A rare, invasive, and challenging cancer in childhood: diffuse sclerosing variant of papillary thyroid carcinoma

Abstract Objectives Pediatric thyroid cancers are rare, with papillary thyroid carcinoma (PTC) being the most common type. The diffuse sclerosing variant (DSV) is a rarer subtype associated with frequent recurrence and extensive lymphatic involvement. Among 51 pediatric patients treated for thyroid carcinoma at our tertiary center over a 20-year period, three were diagnosed with DSV-PTC. We present this retrospective case series to highlight its clinical course and diagnostic challenges. Case presentation Three patients (aged 8–17) presented with neck swelling; one also exhibited high fever and neck pain. While thyroid function tests were normal, serum thyroglobulin levels were significantly elevated. Imaging revealed diverse presentations: a solitary nodule, diffuse enlargement mimicking an abscess, and diffuse inflammation. Following fine-needle aspiration confirmation of PTC, all patients underwent total thyroidectomy and central and bilateral lymph node dissection. Histopathology confirmed DSV-PTC in all cases. Every patient presented with diffuse lymph node metastasis; two showed extrathyroidal extension, and one had distant pulmonary metastasis. Genetic analysis identified a BRAF V600E alteration in one case and RET translocations in the other two, confirmed by fluorescence in situ hybridization (FISH) after negative broad next-generation sequencing (NGS) panels. All patients required revision surgery for residual tissue followed by radioactive iodine (RAI) therapy. At follow-up (13–28 months), outcomes ranged from stable disease and additional RAI requirement to complete remission without relapse. Conclusions Although based on a small case series, our findings suggest that DSV-PTC can behave aggressively in pediatric patients and can mimic benign inflammatory conditions, leading to potential diagnostic delays. Early recognition and a comprehensive multimodal approach, including extensive surgery and RAI, appear vital for managing this challenging variant.