12 May 2010 – Case of the Week #178
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- Dr. Elaine Alt: Low grade dysplasia in ulcerative colitis / pancolitis for the Colon chapter
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Case of the Week #178
A 69 year old obese woman with metastatic pancreatic carcinoma to the liver underwent a diagnostic renal core biopsy for work-up due to three to four months of nephrotic syndrome, with proteinuria increasing from 6 to 12 grams per 24 hours. Her urinary sediment was bland and she had negative serologic studies. The clinical differential diagnosis included membranous glomerulonephritis, minimal change disease, light chain deposition disease and amyloidosis. Her chemotherapeutic regimen included gemcitabine.
What is your diagnosis?
Thrombotic microangiopathy due to gemcitabine therapy
The classic features of thrombotic microangiopathy are present, including fibrin thrombi in arterioles and capillaries, including glomerular capillaries. Immunofluorescence studies were negative for immunoglobulin deposition, and ultrastructural analysis revealed moderate effacement of foot processes and subendothelial fibrin deposition, as well as endothelial swelling. No immune complex type deposits were noted.
Gemcitabine, a nucleoside analog, is used to treat metastatic pancreatic carcinoma as well as many other malignancies. Thrombotic microangiopathy may occur, with rates varying from the manufacturer stated incidence of 0.015% to 1.4% (Expert Opin Drug Saf 2009;8:257, Cancer 2004;100:2664). Diagnosis is often difficult due to the underlying advanced malignancy, and often requires renal biopsy.
Treatment includes cessation of gemcitabine therapy, which was effective in this case. Antihypersensitive medications, plasma exchange therapy (Z Gastroenterol 2009;47:288), or immunoadsorption columns may also be helpful.
The current case is unusual in its presentation with nephrotic syndrome, as most patients present with increasing creatinine, hemolytic anemia, hypertension and thrombocytopenia.
Nat Pernick, M.D., President,
and Kara Hamilton, M.S., Associate Medical Editor
30100 Telegraph Road, Suite 408
Bingham Farms, Michigan (USA) 48025
Alternate email: NatPernick@gmail.com