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Case Reports

Abstract

Indeterminate Cell Histiocytosis (ICH) is an extremely rare neoplasm. Here, we present a case of a 10-year-old male patient who presented with a solitary nodule on the right forehead.  Microscopic examination revealed sheets of large, round/oval cells with some nuclear grooves. No significant eosinophils were identified. Lesional cells were positive for CD1a and S100, but negative for Langerin, as such, was favored to represent immature Langerhans cells (i.e. “indeterminate” cells), compatible with a diagnosis of ICH. ICH cells can exhibit a range of morphologies, from a more Langerhans cell histiocytosis (LCH)-like appearance to a less frequent blastoid morphology. When the morphology resembles LCH, epidermotropism and lack of an eosinophils favor a diagnosis of ICH over LCH; however, a definitive diagnosis cannot be rendered without assessment of Birbeck granules on electron microscopy which are absent in indeterminate cells. Genetic studies of our patient revealed the novel RIPOR2::BRAF fusion, which has not been reported in the literature. Importantly, the breakpoints in BRAF are consistent with other pathogenic BRAF fusions identified in non-LCH cases and were found to result in loss of the autoinhibitory domain and retaining the oncogenic kinase domain. Understanding of ICH and its clinical behavior is significantly constrained by its rarity. Reported cases indicate that unlike ICH in adults, which can be linked to associated hematologic neoplasms, such associations are seldom seen in pediatric populations.  Given rarity of ICH and variable treatment strategies, we hope our case contributes to a better understanding of ICH regarding its etiology, molecular pathway, and prognosis.