Strong transthyretin immunostaining: Potential pitfall in cardiac amyloid typing

Anjali A. Satoskar, Yvonne Efebera, Ayesha Hasan, Sergey Brodsky, Gyongyi Nadasdy, Ahmet Dogan, Tibor Nadasdy

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

Although systemic amyloidosis commonly presents with renal disease, cardiac involvement usually determines the patient's prognosis. Cardiac involvement is seen in light chain amyloid and transthyretin amyloidosis. Distinguishing between these two is critical because prognosis and treatment differ. Our study demonstrates the unreliability of transthyretin immunostaining in subtyping cardiac amyloid. Between January 2003 and August 2010, we retrieved 229 native endomyocardial biopsies, of which 24 had amyloid. Immunohistochemistry for κ, λ, transthyretin, and serum amyloid A protein was performed on formalin-fixed, paraffin-embedded sections. Staining was graded as weak (trace to 1+) or strong (2 to 3+). Mass spectrometry (MS)-based proteomic typing of microdissected amyloid material was performed on selected cases. Fifteen patients had monoclonal gammopathy/plasma cell dyscrasia with cardiac amyloid. Eight of them (53%) showed strong transthyretin staining in the cardiac amyloid deposits. MS was performed in 5 of these 8 biopsies, and all 5 biopsies revealed light chain amyloid-type amyloid. Two of these 5 light chain amyloid biopsies did not even have concomitant strong staining for the appropriate light chain. Among the 15 cases with plasma cell dyscrasia, only 7 biopsies showed strong staining for the corresponding monoclonal light chain. Strong, false-positive immunostaining for transthyretin in cardiac amyloid is a potential pitfall, 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 plasma cell dyscrasia irrespective of transthyretin staining. Confirmation with MS should be sought, particularly if there is any discrepancy between κ/λ staining and serum immunofixation results.

Original languageEnglish (US)
Pages (from-to)1685-1690
Number of pages6
JournalAmerican Journal of Surgical Pathology
Volume35
Issue number11
DOIs
StatePublished - Nov 2011

Fingerprint

Prealbumin
Amyloid
Paraproteinemias
Staining and Labeling
Biopsy
Light
Mass Spectrometry
Immunoglobulin Light Chains
Serum Amyloid A Protein
Amyloid Plaques
Amyloidosis
Paraffin
Proteomics
Formaldehyde
Heart Diseases
Immunohistochemistry
Kidney

Keywords

  • cardiac amyloid
  • immunohistochemistry
  • transthyretin

ASJC Scopus subject areas

  • Anatomy
  • Pathology and Forensic Medicine
  • Surgery

Cite this

Satoskar, A. A., Efebera, Y., Hasan, A., Brodsky, S., Nadasdy, G., Dogan, A., & Nadasdy, T. (2011). Strong transthyretin immunostaining: Potential pitfall in cardiac amyloid typing. American Journal of Surgical Pathology, 35(11), 1685-1690. https://doi.org/10.1097/PAS.0b013e3182263d74

Strong transthyretin immunostaining : Potential pitfall in cardiac amyloid typing. / Satoskar, Anjali A.; Efebera, Yvonne; Hasan, Ayesha; Brodsky, Sergey; Nadasdy, Gyongyi; Dogan, Ahmet; Nadasdy, Tibor.

In: American Journal of Surgical Pathology, Vol. 35, No. 11, 11.2011, p. 1685-1690.

Research output: Contribution to journalArticle

Satoskar, AA, Efebera, Y, Hasan, A, Brodsky, S, Nadasdy, G, Dogan, A & Nadasdy, T 2011, 'Strong transthyretin immunostaining: Potential pitfall in cardiac amyloid typing', American Journal of Surgical Pathology, vol. 35, no. 11, pp. 1685-1690. https://doi.org/10.1097/PAS.0b013e3182263d74
Satoskar, Anjali A. ; Efebera, Yvonne ; Hasan, Ayesha ; Brodsky, Sergey ; Nadasdy, Gyongyi ; Dogan, Ahmet ; Nadasdy, Tibor. / Strong transthyretin immunostaining : Potential pitfall in cardiac amyloid typing. In: American Journal of Surgical Pathology. 2011 ; Vol. 35, No. 11. pp. 1685-1690.
@article{3acfd0f3547847b99d3dca2d87bab17f,
title = "Strong transthyretin immunostaining: Potential pitfall in cardiac amyloid typing",
abstract = "Although systemic amyloidosis commonly presents with renal disease, cardiac involvement usually determines the patient's prognosis. Cardiac involvement is seen in light chain amyloid and transthyretin amyloidosis. Distinguishing between these two is critical because prognosis and treatment differ. Our study demonstrates the unreliability of transthyretin immunostaining in subtyping cardiac amyloid. Between January 2003 and August 2010, we retrieved 229 native endomyocardial biopsies, of which 24 had amyloid. Immunohistochemistry for κ, λ, transthyretin, and serum amyloid A protein was performed on formalin-fixed, paraffin-embedded sections. Staining was graded as weak (trace to 1+) or strong (2 to 3+). Mass spectrometry (MS)-based proteomic typing of microdissected amyloid material was performed on selected cases. Fifteen patients had monoclonal gammopathy/plasma cell dyscrasia with cardiac amyloid. Eight of them (53{\%}) showed strong transthyretin staining in the cardiac amyloid deposits. MS was performed in 5 of these 8 biopsies, and all 5 biopsies revealed light chain amyloid-type amyloid. Two of these 5 light chain amyloid biopsies did not even have concomitant strong staining for the appropriate light chain. Among the 15 cases with plasma cell dyscrasia, only 7 biopsies showed strong staining for the corresponding monoclonal light chain. Strong, false-positive immunostaining for transthyretin in cardiac amyloid is a potential pitfall, 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 plasma cell dyscrasia irrespective of transthyretin staining. Confirmation with MS should be sought, particularly if there is any discrepancy between κ/λ staining and serum immunofixation results.",
keywords = "cardiac amyloid, immunohistochemistry, transthyretin",
author = "Satoskar, {Anjali A.} and Yvonne Efebera and Ayesha Hasan and Sergey Brodsky and Gyongyi Nadasdy and Ahmet Dogan and Tibor Nadasdy",
year = "2011",
month = "11",
doi = "10.1097/PAS.0b013e3182263d74",
language = "English (US)",
volume = "35",
pages = "1685--1690",
journal = "American Journal of Surgical Pathology",
issn = "0147-5185",
publisher = "Lippincott Williams and Wilkins",
number = "11",

}

TY - JOUR

T1 - Strong transthyretin immunostaining

T2 - Potential pitfall in cardiac amyloid typing

AU - Satoskar, Anjali A.

AU - Efebera, Yvonne

AU - Hasan, Ayesha

AU - Brodsky, Sergey

AU - Nadasdy, Gyongyi

AU - Dogan, Ahmet

AU - Nadasdy, Tibor

PY - 2011/11

Y1 - 2011/11

N2 - Although systemic amyloidosis commonly presents with renal disease, cardiac involvement usually determines the patient's prognosis. Cardiac involvement is seen in light chain amyloid and transthyretin amyloidosis. Distinguishing between these two is critical because prognosis and treatment differ. Our study demonstrates the unreliability of transthyretin immunostaining in subtyping cardiac amyloid. Between January 2003 and August 2010, we retrieved 229 native endomyocardial biopsies, of which 24 had amyloid. Immunohistochemistry for κ, λ, transthyretin, and serum amyloid A protein was performed on formalin-fixed, paraffin-embedded sections. Staining was graded as weak (trace to 1+) or strong (2 to 3+). Mass spectrometry (MS)-based proteomic typing of microdissected amyloid material was performed on selected cases. Fifteen patients had monoclonal gammopathy/plasma cell dyscrasia with cardiac amyloid. Eight of them (53%) showed strong transthyretin staining in the cardiac amyloid deposits. MS was performed in 5 of these 8 biopsies, and all 5 biopsies revealed light chain amyloid-type amyloid. Two of these 5 light chain amyloid biopsies did not even have concomitant strong staining for the appropriate light chain. Among the 15 cases with plasma cell dyscrasia, only 7 biopsies showed strong staining for the corresponding monoclonal light chain. Strong, false-positive immunostaining for transthyretin in cardiac amyloid is a potential pitfall, 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 plasma cell dyscrasia irrespective of transthyretin staining. Confirmation with MS should be sought, particularly if there is any discrepancy between κ/λ staining and serum immunofixation results.

AB - Although systemic amyloidosis commonly presents with renal disease, cardiac involvement usually determines the patient's prognosis. Cardiac involvement is seen in light chain amyloid and transthyretin amyloidosis. Distinguishing between these two is critical because prognosis and treatment differ. Our study demonstrates the unreliability of transthyretin immunostaining in subtyping cardiac amyloid. Between January 2003 and August 2010, we retrieved 229 native endomyocardial biopsies, of which 24 had amyloid. Immunohistochemistry for κ, λ, transthyretin, and serum amyloid A protein was performed on formalin-fixed, paraffin-embedded sections. Staining was graded as weak (trace to 1+) or strong (2 to 3+). Mass spectrometry (MS)-based proteomic typing of microdissected amyloid material was performed on selected cases. Fifteen patients had monoclonal gammopathy/plasma cell dyscrasia with cardiac amyloid. Eight of them (53%) showed strong transthyretin staining in the cardiac amyloid deposits. MS was performed in 5 of these 8 biopsies, and all 5 biopsies revealed light chain amyloid-type amyloid. Two of these 5 light chain amyloid biopsies did not even have concomitant strong staining for the appropriate light chain. Among the 15 cases with plasma cell dyscrasia, only 7 biopsies showed strong staining for the corresponding monoclonal light chain. Strong, false-positive immunostaining for transthyretin in cardiac amyloid is a potential pitfall, 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 plasma cell dyscrasia irrespective of transthyretin staining. Confirmation with MS should be sought, particularly if there is any discrepancy between κ/λ staining and serum immunofixation results.

KW - cardiac amyloid

KW - immunohistochemistry

KW - transthyretin

UR - http://www.scopus.com/inward/record.url?scp=80054995001&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80054995001&partnerID=8YFLogxK

U2 - 10.1097/PAS.0b013e3182263d74

DO - 10.1097/PAS.0b013e3182263d74

M3 - Article

C2 - 21945954

AN - SCOPUS:80054995001

VL - 35

SP - 1685

EP - 1690

JO - American Journal of Surgical Pathology

JF - American Journal of Surgical Pathology

SN - 0147-5185

IS - 11

ER -