LAUSR

Abstract Neurofibromatosis type 1 (NF1), predisposes patients to benign and malignant tumors due to lack of suppression of the mitogen activated protein kinase (MAPK) signaling pathway. Langerhans cell histiocytosis (LCH) manifests in numerous ways, from localized lesions to multisystem organ involvement secondary to a constitutively active MAPK signaling cascade often driven by BRAF mutations. While both LCH and NF1 are characterized by overactive MAPK signaling, there are few reports of the two diseases occurring simultaneously. We report a novel case of a patient with underlying NF1 and recurrent LCH without a BRAFV600E mutation. She initially presented at 2 years of age with an aggressive appearing mass of the left temporal bone found on surveillance imaging. Pathology was consistent with Langerhans histiocytosis and she was treated with the LCH-III protocol for patients with high-risk LCH due to the location of her lesion. Five years after completion of therapy, MRI demonstrated development of a calvarial mass consistent with relapsed LCH in a new risk site. Lesional curettage was performed and pathology confirmed recurrence of LCH with juvenile xanthogranulomatous features. BRAF testing of blood and the lesion were negative for any BRAF alterations. Further genomic evaluation of the tumor is in progress at this time to evaluate for other known mutations associated with LCH. The patient is currently receiving monthly cytarabine treatment which she has tolerated to date. Our patient represents a unique presentation of recurrent LCH in a patient with NF1 and further molecular evaluation may help identify other drivers of LCH activation.