A 64-year-old male with a history of CKD Stage 3 with 330 mg/day of proteinuria (eGFR by 4-variable MDRD of 52 mL/min/1.73 m2 with a baseline serum creatinine of 1.7 mg/dL), monoclonal gammopathy with elevated kappa light chains on urine protein electrophoresis, and anemia of chronic disease presented over multiple hospitalizations with complaints of peripheral neuropathy, orthostatic hypotension, and unintentional weight loss. The initial investigation included normal levels of vitamin B-12, folate, heavy metals, and was negative for myelin associated glycoprotein antibodies and lyme antibodies. A bone marrow biopsy was completed to rule out progression to multiple myeloma and demonstrated normocellular bone marrow, no clonal plasma cell populations, and an eosinophilic deposit negative for Congo red stain. A 4 mm osteosclerotic lesion was biopsied and demonstrated similar deposits. An abdominal fat-pad biopsy was also negative for Congo red stain. An echocardiogram demonstrated nonspecific findings suggestive of amyloidosis including concentric left and right ventricle hypertrophy, diastolic dysfunction, biatrial enlargement, and tricuspid and mitral valve regurgitation. A renal biopsy was postponed due to concern for a bleeding diathesis as he developed severe right flank ecchymosis after a short coughing bout and subsequently severe thrombocytopenia. A bone marrow biopsy was repeated and amorphous material was suggestive of amyloid deposits but again negative for Congo red stain by two separate pathology laboratories. The patient subsequently developed nonnephrotic range proteinuria of 2.2 gm g/day and acute kidney injury. The acute kidney injury progressed to dialysis-dependent renal failure. During creation of an arteriovenous fistula for dialysis, a segment of the radial artery and brachial vein were submitted for testing and were also negative for Congo red stain. A renal biopsy was performed and was positive for Congo red stain with characteristic apple-green birefringence in the amyloid deposits involving the glomeruli, vessels, and interstitium (). Immunofluorescent histology confirmed kappa light chain deposition and electron microscopy demonstrated amyloid deposits characterized by relatively straight, nonbranching, randomly arranged fibrils. Following the completion of the renal biopsy, a final analysis of the second bone marrow biopsy by a third facility recognized as a center of excellence confirmed the presence of AL- (kappa-) type amyloid by liquid chromatography tandem mass spectrometry of peptides microdissected from the bone marrow specimen. The patient was referred to an outside facility for treatment where he received melphalan and dexamethasone. He did not have an adequate hematologic response to therapy and died eight months after AL-amyloidosis was confirmed by renal biopsy.
A 71-year-old woman was investigated for a one-year history of deteriorating dyspnoea on a background of well-controlled asthma. Other co-morbidities included cutaneous systemic lupus erythematosus, rheumatoid arthritis and Sjogren’s syndrome. High-resolution computerised tomography (HRCT) showed multiple cysts, solid nodules and aggregate masses – the largest (2 × 1.5 cm) in the peripheral left lower lobe with fine-needle aspiration suggestive of amyloid. Serum biochemistry showed a polyclonal elevation of IgG, no detectable monoclonal band and normal serum-free light chains. Immunohistochemistry showed no specific staining for kappa or lambda antibodies. Mass spectrometry was not performed. Echocardiography excluded cardiac involvement and no visceral uptake by 123I SAP scintigraphy. Pulmonary function tests demonstrated a restrictive pattern, and a further HRCT raised suspicion of lymphocytic interstitial pneumonitis. FDG-PET/CT demonstrated similar low-grade uptake in all lung nodules (). A mini-thoracotomy was performed to obtain tissue from the largest nodule showing evidence of amyloid but too few infiltrating cells were present to confirm clonality.\nA low-grade lymphoplasmocytic lymphoma (LPL) was presumed to be driving the pulmonary amyloid, based on the assumption of low-grade B-cell clonal disorders that can occur with Sjogren’s syndrome. A trial of R-CVP (Rituximab – Cyclophoshamide, Vincristine, Prednisolone) chemotherapy was commenced for four months resulting in no progression of symptoms and stable lesions.