Clinicopathologic and Prognostic Features of Pediatric Follicular Cell–derived Thyroid Carcinomas

Abstract

Pediatric thyroid carcinomas (TCs) are rare and mainly approached based on data extrapolated from adults. We retrospectively reviewed 222 pediatric TCs (patient age less than or equal to 21 y). Lymph node (LN) disease volume at presentation was considered high if the largest positive LN measured ≥1 cm and/or >5 LNs were positive. High-grade follicular cell–derived thyroid carcinoma (HGFCTC) were defined by the presence of marked mitotic count and/or tumor necrosis and considered as high-risk histology along with papillary thyroid carcinomas (PTC) diffuse sclerosing variant (DSV). Disease-free survival (DFS) was analyzed. LN involvement at presentation was significantly associated with male sex, larger tumor size, lymphatic invasion, positive surgical margins, and distant metastases at presentation. Five- and 10-year DFS was 84% and 77%, respectively. Only 1 patient with HGFCTC died of disease. Within PTC variants, PTC-DSV was associated with adverse histopathologic parameters and higher regional disease spread, unlike PTC tall cell variant which did not portend worse behavior. The presence of necrosis conferred worse DFS (P=0.006), while increased mitotic activity did not. While the entire HGFCTC group did not correlate with outcome (P=0.071), HGFCTC with necrosis imparted worse DFS (P=0.006). When restricted to PTC-DSV and HGFCTC with necrosis, high-risk histologic classification emerged as an independent prognostic parameter of DFS (P=0.020). The excellent prognosis of pediatric TCs differs from that of adult TCs showing similar histologic features. While neither increased mitotic activity nor PTC tall cell variant histology predict adverse outcome, PTC-DSV and tumors with necrosis constitute high-risk histologic variants with an increased risk of protracted disease.

Central lymph node ratio is an important recurrence prognostic factor for pediatric differentiated thyroid cancer

“…Our study also revealed a positive correlation between the presence of ETE and CLNR, yet ETE did not show a significant relationship with recurrence in univariate analysis. This is consistent with some studies ( 16 , 26 ) but contrasts with others, including Jeon et al.’s work, which identified ETE as an independent predictive factor for recurrence ( 10 ).…”

Papillary thyroid carcinoma tall cell subtype (PTC‐TC) and high‐grade differentiated thyroid carcinoma tall cell phenotype (HGDTC‐TC) have different clinical behaviour: a retrospective study of 1456 patients

“…In a recent meta-analysis, 12 the estimated frequency of HGDTC-TC was 19% in tumours showing tall cell features based on 89 cases from five studies. [6][7][8][9]13 This estimated proportion was significantly higher than the observed 5.3% rate in the current study, possibly due to the small number of cases included in the meta-analysis. Prior to the WHO 5th edition, 4 mitotic count and tumour necrosis were not routinely evaluated and reported in daily practice or in studies of thyroid carcinoma, including PTC-TC.…”

“…In this study, we have shown that HGDTC‐TC is relatively rare, accounting for only 5% of all differentiated thyroid carcinomas containing at least 30% tall cell area. In a recent meta‐analysis, 12 the estimated frequency of HGDTC‐TC was 19% in tumours showing tall cell features based on 89 cases from five studies 6–9,13 . This estimated proportion was significantly higher than the observed 5.3% rate in the current study, possibly due to the small number of cases included in the meta‐analysis.…”

DICER1 Mutations Occur in More Than One-Third of Follicular-Patterned Pediatric Papillary Thyroid Carcinomas and Correlate with a Low-Risk Disease and Female Gender Predilection

“…As in adults, papillary thyroid carcinoma is the most common histologic type of pediatric follicular cell-derived thyroid carcinoma [1,2]. Despite morphologic similarities, pediatric papillary thyroid carcinomas (PPTCs) differ from their adult counterparts [2][3][4] with respect to genomic alterations (e.g., high prevalence of oncogene fusions, overall lower frequency of BRAF p.V600E and RAS-mutations, universally reported absence with only exceptional occurrence of TERT promoter mutations, increased frequency of inherited neoplasia associated somatic and/or germline pathogenic variants) and distinct clinical and pathological features (e.g., higher frequency for lymph node and/or distant metastases, ionizing radiation-induced pathogenesis, better overall prognosis compared to adults with similar features, lower fraction of tall cell PTC, and higher frequency of diffuse sclerosing PTC) [1,[5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21]. These observations have made PPTC an area of continued interest in thyroid neoplasia.…”