Pediatric/Congenital/Developmental
Recurrence and Complications in Pediatric and Adolescent Papillary Thyroid Cancer in a High-Volume Practice

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Abstract

Background

Treatment approaches for pediatric papillary thyroid cancer (PTC) are historically extrapolated from adult experience. However, pediatric PTC demonstrates a greater propensity for lymph node involvement, early metastases, and recurrence, highlighting the need for pediatric-specific treatment paradigms.

Materials and methods

A retrospective review included patients with PTC aged ≤21 y, with ≥18 mo of follow-up, treated between 2002 and 2015. Fisher's exact test and Cox proportional hazard were used to estimate the effect of risk factors on disease recurrence.

Results

Seventy-two cases of PTC were identified with median age of 17.0 y and median follow-up of 64.1 mo. Disease recurred at a median of 24.6 mo (range 7.8-78.1) in 7 of 51 (13.7%) of patients with disease limited to the thyroid or central neck, 7 of 18 (39%) patients with lateral neck disease at presentation who underwent a compartment-based resection, and three of three patients (100%) with lateral neck disease who sought care after non–compartment-based resection. There were no deaths from disease. Univariate predictors of recurrence included tumor size >2 cm (P = 0.005), lateral neck disease (P = 0.004), lymphovascular invasion (P = 0.017), extracapsular invasion (P < 0.0001), multifocality (P = 0.03), and non-Caucasian race (P = 0.05). Multivariate analysis identified race (P = 0.05) as an independent predictor of recurrence. In patients without lateral neck disease, there was a trend toward lower recurrence in patients undergoing thyroidectomy with central neck dissection compared with thyroidectomy alone (P = 0.07).

Conclusions

Pediatric PTC is associated with excellent survival, although recurrence is common in patients with lateral node involvement. Predictors of recurrence are multifactorial and may be influenced by extent of disease, patient or tumor biology, and aggressiveness of resection.

Level of evidence

Prognosis study, level IV, retrospective case series.

Introduction

Papillary thyroid carcinoma (PTC) is rare in children, and treatment approaches historically have been extrapolated from the adult experience.1 In 2015, an American Thyroid Association (ATA) expert panel published the first guidelines outlining management paradigms for pediatric PTC, but in the absence of pediatric-specific studies, numerous challenges persist in determining the most appropriate management strategies.2,3

These guidelines recommend the surgical strategy of total thyroidectomy (TT) for patients with biopsy-proven PTC combined with central neck dissection (CND) for children with evidence of gross extrathyroidal extension and/or central neck nodal metastasis on preoperative staging.2 The guidelines further state that in the hands of experienced surgeons, prophylactic CND may be considered for all pediatric patients with PTC regardless of evidence of gross extrathyroidal extension and/or locoregional metastasis although this practice remains a point of controversy.4 A modified radical neck dissection (MRND) is recommended for patients with lateral compartment (cervical levels II-V) nodal involvement.

These recommendations, which are more aggressive than those for similar extent of disease in adults, emerge from data suggesting that, in contrast to adults, children with PTC more commonly present with regional lymph node involvement (40%-70%) and distant metastasis (10%-20%).5, 6, 7 Recurrence rates, however, are difficult to pinpoint—not only because pediatric PTC is so rare that there are few series large enough to make a prediction based on tumor size, nodal metastases, and distant metastases (TNM) staging but also because there has been no historic consensus for operative approach. National database studies of pediatric PTC emphasize its favorable prognosis but lack recurrence data which might inform treatment approach.8,9

The differences in clinical behavior and outcome highlight the need for pediatric-specific studies that will help establish estimates of risk of recurrence and standardize treatment guidelines.

Section snippets

Methods

With institutional review board approval, a retrospective review was conducted involving all patients treated for PTC at Yale New Haven Hospital from 2002 to 2015, an endocrine surgery center performing greater than 1100 adult cervical endocrine cases and 25-30 pediatric thyroidectomies annually. Inclusion criteria were age ≤21 y and length of follow-up ≥18 mo. All data were manually extracted on chart review.

Summary descriptive statistics were calculated for demographic and disease

Results

Seventy-two patients with PTC were included in the study (Table 1): 57 girls and 15 boys with a median age at diagnosis of 17.0 y. The median length of follow-up was 64.1 mo. Racial distribution was 77.8% Caucasian, 5.6% black, 9.6% Hispanic, and 6.9% Asian. Sixty-six patients presented to our institution for initial treatment, and six patients underwent initial thyroidectomy at an outside institution. Of these six, one was found to have PTC in a lobectomy specimen and underwent completion

Discussion

Improved risk stratification for recurrence in pediatric PTC has implications for clinical management. Consistent with prior studies, we identified tumor size, lymphovascular invasion, extracapsular extension, multifocality, and lymph node involvement as predictors of recurrence. Our data also suggest that non-Caucasian patients may be at higher risk for recurrence than Caucasians. More controversially, our data suggest that a potential pitfall of foregoing prophylactic CND is that a subset of

Conclusions

Pediatric PTC is rarely fatal but tumor-specific characteristics, the background genome of the host, and choice of operative approach may all influence recurrence.36, 37, 38, 39 Our data concur with previous reports of clinicopathologic predictors of recurrence and additionally suggest that race may also be implicated as a risk factor. Although this study is underpowered to detect a statistically significant decrease in recurrence based on operative approach alone, our institutional outcomes

Acknowledgment

Authors' contributions: J.C.R. contributed to study conception and design, analysis and interpretation of data, and drafting and critical revision of the manuscript; K.H.R. contributed to study conception and design and acquisition of data; C.D. contributed to study conception and design, analysis and interpretation of data, and critical revision of the manuscript; R.M. contributed to acquisition of data and critical revision of the manuscript; G.G.C. contributed to study conception and design,

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