The detection of effaced podocytes by high resolution light microscopy.

Fifteen cases of renal minimal change disease and five normal glomeruli were studied by high resolution light microscopy (HRLM) and transmission electron microscopy (TEM). Effacement of podocytes usually is accompanied by aggregation of microfilaments in the cytoplasm of the epithelial cells parallel to the glomerular basement membrane (GBM). The aggregated microfilaments were detected as a dense blue line by high resolution light microscopy. The presence of this line appears to be a reliable sign for the detection of diffusely effaced podocytes by light microscopy. However, when effacement of podocytes was not accompanied by the condensation of microfilaments, the detection of this change by HRLM was more difficult.

High resolution light microscopy in renal pathology.

Seven hundred renal specimens embedded in epoxy resins and stained with polychromatic stains were compared with paraffin sections stained with Hematoxylin and Eosin (H & E), Perodic and Schiff, (PAS), silver, and trichrome stains. High resolution of light microscopy, never in wax histopathology, may be obtained by the use of plastic embedding and polychromatic stains. Cell boundaries, intracellular organelles, basement membranes, different cellular types, apposition of different substances, and other pathologic changes were readily recognized in a single P + P (Plastic section stained with Polychromatic stains) section, whereas paraffin sections usually needed special stains. The same plastic block may be used for transmission electron microscopy. Slightly elevated cost, special training of the technician and pathologist, and some few remaining technical difficulties are the disadvantages of this method. High resolution light microscopy methods are recommended for routine renal biopsies.

Transmission electron microscopy and serial sections for light microscopy from the same block in routine renal pathology.

Routine serial sections for light microscopy (LM) from one sample and transmission electron microscopy (TEM) from selected areas of another sample are current procedures in renal pathology. At the present time, there are methods available to perform high-resolution light microscopy (HRLM) and TEM from the same block. However, this technology is not directly applicable or convenient for routine renal biopsies. Most methods presently available to obtain TEM studies from different areas of the same large HRLM block use reembedding methods, which considerably delay TEM studies, or mesa technics that fragment and waste the original block. Present methods to obtain serial sections from plastic blocks have been used in plant and animal morphology and need to be modified for renal pathology. In the present article, the authors present a technic that produces immediate TEM sections from different areas of the same HRLM block. This method does not produce fragmentation or waste of the original block, and TEM sections are obtained within two hours after large HRLM sections are screened. The latter sections are mounted serially on a regular microscopic slide on 8-15 separate wells painted with water-repellent ink. The methods are simple and produce large HRLM and TEM sections in 24 hours, avoiding separate samples for LM and TEM studies.

A case of primary amebic meningoencephalitis. Light and electron microscopy, and immunohistologic studies.

A 56-year-old alcoholic developed primary meningoencephalitis and died 3 weeks later. Autopsy revealed multiple areas of necrosis and acute and granulomatous inflammation in the brain and pancreas. Trophozoites and cysts were discovered in the brain and trophozoites alone in the pancreas. Morphologic studies revealed some parasitic features described as characteristic for Naegleria, but clinical, histological and immunohistological features favored in Acanthamoeba infection. This study calls for caution in the use of pure morphological criteria for the differential diagnosis of Naegleria and Acanthamoeba in humans. Cultural characteristics, immunohistology and serologic tests are probably more reliable for differentiating these parasites.

Infantile digital fibroma-like tumor in an adult.

Recurring digital fibrous tumors of childhood are unusual inclusion-bearing fibrous tumors typically located on the fingers and toes of young children. We report here a histologically similar tumor located on the arm of a 44-year-old man.

Fabry's disease in a heterozygous woman.

Fabry's disease is a rare, X-linked disorder of glycolipid metabolism that is usually recognized in men in the third and fourth decades of life. A heterozygous state in women has been documented, but reports about women who are affected are confined to isolated case reports and to rare small series. We report a case of a 42-year-old woman with persistent proteinuria who was found to have Fabry's disease. The characteristic lesion was readily seen using routine high-resolution light microscopy (HRLM) tissue sections without the need of multiple extra tissue sections and special stains. We discuss the correlation of clinical findings, fluorescent microscopy, HRLM, electron microscopy, and biochemical enzymatic studies in establishing the diagnosis.

High-resolution light microscopy. Its use in the study of liver diseases.

Tissue processing methods using methacrylate and epoxy resins, which were developed for transmission electron microscopy, allow histopathologic study of specimens by light microscopy with a degree of resolution unavailable with wax methods. We have routinely used epoxy resins in the study of specimens of diseased liver; this is, to our knowledge, the first reported study of such a procedure. Use of epoxy resins allows optimal tissue preservation and maximum use of the resolving power of the light microscope, and the use of polychromatic stains obviates the need for routine use of special stains. We believe that reexamination of specimens of diseased liver using high-resolution light microscopy will provide additional morphologic information for a better understanding of the pathology of liver and more accurate morphologic diagnosis.

Synovial chondromatosis.

A rare case of synovial chondromatosis of the knee occurring in a 65-year-old man is reported. Electron microscopy of the lesion suggests that the cartilaginous nodules develop through a process of metaplasia from the stromal fibroblasts.

High-resolution light microscopy for interpretation of renal biopsies.

Routine transmission electron microscopy is recommended for all renal biopsies. However, most of the diagnostic lesions in renal pathology are 0.2 micron or larger, and are therefore visible by light microscopy. These lesions are difficult to evaluate in paraffin sections due to problems inherent in the method itself. Full utilization of the resolving power of the light microscope or high-resolution light microscopy is possible with resin (plastic) histotechnology. The replacement of conventional histotechnology by epoxy histotechnology allows the visualization of most subcellular structures needed for accurate diagnosis in renal pathology. Electron microscopy remains a very helpful tool for selected morphological problems.

Paraganglioma of the hepatic duct.

We have described what appears to be the first case of paraganglioma of the hepatic duct at the hilum of the liver. Though extremely rare, this tumor should be included in the differential diagnosis of tumor causing biliary obstruction.

The Mikulicz cell in rhinoscleroma. Light, fluorescent and electron microscopic studies.

The stages in the development of the Mikulicz cell in human rhinoscleroma were studied in biopsy specimens obtained from 10 patients using light, immunofluorescent and electron microscopy. The Mikulicz cell was identified morphologically as a macrophage, not a plasma cell. Acutely inflamed areas of rhinoscleroma presented abundant bacteria with a slime layer. The microorganism was infrequent and the mucopolysaccharide was scanty in rhinoscleromal tissue, where plasma cells predominated, and in cicatricial fibrous tissue. In the granulomatous stage of rhinoscleroma, the mucopolysaccharide was found within the Mikulicz cells. The vacuoles observed in the Mikulicz cells were considered to be phagosomes containing, principally, bacterial mucopolysaccharide and few bacteria and, to a lesser extent, swollen mitochondria. It was concluded that the slime layer of Klebsiella rhinoscleromatis plays an important role in the pathogenesis of the disease. It is postulated that this material is a nondigestible mucopolysaccharide that resides in the phagosomes of macrophages, increases the osmotic pressure and forms multiple hydropic vacuoles that rupture not only the phagosomes but also the cells, resulting in the liberation of the mucopolysaccharide. This would initiate a cycle that would prolong the disease in the absence of the bacteria.

Influence of lead and cadmium on the susceptibility of rats to bacterial challenge.

Intravenous administration of an acute dose of lead acetate or cadmium acetate enhanced the susceptibility of rats to intravenous challenge with E. coli by approximately 1000-fold. Since equivalent vulnerability of lead- or cadmium-treated rats to killed E. coli was observed, toxicity is probably due to the endotoxin content of the bacteria. This postulate is further supported by the observation that equal doses of the Gram-positive bacteria, Staphylococci epidermidis, failed to elicit lethality in the acute lead-intoxicated rats. The synthetic glucocorticoid, methylprednisolone, prevented lethality induced by the Gram-negative bacteria in lead-treated rats. It did not, however, afford significant protection in cadmium-treated rats in the presence of E. coli. Marked alterations in hepatic morphology were apparent in both lead- and cadmium-treated rats challenged with E. coli.

The effects of acute cadmium administration in the liver and kidney of the rat. Light and electron microscopic studies.

A single injection of cadmium acetate givenintravenously to rats produced, at 16 hours, liver damage but no observable kidney changes. Ultrastructure of the liver revealed more profound changes in parenchymal cells than in Kupffer cells. The most prominent changes were single parenchymal cell necrosis, deterioration of rough endoplasmic reticulum, proliferation of smooth endoplasmic reticulum, autophagocytosis, and mitochondrial degenerative changes. Lesions of Kupffer cells were not prominent, although occasional areas of cytoplasmic degradation and increased vacuolation were observed. Dewquamation of these cells appears also to be a frequent finding in cadmium intoxication. Accumulation of platelets, cellular debris, inflammatory cells, and fibrin in the sinusoids may be the cause of the occasionally observed focal necrosis. Although the present experiment does not simulate any known clinical situation, these composite studies provide a morphologic basis for hepatic dysfunction following acute cadmium administration as well as an ultrastructural basis for thebetter understanding of the synergistic actionof cadmium with other substances such as endotoxins.