Deficiency of the lysosomal enzyme, β-glucocerebrosidase, and accumulation of its substrate in cells of the reticuloendothelial system affects multiple organ systems in patients with Gaucher disease (GD). Lipid laden macrophages turn into Gaucher cells (GC) which are the pathological characteristic of GD. GC focally accumulate in the liver, spleen and at extraosseous sites to form benign lesions called Gaucheromas. Gaucheromas pose diagnostic and therapeutic challenges. We studied the pathophysiology of extraosseous Gaucheroma formation in a cohort of patients with GD. Among 63 patients followed at a single center, 3 patients with genotypes L444P/L444P and N370S/N370S, were diagnosed with extraosseous Gaucheromas. Flow cytometry revealed a higher expression of CD16+/CCR4+ non-classical monocytes in blood of GD patients who have developed Gaucheromas. A biopsy showed infiltration of GC, which reactivity against CD163, CD68 and VEGF. The cell proliferative marker Ki67 and CCL2, a factor anti-tumor activity, were negative. Our study indicates that extraosseous Gaucheromas are comprised of cellular elements with characteristics of tumor-associated macrophages, the major players in cancer related inflammation. The occurrence of non-classical CD16+/CCR4+ monocytes reflect the underlying cause for the accumulation of the macrophages capable of migrating to distant sites outside the reticuloendotheial system, and giving rise to tumor-like Gaucheromas.
Keywords: GBA; Gaucher disease; Gaucheroma; Glucosylceramidase beta; Macrophages; Tumor.
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