David Thorning

Peripheral neuroepithelioma: a light and electron microscopic study.

A primitive neuroectodermal tumor of peripheral nerve origin was examined by light and electron microscopy. The lesion arose in association with the SI nerve root of the lumbosacral plexus in a 22‐year‐old female. Following a surgical biopsy, the patient received systemic chemotherapy; however, approximately one‐and‐a‐half years later, she suffered a clinical relapse with locally recurrent tumor. An excisional biopsy was performed, and pathologic examination revealed progressive neuroblastic differentiation. The ultrastructural features of neoplastic Homer‐Wright rosettes will be illustrated, and the non‐specificity of cytoplasmic glycogen in the evaluation of „small round cell neoplasms”︁ will be emphasized.

Hepatic cholesterol crystals and crown-like structures distinguish NASH from simple steatosis

We sought to determine whether hepatic cholesterol crystals are present in patients or mice with nonalcoholic fatty liver disease/nonalcoholic steatohepatitis (NASH), and whether their presence or distribution correlates with the presence of NASH as compared with simple steatosis. We identified, by filipin staining, free cholesterol within hepatocyte lipid droplets in patients with NASH and in C57BL/6J mice that developed NASH following a high-fat high-cholesterol diet. Under polarized light these lipid droplets exhibited strong birefringence suggesting that some of the cholesterol was present in the form of crystals. Activated Kupffer cells aggregated around dead hepatocytes that included strongly birefringent cholesterol crystals, forming “crown-like structures” similar to those recently described in inflamed visceral adipose tissue. These Kupffer cells appeared to process the lipid of dead hepatocytes turning it into activated lipid-laden “foam cells” with numerous small cholesterol-containing droplets. In contrast, hepatocyte lipid droplets in patients and mice with simple steatosis did not exhibit cholesterol crystals and their Kupffer cells did not form crown-like structures or transform into foam cells. Our results suggest that cholesterol crystallization within hepatocyte lipid droplets and aggregation and activation of Kupffer cells in crown-like structures around such droplets represent an important, novel mechanism for progression of simple steatosis to NASH.

Mesotheliomas. A light- and electron-microscopical study concerning histogenetic relationships between the epithelial and the mesenchymal variants

Mesotheliomas have variable histological patterns which may suggest a predominance of epithelial cells, a predominance of mesenchymal cells, or a mixture of epithelial and mesenchymal cells. An adenomatoid tumor of the testis, a fibrous mesothelioma, and an epithelial mesothelioma were studied by light and electron microscopy to search for evidence of a histogenetic link between the various cell types. Each neoplasm was composed of poorly differentiated spindle-shaped cells and variably differentiated cells having epithelial, mesenchymal, and combined epithelial and mesenchymal features. The differentiated neoplastic cells exhibited a spectrum of cytodifferentiation with typical mesothelial cells at one end, typical fibroblasts at the other end, and trasitional forms in between. These observations are presented in detail as morphological evidence for a direct histogenetic relationship between the epithelial-appearing cells and the mesenchymal-appearing cells of human mesothelial neoplasms.

Anthracycline cardiotoxicity: clinical and pathologic outcomes assessed by radionuclide ejection fraction.

A clinical syndrome of severe cardiomyopathy often accompanies administration of high doses of anthracycline agents. We studied 36 patients serially with radionuclide angiography. At three weeks following drug administration, 8 of 36 patients showed depression of ejection fraction (EF). All had received at least 280 mg/M2 of the drug and 7 had received more than 380 mg/M2. Definite clinical syndromes of congestive cardiomyopathy developed only in patients showing EF depression and in some patients, EF depression developed without signs of congestive heart failure. Ejection fraction studies at 5 minutes, 1 hour, 4 hours, 24 hours, 72 hours, and one week following drug administration showed no changes when compared to immediate pre‐drug EF. Seven patients who died during the study underwent histologic examination. Only the single patient with a depressed EF showed histologic evidence of anthracycline cardiotoxicity, although all but 1 of these patients had received at least 400 mg/M2. We conclude that serial radionuclide EF just prior to anthracycline administration is a potentially useful predictor of cardiac toxicity, and that EF depression and/or preservation of a normal EF should be weighed in the decision for administering a drug of this type at high dosage levels.

Lipomembranous polycystic osteodysplasia (brain, bone, and fat disease): A genetic cause of presenile dementia

Progressive presenile dementia with lipomembranous polycystic osteodysplasia was first described by Jarvi and Hakola in an isolated region of Finland. We report the occurrence of this disorder in 4 of 10 siblings in an American family of Czechoslovakian ancestry. Characteristics of the disease include multiple bone cysts with pathologic fractures, progressive dementia with seizures and abnormal EEG, calcification of basal ganglia, and death in the fourth to sixth decades. Autosomal-recessive inheritance is likely. Electronmicroscopy of fat cells reveals peculiar membrane convolutions. Limited neuropathologic material has shown gliosis and demyelination of white matter, senile plaques, and neurofibrillary tangles. Leukemia and a disorder of intestinal motility may be associated findings. Prevalence of the disorder is unknown, partly because it may be confused with Alzheimer disease and fibrous dysplasia of bone. Radiographs of hands and feet should be part of the evaluation of patients with unexplained presenile dementia.

Spindle-cell lipoma. A clinical, light- and electron-microscopical study

Five spindle-cell lipomas, all in male patients, were examined by light and electron microscopy. Four were located in the subcutaneous tissues of the upper back or posterior neck and one behind the left ear. They exhibited a spectrum of histological growth patterns. Electron microscopy demonstrated two distinct populations of tumor cells; one, a spindled non-fat-storing mesenchymal cell and the other a mature lipocyte. It is hypothesized that the spindled cells are analogous to the stellate mesenchymal cell of the primitive fat lobule.

Nerve fibers in human myocardial scars

The relationships between ischemic heart disease, myocardial scars, ventricular nerve fibers, and ventricular arrhythmias have not been established despite considerable evidence suggesting important correlations. We recently described the reactions of nerve fibers in necrotic, healing, and healed rat myocardium. Prompted by these studies and by the lack of similar information for humans, we studied the structural relationships between nerve fibers and human myocardial scars. Hearts were obtained from transplant surgery and autopsy. Nerve fibers were labeled with antibody to S-100 protein. Light and electron microscopy of left ventricular scars revealed (1) fiber densities greater than those in adjacent intact myocardium, (2) fiber aggregates concentrated irregularly along the periphery of lesions, (3) fibers few in number or absent in the deeper aspects of scars, and (4) axonal enlargements containing clear and dense storage granules within the fiber aggregates. Like all other elements of the scars, the nerve fibers appeared to be oriented predominantly in the long axis of myocytes located at the edges of the lesions. Based on our experimental findings in rat hearts, these studies suggest that human myocardial nerve fibers regenerate after necrotizing injuries and that at least some of the resulting scar-associated fibers have structural features differing from those in uninjured myocardium. We suspect that these structural differences might be associated with functional alterations that could affect the triggering of ventricular arrhythmias.

Pulmonary responses to smoke inhalation: Morphologic changes in rabbits exposed to pine wood smoke

Inhalation of smoke can adversely affect pulmonary function; however, the lack of detailed knowledge of exposure conditions and the overall complexity of ensuing clinical problems generally preclude an understanding of the specific role played by smoke in human victims. Using controlled exposures of rabbits to white pine wood smoke, an animal model of smoke inhalation has been created. Light and electron microscopic examinations of injured respiratory tissues from these animals have revealed a reproducible, necrotizing tracheobronchial epithelial cell injury. By six hours after injury, the epithelium remains largely intact but is infiltrated by inflammatory cells; by 24 hours its ciliated and secretory lining cells are largely destroyed, the inflammatory reaction is maximal, but basal epithelial cells retain their normal structural appearances; by 72 hours, its surfaces are largely covered by a nonciliated, stratified reparative epithelium, apparently derived from proliferating and migrating basal cells. The acute injury and early reactions to injury resemble lesions observed in the lungs of human smoke-injured victims, and suggest several physiologic consequences that would provide likely explanations for some of the disabilities observed in these victims.

Benign lipoblastoma and myxoid liposarcoma: A comparative light-and electron-microscopic study

ABSTRACTA benign lipoblastoma and a myxoid liposarcoma were studied by light and electron microscopy. Both of these neoplasms had prominent plexiform vascular networks, early acquisition of fat by vascular pericytes, and progressive accumulation of fat by cells located away from the vasculature. Their component cells had investing basal laminae, pinocytotic vesicles, and cytoplasmic glycogen stores as well as cytoplasmic lipid. The process of neoplastic lipogenesis and the structural features of the neoplastic cells in both neoplasms resembled those of developing non-neoplastic fat tissue. The benign lipoblastoma appears to be analogous to developing fat, while the myxoid liposarcoma appears to recapitulate the actively proliferating zone of developing fat. The relationship between proliferating cells and the plexiform vascular network in all three processes is emphasized. We hypothesize that the vascular pericyte serves as a source for new fat storing cells.

Enhanced expression of Duffy antigen in the lungs during suppurative pneumonia.

Duffy antigen is a chemokine binding protein expressed on the surface of erythrocytes and postcapillary venular endothelial cells. It binds selective CXC and CC chemokines with high affinity. Although Duffy antigen is present in the normal pulmonary vascular bed, it is not known whether its expression is altered by innate inflammatory responses in the lungs. We studied Duffy antigen expression by immunohistochemistry in autopsy lung specimens from 16 cases of suppurative pneumonia, 11 cases of acute lung injury, and seven normal lungs. In lungs with suppurative pneumonia, Duffy antigen was expressed in higher numbers of pre- and postcapillary parenchymal vessels compared to normal specimens or specimens with acute lung injury (p<0.03 and p<0.02, respectively). Lungs with suppurative pneumonia also showed Duffy antigen expression on the alveolar septa, whereas this was a rare finding in normal specimens or in acute lung injury (p<0.02). Furthermore, Duffy antigen labeling of the alveolar septa localized to regions with airspace accumulation of neutrophil-rich exudates. In summary, Duffy antigen expression is increased in the vascular beds and alveolar septa of the lung parenchyma during suppurative pneumonia, suggesting that Duffy antigen may have a functional role in the lung parenchyma during inflammation.