Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (383 page)

Middle-aged (median age 64) male patients with clinical or laboratory findings of MGUS, PCM, or Waldenström macroglobulinemia. Common clinical manifestations include edema due to cardiac failure (restrictive cardiomyopathy) and nephrotic syndrome, malabsorption, macroglossia, hepatomegaly, purpura, bone pain, peripheral neuropathy, and carpal tunnel syndrome. Bleeding diathesis may be seen due to increased fragility of blood vessels resulting from amyloid deposition, in combination with factor X deficiency (due to binding to amyloid fibrils), decreased synthesis of clotting factors, or acquired von Willebrand disease.

   Laboratory Findings

   Confirmation and typing of amyloid are essential to initiate type-specific treatment. These are achieved by sophisticated techniques that may not be available in a routine clinical practice.

   
Bone marrow biopsy and aspirate
: Evidence of overt myeloma or lymphoplasmacytic lymphoma along with replacement by amyloid is seen. β sheets stain pink with Congo red. New technologies (e.g., tandem mass spectrometry–based proteomic analysis) for the typing of amyloidosis in biopsy specimens are being developed.

   
Tissue biopsy of involved organs
, for example, kidney or liver, have the highest yield in showing amyloid deposition in specific locations. The most accessible site is periumbilical fat. The diagnosis is established by demonstrating amyloid deposition by Congo red staining. LCCD is negative for Congo red staining but positive for anti-κ or anti-λ antibody staining. Secondary amyloidosis (AA) is negative for both.

   
CBC
: Usually rouleaux formation (due to paraproteinemia) may be seen.

   Hypogammaglobulinemia may be present.

   
Immunofixation
reveals a monoclonal light chain (λ in 70% cases) in nearly 90% of cases. By contrast, serum protein electrophoresis demonstrates a localized band in <50% of patients with AL amyloidosis.

   
Urine protein electrophoresis and immunofixation
demonstrate M protein (Bence Jones protein), which is composed of urine light chains. Secretion of λ light chain is associated with poor prognosis.

   
Serum free light chain immunoassay
: Altered κ:λ ratio is present in PA.

   
Renal function tests
may be abnormal in cases of monoclonal light chain proteinuria. Urine albumin should be assessed regularly in patients with MGUS or plasma cell myeloma considered at risk to develop amyloidosis. Increased serum creatinine is associated with poor prognosis.

   NT-proBNP, cardiac troponin-T, and echocardiography are tests of choice in the early detection and staging with respect to heart involvement in patients predisposed to amyloidosis.

   
Immunophenotype
: Plasma cell immunophenotype is similar to that of PCM and MGUS.