Clear cell myeloma. Report of two cases with comments on morphogenesis and ubiquitin expression

Three bone marrow trephine biopsies from two multiple myeloma patients were involved by a diffuse infiltrate of microvacuolated plasma cells with a variable number of signet ring cells, CD138, κ-light chains, and ubiquitin positive. The vacuoles remained clear on PAS and in May–Grunwald–Giemsa-stained bone marrow aspirates. Differential diagnosis on conventional stains included malignant epithelial and mesenchymal tumors, non-neoplastic histiocytes, and fixation artifacts. Electron microscopy revealed translucent vacuoles with no apparent membrane and a fuzzy internal surface occasionally merging with smaller membrane-delineated spaces filled with granular material, without communication with cisternae of rough endoplasmic reticulum. Rare multivesicular bodies with dilated intralumenal vesicles were noted. The findings concur with the presumed derivation of the vacuoles from the endolysosomal compartment. Strong ubiquitin expression was encountered in neoplastic plasma cells but not in non-neoplastic plasma cells, presumably due to the endoplasmic reticulum-associated degradation, triggered by excessive production of misfolded immunoglobulins in the former.