Erdheim–Chester Disease

Abstract

Erdheim-Chester disease (ECD) is a rare (approximately 500 known cases worldwide), non-inherited, nonLangerhans form of histiocytosis of unknown origin, first described in 1930. It is characterized by xanthomatous or xanthogranulomatous infiltration of tissues by foamy histiocytes, "lipid-laden" macrophages, or histiocytes, surrounded by fibrosis. Diagnosis of ECD involves the analysis of histiocytes in tissue biopsies: these are typically foamy and CD68+ CD1a− in ECD, whereas in Langerhans cell histiocytosis (LCH) they are CD68+ CD1a+. 99 Technetium bone scintigraphy revealing nearly constant tracer uptake by the long bones is highly suggestive of ECD, and a "hairy kidney" appearance on abdominal CT scan is observed in approximately half of ECD cases. Central nervous system involvement is a strong prognostic factor and an independent predictor of death in cases of ECD. Optimum initial therapy for ECD seems to be administration of interferon α (or pegylated interferon α), and prolonged treatment significantly improves survival; however, tolerance may be poor. Cases of ECD present with strong systemic immune activation, involving IFNα, IL-1/IL1-RA, IL-6, IL-12, and MCP-1, consistent with the systemic immune Th-1-oriented disturbance associated with the disease. More than half of ECD patients carry the BRAF V600E mutation, an activating mutation of the protooncogene BRAF. A small number of patients harboring this mutation and with severe multisystemic and refractory ECD have been treated with vemurafenib, a BRAF inhibitor, which was proved very beneficial.

Erdheim-Chester disease mimicking an intracranial trigeminal schwannoma: case report

“…14,17,18 Almost all studies have reported a strong male predominance, which also occurs in the above-mentioned series (75%). 18 By 2014, only 8 pediatric cases were reported in the medical literature.…”

“…14,17,18 Almost all studies have reported a strong male predominance, which also occurs in the above-mentioned series (75%). 18 By 2014, only 8 pediatric cases were reported in the medical literature. 17,20,29 For a long time, it remained unclear whether ECD was the histological manifestation of some kind of abnormal immune response or whether it was a neoplastic lesion.…”

“…27 The typical pattern is a polymorphic granuloma composed of lipid-laden (foamy or spumous) histiocytes and fibrosis or xanthogranulomatosis. [16][17][18]30 The characteristic multinucleated Touton-type giant cells are often present. On immunohistochemical staining, the histiocytes are uniformly positive for CD68, negative for CD1a, and only rarely positive for S100 (negative for S100 in 80% of cases).…”

“…On immunohistochemical staining, the histiocytes are uniformly positive for CD68, negative for CD1a, and only rarely positive for S100 (negative for S100 in 80% of cases). 14,18,27,32 The Langerhans cells seen in Langerhans cell histiocytosis (LCH) are differentiated from those seen in ECD by their immunohistochemical features: they are positive for CD1a and S100. 14,32 Rosai-Dorfman disease (RDD) is another type of non-Langerhans histiocytosis which may also involve the CNS.…”

“…It typically affects middle-aged patients and has a significant male predominance. 3,5,8,14,17,18,23,27,28,32 Only 8 pediatric cases have ever been reported. 17,20,29 This disease is known to involve multiple organ systems, including the skeletal, cutaneous, cardiovascular, respiratory, urinary, and central nervous systems.…”