A 67-year-old male ex-smoker (>20 years) with a 30 pack-year history was investigated for morning cough and clear sputum with no constitutional symptoms and an active lifestyle. Past medical history included chronic obstructive pulmonary disease and ischaemic heart disease. External physical examination was unremarkable. Chest computed tomography (CT) showed a right middle lobe nodule which increased from 11 mm to 16 mm over six months. A positron emission tomography (PET) scan showed low radiolabeled [18F]-2-fluoro-2-deoxy-D-glucose (FDG) uptake with a standardised uptake value (SUV) max of 2.0 and no evidence of metastatic disease (). CT-guided biopsy identified eosinophilic amorphic material, which was Congo red negative, with no definitive diagnosis reached. Due to the volume increase of the suspicious lesion, a right middle lobe lobectomy was performed.
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.