title: Gaucheromas: When macrophages promote tumor formation and dissemination.
abstract: 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.
authors.affiliation: Lysosomal and Rare Disorders Research and Treatment Center, 11212 Waples Mill Rd, Ste 103, Fairfax, VA, USA; O&O Alpan, LLC, 11212 Waples Mill Rd, Ste 100, Fairfax, VA, USA.
authors.forename: Margarita
authors.initials: M
authors.lastname: Ivanova
authors.affiliation: Lysosomal and Rare Disorders Research and Treatment Center, 11212 Waples Mill Rd, Ste 103, Fairfax, VA, USA; O&O Alpan, LLC, 11212 Waples Mill Rd, Ste 100, Fairfax, VA, USA.
authors.forename: Renuka Pudi
authors.initials: RP
authors.lastname: Limgala
authors.affiliation: Lysosomal and Rare Disorders Research and Treatment Center, 11212 Waples Mill Rd, Ste 103, Fairfax, VA, USA.
authors.forename: Erk
authors.initials: E
authors.lastname: Changsila
authors.affiliation: Fairfax Radiological Consultants, PC, Fairfax, VA, USA.
authors.forename: Ravi
authors.initials: R
authors.lastname: Kamath
authors.affiliation: Lysosomal and Rare Disorders Research and Treatment Center, 11212 Waples Mill Rd, Ste 103, Fairfax, VA, USA; O&O Alpan, LLC, 11212 Waples Mill Rd, Ste 100, Fairfax, VA, USA.
authors.forename: Chidima
authors.initials: C
authors.lastname: Ioanou
authors.affiliation: Lysosomal and Rare Disorders Research and Treatment Center, 11212 Waples Mill Rd, Ste 103, Fairfax, VA, USA; O&O Alpan, LLC, 11212 Waples Mill Rd, Ste 100, Fairfax, VA, USA. Electronic address: ogokeralpan@oandoalpan.com.
authors.forename: Ozlem
authors.initials: O
authors.lastname: Goker-Alpan
mesh_terms: D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D063646:Carcinogenesis / Q000235:genetics / Q000473:pathology*; D015331:Cohort Studies; D005260:Female; D005776:Gaucher Disease / Q000150:complications* / Q000235:genetics / Q000473:pathology*; D005838:Genotype; D006801:Humans; D008264:Macrophages / Q000378:metabolism / Q000473:pathology*; D008297:Male; D054398:Receptors, CCR4 / Q000032:analysis; D011956:Receptors, Cell Surface / Q000032:analysis; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis; D055815:Young Adult; D000098902:CD163 Antigen
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; C515354:CCR4 protein, human; D000098902:CD163 Antigen; D054398:Receptors, CCR4; D011956:Receptors, Cell Surface; D042461:Vascular Endothelial Growth Factor A
keywords: GBA; Gaucher disease; Gaucheroma; Glucosylceramidase beta; Macrophages; Tumor