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 64-year-old man presented with an incidental right lung mass on chest X-ray. Mediastinoscopy and lymph node biopsy confirmed amyloid, remaining asymptomatic until four years later, developing exertional dyspnoea matched by significant increase of the mass by chest radiography. Basic laboratory evaluation and immunohistochemistry was unremarkable. Immunoelectrophoresis revealed a faint immunoglobulin G (IgG) kappa band. No mass spectrometry was performed. Colonic biopsy, bone marrow aspirate, immunophenotyping and trephine were normal. 123I Serum amyloid P-component (SAP) scintigraphy showed abnormal uptake within the mass only. Computerised tomography (CT) revealed mediastinal and hilar lymphadenopathy, with a 9.5 × 6.5 × 10 cm right mediastinal mass containing fat and calcification with a radiological differential diagnosis of a teratoma. F-18 fluorodeoxyglucose (FDG)-Positron Emission Tomography (PET)/CT demonstrated intermediate to high-grade uptake within the soft tissue and low-grade uptake in the fatty component (). Cardiac magnetic resonance imaging excluded cardiac involvement. Repeat core biopsy demonstrated fibrovascular tissue with focal amyloid deposition. The patient proceeded to surgical mass de-bulking for diagnosis and symptom relief and histology confirmed evidence of amyloid. The patient’s postoperative course was uneventful; no evidence of recurrence three months following surgery and marked symptomic improvement, with disappearance of the IGgk paraprotein following resection, currently planned for local consolidation radiotherapy.