新生児におけるBRAF V600E変異を伴うランゲルハンス細胞組織球症：診断、治療、および転帰に関するまれな症例報告

Langerhans cell histiocytosis (LCH) is a rare histiocytic disorder characterized by clonal proliferation of abnormal Langerhans cells. We report a case of neonatal LCH diagnosed shortly after birth, an exceptionally early presentation in the neonatal period that is exceedingly rare. The BRAF V600E mutation was detected in this neonate.

We report a full-term male neonate delivered via forceps assistance. Within 24 hours of birth, a firm 1×1 cm subcutaneous nodule on the left medial thigh progressively enlarged and ulcerated. By postnatal day 19, a dark red non-blanchable papule appeared on the left sole and rapidly spread to postauricular, cervical, truncal, and palmar regions, developing multiple ulcerative lesions. Skin biopsy confirmed Langerhans cell histiocytosis (LCH), with immunohistochemistry demonstrating diagnostic markers CD1a(+), Langerin(+), and S-100(+). Molecular testing detected the BRAF V600E mutation. Based on the early onset of the disease, rapidly progressive multifocal ulcerative skin lesions, and the presence of a high-risk BRAF mutation suggesting potential systemic dissemination, we initiated induction chemotherapy with vincristine combined with prednisone. Following treatment, the skin lesions resolved completely. The child is now 30 months old. During follow-up, an episode of otitis media occurred, but no recurrence or systemic organ involvement has been observed since.

In this neonate, the initial localized skin lesions suggested potential spontaneous resolution. However, subsequent detection of the poor-prognosis BRAF V600E mutation indicated risk of systemic dissemination, prompting initiation of combination chemotherapy. Skin lesions resolved completely following vinblastine/prednisone therapy. Otitis media (an extracutaneous manifestation) emerging during follow-up further validated the treatment necessity, with no recurrence or new systemic manifestations observed thereafter.