What is the pathology of Langerhans cell histiocytosis (LCH)?

Updated: Sep 16, 2020
  • Author: Cameron K Tebbi, MD; Chief Editor: Vikramjit S Kanwar, MBBS, MBA, MRCP(UK), FAAP  more...
  • Print

Some articles suggest classification of high-risk Langerhans cell histiocytosis (LCH) as a myeloid neoplasia and hypothesize that the high-risk disease arises from somatic mutation of a hematopoietic progenitor. Some authors propose that low-risk disease arises from somatic mutation of tissue-restricted precursor dendritic cells. These hypotheses are based on the finding of BRAF-V600E mutation in circulating CD11C(+) and CD14(+) fractions and in bone marrow CD34(+) hemopoietic progenitor cells. On the other hand, the mutation was restricted to lesional CD207(+) dendritic cells in patients with low-risk Langerhans cell histiocytosis. [44, 45]

Histiocytic diseases include disorders of dendritic cells, ie, Langerhans cell histiocytosis (LCH); abnormal multiplication of macrophages, as in polyostotic sclerosing histiocytosis (also known as Erdheim-Chester disease or syndrome [ECD]) and xanthogranuloma; and macrophage/monocytoid lineage conditions, including Rosai-Dorfman disease and hemophagocytic lymphohistiocytosis. Malignant histiocytosis and monocytic or myelomonocytic leukemias, while related, traditionally are separated as malignant disorders. Approximately 60% of biopsy specimens in Langerhans cell histiocytosis reveal V600E mutation in the BRAF oncogene, demonstrating that the disease is a clonal disorder. There is controversy as to whether this is a result of malignant transformation or immunologic stimulus. It should be noted that the same mutation is seen in benign lesions such as nevi. 

The function of normal Langerhans cells is cutaneous immunosurveillance. These cells can migrate to the regional lymph nodes and potentially present antigen to paracortical T cells and cause their transformation to interdigitating dendritic cells. Some cancer cells disrupt dendritic-cell function, blocking the development of tumor-specific immune responses and allowing tumors to evade recognition. [46] To counteract this effect, dendritic cells may produce the antiapoptotic protein Bcl-xL. Stimulation of dendritic cells by CD154, IL-12, or IL-15 increases expression of Bcl-xL. The information gained from normal physiology of dendritic cells may potentially lead to treatment modalities for histiocytic disorders.

Did this answer your question?
Additional feedback? (Optional)
Thank you for your feedback!