Batts, Kenneth P.

A 59‐year‐old female developed symptoms of graft‐versus‐host disease 3½ weeks after liver transplantation for primary biliary cirrhosis. Symptoms of graft‐versus‐host disease included fever, erythroderma with bullae formation, and mucosal surface ulceration. Donor lymphocytes were present in the peripheral blood. Despite treatment with equine antilymphoblast globulin, steroids and, eventually, cyclosporine withdrawal, she developed neutropenia and succumbed to sepsis. At autopsy, she had marked lymphocyte depletion involving the bone marrow and both native and donor origin lymph nodes. As expected, the liver was normal. The clinical and pathological features were remarkably similar to those of the few other reported cases of graft‐versus‐host disease after liver transplantation and transfusion‐associated graft‐versus‐host disease; therapy is usually ineffective, and progression of disease leads to pancytopenia and death from sepsis.

AimsThe diagnosis of focal nodular hyperplasia (FNH) and the interpretation of glutamine synthetase (GS) staining can be challenging on biopsies. We aimed to evaluate the reproducibility of needle biopsy diagnosis of FNH, the effect of GS immunohistochemistry on FNH diagnosis, and which histological features are most useful for the diagnosis of FNH.Methods and resultsThe study included virtual needle biopsies generated from 75 resection specimens (30 FNHs, 15 hepatocellular adenomas, 15 hepatocellular carcinomas, and 15 non‐lesional liver specimens). Pathologists were reasonably accurate (83.1%) in the diagnosis of FNH with haematoxylin and eosin alone. Ductular reaction and nodularity had the highest sensitivity for a diagnosis of FNH (88.1% and 82.2%, respectively), whereas central scar was the most specific feature (90.6%). The presence of two or more of the classic histological features had 89.6% sensitivity and 86.2% specificity for a diagnosis of FNH. Diagnostic accuracy was significantly higher with the addition of a GS stain. A map‐like GS staining pattern was highly specific (99.3%) for FNH. However, GS staining was interpreted as non‐map‐like in 14.4% of reviews of true FNH cases, and overall interobserver agreement for interpretation of the GS staining pattern was only moderate (kappa = 0.42).ConclusionsPathologists are reasonably accurate in the diagnosis of FNH on virtual biopsies, and GS staining improves accuracy. However, a subset of FNH cases remain challenging. Steatosis and a pseudo‐map‐like GS staining pattern were associated with increased difficulty. Therefore, although a map‐like GS staining pattern is useful for confirmation of a diagnosis, the lack of a map‐like GS staining pattern on needle biopsy does not necessarily exclude a diagnosis of FNH.

Abstract The precise characterization of the lobular architecture of the liver has been subject of investigation since the earliest historical publications, but an accurate model to describe the hepatic lobular microanatomy is yet to be proposed. Our aim was to evaluate whether Voronoi diagrams can be used to describe the classic liver lobular architecture. We examined the histology of normal porcine and human livers and analyzed the geometric relationships of various microanatomic structures utilizing digital tools. The Voronoi diagram model described the organization of the hepatic classic lobules with overall accuracy nearly 90% based on known histologic landmarks. We have also designed a Voronoi-based algorithm of hepatic zonation, which also showed an overall zonal accuracy of nearly 90%. Therefore, we have presented evidence that Voronoi diagrams represent the basis of the two-dimensional organization of the normal liver and that this concept may have wide applicability in liver pathology and research.

Abstract The concentrations of five essential elements and six potentially toxic elements were determined in seven organs collected at autopsy from 30 human subjects. Elemental analyses were carried out by graphite furnace atomic absorption spectroscopy, and inductively coupled plasma emission spectroscopy, and inductively coupled plasma mass spectroscopy, and concentrations in fresh and formalin-fixed tissues were compared. Formalin-fixation long-term storage has little effect on most element concentrations in tissue, except for Al and Mn, which changed with prolonged storage in formalin. The kidney and liver contained the greatest concentrations of toxic elements compared with other organs, whereas the essential elements were uniformly distributed among all organs. There was no more than a 10-fold difference in the tissue concentration of the elements studied among the organs, except for the concentration of Fe in liver, and Ca and Mg in bone. We also demonstrate that these elements are homogeneously distributed in tissues.

Patients with ischemic or hemorrhagic stroke are at risk for systemic complications. The reasons why gastrointestinal bleeding occurs after stroke are unknown and have intuitively been attributed to stress ulcers. No study to date has addressed causes of gastrointestinal hemorrhage in stroke. Between 1976 and 1994, 17 patients identified from the Mayo Clinic medical record system as having gastrointestinal hemorrhage and ischemic stroke (n = 14) or intracerebral hemorrhage (n = 3) were reviewed for presentation, associated causes, and outcome. Results of the endoscopic procedures were compiled, and available gastric biopsies were reviewed. In 17 patients with gastrointestinal bleeding after stroke, sudden hematemesis, a decrease in hemoglobin level, or orthostatic hypotension was found as a presenting feature. One patient presented with massive hematemesis, exsanguination, and cardiac arrest. Endoscopic findings were available in 14 patients and included gastroesophageal erosions, hemorrhagic gastritis, and gastric ulcer. In one patient, an adenocarcinoma of the gastric cardia was found. Putative pathogenetic agents were found in 16 of 17 patients and included a long history of nonsteroidal anti-inflammatory drugs (n = 6), acetylsalicylic acid (n = 3), grossly prolonged anticoagulation (n = 4), Helicobacter pylori (n = 2), and corticosteroids (n = 1). Gastrointestinal bleeding after stroke is rarely severe and may not contribute significantly to mortality. Medication-induced gastrointestinal hemorrhage may be underappreciated in this setting.