A patient presented with nephrotic range proteinuria and lung cancer, so we performed a routine kidney biopsy. During our pathology conference, we discussed a classic run-of-the mill case of membranous nephropathy secondary to malignancy. Our pathologist showed us the silver stain slide, as we typically do for most membranous cases. We reviewed the formation of the classic membranous “spikes” and thickening of the basement membrane – but then we noticed something unusual.
The podocytes seemed to have dark clusters of spots inside of them. The silver stain, or Jones stain, is a methenamine silver-Periodic-acid-Schiff stain that pathologists use to to stain collagen so the basement membrane can be visualized. What could be inside the podocytes that would stain in a similar pattern as the basement membrane?
The electron microscopy (EM) had the answer: “zebra bodies”! Zebra bodies, or myelin-like, lamellar bodies, are intralysosomal inclusion bodies that suggest kidney phospholipidosis (KPL). KPL is the accumulation of phospholipids within any type of kidney cell, including mesangial cells, glomerular endothelial cells, podocytes, or tubular cells.
We typically think of the inherited, X-linked Fabry disease (FD) when we see zebra bodies. In addition to kidney involvement, affected individuals can experience acute pain crises, gastrointestinal symptoms, cerebrovascular, and cardiovascular abnormalities. Any female with consistent pathology or symptoms suggestive of FD should have genetic testing while males can be diagnosed simply by measuring plasma or leukocyte levels of ?-galactosidase A.
Interestingly KPL can be either hereditary (like FD) or drug-induced. Both hereditary and drug-induced KPL share the reduced activity of lysosomal phospholipases and can be indistinguishable by histology. Cation amphiphilic drugs are able to directly interact with phospholipids and accumulate within the acidic environment of the lysosome.
Commonly used medications that can lead to KPL include:
Though our patient was not on one of the medications most commonly associated with drug-induced KPL, he was on a statin – which has been associated with phospholipidosis of the lung.
If you find a herd of zebra bodies, check the medication list before you make a new diagnosis of Fabry disease!
Samira Farouk, MD
NSMC Intern 2018
Chief Fellow, Division of Nephrology
Icahn School of Medicine at Mount Sinai