A Striking Case of Light Chain Amyloidosis Visible on Bone Marrow Aspirate Smear

Light chain amyloidosis is the most common form of systemic amyloidosis and is often associated with plasma cell neoplasms. Clonal or malignant plasma cells produce excess free immunoglobulin light chains, which leads to protein misfolding, aggregation, and multisystem amyloid deposition, most commonly in antiparallel beta-pleated sheets [1]. Amyloid deposits can be seen in any tissue but are often found in vessel walls, which are particularly susceptible. Over 60% of bone marrow (BM) biopsies in patients with light chain amyloidosis will demonstrate amyloid deposits in vessel walls or stroma [1]; however, deposits in the BM aspirate smear are rare.

A 50-year-old male presented with multiorgan imaging abnormalities, biventricular cardiac hypertrophy, and elevated serum lambda light chains (402 mg/L). An endomyocardial biopsy revealed cardiac amyloidosis, with liquid chromatography tandem mass spectrometry (LC/MS) demonstrating AL (lambda)-type amyloid deposition. A BM biopsy was performed for further workup. Peripheral blood (PB) demonstrated mild normocytic anemia (Hgb 12.2 g/dL) and thrombocytosis (platelets 768 × 10⁹/L). BM aspirate, clot section, and core biopsy showed increased neoplastic plasma cells (∼20%) with cytologic atypia and extensive interstitial and vascular deposition of amorphous material within vessel walls and the interstitium (Figure 1A). Strikingly, these deposits were even visible on the aspirate smear as thick, amorphous, and waxy basophilic globules (Figure 1B). Congo red stains performed on the aspirate smear and core biopsy confirmed these amorphous deposits to be apple-green birefringent under polarized light (Figure 1C,D). Ancillary studies, including flow cytometric immunophenotyping and cytogenetic/FISH studies confirmed an aberrant monotypic lambda-restricted plasma cell population demonstrating gains of Chromosomes 3, 7, 11, 15, 18, 19, and 21; Trisomy 9 and 15; and an extra copy of CCND1 (11q13). The constellation of these findings led to a diagnosis of extensive amyloidosis (AL-lambda type) in the setting of a plasma cell neoplasm. The patient was treated with six cycles of daratumumab, cyclophosphamide, bortezomib, and dexamethasone and underwent autologous stem cell transplant. He is currently on bortezomib maintenance therapy at 35-month follow-up, postdiagnosis.

Amyloid deposits in AL-amyloidosis can be found in any tissue and can lead to organ dysfunction and death, with a major prognostic indicator being the extent of cardiac involvement [1, 2]. In the BM, deposits are usually identified on core biopsy, most commonly within vessel walls, but also in periosteal areas and within the interstitium. Our case demonstrates very striking, extensive involvement by AL-amyloidosis, with amorphous, and Congo red birefringent amyloid deposits that also visible on aspirate smear. This is a rare and interesting finding with only a few cases reported in the literature [2, 3]. While uncommon, our case highlights the importance of careful review of the aspirate smears, as identification of similar findings can allow a quick diagnosis of amyloidosis if BM biopsy sections are not available.

A.K. and W.C. contributed to the writing of the manuscript.

The authors have nothing to report.

The authors have nothing to report.

The authors declare no conflicts of interest.