Pathology of the liver in mucopolysaccharidosis: light and electron microscopic assessment before and after bone marrow transplantation.

Serial liver biopsies were obtained in 20 patients undergoing bone marrow transplantation (BMT) for mucopolysaccharidosis (MPS). The 13 patients with MPS I, one with MPS II, four with MPS III, and two with MPS VI underwent liver biopsy prior to and from 1 to 37 months after BMT. The amount of accumulated glycosaminoglycan (GAG) was assessed by semiquantitation of Kupffer cell staining with colloidal iron and by counting the number of hepatocellular GAG-containing lysosomes in electron micrographs. Eleven of 13 patients with MPS I achieved engraftment, and 10 of the 11 cleared the Kupffer cells and hepatocytes of GAG by 3 to 19 months post-BMT. Two patients with autologous recovery demonstrated persistent hepatocyte inclusions. The three patients with MPS II and MPS VI engrafted and showed clearance of hepatocyte and Kupffer cell GAG by 7 months after BMT. All four patients with MPS III engrafted. Although the Kupffer cells in these patients were cleared of GAG by 12 months after BMT, hepatocellular inclusions persisted in all four. For MPS I, II and VI, donor engraftment was associated with resolution of lysosomal storage material in donor-derived Kupffer cells and untransplanted hepatocytes, indicative of transcellular metabolic correction. Failure of hepatocyte clearance in one case of MPS I and all patients with MPS III suggested a diminished capacity of the graft-derived enzyme to enter the hepatocyte lysosomes in these patients.

Intraobserver and interobserver variation in the histopathological assessment of liver allograft rejection. The Liver Transplantation Database (LTD) Investigators.

A study to determine the reproducibility of histopathological findings and diagnoses of rejection was carried out on a series of 42 liver allograft needle biopsy specimens by five pathologists practicing at four liver transplant centers. Pathologists from each of the four centers read each slide independently on two different occasions and were asked to assess 12 histopathological features and render a diagnosis. For all histological variables, the intrarater agreement was higher than the interrater agreement. Moderate to excellent agreement occurred among the pathologists about all histological variables thought to be important in establishing the diagnosis of acute rejection (i.e., portal tract inflammation, subendothelial inflammation and bile duct damage). Other variables such as lobular disarray, bile duct proliferation and particularly arteritis, however, were only fairly or poorly reproducible. Surprisingly, the diagnosis of acute rejection was more reproducible than the individual histopathological findings that were thought to be the basis for the diagnosis. The agreement for the diagnosis of chronic rejection, however, varied according to observer. We noted that relatively inexperienced observers within this group had some difficulties agreeing with more experienced observers in establishing a diagnosis of chronic rejection. These findings demonstrate that the histopathological diagnosis of acute cellular liver allograft rejection is highly reproducible within a group of experienced pathologists and that this diagnosis can be pooled in a common data base with confidence.

Aspergillosis in 25 renal transplant patients. Epidemiology, clinical presentation, diagnosis, and management.

In immunocompromised renal transplant patients, aspergillosis can be a life-threatening opportunistic infection. During an 8-year period, 25 renal transplant recipients at the University of Minnesota Hospitals developed unequivocal invasive aspergillosis that occurred in epidemic-like patterns in immunocompromised patients throughout the hospital. The premortem diagnosis was made in only 14 of the 25 patients. Seventeen patients died, and three of the eight survivors lost their allografts. The prognosis was dependent upon the clinical pattern of illness: three clinical patterns emerged: (1) cavitary lung disease, (2) diffuse pulmonary disease, and (3) central nervous system disease. All patients in the latter two categories died. The best results were with those patients treated with both amphotericin B and excision of cavitary lung lesions. All three patients treated in this manner survived with functioning grafts. Traditionally, sputum cultures have been thought to be unreliable because Aspergillus is a common colonizer of the upper respiratory tract and a contaminant in laboratories. In this study, false positive sputum cultures were common. A positive sputum culture can be helpful, however, all patients with two positive sputum cultures proved to have invasive aspergillosis. In addition, 86% of patients with positive sputum cultures who were clinically ill proved to have invasive infection. Bronchoscopy is a useful technique to follow up a positive sputum culture or investigate negative sputum cultures with typical clinical patterns. Routine bronchoscopy, unfortunately, also yields a high incidence of false positive cultures. Since the use of covered brush bronchoscopy technique, however, no false positive transbronchial cultures have been found. Transbronchial biopsy is a useful adjunct and is proof of the presence of invasive disease when the results are positive. However, false negative results are also found. Overall, the highest diagnostic yield is obtained both with transbronchial lung biopsy and covered brush bronchoscopy culture. All eight patients with both these procedures were correctly identified as having invasive pulmonary aspergillosis.