Multiorgan Distribution of Gadolinium Deposits at Autopsy in Nephrogenic Systemic Fibrosis (NSF)
S Sanyal, P Marckmann, S Scherer, JL Abraham. SUNY Upstate Medical University, Syracuse, NY; Odense University, Odense, Denmark; Herlev Hospital, Herlev, Denmark
Background: Initially recognized as a fibrosing dermopathy, the multitude of organs involved in NSF was first identified in 2003. Epidemiologic studies implicated Gadolinium (Gd) from MRI contrast agents as a trigger for the development of NSF, and scanning electron microscopy (SEM) with energy dispersive x-ray analysis (EDS) demonstrated insoluble Gd deposition in lesional skin. Until now, there have been only limited studies examining the distribution of Gd in tissues apart from skin.
Design: To evaluate the tissue distribution, correlation with histopathology and relative amounts of Gd in various organs in a case of NSF, freshly cut paraffin block surfaces of autopsy tissues were examined under standardized conditions using the variable pressure mode of the SEM. This allows detection and multi-elemental EDS analysis of Gd-containing deposits in situ in tissues, and also semi-quantitative morphometric analysis with a spatial resolution of less than 1 m.
Results: Gd was present in skin, skeletal muscle, lung, kidney, lymph node, liver, intestine, dura mater and the cerebellum. It was present in the form of insoluble hydroxyapatite-like deposits. These deposits had Ca, P, Na and sometimes Fe. In the skeletal muscle these deposits were associated with Zn and in the cerebellum, many of these deposits additionally contained K. Although the location of Gd was predominantly in the vascular walls of all organs, these deposits were also found in the parenchyma of the organs, in between muscle bundles, around fat compartments, in the alveolar septa, in the basement membrane of renal tubules and in and around hepatocytes. Gadolinium deposits could not be demonstrated in heart, major blood vessels (aorta, superior vena cava), bone, bone marrow, pons, corpus striatum, thalamus. Highest amounts of Gd were found in affected skin, skeletal muscle, lymph node and dura mater. Lungs, kidney and liver had moderate amounts and unaffected skin, intestine and cerebellum had relatively low quantities of Gadolinium.
Conclusions: The widespread deposition of Gd in tissues and organs supports the systemic nature of NSF. Gd undergoes transmetallation and deposits as hydroxyapatite-like particles. The composition of these particles can vary according to the local milieu of the tissue including the inflammatory state. We could not demonstrate Gd in decalcified bone, from which Gd-containing deposits may have been dissolved.
Monday, March 9, 2009 9:30 AM
Poster Session I Stowell-Orbison/Autopsy Award # 9, Monday Morning