In some forms with adult-onset (multicentric reticulohistiocytosis, Erdheim-Chester disease), patients can display severe joint involvement, typically associated to abnormal sub-lining infiltration of CD68-positive (CD1a- and S100-negative) histiocytes and multinucleated giant cells with a lipid-laden or PAS-positive ground-glass cytoplasm (44–46). The gene discussed is CD68; the disease is Erdheim-Chester disease.