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PATIENT CASE

JS, a 45-year-old Caucasian man, was referred to the Mayo Clinic in consultation for progressive congestive heart failure (CHF) of unclear etiology. A year prior to his symptoms, he had been a healthy and active person playing tennis 4 times a week and leading a very busy life as a farmer in the Midwest and as a father of 3 young children with no medical problems except for well-controlled essential hypertension (HTN). Six to eight months prior to presentation he experienced a decline in exercise capacity and gradually gave up tennis. Three months prior to presentation he developed dyspnea on moderate exertion and intermittent swelling of his legs. Medical evaluation included normal renal function, blood counts, and pulmonary computed tomography (CT) angiogram. Nuclear medicine cardiac stress test was normal; pulmonary function tests indicated a mild reversible obstructive defect and 2D echocardiogram revealed mildly thickened left ventricle with an ejection fraction of 60% and borderline diastolic dysfunction. Treatment with bronchodilators was empirically started for a provisional diagnosis of atypical asthma. His symptoms progressed rather rapidly over the course of 2 to 3 weeks and he underwent a coronary angiogram, which demonstrated normal coronary arteries. At his evaluation at Mayo Clinic he was found to be in New York Heart Association (NYHA) class III CHF. Based on the review of his electrocardiograph (ECG) and echocardiogram a diagnosis of infiltrative cardiomyopathy was suspected and further work demonstrated an immunoglobulin lambda light chain gammopathy in the serum with 8% lambda restricted plasma cells in the bone marrow. Congo red staining of the bone marrow and abdominal fat aspirate was positive for extracellular amorphous material that demonstrated apple green birefringence under polarized microscope. He was diagnosed with immunoglobulin lambda light chain amyloidosis (AL) with stage IV cardiac disease.

AMYLOIDOSIS

HISTORY AND INTRODUCTION

Matthias Schleiden, a German botanist, first used the term amyloid in 1838 to describe a normal constituent of plants.1 In 1858, Rudolph Virchow described amyloid deposits in spleen that stained blue with iodine and sulfuric acid, similar to the chemical reaction markers of starch. Virchow concluded that the substance was composed of starch and used the word amyloid to describe it.2 In 1859, Friedreich, Nikolau, and Kekule recognized that the waxy spleen described by Virchow did not contain any starchlike substances and that the deposits probably were derived from modified proteins.3

Amyloidosis, as understood today, is a unique, yet remarkably heterogeneous group of diseases characterized by the deposition of misfolded protein precursors in a beta-pleated sheet configuration in the extracellular space in various tissues. This characteristically conserved structure renders the amyloid fibrils of different origins resistant to proteolytic cleavage under physiological condition and forms the basis of characteristic staining of amyloid fibrils by Congo red, thioflavin T, and Alcian blue, a feature essential for establishing the diagnosis on histopathologic examination (Figure 11-1).4 Widely divergent ...

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