Detection of vascular amyloid deposits in a bone marrow aspirate

During an evaluation for plasma cell dyscrasia in an 80-year-old man, we observed in the bone marrow aspirate an unusual, and previously unreported, alteration of small blood vessels which helped us establish a diagnosis of systemic amyloidosis. The patient had presented to the nephrology clinic with pitting oedema in both legs, proteinuria (5.4 g per day) and serum creatinine 256.4 μmol/L, elevated from a baseline of 81.3 μmol/L measured 4 months earlier. His medical history included diabetes mellitus treated with metformin. Tests for anti-neutrophil cytoplasmic antibodies and antinuclear antibodies were negative, and no monoclonal immunoglobulin was detected in serum or urine. Serum-free light-chain analysis, however, identified a level of free lambda light chain 197 mg/L (reference range, 8.3–27.0), free kappa light chain 22 mg/L (3.0–19.0) and serum-free light-chain ratio 0.11 (0.26–1.65) raising suspicion for plasma cell disorder; therefore, bone marrow aspiration was performed. Examining the aspirates, we were struck by the presence of blood vessels with markedly thickened walls due to the accumulation of a cloudy, homogeneous, purplish material along vascular endothelial cells (top) (May–Grünwald–Giemsa stain, objective ×60). Some were more than three times the normal size (bottom left) (May–Grünwald–Giemsa stain, objective ×60). Several mature-appearing plasma cells were noted around thickened blood vessels (arrowheads). Bone marrow biopsy confirmed that the wall of blood vessels was extremely thickened by an amorphous substance which stained positively with Congo red (bottom right) (objective ×400) and showed green birefringence under polarised light (inset), consistent with amyloid. The plasma cell count was 10%, with lambda light-chain restriction. A diagnosis of immunoglobulin amyloid light-chain (AL) amyloidosis was made. An abdominal fat-pad biopsy specimen was negative for amyloid deposits. Despite treatment with cyclophosphamide, bortezomib and dexamethasone, severe renal insufficiency with anuria developed. He was admitted to the high dependency unit, but his clinical status deteriorated and he died. Endothelial cells derived from capillaries within the bone marrow are occasionally seen in aspirates forming a lining, one cell thick. They have an elongated shape, weakly basophilic cytoplasm, round-to-oval nuclei, which may be grooved and variably condensed chromatin. The bone marrow vasculature may be altered as a consequence of bone marrow diseases but, in addition, may be involved in a variety of systemic diseases. Deposition of amyloid in the bone marrow occurs mainly in AL amyloidosis. In general, a bone marrow aspirate does not give relevant information and a trephine biopsy is necessary. Rarely, bone marrow films may reveal amyloid in the form of clumps of a purplish proteinaceous material scattered about the fields. This case shows that bone marrow films may also reveal blood vessel deposits. When interpreting bone marrows, it is necessary to recognise any non-haematopoietic cells that are present. We should like to highlight the value of an examination of non-haematopoietic elements such as vascular endothelial cells because it can provide important information. Familiarity with this morphologic finding should alert haematologists to the possibility of underlying systemic amyloidosis. The publication of this article in OA mode was financially supported by HEAL-Link. The publication of this article in OA mode was financially supported by HEAL-Link. Consent has been obtained from the patient's family. This manuscript contains original material that has not been published elsewhere or submitted previously to another journal.