Pitfalls in the Diagnosis of Primary Amyloidosis

Cheng E. Chee; Martha Q. Lacy; Ahmet Dogan; Steven R. Zeldenrust; Morie A. Gertz

Disclosures

Clin Lymphoma Myeloma. 2010;10(3):177-180. 

In This Article

Case 1

Patient A is a 74-year-old white man who presented with weight loss, increasing peripheral edema, and worsening dyspnea. He was diagnosed with congestive heart failure 2 months before his evaluation at our institution. Symptoms included paresthesias in his feet for the past 2 years. Medical history was significant for B-cell chronic lymphocytic leukemia (CLL), which was diagnosed 7 years earlier and treated with fludarabine. He had carpal tunnel surgery 2 years prior, in which pathology revealed amyloid.

Evaluation

Laboratory studies at our institution were as follows: hemoglobin, 13.5 g/dL (normal, 13.5–17.5 g/dL); normal albumin, carotene, kidney, and liver function, factor X activity, and 24-hour urine protein; troponin T, 0.04 ng/mL (normal, < 0.01 ng/mL); N-terminal probrain natriuretic peptide (NT-proBNP), 3562 pg/mL (normal, ≤ 110 pg/mL); small monoclonal immunoglobulin (Ig)G λ on serum and urine immunofixation without a visible peak on electrophoresis; normal κ/λ FLC ratio, 0.36 (normal, 0.26–1.65); β2-microglobulin, 6.23 μg/mL (normal, 0.7–1.8 μg/mL). Transthoracic echocardiogram showed increased concentric left ventricular wall thickness, increased right ventricular wall thickness, grade 3/4 left ventricular diastolic dysfunction with an ejection fraction of 44%, and increased ventricular septum was thickness of 18 mm (normal, 10–13 mm). Fat aspirate was negative for amyloid. Bone marrow biopsy and aspirate showed B-cell CLL, and Congo red staining confirmed amyloid in the dense connective tissue. A clonal small lymphocytic population was identified. Liquid chromatography tandem mass spectrometry (LC MS/MS) was performed on peptides extracted from Congo red–positive, microdissected areas of paraffin-embedded bone marrow tissue, and a peptide profile consistent with TTR-type amyloid deposition was detected. Because the type of amyloid had been determined, cardiac biopsy was not pursued, which avoided unnecessary risk from the procedure. Transthyretin DNA sequencing studies were negative. No treatment was recommended for treatment of his amyloidosis.

Discussion

Patient A had normal (wild-type) TTR amyloidosis, also known as senile systemic amyloidosis (SSA). Our initial clinical impression, based on the λ light chain elevation, the clonal B-cell proliferative disorder, and consistent echocardiogram findings, was that this was AL λ amyloidosis with cardiac involvement and that systemic chemotherapy for the underlying CLL was the best way to prevent further cardiac amyloid deposition.

In SSA, the amyloid protein preferentially accumulates in cardiac ventricles of elderly patients, and echocardiographic findings may be similar to those found in patients with AL amyloidosis.[4] The extent of amyloid infiltration in the myocardium in TTR amyloidosis can produce septal thickness in excess of 20 mm, which is a rare finding in cardiac AL amyloidosis as patients would have died when the amyloid deposition became that extensive.[5] Patients might present with arrhythmia, congestive heart failure, and/or restrictive cardiomyopathy. Typical amyloid deposits are found on endomyocardial biopsy, and they tend to exhibit strong immunohistochemical staining with TTR, but no mutation is found with TTR gene sequencing.[6] No plasma cell disorder is identified, and overall survival in patients with SSA is better than that in patients with AL amyloidosis. No specific treatment is available; chemotherapy or stem cell transplantation is contraindicated in the management Chemotherapy in this patient would have been ineffective and potentially harmful.

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