piperidines and Histiocytosis--Langerhans-Cell

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 rare malignancy which was first described in 2008 and recognized as a systemic histiocytic disorder that can affect multiple organs. Less than 20 cases were reported to date, and much fewer cases were presented as disseminated disease, especially with lung and central nervous system (CNS) involvement. The clinical presentation, cytologic and histologic features were diverse in prior reported cases. Diagnosis relied on clinical, pathological findings and might be determined by molecular identification of anaplastic lymphoma kinase (ALK) gene translocation. Exclusion of other tumors such as Erdheim-Chester disease, Langerhans cell histiocytosis (LCH) and histiocytic sarcoma are required. Because of their rarity and diverse features, no standard treatment was applied so far. Here we reported a 51-year-old Asian female patient documented as ALK-positive histiocytosis with lung, intracranial and lymph nodes involvement. Surgery for left frontal tumor resection was performed. Of note was the presence of foam-like histiocytes, epithelioid cells and Touten-like histiocytes scattered in the lesion, emperipolesis also could be observed. Histiocytes were positive immunostaining for CD68/PGM-1, CD163 and ALK1 in cytoplasmic pattern. Fluorescence in situ hybridization (FISH) analysis confirmed ALK gene translocation and next generation sequencing (NGS) revealed KIF5B-ALK fusion. The patient received treatment of second-generation ALK inhibitor-alectinib after diagnosed and showed durable remission. Therefore, our case highlights a new treatment option for this rare entity.

Topics: Carbazoles; Female; Histiocytosis, Langerhans-Cell; Humans; In Situ Hybridization, Fluorescence; Middle Aged; Piperidines; Receptor Protein-Tyrosine Kinases

Topics: Adult; Azetidines; Female; Histiocytosis, Langerhans-Cell; Humans; Piperidines; Skin; Synovial Membrane

Topics: Adrenal Cortex Hormones; Adult; Aged, 80 and over; Azetidines; Bone Diseases; Dermatologic Agents; Female; Histiocytosis, Langerhans-Cell; Humans; Male; Middle Aged; Off-Label Use; Piperidines; Skin Diseases; Thalidomide