Abstract Introduction Juvenile xanthogranuloma (JXG) is a benign non-Langerhans cell histiocytosis that typically presents as cutaneous papules or nodules in infancy and early childhood. Visceral involvement, particularly isolated pulmonary disease, is exceedingly rare and may mimic malignancy or infection radiographically. We present a case of primary pulmonary JXG with anaplastic lymphoma kinase (ALK) positivity in a child initially misdiagnosed on imaging, underscoring the diagnostic and management challenges of this uncommon entity. Case Description A 7-year-old female with moderate persistent asthma was referred from an outside hospital for evaluation of three episodes of apparent hematemesis. Chest radiograph at the referring facility revealed a right middle lobe pulmonary nodule, which had increased in size compared to prior imaging from one year earlier. On review, the bleeding episodes were thought to represent hemoptysis rather than gastrointestinal bleeding. The mass was initially suspected to be a hamartoma given its imaging features, clinical presentation, and the fact that pulmonary hamartomas represent the most common benign lung tumor. The patient underwent video-assisted thoracoscopic (VATS) wedge resection on May 12, 2025. Gross pathology demonstrated complete excision with negative margins. Histological examination showed a fibrohistiocytic proliferation composed of foamy histiocytes and Touton-type giant cells with mitotic activity but no atypia. Immunohistochemistry was positive for Factor XIIIa and ALK, with CD68 highlighting a subset of histiocytes and S100 outlining a dendritic network. Keratin and BRAF were negative, consistent with ALK-positive juvenile xanthogranuloma, suggestive of a KIF5B-ALK translocation. The postoperative course was uneventful with resolution of symptoms. Follow-up imaging demonstrated no recurrence or new lesions. Whole-body MRI showed no evidence of systemic involvement. She remains clinically well with stable pulmonary findings under hematology-oncology follow-up. Discussion Primary pulmonary ALK-positive JXG is exceedingly rare in children. This case illustrates the importance of distinguishing hemoptysis from hematemesis in pediatric presentations and emphasizes the need for careful review of serial imaging to identify progressive pulmonary lesions. Recognition of ALK-rearranged histiocytic proliferations as a biologically distinct subset is essential to avoid misdiagnosis and overtreatment. Long-term monitoring is warranted to detect potential recurrence or multisystem involvement. This abstract is funded by: None
Ahmed et al. (Fri,) studied this question.