piperidines and Histiocytosis

Histiocytic neoplasms are a heterogeneous group of clonal haematopoietic disorders that are marked by diverse mutations in the mitogen-activated protein kinase (MAPK) pathway

Topics: Azetidines; Histiocytic Disorders, Malignant; Histiocytosis; Humans; MAP Kinase Kinase 1; MAP Kinase Kinase 2; MAP Kinase Signaling System; Mitogen-Activated Protein Kinase Kinases; Mutation; Piperidines; Progression-Free Survival; Proto-Oncogene Proteins B-raf; Proto-Oncogene Proteins c-raf

Progressive nodular histiocytosis is a rare variant of non-Langerhans cell histiocytosis that affects the skin and mucous membranes and displays a progressive clinical course and poor response to treatment. We describe a case of severe progressive nodular histiocytosis harboring a KRAS p.G12S mutation in a 9-year-old boy, refractory to chemotherapy, who was successfully treated with the MEK inhibitor cobimetinib. This is the first report of the use of MEK inhibition for this histiocytosis subtype in a pediatric patient.

Topics: Azetidines; Child; Histiocytosis; Histiocytosis, Langerhans-Cell; Humans; Male; Piperidines; Skin Diseases

ALK-positive histiocytosis is a recently described entity with few reported cases in literature. Herein, we report an unusual case of ALK-positive histiocytosis showing an Erdheim-Chester disease (ECD)-like presentation, occurring in a 37-year-old woman with a 2-year history of chronic lymphocytic leukaemia (CLL). Our CLL patient relapsed 6 months after the end of fludarabine, cyclophosphamide and rituximab frontline therapy and complained of lower limb pains. A bone marrow biopsy was performed and showed concomitant CLL/small lymphocytic lymphoma and ALK-positive histiocytosis with an identical immunoglobulin heavy-chain gene rearrangement in both neoplasms, suggesting clonal relationship. After 4 years under ibrutinib therapy, our patient remains free of both diseases. This report extends the spectrum of composite hematolymphoid neoplasms and shows that ALK rearrangement should be considered in all histiocytosis subtypes. Moreover, both tumours eradication under ibrutinib suggests that BTK inhibitors may also be effective in histiocytic neoplasms.

Topics: Adenine; Adult; Anaplastic Lymphoma Kinase; Biomarkers; Female; Histiocytosis; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Piperidines; Protein Kinase Inhibitors