L. Clarke Stout

Focal mesangiolysis and the pathogenesis of the Kimmelstiel-Wilson nodule

Kidneys from 74 consecutively autopsied primarily non-insulin-dependent diabetes cases and 59 age-, sex-, and ethnic group-matched controls were examined qualitatively and semiquantitatively to determine whether focal mesangiolyses (FMs), Kimmelstiel-Wilson (KW) nodules, and glomerular capillary microaneurysms (GCMs) were related lesions, to determine their extent and pathogenic sequence, and to look for associations with structural and functional factors. Light microscopic examination of serial sections, immunohistochemical stains, image analysis, and electron microscopy were used. Focal mesangiolyses, KW nodules, and GCMs occurred in 31 of the 74 diabetes cases (27 had FMs, 29 had KW nodules, and nine had GCMs) and were positively correlated with each other semiquantitatively (r = .71, .70, and .68, respectively). Numerous FMs were found, involving 62% and 78% of the glomeruli in the two most severely affected cases. Most FMs were located at the periphery of KW nodules, but de novo FMs were documented in six cases. Glomerular capillary microaneurysms were deemed occasional complications of FMs because they were much less common, and 25 of the 27 GCMs identified were contiguous with FMs. Focal mesangiolyses and GCMs were deemed transient lesions, being absent in end-stage kidneys. Both FMs and KW nodules consisted of a spectrum of lesions. For the sake of clarity they were arbitrarily divided into two types: edematous and proliferative FMs and simple and complicated KW nodules. Their characteristics suggested the following pathogenic sequence: edematous FM-->proliferative FM-->focal nodular mesangial expansion-->simple KW nodule-->recurrent FM-->complicated KW nodule. Complicated nodules were associated with marked alterations in the lobular capillary. The number of mesangial cells was increased in FMs and they were thought to be responsible for increased matrix production. Focal mesangiolyses and KW nodules were positively associated with diabetes, proteinuria, and hyalinization of afferent and efferent arterioles, but were weakly or not associated with hypertension, arcuate and interlobular artery stenosis, hydroenphrosis, acute pyelonephritis, renal arterial atheromatous emboli, glomerular platelet-fibrin thromboemboli, and congestive heart failure.

Insudative lesions—Their pathogenesis and association with glomerular obsolescence in diabetes: A dynamic hypothesis based on single views of advancing human diabetic nephropathy

Kidneys from 74 consecutive, primarily non-insulin-dependent diabetics at autopsy and 59 age-, sex, and ethnic group-matched controls were examined qualitatively and semiquantitatively to determine the prevalence and severity of insudative lesions (ILs) and obsolescent glomeruli with (OGcFC) and without (OGsFC) insudative (fibrin cap) lesions. A subset of 25 cases with advanced diabetic changes was examined using serial sections, immunohistochemical stains, and electron microscopy to determine the pathogenesis of ILs and OGcFCs. Insudative lesions consisted of intramural accumulations (hereafter called deposits) of presumably imbibed plasma proteins and lipids within renal arterioles, glomerular capillaries, Bowmans capsule, and proximal convoluted tubules. Insudative lesions in Bowmans capsule are called capsular drop lesions (CDs), in glomerular capillaries they are called fibrin cap lesions (FC), and in afferent and efferent arterioles they are called hyalinized afferent (HA) and hyalinized efferent (HE) arterioles, respectively. All ILs were much more numerous and/or larger in diabetics than in controls. Contrary to previous opinion, CDs and HE arterioles were not specific for diabetes, being present in small numbers in nine (15%) controls. Controls with CD/HE arterioles had far more HA arterioles and focal mesangiolyses (FMs) than those without. Insudative lesions consisted of the well known homogenous eosinophilic deposits (homogenous eosinophilic ILs) and the less familiar foamy, reticulated, and vacuolar deposits (heterogenous lucent ILs). Homogenous eosinophilic ILs were predominant in afferent arterioles and more so in efferent arterioles, and were segregated into globules of varying density with the denser deposits located peripherally. Two types of CDs, which differed sharply in location and composition, were found. The first was mostly homogenous eosinophilic, usually without capsular adhesions and located near the vascular pole close to preglomerular arterioles. The second was mostly heterogenous lucent, located away from the vascular pole, and consistently connected by adhesions to the capillary tuft usually near FMs and/or Kimmelstiel-Wilson (KW) nodules. The latter ILs sometimes extended in continuity along the internal surface of the basement membrane from Bowmans capsule into the proximal convoluted tubule. It was hypothesized that ILs traveled centrifugally through the walls of preglomerular arterioles to form the first type of CD and longitudinally within the walls of afferent arterioles and glomerular capillaries and through adhesions to form the second. Contrary to previous opinion, FCs were consistently intramural. When numerous, FCs were associated with a form of glomerular obsolescence called OGcFC.(ABSTRACT TRUNCATED AT 400 WORDS)

Histology of normal aortas in birds with emphasis on intimal thickening

Published studies of normal aortic structure have been infrequent in birds despite a high prevalence of spontaneous atherosclerosis relative to mammals, and a feeling that this prevalence of atherosclerosis might be related to the pecularities of aortic structure in birds. We describe aortic structure in 26 birds, including 22 species and 12 families. All aortas had a complex structure similar to hat of the White Carneau pigeon which has been carefully studied. Diffuse intimal thickening (DIT) was found in the elastic zones in 22 of the 26 aortas. This lesion has not been previously described as such, and consisted of multiple longitudinally oriented elastic laminae apparently synthesized by interlamellar connective tissue cells, the latter being peculiar to the avian aorta. Focal intimal thickenings were very common in the non-elastic zones of the aortas, and were composed of smooth muscle cells and elastic laminae similar to the DIT of mammals. Their location suggested that blood flow patterns might be an important influence in their development. The fact that atherosclerotic lesions usually occurred in the non-elastic zones of the avian aorta suggested that some property of the elastic zone or the interlamellar connective tissue cells might inhibit the development of atherosclerosis.

Water-clear-cell hyperplasia mimicking parathyroid adenoma

The case of a patient with primary hyperparathyroidism in whom water-clear-cell hyperplasia (WCCH) involved only the superior glands, and disproportionately so, is presented. In addition, unlike the cases of WCCH described previously, a rim of normal parathyroid tissue was observed at the periphery of each gland in this case. It is speculated that these findings are not necessarily peculiar, but may reflect an earlier stage of the disease. Such cases may mimic parathyroid adenoma, thereby leading to inadequate surgical therapy.

Pathogenesis of diffuse intimal thickening (DIT) in non-human primate thoracic aortas

The pathogenesis of diffuse intimal thickening (DIT) is not well understood. In animals, it is positively correlated with size, and with the exception of the pig, is thought to involve the proximal more than the distal portions of vessels. DIT is often not visible grossly, so that its study requires extensive microscopic sampling of tissue. Review of previous studies in animals suggests that microscopic sampling may not have been sufficient to determine exactly where DIT occurs throughout the entire length of a vessel. The present study is a longitudinal step-serial section examination of the entire descending thoracic aorta from 12 adult non-human primates of varying size and species and with varying degrees of DIT as determined previously by more limited cross-section techniques. The findings indicate that DIT is not more pronounced in the proximal versus the distal segments of the vessel, and is not correlated with branch orifices. Review of the literature suggests that DIT may not be a single process, but may vary in pathogenesis from vessel to vessel and from species to species.

Pathogenesis of diffuse intimal thickening (DIT) in aortas and coronary arteries of 212-year-old minature pigs

Abstract Lesions resembling diffuse intimal thickening (DIT) in morphology are reported in the left anterior descending coronary arteries and aortas of 2 1 2 - year-old miniature swine. The lesions are similar in composition and location to those previously described under a variety of names in swine, either large or miniature. The lesions are intermediate in size when compared with those of younger and older swine, and when all the data are seen together, a picture emerges of gradually enlarging musculoelastic lesions which eventually assume a double or triple-layered structure. The lesions are mostly focal, and are most pronounced in the abdominal aortas where their rather constant localization to proximal posterior and distal anterior walls suggests thay they are caused in part by hemodynamic stresses.

Histology of normal aortas in non-human primates with emphasis on diffuse intimal thickening (DIT)

Little information is available on the histology of the normal aorta in non-human primates, despite their extensive use in atherosclerosis research. This paper consists of a detailed histologic description of normal aortas from 28 non-human primates, including 20 species. Medial and adventitial coats were essentially normal in all animals, and the former were composed of lamellar units similar in structure to those described in detail by other investigators. Intimal thickenings were present in 24 of the 28 individuals. These thickenings were similar in morphology to those of diffuse intimal thickening (DIT) in humans and other animals, and were more prevalent in older animals and in larger animals. The thickenings were not more prevalent or more pronounced in any particular region of the aorta, and their distribution did not provide a clue as to their etiology. Findings suggested that the thickenings underwent recognizable states of growth and maturation, and that growth was accomplished by the addition of smooth muscle cells at the intimomedial junction.

Myofibroblastic proliferation on mitral valve chordae tendineae: a distinctive lesion associated with alcoholic liver disease.

Hearts from 1,676 consecutive autopsies were examined over a 4 1/2 year period between 1980 and 1984. Forty-seven (4.3%) of 1,083 adult hearts were found to have from one to nine distinctive bulbous thickenings (BTs) involving the mitral valve chordae tendineae. By light- and electron-microscopy, the BTs were found to consist of numerous myofibroblasts, collagen, and elastin layered over otherwise normal chordae and occasionally involving adjacent valve leaflets. No evidence of inflammation, rheumatic or otherwise, was found in histologic sections of the mitral, aortic, and tricuspid valves, or in samples of myocardium from all chambers. No BT was present in 593 hearts from infants and children, indicating that the lesions were acquired. Review of autopsy diagnoses showed that 14 (29.8%) of the 47 patients with BT had alcoholic hepatitis or micronodular cirrhosis, as opposed to 80 (7.7%) of the 1,036 patients without BT. This difference was highly statistically significant (P less than 0.01). The prevalence of viral liver disease was similar in the two groups. Of all patients with alcoholic liver disease, those with BT tended to be male and older. BT appears to be a distinctive process that is strongly correlated with alcoholic liver disease.

Studies on the distribution of lipids within fibrous plaques

The present report is an attempt to determine the nature of the circulation of lipids within fibrous plaques by studying the pattern of lipid distribution within the plaques. The material was obtained from aortas from 405 mammals and birds dying in the Oklahoma City Zoo. Analysis of the pattern of lipid distribution in 187 lipid containing aortic fibrous plaques suggested that most of the lipids entered the plaques at the shoulders and circulated from there toward the centers, usually in the outermost layers of the plaques.

Complete step section microscopic study of a Swan–Ganz catheter-related pulmonary artery rupture: a frequently lethal complication that to our knowledge has not had a comprehensive microscopic examination: case report and literature review

BACKGROUND Introduced in 1970, the Swan-Ganz catheter (SGC) soon became widely used because of its unique usefulness in managing intensive care patients. Unfortunately, SGC usage was complicated by pulmonary artery rupture (PAR) with a 50% mortality rate that led to a near banning of the SCG in the late 1980s. Increasing knowledge and decreasing incidence of SGC-related PARs (SGPARs) led to the current feeling that the present SGPAR incidence is now low enough to tolerate given the lives saved by SGC usage. However, an important unknown is that, to our knowledge, pathologists have never published a comprehensive microscopic description of a SGPAR. CASE REPORT A 73-year-old woman with moderate pulmonary hypertension died from a SGPAR soon after single SGC measurements of right ventricular and pulmonary capillary wedge pressures. By using what we thought to be an appropriate method of dissection, we did a complete microscopic step section study of the 1.6 cm SGPAR revealing 12 relatively uniform longitudinal tears (one perforating) consistent with an overinflated SGC balloon or a weakened arterial wall. LITERATURE REVIEW A MEDLINE search of 38 consecutive SGPARs from 2014 to 1980 found 52 cases in 38 papers. Analysis revealed that all 46 SGPARs suitable for study came from large institutions, and confirmed that elderly women were more likely to have SGPARs than elderly men. CONCLUSIONS More and better data are needed before fully informed decisions can be made regarding future SGC usage.