An 82-year-old woman was admitted to the Department of Cardiovascular Medicine at Hamanomachi Hospital for treatment of atrial fibrillation. She complained of exertional dyspnea spanning four months. Her medical history included end-stage renal failure of unknown etiology and maintenance dialysis for two years. Her medication included 2.5 mg of bisoprolol.
She had a temperature of 36.5  C, blood pressure of 95/59 mmHg, a heart rate of 68 beats per minute, oxygen saturation of 98% under room air. Physical examination revealed slight late inspiratory crackles in both sides of her chest with no peripheral edema. Multiple nodules and tooth indentation were noted on the tongue (Fig. 1).
An echocardiogram showed a decreased left ventricular ejection fraction of 41%. Myocardial biopsy was performed, but there were no specific features. The patient underwent electrical cardioversion, and the atrial fibrillation returned to sinus rhythm.
The patient was then referred to the Department of Respiratory Medicine for abnormal chest imaging. High-resolution CT of the chest revealed diffuse ground-glass opacities (GGO) with mosaic attenuation, consolidation in the left lingular lobe, and subpleural, wedge-shaped nodules in the bilateral lower lobes (Fig. 2). To facilitate diagnosis, bronchoscopy was performed. Bronchoscopy revealed enlarged tortuous submucosal vessels at the main carina and left main bronchus (Fig. 3), suggesting tracheal amyloidosis. A transbronchial lung biopsy (TBLB) of the left lingular lobe was performed. Microscopic examination of the TBLB showed deposition of amorphous eosinophilic amyloid at the smooth muscle layer of the bronchial tissue (Fig. 4A). Congo red staining displayed a positive signal in polarized light (Fig. 4B and C). Immunohistochemical staining for amyloid P was positive (Fig. 4D). No pathogen or malignancy was detected. From these findings, she was diagnosed with pulmonary amyloidosis. Bronchoalveolar lavage fluid from left B3 was brownish-yellow and numerous hemosiderin-laden macrophages were detected with Berlin blue staining (Fig. 5), indicating chronic alveolar hemorrhage, resulting in pulmonary hemosiderosis. Cytology of the lavage showed alveolar macrophage predominance (99% macrophages and 1% neutrophils).
Additional serological examinations to evaluate the etiology of pulmonary hemorrhage causing hemosiderosis, anti-neutrophil cytoplasmic antibody (ANCA), antinuclear antibody (ANA), and rheumatoid factor (RF), were negative. Therefore, pulmonary hemosiderosis was considered related to pulmonary amyloidosis.
An upper gastrointestinal endoscopy was also performed, and a duodenal biopsy confirmed amyloidosis. In addition, A CT of the body showed soft tissue masses around the hip joints, which were thought to be amyloidosis lesions. These findings suggested systemic amyloidosis.
To investigate the etiology of amyloidosis, further serological examinations were performed. Serum IgG, IgA, and IgM levels were low (380 mg/dL, 19 mg/dL, and 4 mg/dL, respectively). Serum free light-chain analysis showed greatly increased lambda light chain of 28,900 mg/L with kappa light chain of 36.8 mg/L. Serum immuno-electrophoresis showed a monoclonal lambda light-chain peak, and urinary Bence-Jones protein was positive.
Suspecting multiple myeloma, bone marrow examination was performed. Bone marrow examination showed plasma cell neoplasms with lambda light-chain restriction. Flow cytometry analysis of bone marrow cells revealed a CD19-CD38highCD45-CD56+CD138+cyLambda+ cell population, which is a typical immunophenotype of myeloma cells. This confirmed the diagnosis of multiple myeloma, lambda light chain type, international staging system Stage 3. Chemotherapy of bortezomib, lenalidomide and dexamethasone was initiated, followed by oral ixazomib, lenalidomide, and dexamethasone. Six months after diagnosis, she is still receiving chemotherapy on an outpatient basis.
Radiological findings of the patient. (B) Chest CT images on admission showing diffuse ground-glass opacities (GGO) with mosaic attenuation, consolidation in the left lingular lobe (arrow), and subpleural, wedge-shaped nodules in the bilateral lower lobes (arrowhead).