Faculty Bibliography

It has been shown in animal models that hepatocytes and cholangiocytes can derive from bone marrow cells. We have investigated whether such a process occurs in humans. Archival autopsy and biopsy liver specimens were obtained from 2 female recipients of therapeutic bone marrow transplantations with male donors and from 4 male recipients of orthotopic liver transplantations from female donors. Immunohistochemical staining with monoclonal antibody CAM5.2, specific for cytokeratins 8, 18, and 19, gave typical strong staining of hepatocytes, cholangiocytes, and ductular reactions in all tissues, to the exclusion of all nonepithelial cells. Slides were systematically photographed and then restained by fluorescence in situ hybridization (FISH) for X and Y chromosomes. Using morphologic criteria, field-by-field comparison of the fluorescent images with the prior photomicrographs, and persistence of the diaminiobenzidene (DAB) stain through the FISH protease digestion, Y-positive hepatocytes and cholangiocytes could be identified in male control liver tissue and in all study specimens. Cell counts were adjusted based on the number of Y-positive cells in the male control liver to correct for partial sampling of nuclei in the 3-micron thin tissue sections. Adjusted Y-positive hepatocyte and cholangiocyte engraftment ranged from 4% to 43% and from 4% to 38%, respectively, in study specimens, with the peak values being found in a case of fibrosing cholestatic recurrent hepatitis C in one of the liver transplant recipients. We therefore show that in humans, hepatocytes and cholangiocytes can be derived from extrahepatic circulating stem cells, probably of bone marrow origin, and such 'transdifferentiation can replenish large numbers of hepatic parenchymal cells

Cirrhosis is a progressive, diffuse process of liver fibrosis that is characterized by architectural distortion and the development of a spectrum of nodules ranging from benign regenerative nodules to premalignant dysplastic nodules to overtly malignant hepatocellular carcinoma. The purpose of this essay is to demonstrate the ex vivo MR and pathology findings of these nodules as well as other masses that can be seen in the cirrhotic liver. The optimal conditions under which ex vivo imaging can be performed allow greater spatial resolution than that achieved with in vivo imaging, without artifacts that may degrade image quality. Clearly, contrast-enhanced MRI is essential for both the diagnosis and the characterization of focal lesions in the cirrhotic liver. However, the use of ex vivo imaging precludes the evaluation of these important in vivo pulse sequences

OBJECTIVE: To determine if iron containing 'siderotic' nodules detected at magnetic resonance (MR) imaging are regenerative (RN) or dysplastic (DN) and to attempt to identify features that may distinguish them. MATERIAL AND METHODS: MR imaging (1.5 T) was performed on 77 cirrhotic patients who underwent orthotopic liver transplantation within 0-117 days (mean 30 days) of MR imaging. Two readers retrospectively evaluated breath-hold gradient-echo pulse sequences (echo time > or =9.0 ms, flip angle < or =45 degrees) for the presence of hypointense nodules, which were classified as micronodular (< or =3 mm), macronodular (>3 mm), or mixed. Nodule distribution was classified as focal (<5), scattered (5-20), or diffuse (>20) per slice. Thin section pathologic correlation was available in all cases, and Prussian blue iron stains were performed. RESULTS: Of 35 patients with pathologically proven siderotic nodules, 10 (29%) had at least 2 siderotic DN. MR detected siderotic nodules in 10 of 10 (100%) patients with siderotic DN and RN, and in 18 of 25 patients (72%) with siderotic RN only. CONCLUSION: Siderotic RN cannot be reliably distinguished from siderotic DN with MR imaging, and therefore the widely used term 'siderotic regenerative nodule' should be avoided and replaced by 'siderotic nodule.'