A man with sickle cell disease with generalized pain and progressive jaundice originally thought to have cholangiocarcinoma was eventually found to have Rosai-Dorfman disease, researchers report in the February issue of Clinical Gastroenterology and Hepatology.
Arian Teymoorian et al describe the case of a 38-year-old black man with a history of sickle cell disease with jaundice and worrisome laboratory test results, including a total bilirubin level of 37 mg/dL, direct bilirubin level above 20 mg/dL, alkaline phosphatase level of 1004 U/L, alanine aminotransferase level of 226 U/L, and aspartate aminotransferase level of 170 U/L. His level of gamma-glutamyltransferase was 745 U/L, white blood cell count was 15.3 × 109/L, hemoglobin level was 9.4 g/dL, hematocrit was 26.6%, and platelet count was 550 × 109/L.
The patient had normal levels of CA 19-9, carcinoembryonic antigen, and alpha fetoprotein, and normal findings from coagulation studies.
Liver biopsy analysis showed sinusoidal obstruction that was due to sickled red blood cells in zone 2, transfusion hemosiderosis of grade 3/4, and a centrilobular cholestasis without portal tract changes or any large duct obstruction. The patient had no evidence of cirrhosis.
An MRI scan showed a 2.5 x 2.0 cm enhancing mass at the porta hepatitis, causing mild to moderate intrahepatic biliary dilatation that affected both the right and left hepatic ducts,
Endoscopic retrograde cholangiopancreatography (ERCP) revealed biliary obstruction at the confluence. Brush cytology analysis revealed only honeycombed sheets of ductal epithelial cells, without atypia or malignant cells. Stent placement in the right and left hepatic ducts provided partial relief of the patient’s obstructive jaundice and reduced levels of bilirubin.
An exploratory laparotomy revealed dense inflammation in the porta hepatis that extended into the intrahepatic right anterior and posterior sectoral ducts. A mass completely encased the right and left hepatic arteries was found; it was biopsied, and an abnormal portal node was removed. Pathology examination of the node revealed a focal, pronounced dilation of lymphatic sinuses—within it were numerous histiocytes. Then, within these histiocytes were numerous intact lymphocytes—a histologic hallmark of Rosai-Dorfman disease (see figure for S100 staining).
Rosai-Dorfman disease is a rare histiocytic disorder that involves over-production of non-Langerhans sinus histiocytes. These cells then accumulate—most often in the lymph nodes but also in other areas of the body—which can lead to organ damage. It is not clear why these cells are over-produced; viral, bacterial, infection, environmental, and genetic causes have been proposed.
Teymoorian et al explain that Rosai-Dorfman disease typically manifests in men in their 20s–40s. It can affect almost any organ system, but intra-abdominal organ involvement is rare. Rosai-Dorfman disease is generally thought to be a benign disease, and many patients do not require treatment, although patients with symptoms can require surgery.
The patient in this report had persistent disease, including continued obstructive jaundice (thought to be a result of prolonged biliary stasis and stricture formation), despite long-term use of prednisone. He therefore underwent ERCP with stent placement periodically for biliary decompression, and had mild improvements in levels of bilirubin.
Teymoorian et al state that this case showed how a well-known condition such as sickle cell hepatopathy can delay the appropriate diagnosis of a comorbid condition. The similarities with cholangiocarcinoma prompted further investigation by surgical exploration, which led to the correct diagnosis. The relationship between sickle cell hepatopathy and/or sickle cell disease with Rosai-Dorfman disease is not well-understood.