ALK-Positive Histiocytosis—A Distinct Histiocytic Entity Deserving Recognition—Reply

Abstract

COMMENT & RESPONSEIn Reply We read the Letter to the Editor by Kemps et al with interest. We believe that these cases belong to the spectrum of juvenile xanthogranuloma (JXG). 1 Conventionally, JXG is divided into 3 clinical stages during the disease process (the early developed, xanthomatous, and regression stages) and 3 histopathological changes are observed accordingly (the early, classic, and transitional stages). 2 In our previous study, 3 approximately 34.8% of systemic JXG exhibited ALK-positive immunostaining and ALK translocation verified via ALK fluorescence in situ hybridization assays. Furthermore, 17.4% were BRAFV600E-variants. This portion of JXG with genetic aberrations in our study mainly showed the early developed and xanthomatous clinical stages with corresponding histopathological presentations, including the pathological changes described by Kemps et al. In the case reported by Wolter et al, 4 ALK translocation was observed in the lesion involving the single subglottic mucous membrane. The lesion showed a diffuse infiltrate of histiocytic cells mixed with spindle cells, clinicopathologically exhibiting the transitional stages of JXG with ALK translocations. Hence, the clinical and histopathological presentations of JXG with ALK translocations belong to JXG.Although rare, JXG is the most common type of non-Langerhans cell histiocytosis, with a predilection for children and frequent cutaneous involvement. JXG includes the meanings of juvenile, xanthomatous, and granulomatous, emphasizing its clinical and histopathological characteristics. These characteristics provide the clues for medical professionals, especially dermatologists and pediatricians confronting JXG. The term ALK-positive histiocytosis suggests the importance of genetics and histopathology in etiology and pathogenesis. However, it is less favorable to identify the disease based on the clinical findings to fulfill the term ALK-positive histiocytosis.We have conducted studies in JXG for decades and maintained a high interest in ALK-positive histiocytosis. Considerable overlaps exist between systemic JXG with ALK translocations and ALK-positive histiocytosis, as mentioned in our previous study. 3 Similarly, commonalities exist between BRAFV600E-variant JXG and Erdheim-Chester disease. Therefore, we suggest genetic testing and systemic screening as novel modalities in the diagnosis and management of JXG, espe-