Novel ANKRD26 and PDGFRB gene mutations in pediatric case of non‐Langerhans cell histiocytosis: Case report and literature review

Abstract

Cutaneous non‐Langerhans cell histiocytosis (NLCH) is a rare and biologically benign entity that can be broadly classified into two categories: xanthogranuloma and non‐xanthogranuloma. The xanthogranuloma family is characterized by a proliferation of histiocytes with both macrophage and dendritic cell differentiation, negative BRAF mutation, and rare Touton‐type giant cells. Molecular studies have reported that mutations involved in the MAPK signaling pathways are implicated in the pathophysiology of histiocytoses. While LCH is associated with the somatic mutation of BRAF v600e, however, mutations and gene fusions in NLCH cases are undefined. We hereby present a 19‐month‐old female with recalcitrant nodular rashes diagnosed as NLCH with associated novel genetic mutation involving ANKRD26 and PDGFRB genes, as well as PDGFRB::CD74 fusion mRNA. Immunohistochemical staining showed strong and diffuse CD68 and CD163 positivity, and negative CD1a, CD207, ALK D5F3, S100 protein, and BRAF V600E (VE1). Albeit unknown significance, this case of an ANKRD26 and PDGFRB gene mutation in cutaneous NLCH has not been reported prior in the literature. Our case highlights the advantage of pathology and genetic studies in cutaneous NLCH to increase the understanding of this heterogeneous enigmatic disorder and identify further options in management.

Analysis of CD74 Occurrence in Oncogenic Fusion Proteins

“…This fusion lacked an open reading frame to drive the translation of a functional fusion protein [56]. Additionally, a 2023 published case study identified a PDGFRB::CD74 fusion mRNA in a 19-month-old female patient diagnosed with an aggressive case of cutaneous non-Langerhans cell histiocytosis (NLCH) [146]. Although the biopsy specimen was benign, the mutations that led to the PDGFRB::CD74 fusion mRNA had not been previously associated with pediatric or adult NLCH [146].…”

“…While this fusion has been documented in the literature several times, its oncogenic variant remains to be further studied and characterized as the oncogenic signaling pathway that is activated is still unknown. But, it is likely that the presence of CD74-PDGFRB leads to the activation of PDGFRB [146].…”