Objectives

The Bethesda system for reporting cytopathology (TBSRTC) has been widely adopted in the management of thyroid nodules. Based on the limited pediatric data available, the implied malignancy risk for each of the categories may be significantly different in pediatrics vs. adults, especially in the indeterminate categories (Bethesda Class III or IV). We report the diagnostic utility of fine needle aspiration (FNA) biopsy at our institution based on the Bethesda system and the risk of malignancy in each category.

Methods

We retrospectively reviewed all patients who underwent a thyroid FNA at our tertiary pediatric hospital from 12/1/2002 to 11/30/2018. FNA results were classified according to TBSRTC. Patient demographics, cytology, histopathology, radiological and clinical follow-ups were examined.

Results

A total of 171 patients were included with 203 cytological samples. Average age at initial FNA was 14.7 years (range 6.9-18.6 years). The numbers of nodules reported for Bethesda categories I-VI were 29, 106, 22, 14, 6 and 26, respectively, and the rate of malignancy was: 13.8, 4.7, 22.7, 35.7, 83.3 and 100%, respectively. Use of ultrasound guidance reduced the non-diagnostic rate from 38.1 to 11.5%. Introduction of on-site adequacy testing further reduced the non-diagnostic rate to 6.5% since 2014.

Conclusions

The risk of malignancy for thyroid nodules in this pediatric cohort is higher than reported in adults. However, rates described here are much closer to adult ranges than previously published pediatric cohorts. The addition of adequacy testing improved the non-diagnostic rate of FNA procedures performed with ultrasound guidance.

Background

Activated phosphoinositide 3-kinase (PI3K) δ syndrome (APDS) is a rare form of primary immunodeficiency with 243 known cases reported in the literature. Known findings associated with the condition include recurrent sinusitis and bronchitis, bronchiectasis, immune cytopenias, mild developmental delay, splenomegaly, and lymphadenopathy. We report the case of a child with APDS accompanied by unique clinical features: nephromegaly and growth hormone deficiency with associated pituitary anatomic abnormality.

Case presentation

The patient is a nine-year-old boy with a heterozygous de novo variant in phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit δ (p.E1021K), previously reported in association with APDS. Our patient, who had no family history of immunodeficiency, exhibits classic findings of this syndrome but also has unique features that extend the phenotypic spectrum of this disorder. At 5 years of age, the patient showed marked growth deceleration and was demonstrated to have growth hormone (GH) deficiency with associated pituitary anatomic abnormality. He started GH therapy with an excellent response. He additionally has bilateral nephromegaly of unclear etiology, microscopic hematuria and proteinuria, asthma, and has developed left hip pain with arthrocentesis consistent with oligoarticular juvenile idiopathic arthritis. At age nine, the patient was referred to genetics and whole exome sequencing revealed APDS. Though there was initial concern that GH may increase risk for malignancy as GH signals through the PI3K pathway, he was allowed to continue treatment as the PI3K pathway was considered constitutively active at baseline.

Conclusions

Our patient's unique presentation adds to the clinical information regarding APDS, demonstrates the utility of genetic testing and illustrates the importance of a multidisciplinary collaborative approach in managing this complex syndrome.