Cardiac Pathology in Nephrogenic Systemic Fibrosis: Correlative Histopathology and Gadolinium Analysis Using Scanning Electron Microscopy/Energy Dispersive X-Ray Spectroscopy.
Richard L Davis, Daniel Xia, Jerrold L Abraham. SUNY Upstate Medical University, Syracuse, NY
Background: Nephrogenic systemic fibrosis (NSF) is a skin and frequently systemic fibrosing disorder seen in patients with impaired renal function, related to Gadolinium (Gd) release from its chelated form in MRI contrast agents. Little is known about the cardiac pathology of NSF. We review cardiac findings in 11 NSF autopsy cases sent to our lab for review and multi-organ Gd analysis.
Design: Autopsy slides containing myocardial tissue were reviewed for consensus grading of pattern and extent of calcification, fibrosis, and other findings. Analyses of tissues in situ in paraffin blocks using variable pressure scanning electron microscopy and energy-dispersive x-ray spectroscopy (SEM/EDS) were done by one pathologist (RLD).
Results: Patients ages range from 41-80 (median 64) yr., with 5 women, 6 men. The only consistent histopathologic findings in the hearts in these NSF autopsies are vascular calcification and interstitial myocardial fibrosis. Some cases also show calcification in cardiomyocytes. Gd deposition was detected in hearts of 11 of 11 cases examined to date using SEM/EDS. Gd-containing deposits are confirmed in vascular calcification as well as in interstitial fibrotic areas, including in fibrocytes. In some cases, the Gd-containing deposits are visible by light microscopy (confirmed by correlative LM-SEM/EDS analysis; see Figure 1). As in all tissues in NSF cases analyzed to date, the Gd deposits in cardiac tissues are in the form of insoluble Gd-phosphate-calcium compounds.
Figure 1. Myocardium, H&E showing tiny basophilic deposits in cardiomyocytes and interstitium (top left); backscattered electron SEM image of corresponding area in paraffin block with dark deposits of higher atomic number (top right); EDS spectrum collected from one of dark deposits shows peaks for Gd, Ca, P, Na (bottom).
Conclusions: Many of the myocardial changes seen in NSF may be related to tissue calcification, congestive heart failure and other changes common in advanced renal failure. Gd is known to promote formation of calcium-phosphate deposition. Whether NSF promotes more rapid and severe progression of these findings than in renal failure patients without NSF remains in need of further investigation.
Wednesday, March 2, 2011 1:00 PM
Poster Session VI # 28, Wednesday Afternoon