One pathology, two morphologies: Plasma cell crystalline inclusions in monoclonal gammopathy of undetermined significance

A man in his sixties, with a 2-month history of lower rib pain and generalised weakness, was diagnosed with monoclonal gammopathy of undetermined significance (MGUS). The bone marrow aspirate was normocellular with trilineage haematopoiesis, revealing less than 10% monoclonal plasma cells (characterised as a monotypic, cytoplasmic kappa light chain-restricted CD38+, CD138+ population with dim CD45 expression). A subset of these plasma cells exhibited round, inconspicuous nucleoli and contained intracytoplasmic, non-birefringent translucent crystalline structures, rhomboid in shape (upper panel, May-Grünwald Giemsa [MGG], ×100 objective). Upon admission, laboratory evaluation revealed a haemoglobin level of 120 g/L (normal: 135–175 g/L). Serum protein electrophoresis, immunofixation and free light-chain (FLC) studies identified a monoclonal immunoglobulin G (IgG) kappa of 13 g/L with normal FLC values. A low-dose whole-body computed tomography scan showed no lytic lesions. The anaemia and rib pain resolved within weeks. One year later, a follow-up bone marrow aspirate was performed due to worsening anaemia (95 g/L), though the monoclonal protein level remained stable. The aspirate again revealed less than 10% monoclonal plasma cell infiltration but with a different morphology, showing abundant intracytoplasmic crystalline structures, now more rectangular or square-shaped (bottom panel, MGG, ×100 objective). In the absence of disease progression, simple monitoring was continued. Also, no symptoms of Fanconi syndrome were observed during this period, contrary to what is typically seen in similar cases with plasma cell crystalline inclusions. This case highlights the unusual plasma cell morphology in the context of MGUS at two distinct time points. The presence of intracellular crystalline inclusions, although rare, is a recognised phenomenon. The abnormal trafficking of microvesicles, originating from the Golgi apparatus and driven by excessive immunoglobulin production, may lead to fusion with lysosomes and limited proteolysis. This process results in the crystallisation of light chain fragments, contributing to the formation of crystalline inclusions in these plasma cells. The presence of crystalline inclusions has been hypothesised to correlate with a non-progressive clinical course, though its prognostic significance remains largely undefined due to the rarity of this morphological feature. The author did not receive support from any organization for the submitted work. This manuscript respects the ethic policy of CHU Lyon for the treatment of human research participants. The author has confirmed that a patient consent statement is not required for this submission, as no patient-identifying data were used. The author declares no use of third-party material in this study for which formal permission is required.