Intraglomerular fibrin, platelet aggregation, and subendothelial deposits in lipoid nephrosis.

We have investigated the formation of fibrin, platelet aggregates, and subendothelial deposits in lipoid nephrosis. Fibrin formation was found in 10 cases of active lipoid nephrosis. Platelet aggregates were found in eight cases and subendothelial deposits in nine. Fibrin and platelets were also found in cases of nephrotic syndrome due to other causes, and in glomerulonephritis. Fibrin was generally absent in lipoid nephrosis in remission and in benign recurrent hematuria. It is suggested that what seems to be a lower incidence in females is more apparent than real and that fibrin or related material may be present in a less easily identifiable form. Steroid therapy apparently had no effect on the presence or absence of fibrin. Most instances were associated with elevated serum cholesterol and alpha(2)-globulin. It is suggested that elevated serum lipids as well as the disease process in the kidney play a role in this phenomenon. It is further suggested that intraglomerular fibrin formation could lead to irreversible renal damage in lipoid nephrosis.

Resolution of renal amyloidosis.

A patient with renal amyloidosis and the nephrotic syndrome consequent to extensive infected burns demonstrated both clinical resolution of the nephrotic syndrome and morphologic regression of the renal amyloid deposits over a six year period. The regression of the amyloid deposits was associated with several changes in the glomerular capillary wall resulting in a double capillary wall contour. This case indicates that deposits of amyloid in the kidney may regress and suggests a sequence of events in this resolution.

Lectin-peroxidase conjugate reactivity in normal human kidney.

The carbohydrate histochemistry of normal human kidney has been investigated by the use of four peroxidase-labeled lectins at the light and electron microscopic level. The results show that the lectin of Lotus tetragonolobus, specific for l-fucose, binds exclusively to the proximal convoluted tubules of the nephron. While peanut and soybean lectins, specific for D-galactose and N-acetyl-D-galactosamine, respectively, are confirmed to the collecting ducts, wheat germ lectin, specific for sialic acid and N-acetyl-D-glucosamine, stains several parenchymal structures, including the glomerular capillary wall, particularly its podocyte cell coat. Sialidase digestion reveals strong binding sites for peanut and soybean lectin in the glomeruli. At the ultrastructural level most of the binding is shown to be on the podocyte surface and within the lamina rara externa of the basement membrane. The technique represents a potentially very useful tool for the study of various pathological states in the kidney.

Mesangiolysis: an update.

Mesangiolysis occurs in many renal diseases, both human and experimental. At least three types of mesangiolysis may be recognized, which differ in their mode of origin and in morphologic features. The first type is severe mesangiolysis with formation of glomerular cysts and subsequent cellular proliferation resembling glomerulonephritis. In the second type, mesangiolysis is associated with extensive widening of the subendothelial space and is thought to follow endothelial injury. The third type is mesangiolysis with lamellated mesangial nodules which is believed to result from relatively mild but persistent or recurrent localized mesangial, and perhaps also endothelial damage, with lysis of mesangial anchor points.

Mesothelioma in man and experimental animals.

Asbestos has been established as the cause of most cases of diffuse malignant mesothelioma occurring in the industrialized world. The morphology of mesothelioma may be complex, and the employment of chemical, histochemical and ultrastructural studies are often helpful in identification. Diagnostic difficulties may to some degree blur the extent of its prevalence and reliance on exposure history may not reveal its association with asbestos. Reference panels can be useful in assessing the former and analysis of lung tissue asbestos content may help to clarify the latter, especially in the low dose range. Electron microscopy may prove to be of assistance in this respect, possibly with particular attention to the peripheral areas of the lung. Animal experimentation has supported epidemiologic conclusions and revealed the phenomenon of fiber carcinogenesis. The morphology of mesothelioma in experimental animals is very similar to that in humans, including ultrastructural and biochemical features.

Peritoneal mesothelioma.

The cytohistology in 82 cases diagnosed as malignant peritoneal mesothelioma was correlated with available clinical and gross pathologic information. The cases were then evaluated as to ceratainty of diagnosis. The material had come from a large number of sources, most of it having been traced by a history of occupational exposure to asbestos. A relatively short interval of significant symptoms, with already existent diffuse peritoneal involvement and ascites, and an average survival time of less than a year characterized the group. The microscopic morphology formed a spectrum from highly characteristic, pure epithelial and mixed epithelial and sarcomatoid types, through nonspecific although relatively differentiated appearances, to pleomorphic analplatic proliferations. Local invasion and metastasis were common but much more limited than with tumors of other histogenesis showing comparable serous membrane involvement. Autopsy was of considerable exclusionary value although not in itself always determinative, and mucopolysaccharide histochemistry was occasionally decisive in diagnosis. Because of the microscopic versatlity of mesothelioma and the clinical and gross morphologic overlap with other neoplasms, all available data must be taken into consideration in arriving at a diagnosis. We believe that the dgree of certainty of diagnosis should be indicated by a succinct but reasonably explicit terminology.

Morphologic and clinical correlates in renal amyloidosis.

Morphologic studies and clinical correlations were undertaken in 59 patients with renal amyloidosis. Spicularly arranged amyloid deposits in the glomerular capillary wall were found in all clinical groups but were more frequent and more extensive in primary amyloidosis and multiple myeloma. The severity of proteinuria correlated with the presence of spicules and podocyte destruction rather than with the amount of amyloid in the glomerulus. The spicules were associated with morphologic and clinical evidence of rapid amyloid deposition and a fulminant clinical course. The absence of spicules and the presence of extensive new basement membrane material may produce basement membrane thickening, lamination, and double capillary wall contours, which are associated with mild proteinuria and, rarely, resolution of amyloidosis. Nodular or mixed nodular-diffuse patterns of glomerular amyloid deposits were more frequent in patients with secondary amyloidosis and a longer clinical course. Renal failure generally corresponded to severe glomerular amyloidosis and tubular atrophy. However, a relatively precipitous, usually irreversible decrease in renal function frequently occurred in patients with renal amyloidosis and did not always have a morphologic explanation. The duration of life from the time of biopsy no death in patients with primary amyloidosis (nine months) was markedly shorter than in those with secondary amyloidosis (more than 50 months).

Electron microscopy of a feminizing Leydig cell tumor of the testis.

The ultrastructural characteristics of a feminizing interstitial (Leydig) cell tumor of the testis were compared with those of normal Leydig cells and with the findings described in 10 published cases of Leydig cell tumor. The neoplastic Leydig cells superficially resembled normal Leydig cells. Similarities included abundant smooth endoplasmic reticulum, lipid, and microbodies. Contrastingly, Reinke crystalloids and paracrystalline inclusions were absent and lipochrome pigment and lysosomes very rare. The nuclei were large and contained enlarged, often multiple, nucleoli. The nuclear membranes tended to be irregular and undulating. Cytoplasmic membranous whorls and myelin figures were conspicuous. Fairly homogeneous fibrous septa were evident between single and grouped tumor cells. Despite several individual variations, there is a general resemblance between the neoplastic Leydig cells in this patient and those previously reported. No distinguishing ultrastructural characteristics were discerned between feminizing and virilizing Leydig cell tumors.

Formes frustes of Churg-Strauss syndrome.

We report 4 cases of Churg-Strauss syndrome (CSS) that occurred in patients being treated with corticosteroids for a diagnosis of asthma. One patient had asthma, eosinophilia, and eosinophilic lymphadenopathy that regressed with higher doses of corticosteroids. The second patient had both eosinophilic tissue infiltration and symptoms suggestive of vasculitis, while the remaining two patients had overt vasculitis; in all three, vasculitis developed after tapering or discontinuation of corticosteroid therapy. Two patients died of their disease. We have labelled these cases as formes frustes CSS. Our observations suggest that some cases of CSS may be partially or totally suppressed by corticosteroid therapy for asthma for very long periods and that asthmatic subjects maintained on low-dose corticosteroid therapy or asthmatic subjects whose corticosteroid doses are being tapered should be carefully monitored for the development of CSS signs and symptoms.

Systemic necrotizing vasculitis.

Systemic necrotizing vasculitis may be idiopathic or associated with a variety of diseases of known etiology. A typical example is polyarteritis nodosa, which is characterized by fibrinoid necrosis and severe inflammation leading to destruction of the wall, narrowing of the lumen, and interference with blood circulation. In addition to the idiopathic form, histologically similar lesions are seen in hepatitis B, rheumatoid arthritis, Kawasaki mucocutaneous lymph node syndrome, and other diseases. Microscopic polyangitis involves mainly small vessels-venules more often than arterioles-but occasionally also small arteries. Its characteristic feature is leukocytoclasia of neutrophilic leukocytes, but fibrinoid necrosis also occurs. Churg-Strauss syndrome consists of granulomas in patients with a background of severe allergy, such as asthma, allergic rhinitis, or occasionally drug sensitization.

Renal biopsy: why and when.

The purpose of this paper is to emphasize the importance of information obtained by renal biopsy in the diagnosis, prognosis, and therapy of patients with renal disease. Because controversy persists regarding the value of renal biopsy as an aid in determining prognosis and in choosing appropriate therapy, there has been some reluctance to use it early after the onset of obvious signs, symptoms, and laboratory findings indicative of renal disease with or without involvement of other organs. Although all such patients may not benefit from the information provided by a proper biopsy, we will illustrate some of the characteristic histologic details found in specific circumstances in our experience where the biopsy has been particularly helpful in reaching a diagnosis, in assessing prognosis, and in choosing therapy.

Focal segmental lupus nephritis.

Nineteen renal biopsies and one autopsy from fifteen patients with focal segmental lupus nephritis were examined by light and electron microscopy, and seven biopsies also by immunofluorescence microscopy. Histopathologic data were correlated with clinical course. Patients were selected on the basis of strict histologic criteria, and had to have a minimum of 2 years clinical follow-up after biopsy. All patients were treated with steroids. It could be demonstrated by light and electron microscopy that segmental lesions go through several stages of evolution, starting with mesangial proliferation, followed by necrosis and terminating as a nodule composed mainly of collagen. The necrotic lobule sometimes contains electron dense deposits, but no wire loop lesions. Prognosis was generally good with an average of 6.3 year survival of 86%. Factors contributing to outcome include number of involved glomeruli, amount of mesangial deposits outside the segmental lesions, and the presence of vasculitis. The pathogenesis of segmental lesions probably differs from that of diffuse lupus nephritis, constituting a localized reaction, independent of immune deposits in the remainder of the glomerulus, and with a considerable tendency to heal, particularly when treated with steroids.

Renal failure due to tubular obstruction by large protein casts in patients with massive proteinuria.

We describe two patients with nephrotic syndrome whose histologic findings on renal biopsy and at autopsy are characterized by numerous large protein casts in dilated cortical tubules, as well as podocyte swelling with effacement of foot processes in the glomeruli. Both patients progressed rapidly to renal failure. The casts and the protein precipitate in the Bowman's capsule were found to be composed of varying proportions of albumin and globulin but contained no Tamm-Horsfall protein. This suggests a glomerular rather than tubular origin of proteins. Light and electron microscopic examination of tubules revealed changes mainly due to compression by the casts. We propose that tubular obstruction due to the large casts was the main cause of renal failure.

Morphometric analysis of glomerular basement membranes (GBM) in thin basement membrane disease (TBMD).

We measured the thickness of glomerular basement membrane in 46 patients with thin basement membrane disease (TBMD), (age range 15-50 years, almost equal M:F ratio), and compared with that in a control group of 5 patients (age range 5-38 years) with normal glomerular morphology. The measurements of glomerular basement membrane taken from electron micrographs (magnification x 12,500) were analyzed using an interactive image analysis system assembled around an INTEL 10 microcomputer, with a high resolution touch sensitive screen as the interactive peripheral. Calculation was done by printing on an electron micrograph a grating replica (21,600 lines/cm), with the same magnification as the electron micrographs of the glomeruli and calibrating the arithmetic (AM) and harmonic (HM) mean for each case. Comparing the results of TBMD cases (AM 129-202 nm; HM 128-213 nm) with those of the control group consisting of 5 cases of "minimal change nephrotic syndrome" (AM 287-317 nm; HM 300-333 nm) it was found that GBM in TBMD is remarkably thin. The thinning was caused mainly by the decreased width of the lamina densa (TBMD group: 71.4-147.0 nm; HM 72.4-154.4 nm in comparison with the control group: AM 174.4-235.5 nm; HM 184.2-249.6 nm). This finding allows us to differentiate thin basement membrane disease from other glomerulopathies presenting primarily with isolated or recurrent hematuria.

Recurrent hemolytic-uremic syndrome: a case report.

A girl who developed HUS at 2 years of age had four further episodes of the disease during the next 2 1/2 years. No renal or hematologic abnormalities were detected during or between the attacks. Reduced levels of serum complement were found during three of the episodes.

Renal biopsies in cystic fibrosis.

Pharmacokinetic studies on antibiotics as well as other studies on renal function indicate renal malfunction in cystic fibrosis. Renal biopsies from two children, and post mortem examination from one child, with this disorder were normal by light microscopy and close to normal by immunofluorescence examination and transmission and scanning electron microscopy, even in cases with advanced disease and marked renal malfunction. Renal biopsy interpretation thus seems to be of little value in the evaluation of renal malfunction in this disorder, and this suggests that the functional abnormalities are caused by metabolic/biochemical defects.

Ultrastructure of hematoxylin bodies in systemic lupus erythematosus.

Two specimens, the first from a percutaneous renal biopsy and the second autopsy tissue of ovary, from two subjects with active systemic lupus erythematosus were found to contain many striking hematoxylin bodies in the walls of several small arteries. The specimens were reprocessed for electron microscopy; in one case, corresponding plastic embedded sections were also stained with hematoxylin-eosin and Feulgen stain. Hematoxylin bodies were easily identified on electron microscopy. They were found to be dense, homogeneous structures, approximately the size of a nucleus. They probably represent mainly altered nuclear material with occasional small chromatin remnants or minor cytoplasmic inclusions.

Identification of dense deposit disease: a report for the International Study of Kidney Diseases in Children.

The fluorescent dye thioflavin T stains intensely the deposits in dense deposit disease and can be used for identification purposes. Comparison of thioflavin T staining with electron microscopy was carried out in 25 patients and showed excellent congruity. Thioflavin T is much easier to use, but is less specific than electron microscopy. Cases of light chain disease and of some gammopathies can be a source of confusion. In nearly all other instances, the pattern of staining helps to differentiate dense deposits from other types of deposits and from amyloid.

Pathogenic effects of asbestos.

The enormous increase in the use of asbestos during this century has necessitated the intensive study of its pathogenic effects. The occurrence of pulmonary parenchymal and pleural fibrosis and an increased prevalence of pulmonary and gastrointestinal carcinoma and of pleural and peritoneal mesothelioma have been established. A relationship, also, to laryngeal carcinoma is probable. Mesothelioma has been associated with indirect occupational, domestic, and neighborhood exposure, and the possibility of a similar correlation of pulmonary carcinoma with low exposure has been suggested. Pulmonary fibrosis and pleural plaques have been demonstrated under these circumstances. The physical characteristics of the asbestos fiber appear to be the principal factors in its carcinogenic action. The ability of fine, short fibers, especially fragmented chrysotile, to reach the pleura would appear to account for many of the pathogenetic and anatomical features of asbestos-related disease.

Unilateral glomerulonephritis.

Three patients had unilateral glomerulonephritis. In two, the protected kidney was associated with stenosis of its renal artery, and in the third patient, a hydronephrotic kidney was spared. These clinical examples of unilateral glomerulonephritis and similar experimental models illustrate the effect of hemodynamic and hydrostatic influence in the manifestation of glomerulonephritis. Glomerulonephritis associated with unilateral arterial or ureteral disease may cause clinical confusion and error in diagnosis and treatment.