancer, the volume of cases in children still remains relatively low, making it difficult to conduct large studies to fully assess multifocality in this population. A handful of studies have explored risk factors for multifocal as well as bilateral multifocal disease in small, single-center cohorts.14,16 In a retrospective cohort study of 150 pediatric patients with thyroid cancer by Lee et al,14 younger age was found to be statistically significantly associated with multifocal disease. Baumgarten et al16 identified multifocal disease, larger tumor size, extrathyroidal extension, lymphovascular invasion, lymph nodal involvement, extranodal extension, and the diffuse sclerosing pathologic variant of PTC to be predictors of bilateral multifocal disease in a series of 172 children. An association between multifocal disease in the primary lobe and bilateral multifocal disease was also demonstrated in a recent study of 115 pediatric patients with thyroid cancer by Cherella et al.21
Limitations
The current study has several limitations, including the retrospective nature of the study and the small number of certain patient groups, including those 10 years or younger and those with T4 disease or unilateral multifocal disease. There were no considerable risk factors identified for unilateral multifocal disease; however, this was likely because of the small number of these patients in this cohort. Additionally, inaccuracies in the history and family history data are possible because standardized data-collection tools were not used. Another limitation of the current study was the inability to assess certain clinical variables such as extrathyroidal and extranodal extension that were not available for a large proportion of patients. Finally, the association between multifocal disease and long-term outcomes remains controversial and was not assessed in this study.
Despite these limitations, one of the major strengths of this study is its multicenter approach, which enabled the relatively large study population and increases the generalizability of the results. The LASSO analysis represents an additional strength of the study as a potentially more accurate predictor of important and strong associations between variables than the typical univariate and multivariate analyses used. LASSO analysis has successfully been applied in several studies, ranging from identification of glioblastoma prognosticators to risk stratification in blood, lung, and breast cancers.33,34,35,36 Ultimately, further large, multicenter studies are needed to overcome historic limitations in pediatric thyroid cancer research and guide the development of more nuanced, evidence-based recommendations.
Conclusions
This large, multicenter cohort study demonstrates a prevalence of 46% for multifocal disease and 34% for bilateral multifocal disease in pediatric patients with PTC. Only approximately one-third of unilateral multifocal disease and two-thirds of bilateral multifocal disease were predicted on preoperative imaging. These results suggest several potential patient characteristics associated with multifocal and bilateral multifocal disease, including age, advanced T and N stages, and presence of distant metastasis. These risk factors and the high prevalence of multifocal disease should be considered when weighing the risks and benefits of lobectomy as a surgical management option in pediatric PTC.
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