Imaging fibrosis in pediatric kidney transplantation: A pilot study.

2023

e14540

05/2023

1399-3046

BACKGROUND: Noninvasive alternatives to biopsy for assessment of interstitial fibrosis and tubular atrophy (IFTA), the major determinant of kidney transplant failure, remain profoundly limited. Elastography is a noninvasive technique that propagates shear waves across tissues to measure their stiffness. We aimed to test utility of elastography for early detection of IFTA in pediatric kidney allografts.

METHODS: We compared ultrasound (USE) and MR elastography (MRE) stiffness measurements, performed on pediatric transplant recipients referred for clinically indicated biopsies, and healthy controls.

RESULTS: Ten transplant recipients (median age 16 years) and eight controls (median age 16.5 years) were enrolled. Three transplant recipients had "stable" allografts and seven had Banff Grade 1 IFTA. Median time from transplantation to biopsy was 12 months. Mean estimated glomerular filtration rate was 61.5 mL/min/1.73m by creatinine-cystatin-C CKiD equation at time of biopsy. Mean stiffness, calculated through one-way ANOVA, was higher for IFTA allografts (23.4 kPa USE/5.6 kPa MRE) than stable allografts (13.7 kPa USE/4.4 kPa MRE) and controls (9.1 kPa USE/3.6 kPa MRE). Pearson's coefficient between USE and MRE stiffness values was strong (r = .97). AUC for fibrosis prediction in transplanted kidneys was high for both modalities (0.91 USE and 0.89 MRE), although statistically nonsignificant (p > .05). Stiffness cut-off values for USE and MRE were 13.8 kPa and 4.6 kPa, respectively. Both values yielded a sensitivity of 100% but USE specificity (72%) was slightly higher than MRE (67%).

CONCLUSION: Elastography shows potential for detection of low-grade IFTA in allografts although a larger sample is imperative for clinical validation.

10.1111/petr.14540

Pediatr Transplant

37166372

Clinicopathologic Characteristics of Pediatric Follicular Variant of Papillary Thyroid Carcinoma Subtypes: A Retrospective Cohort Study.

2022

1353-1361

11/2022

1557-9077

Follicular patterned thyroid nodules with nuclear features of papillary thyroid carcinoma (PTC) encompass a range of diagnostic categories with varying risks of metastatic behavior. Subtypes include the invasive encapsulated follicular variant of PTC (Ienc-fvPTC) and infiltrative fvPTC (inf-fvPTC), with tumors lacking invasive features classified as noninvasive follicular thyroid neoplasms with papillary-like features (NIFTPs). This study aimed to report the clinical and histological features of pediatric cases meeting criteria for these histological subtypes, with specific focus on Ienc-fvPTC and inf-fvPTC. In this retrospective cohort study, pediatric patients with thyroid neoplasms showing follicular patterned growth and nuclear features of PTC noted on surgical pathology between January 2010 and January 2021 were retrospectively reviewed and classified according to the recent 2022 World Health Organization (WHO) criteria. Clinical and histopathologic parameters were described for NIFTP, Ienc-fvPTC, and inf-fvPTC subtypes, with specific comparison of Ienc-fvPTC and inf-fvPTC cases. The case cohort included 42 pediatric patients, with 6 (14%), 25 (60%), and 11 (26%) patients meeting criteria for NIFTP, Ienc-fvPTC, and inf-fvPTC, respectively. All cases were rereviewed, and 5 patients originally diagnosed with Ienc-fvPTC before 2017 were reappraised as having NIFTPs. The NIFTP cases were encapsulated tumors without invasive features, lymph node or distant metastasis, or disease recurrence. Ienc-fvPTC tumors demonstrated clearly demarcated tumor capsules and capsular/vascular invasion, while inf-fvPTC tumors displayed infiltrative growth lacking a capsule. inf-fvPTC cases had increased prevalence of malignant preoperative cytology, lymph node metastasis, and distant metastasis ( < 0.01). These cases were treated with total thyroidectomy, lymph node dissection, and subsequent radioactive iodine therapy. Preliminary genetic findings suggest a predominance of fusions in inf-fvPTC cases versus point mutations in Ienc-fvPTC ( = 0.02). Pediatric NIFTP and fvPTC subtypes appear to demonstrate alignment between clinical and histological risk stratification, with indolent behavior in Ienc-fvPTC and invasive features in inf-fvPTC tumors.

10.1089/thy.2022.0239

Thyroid

36103376

Indeterminate Thyroid Fine-Needle Aspirations in Pediatrics: Exploring the Clinicopathologic Features and Utility of Molecular Profiling.

2022

07/2022

1663-2826

INTRODUCTION: The diagnostic utility of molecular profiling for the evaluation of indeterminate pediatric thyroid nodules is unclear. We aimed to assess pediatric cases with indeterminate thyroid fine-needle aspiration (FNA) alongside clinicopathologic features and mutational analysis.

METHODS: A retrospective review of 126 patients with indeterminate cytology who underwent FNA between January 2010 and December 2021 at the Children's Hospital of Philadelphia was performed. Indeterminate cases defined by The Bethesda System for Reporting Thyroid Cytopathology (AUS/FLUS or TBSRTC III; FN/SFN or TBSRTC IV; SM or TBSRTC V) were correlated to clinicopathologic and genetic characteristics.

RESULTS: Of the 114 surgical cases, 48% were malignant, with the majority of malignant cases diagnosed as follicular variant of papillary thyroid carcinoma (28/55). Risk of malignancy increased with TBSRTC category: 23% for AUS/FLUS, 51% for FN/SFN, and 100% for SM nodules. There were significant differences in surgical approach (p < 0.01), performance of lymph node dissection (p < 0.01), histological diagnosis (p < 0.01), primary tumor focality/laterality (p = 0.04), and lymphatic invasion (p = 0.02) based on TBSRTC classification, with resultant differences in post-surgical risk stratification per American Thyroid Association (ATA) pediatric guidelines (p = 0.01). Approximately 89% (49/55) of cases were classified as ATA low-risk, and 5 of 6 patients with ATA intermediate- or high-risk disease had SM cytology. Somatic molecular testing was performed in 40% (51/126) of tumors; 77% (27/35) of malignant cases and 38% (6/16) of benign cases harbored driver alteration(s). Of the driver-positive malignant cases, 52% (14/27) were associated with low-risk (DICER1, PTEN, RAS, and TSHR mutations), 33% (9/27) were associated with high-risk (BRAF mutations and ALK, NTRK, and RET fusions), and 15% (4/27) had unreported risk for invasive disease (APC, BLM, and PPM1D mutations and TG-FGFR1 fusion). Incidence of high-risk drivers increased with TBSRTC category. Approximately 23% (8/35) of patients harboring thyroid malignancy did not have an identifiable driver alteration.

CONCLUSIONS: Molecular analysis is useful to discriminate benign and malignant thyroid nodules with indeterminate cytology. Patients with driver genetic alteration(s) and indeterminate cytology should consider surgical management secondary to the high incidence (82%; 27/33) of thyroid malignancy in these patients.

10.1159/000526116

Horm Res Paediatr

35871517

Clinicopathologic Characteristics of Pediatric Follicular Variant of Papillary Thyroid Carcinoma Subtypes: A Retrospective Cohort Study.

2022

09/2022

1557-9077

Follicular patterned thyroid nodules with nuclear features of papillary thyroid carcinoma encompass a range of diagnostic categories with varying risks of metastatic behavior. Subtypes include invasive encapsulated fvPTC (Ienc-fvPTC) and infiltrative fvPTC (inf-fvPTC) with tumors lacking invasive features classified as non-invasive follicular thyroid neoplasm with papillary-like features (NIFTP). This study aimed to report the clinical and histologic features of pediatric cases meeting criteria for these histological subtypes with specific focus on Ienc-fvPTC and inf-fvPTC. In this retrospective cohort study, pediatric patients with thyroid neoplasms showing follicular patterned growth and nuclear features of papillary thyroid carcinoma noted on surgical pathology between January 2010 and January 2021 were retrospectively reviewed and classified according to the recent 2022 World Health Organization (WHO) criteria. Clinical and histopathologic parameters were described for NIFTP, Ienc-fvPTC, and inf-fvPTC subtypes, with specific comparison of Ienc-fvPTC and inf-fvPTC cases. The case cohort included 42 pediatric patients, with 6 (14%), 25 (60%), and 11 (26%) patients meeting criteria for NIFTP, Ienc-fvPTC, and inf-fvPTC, respectively. All cases were re-reviewed, and 5 patients originally diagnosed with Ienc-fvPTC prior to 2017 were reappraised as NIFTP. The NIFTP cases were encapsulated tumors without invasive features, lymph node or distant metastasis, or disease recurrence. Ienc-fvPTC tumors demonstrated clearly demarcated tumor capsules and capsular/vascular invasion, while inf-fvPTC tumors displayed infiltrative growth lacking a capsule. Inf-fvPTC cases had increased prevalence of malignant pre-operative cytology, lymph node metastasis, and distant metastasis ( < 0.01). These cases were treated with total thyroidectomy, lymph node dissection, and subsequent radioactive iodine therapy. Preliminary genetic findings suggest a predominance of fusions in inf-fvPTC cases versus point mutations in Ienc-fvPTC ( < 0.01). Pediatric NIFTP and fvPTC subtypes appear to demonstrate alignment between clinical and histological risk stratification, with indolent behavior in Ienc-fvPTC and invasive features in inf-fvPTC tumors.

10.1089/thy.2022.0239

Thyroid

36103376

Thyroid Lobectomy for T1 Papillary Thyroid Carcinoma in Pediatric Patients.

2021

2021 Sep 23

2168-619X

<p><strong>Importance: </strong>The current recommendation for pediatric patients with papillary thyroid cancer (PTC) is a total thyroidectomy. This recommendation applies to all stages of PTC, including papillary thyroid microcarcinoma (≤1 cm, T1a) tumors.</p>

<p><strong>Objective: </strong>To evaluate the characteristics of American Joint Committee on Cancer T1 PTC tumors in a large pediatric population and to identify a subgroup of patients who may benefit from a thyroid lobectomy instead of a total thyroidectomy.</p>

<p><strong>Design, Setting, and Participants: </strong>This retrospective cohort study was conducted from January 1, 2009, to May 31, 2020. The study took place at a tertiary care medical center and included 102 patients who were surgically treated for T1 PTC: 52 with stage T1a (≤1 cm) tumors and 50 with stage T1b (&gt;1 cm but ≤2 cm) tumors.</p>

<p><strong>Main Outcomes and Measures: </strong>Primary outcomes included the presence of bilateral disease and lymph node metastasis.</p>

<p><strong>Results: </strong>A total of 102 patients (mean age, 15.3 years [range, 9.7-18.9 years]; 84 girls [82.4%]) were included in the analysis. Among 52 patients with T1a tumors, 10 (19.2%) had bilateral disease, and 15 (28.8%) had central neck lymph node (N1a) metastasis. Among 50 patients with T1b tumors, 10 (20%) had bilateral and 13 (26%) had N1a disease. Of those with T1a, unilateral multifocality was associated with bilateral disease (odds ratio [OR], 2.1; 95% CI, 1.3-3.4) and N1a disease (OR, 5.1; 95% CI, 1.5-17.6). Both N1a disease (OR, 20.0; 95% CI, 3.5-115.0) and ≥4 positive lymph nodes (OR, 8.6; 95% CI, 1.2-60.9) were associated with bilateral disease. In patients with no pathologic evidence of lymph node metastasis (N0), there was a 95% rate of unilateral PTC. In patients with T1b tumors, unilateral multifocality was also associated with bilateral disease (OR, 1.8; 95% CI, 1.3-2.7). Patients with T1b tumors had an increased risk of lateral (N1b) neck lymph node metastasis when compared with those with T1a tumors (OR, 3.7; 95% CI, 1.0-14.5).</p>

<p><strong>Conclusions and Relevance: </strong>The findings of this cohort study suggest that, in patients with unifocal T1a PTC without clinically evident nodal disease on preoperative ultrasonography, a thyroid lobectomy and central neck dissection may be considered. If there is no evidence of unilateral multifocality or if there are fewer than 4 positive lymph nodes on postoperative pathology, then close observation may be considered. These findings have substantial clinical implications and may result in practice changes regarding the extent of thyroid surgery on low-stage pediatric PTC.</p>

10.1001/jamaoto.2021.2359

JAMA Otolaryngol Head Neck Surg

34554217

Utility of Fine-Needle Aspirations to Diagnose Pediatric Thyroid Nodules.

2021

2021 Sep 01

1663-2826

10.1159/000519307

Horm Res Paediatr

34469888

Bilateral papillary thyroid cancer in children: Risk factors and frequency of postoperative diagnosis.

2020

2020 Feb 27

1531-5037

<p><strong>BACKGROUND: </strong>The recommendation for children with papillary thyroid cancer (PTC) is total thyroidectomy (TT) based on the incidence of bilateral disease. Evaluating this assumption, we reviewed the characteristics of bilateral PTC in a large cohort of children.</p>

<p><strong>METHODS: </strong>A retrospective chart review for patients surgically treated for PTC from 2009 to 2018 analyzing preoperative risk factors, ultrasound findings, and pathology results was performed. Bilateral disease was defined as pathologic PTC in the contralateral lobe, including microscopic disease.</p>

<p><strong>RESULTS: </strong>Of the 172 patients included, 38.4% had bilateral disease with 23% diagnosed postoperatively. Multifocal disease on ultrasound was associated with bilateral disease (OR 2.9, 95% CI 1.5-5.9, p = 0.002). Nodule dimension &gt;2 cm was associated with increased risk for postoperative bilateral disease (OR 3.5, 95% CI 1.6-7.4, p = 0.001). Patients with bilateral disease were more likely to have extrathyroidal extension, lymphovascular invasion, positive central lymph nodes, and extranodal extension (p &lt; 0.001 for all). Diffuse-sclerosing variant PTC was also associated with bilateral disease.</p>

<p><strong>CONCLUSION: </strong>Thirty-eight percent of children were diagnosed with PTC demonstrate bilateral disease. Nearly one in four have occult bilateral disease. The features that predicted bilateral disease were multifocality, widely invasive PTC on ultrasound, and the presence of lymphadenopathy. Thus, TT is the appropriate surgical approach for pediatric patients with PTC.</p>

<p><strong>TYPE OF STUDY: </strong>Clinical Research, Retrospective Review.</p>

<p><strong>LEVEL OF EVIDENCE: </strong>Level IV.</p>

10.1016/j.jpedsurg.2020.02.040

J. Pediatr. Surg.

32171533

Characteristics of Follicular Variant Papillary Thyroid Carcinoma in a Pediatric Cohort.

2018

1639-1648

2018 Apr 1

1945-7197

<p><strong>Context: </strong>In adults, non-invasive follicular variant papillary thyroid carcinoma (FVPTC) is considered low risk for metastasis and persistent/recurrent disease.</p>

<p><strong>Objective: </strong>The goal of this study was to assess the clinical, sonographic, and histopathological features of FVPTC in a pediatric cohort.</p>

<p><strong>Design: </strong>A retrospective review of subjects &lt; 19 years of age with papillary thyroid carcinoma (PTC) who underwent thyroidectomy between January 2010 and July 2015.</p>

<p><strong>Setting: </strong>Multidisciplinary, academic referral center.</p>

<p><strong>Patients: </strong>Patients with FVPTC, defined as a tumor ≥1.0 cm in largest dimension with predominant follicular growth, complete lack of well-formed papillae, and nuclear features of PTC.</p>

<p><strong>Main Outcome Measure: </strong>Tumor size and location, presence of a tumor capsule, capsule and vascular invasion, lymph node and distant metastasis.</p>

<p><strong>Results: </strong>Eighteen patients with FVPTC were identified from a case cohort of 110 patients with PTC. On histopathology, 13 (72%) had unifocal nodules and 14 (78%) were completely encapsulated. Capsule invasion was frequent (9/14; 64%) and vascular invasion was found in one third of patients (6/18; 33%). No lymph node metastases were found in the 13 (72%) patients who had a central neck lymph node dissection. One patient with vascular invasion had distant metastases.</p>

<p><strong>Conclusion: </strong>When strictly defined, FVPTC in pediatric patients has a low risk for bilateral disease and metastasis. Prospective studies are needed to confirm whether lobectomy with surveillance is sufficient to achieve remission in pediatric patients with low risk FVPTC.</p>

10.1210/jc.2017-02454

29438531

Management of adrenal masses in patients with Beckwith-Wiedemann syndrome.

2017

2017 Jan 09

1545-5017

<p>Beckwith-Wiedemann syndrome (BWS) is a genetic overgrowth and cancer predisposition syndrome, associated with both benign and malignant adrenal findings. Literature review and an institutional case series elucidate the wide spectrum of adrenal findings in BWS patients. The altered expression of the 11p15 region is likely related to adrenal gland hyperplasia and growth dysregulation. Given the absence of guidelines for managing adrenal findings in BWS, we propose a systematic approach to adrenal findings in BWS patients, to allow for maximum detection of potentially malignant pathology without posing additional risk to patients.</p>

10.1002/pbc.26432

Pediatr Blood Cancer

28066990