[323] Strong Tranthyretin (Prealbumin) Immunostaining in Cardiac Amyloid Deposits, a Potential Pitfall for Surgical Pathologists.

Anjali A Satoskar, Yvonne Efebera, Ayesha Hasan, Sergey Brodsky, Ahmet Dogan, Tibor Nadasdy. The Ohio State University, Columbus; Mayo Clinic, Rochester, MN

Background: Although systemic amyloidosis often presents first with renal disease, cardiac involvement usually determines the patient's prognosis. Heart involvement is common in AL type and transthyretin (ATTR) amyloidosis, and distinguishing between these two types is critical because prognosis and treatment differ greatly. Our study demonstrates the unreliability of transthyretin immunostaining in cardiac amyloid typing, even if it is strongly positive.
Design: From January 2003 to August 2010, we retrieved 229 native endomyocardial biopsies, out of which 24 were diagnosed as cardiac amyloidosis. Immunohistochemistry for kappa and lambda light chains, transthyretin (prealbumin) and serum amyloid A protein were performed on formalin fixed paraffin-embedded tissue sections. The staining of the amyloid deposits was graded as weak (trace to 1+); or strong (2 to 3+). Mass spectrometry (MS) based proteomic typing of microdissected amyloid plaques was performed on selected cases.
Results: Fifty-three percent (8/15) patients with monoclonal gammopathy/plasma cell dyscrasia showed strong transthyretin staining in the cardiac amyloid deposits (Table 1).

Table 1. Strong TTR and light chain staining in cardiac amyloid deposits.
 Strong TTR staining presentStrong light chain staining presentBoth TTR and light chain staining strong
MG/PD present (n=15)864
MG/PD absent (n=8)633
No followup (n=1)100
TTR=transthyretin; MG=monoclonal gammopathy; PD=plasma cell dyscracia

MS was performed in five out of these 8 cases with strong transthyretin staining, and all five revealed AL type amyloid. Three of the confirmed cases, did have concomitant strong staining for kappa or lambda light chain, but two did not stain for light chains. Among the 15 cases with plasma cell dyscrasia, only six biopsies showed strong staining for the corresponding monoclonal light chain.
Conclusions: Strong false positive staining for transthyretin is a potential pitfall in subtyping cardiac amyloid, augmented by the frequent lack of staining for immunoglobulin light chains. Therefore, the presence of amyloid in the cardiac biopsy should prompt a search for possible plasma cell dyscrasia despite strong transthyretin positivity by immunostaining. Confirmation with MS should be sought if there is any discrepancy between kappa/lambda staining and serum immunofixation results.
Category: Cardiovascular

Wednesday, March 2, 2011 1:00 PM

Poster Session VI # 32, Wednesday Afternoon


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