临床病例报告杂志

Erdheim Chester disease: a complex case report and review of literature

Abstract

Carola Maria Gagliardo, Antonina Giammanco, Augusto Vaglio, Francesco Pegoraro, Angelo Baldassare Cefalu, Maurizio Averna and Davide Noto*

Background: Erdheim-Chester Disease (ECD) is a rare multisystemic disease, characterized by the infiltration of multiple organs by foamy CD68+CD1a- histiocytes. ECD is classified within the group of “L” histiocytosis, together with Langerhans Cell Histiocytosis (LCH), Indeterminate Cell Histiocytosis (ICH) and mixed LCH and EDC. Histiocytic Neoplasms (HNs) are a rare and heterogeneous group of disorders which involve the myeloid lineage and include different clinical entities, ranging from isolated cutaneous manifestations to multisystemic disease. ECD involves the long bones of the lower limbs, the cardiovascular system, the retroperitoneum, the endocrine system, the central nervous system, lungs, skin and the facial sinus or the orbits. This process results in multiorgan damage, mimicking that of neoplastic and systemic immune-mediated diseases. The genetic background consists of gain of function somatic mutations in MAPK pathway, found in almost 80% of ECD patients. The mutation BRAF c.1799T>A, p.Val600Glu (BRAFV600E) is detected approximately in the 50% of ECD patients, followed by the activating mutations in MAP2K1 in close of 20% of cases. The individualization of the specific mutation allows the clinician to practice a targeted therapy. Methods: We report on the complex case of a 70-year-old man consulting for arthralgias due to multiple bone areas of sclerosis, first diagnosed as metastases of a prostatic neoplasm. Results: Despite three bone biopsies and various imaging exams, the diagnosis was reached after one year, when a xanthelasma biopsy showed histopathological signs compatible with ECD, but the immunohistochemistry didn’t evidence positivity for BRAFV600E stain. The diagnosis of ECD was confirmed later by the genetic analysis, which showed the mutation BRAFV600E. Conclusion: The present case report testimonies how ECD diagnosis could represent a challenge for the clinicians due to its heterogeneous clinical presentation.