Interstitial capillary in normal and in transplanted kidneys: an ultrastructural study

Knowledge about the normal structure and pathology of interstitial capillary is limited. Splitting and multilayering of the basal membrane (BM), as a marker of chronic rejection, has been published in association with transplant glomerulopathy. The authors investigated the ultrastructural features of the interstitial capillary basal membrane in normal (15 biopsies) and in transplanted kidneys (27 biopsies from 21 patients), expressing transplant glomerulopathy (8 biopsies from 6 patients), acute tubulo-interstitial rejection (9 biopsies from 6 patients), and recurrent or de novo glomerulonephritis (10 biopsies from 8 patients). All biopsies were fixed in 1%OsO 4 , embedded in Epon, and examined by electron microscope. Measurements of the interstitial capillary BM were made. The BM of interstitial capillary of intact kidney was a homogenous continuous structure, 88 nm in width on average. Thickening with diffuse multilayering of BM was most intensive in patients with transplant glomerulopathy, and much less intensive in patients with acute tubulointerstitial rejection and in patients with recurrent or de novo glomerulonephritis. These findings may provide the first information about the morphology of the normal basal lamina of interstitial capillary and support the diagnostic value of interstitial capillary changes in chronic rejection.     

Pigmented Carcinoma of the Breast: An Ultrastructural Study

A pigmented skin lesion on a breast removed for carcinoma resembled melanoma by routine light microscopy, but correlation with immunohistochemistry and electron microscopy established that carcinoma cells within the upper dermis were intermingled with a proliferation of non-neoplastic melanocytic cells. Ultrastructurally, the tumor cells possessed desmosomes and intracytoplasmic lumina and mature melanosomes were present in their cytoplasm. The melanocytic cells were identified as melanocytes or melanophages, and it was concluded that the tumor in the skin was a passively pigmented carcinoma and not a melanoma or metaplastic breast carcinoma.     

Intercellular Junctions,Apical Differentiation,and Infiltrative Features in Colon Cancer: An Ultrastructural Study

Changes in the structure and number of cell junctions have been related to the infiltrative and metastatic potential of tumor cells. Apparently, the loss of cell adhesion should be coordinated with significant changes in the apical and basal cell domains. The authors have performed a sequential ultrastructural study of cells in the superficial, middle, and deep regions of well- and moderately differentiated colon adenocarcinomas. This was to investigate the differencesin the organization of different membrane domains among tumor cells in the in situ areas, the advancing, infiltrative edge of the tumors, and the infiltrating zones between these two extreme zones. The results of the study suggest that the organization of these domains is not strictly coordinated, and that, for each infiltration level, both a settling and an infiltrating cell population can be found. These findings could explain the fact that apparently well-differentiated tumors are able to seed distant tissues with individual cells, rather than with well-differentiated glandular aggregates that would hardly be able to reach the vessel lumina without significantly modifying their organization.     

Odontoblast Dysfunction in Osteogenesis Imperfecta: An LM,SEM, and Ultrastructural Study

The inherited dentin defect dentinogenesis imperfecta (DI), while clinically obvious in osteogenesis imperfecta (OI) Types IB and IC, II, III, and IVB, is now thought to be present in all children with OI, in a continuum from minimal to severe dentin pathology. This collaborative study further clarifies the structural and ultrastructural dentin changes in the teeth of OI children with clinically obvious DI, and attempts to explain these in terms of odontoblast dysfunction. Collaborative studies were carried out in Melbourne, Australia, and Strasbourg, France, using light and polarized-light microscopy, scanning and transmission electron microscopy (SEM, TEM), selected-area diffraction (SAD), and x-ray spectroscopy (EDX). These showed structurally normal enamel (but containing long and broad lamellae) and a normally scalloped dentino-enamel junction (DEJ), but severe pathologic changes in the dentin. An initial narrow band of normal-appearing dentin tubules (including the mantle layer) ceased abruptly and was replaced by a wavelike laminar zone parallel to the DEJ with occluded tubules. Multiple parallel channels of 5-10 &#119 m diameter were present at right angles to the DEJ indenting this zone, some terminating in retro-curved "processes." The abnormal dentin containing these channels almost completely occluded the pulp chamber. The structural and ultrastructural changes seen can be explained on the basis of the collagen defect in OI resulting in odontoblast dysfunction, which produces a distinct phenotype and one that is different from that in bone.     

Intertubular Capillary Changes in the Cortex and Medulla of Transplanted Kidneys and Their Relationship with Transplant Glomerulopathy: An Ultrastructural Study of 12 Transplantectomies

Twelve kidney allografts removed 3 to 98 months (mean, 44.8 months) after transplantation were investigated. The presence and severity of intertubular capillary changes, which were characterized by splitting and multilayering of the basement membrane, were carefully noted. These changes were graded as mild, moderate, and severe according to the number of basement membrane layers. They were found in both cortical and medullary capillaries in all but one kidney and were always associated with transplant glomerulopathy. Ultrastructural changes observed in the glomeruli and capillaries were similar, suggesting that they share the same pathogenetic mechanisms, probably connected to immune-mediated endothelial cell damage. Although glomeruli can be absent in small biopsy specimens, intertubular capillaries are easily detectable. Because capillary changes can be considered a marker of transplant glomerulopathy, which is known to have ominous prognostic significance, the identification of such changes acquires clinical relevance. Electron microscopic investigation is therefore strongly advisable whenever a renal biopsy is performed to identify transplant glomerulopathy.     

Intertubular Capillary Changes in the Cortex and Medulla of Transplanted Kidneys and Their Relationship with Transplant Glomerulopathy: An Ultrastructural Study of 12 Transplantectomies

Twelve kidney allografts removed 3 to 98 months (mean, 44.8 months) after transplantation were investigated. The presence and severity of intertubular capillary changes, which were characterized by splitting and multilayering of the basement membrane, were carefully noted. These changes were graded as mild, moderate, and severe according to the number of basement membrane layers. They were found in both cortical and medullary capillaries in all but one kidney and were always associated with transplant glomerulopathy. Ultrastructural changes observed in the glomeruli and capillaries were similar, suggesting that they share the same pathogenetic mechanisms, probably connected to immune-mediated endothelial cell damage. Although glomeruli can be absent in small biopsy specimens, intertubular capillaries are easily detectable. Because capillary changes can be considered a marker of transplant glomerulopathy, which is known to have ominous prognostic significance, the identification of such changes acquires clinical relevance. Electron microscopic investigation is therefore strongly advisable whenever a renal biopsy is performed to identify transplant glomerulopathy.     

Duodenal Periampullary Gangliocytic Paraganglioma: Report of Two Cases with Immunohistochemical and Ultrastructural Study

In an ultrastructural study of 24 cases of histiocytosis X, we were able to demonstrate Langerhans cell granules in all of 18 cases from which tissue had been submitted primarily for electron microscopy and in 4 of 6 cases from which only tissue retrieved from paraffin blocks was available for examination. In a subsequent correlative study we were able to demonstrate Langerhans cell granules in deparaffinized material from 11 of 14 cases (79%) in which they were known to exist. The incidence of histiocytes displaying Langerhans cell granules (in a single plane of section) fell from a median of 48% in samples processed primarily for electron microscopy to 14% in those retrieved from paraffin blocks. Our data suggest that electron microscopy, even when applied to the study of suboptimally preserved material, is a highly sensitive technique for confirming a diagnosis of histiocytosis X.     

Duodenal Periampullary Gangliocytic Paraganglioma: Report of Two Cases with Immunohistochemical and Ultrastructural Study

We report two cases of Gangliocytic Paraganglioma (GP) of the ampulla of Vater occurring in a 63-year-old and a 34-year-old individual. The patients were both admitted for a long history of intermittent gastrointestinal bleeding and abdominal discomfort, with no other symptoms. At endoscopy, the GP appeared as a polypoid, ulcerated mass in the ampullar region, measuring 2.5x1.8 and 2 cm, respectively. Microscopically, the tumors showed similar features and were composed of epithelial cells (more than 50%), spindle cells, and ganglion-like cells. The epithelial cells showed clear cytoplasm and formed nests (zellballen or paraganglioma-like groups), and less frequently, cords (carcinoid-like), extending to mucosa and submucosa. Ganglion cells were sparse, constantly associated with the spindle cells. Both epithelial and ganglion cells were synaptophysin, chromogranin A, and anti-neurofilament immunoreactive. The spindle cells were all S-100 positive. Ultrastructural studies revealed dark and light cells, rare elongated cellular processes, secretory granules, and fine fibrils resembling neurofilaments. The histogenesis of GP is still a matter of debate, however its neoplastic nature is supported by the occasionally reported malignant evolution.     

Pituitary Corticotroph Adenoma Containing Many Apoptotic Cells: A Histologic,Immunohistochemical, Ultrastructural and Molecular Study

Apoptosis regulates cell turnover in normal tissues and occurs during the neoplastic process. Owing to difficulties in recognizing apoptotic cells by histology alone, several complementary approaches have been introduced, which disclosed the presence of cells with typical nuclear and cytoplasmic changes characteristic of apoptosis. Electron microscopy remains the most conclusive method to reveal the structural changes. Identification of caspase cleaved keratin 18 intermediate filament rearrangements can contribute to the identification of early apoptotic changes. The authors present here an unusual case of a pituitary corticotroph adenoma removed surgically from a young woman with Cushing disease. The tumor contained many apoptotic cells identified by histology. In addition, the apoptotic events were investigated using various morphologic techniques, including electron microscopy, the in situ end-labeling technique, and immunohistochemistry to confirm the caspase-cleaved keratin 18 rearrangements.     

Specificity of Intertubular Capillary Changes: Comparative Ultrastructural Studies in Renal Allografts and Native Kidneys

The pathophysiology of chronic rejection of renal allografts is poorly understood and specific morphologic markers are being sought for its diagnosis. Ultrastructural splitting and reduplication of the basal lamina of the intertubular capillaries (ITCs) have been shown to be consistently associated with transplant glomerulopathy (TG) in renal allografts and have been used as a marker of chronic allograft rejection. Although the presence of ITC abnormalities is extremely helpful diag-nostically and has been considered a surrogate for the diagnosis of TG when glomeruli are not available for examination, their specificity has not been tested. This study examined 135 biopsy specimens from renal allografts and native kidneys and categorized the ITC basal lamina alterations into 5 patterns. The results showed that although marked ITC basal lamina abnormalities are characteristically seen in association with TG, lesser degrees of these changes may also be found in native kidneys and in transplants with other types of glomerulopathies. In native kidneys, splitting and reduplication of the ITC basal lamina were observed in cases of active lupus nephritis, membranoproliferative glomerulonephritis type I, crescentic glomerulonephritis, cryoglobulinemia, and hypertension. In allografts, ITC changes were seen in postinfectious proliferative glomerulonephritis, acute cyclosporin toxicity, and hemolytic uremic syndrome, in addition to cases with TG. The histopathologic diagnosis in renal diseases relies heavily on clinical, immunofluorescence, and ultrastructural findings. Therefore, in the transplantation setting, with other less common pathological processes ruled out, the presence of abnormalities of the ITC basal lamina is highly indicative of TG. This association is particularly true for cases with severe ITC abnormalities.     

Brenner Tumor of the Ovary: A Comparative Immunohistochemical and Ultrastructural Study With Transitional Cell Carcinoma of the Bladder

Because of a fancied light microscopic resemblance to transitional epithelium (urothelium), Brenner tumor (BT) of the ovary is commonly described as a transitional cell neoplasm. An inability to detect a great deal of similarity between the two at the ultrastructural level prompted this electron microscopic study comparing 3 benign Brenner tumors with normal urothelium and 6 transitional cell carcinomas (TCC) of varying histologic grade from the urinary bladder. To complement the ultrastructural observations, the immunophenotype of 8 benign BTs was evaluated together with that of 12 TCCs of the bladder using antibodies to thrombomodulin (TM), cytokeratin 20, cytokeratin 7, and carcinoembryonic antigen (CEA), all of which havebeen shown to react with TCCs of urothelial origin. At the ultrastructural level, there was only limited evidence of a morphologic likeness between the epithelial cells of BTs and those of the benign or neoplastic urothelium. The immunophenotype of the two tumors also differed significantly in that there was no reactivity for TM or cytokeratin 20 in the BTs, while these markers were expressed in the TCCs. Both BTs and TCCs were positive for cytokeratin 7 and may express CEA.     

Pituitary Adenoma in Carney Complex: An Immunohistochemical,Ultrastructural, and Immunoelectron Microscopic Study

First described in 1985, Carney complex is a rare, heritable disorder featuring abnormal skin pigmentation, cardiac and cutaneous myxoma, melanotic schwannoma of psammomatous type, and endocrine abnormalities, including pituitary adenomas. Patients with the latter present with elevated growth hormone (GH) levels and acromegaly or gigantism. Prolactin (PRL) elevation may also be seen. The authors have investigated 2 resected pituitary adenomas from patients with Carney complex. One, a 19-year-old female acromegalic with elevated GH, IgF-1, and PRL levels, had a mammosomatotroph adenoma immunoreactive for GH and PRL. Ultrastructurally, GH and PRL were present in the same secretory granules. The second patient, a 27-year-old acromegalic, had a sparsely granulated GH cell adenoma that by immuno-electron microscopy revealed GH immunoreactivity only. The lack of morphologic similarity between the 2 adenomas indicates that pituitary tumors in patients with Carney complex may not exhibit the same phenotype.     

Tracheomalacia in a Neonate with Kniest Dysplasia: Histopathologic and Ultrastructural Features

Kniest dysplasia is an autosomal-dominant chondrodysplastic condition characterized by disproportionate dwarfism, short trunk, small pelvis, kyphoscoliosis, short limbs, prominent joints, premature osteoarthritis, and craniofacial manifestations. The craniofacial abnormalities include tracheomalacia, midface hypoplasia, cleft palate, early onset myopia, retinal detachment, prominent eyes, and sensorineural hearing loss. Radiologic features include dumbbell-shaped femora, platyspondylia with anterior wedging of vertebral bodies, coronal clefts of thoracolumbar vertebral bodies, low broad ilia, and short tubular bones with broad metaphyses and deformed large epiphyses. This form of chondrodysplasia is associated with mutations in type II collagen splicing sequences. Mutations have been identified in the COL2A1 (type II collagen) gene between exons 12 and 24. Type II collagen is the predominant structural protein in cartilage, and mutations in this collagen account for the Kniest dysplasia phenotype. Histopathologic and ultrastructural features of epiphyseal plate cartilage have been described, but tracheal cartilage in an affected neonate has not been examined. The authors report the histopathologic and ultrastructural findings of anterior tracheal cartilage from a 35-day-old female with suspected chondrodysplasia who had tracheomalacia with airway obstruction. The tracheal cartilage was moderately cellular, but lacked cystic and myxoid changes in its matrix. The chondrocytes had abundant cytoplasmic PAS-positive inclusions. Some of these inclusions were diastase-resistant and were also highlighted on Alcian blue staining. Ultrastructural examination revealed chondrocytes with greatly dilated rough endoplasmic reticulum containing granular proteinaceous material. There were also frequent aggregates of typical glycogen. The defect in the COL2A1 gene is secondary to mutations, especially at splice junctions, and this markedly disrupts triple helix formation. The mutated type II procollagen results in intracellular retention within the chondrocytes, as abundant granular proteinaceous material within the dilated RER. A relationship is known to exist between the proportion of mutated to normal type II collagen in the matrix and the severity of the phenotype. With low levels of normal type II collagen, the phenotypic manifestations become more severe, such as in achondrogenesis type II. Both the quantity and quality of type II collagen modulates the phenotypic expression of type II collagenopathies.     

The Myofibroblast: An Assessment of Controversial Issues and a Definition Useful in Diagnosis and Research

Histopathological and ultrastructural findings in the liver of a female patient who suffered from Wilson's disease (WD) and viral hepatitis type C (HCV) are reported. Light and electron microscopy examinations demonstrated a variety of morphological alterations-many of them frequently seen in livers of patients with WD and others that can be found in cases presenting HCV infection. The influence of coexistence of these two diseases on morphological changes is discussed.     

Dilatation of Sinusoidal Capillary and Swelling of Sinusoidal Fenestration in Obesity: An Ultrastructural Study

Obesity, which is one of the causes of the lifestyle-related disease, is a hepatopathic exacerbation factor that causes a chronic hepatic disorder. In this study, we examined the pathological changes in the liver in mice with obesity induced by monosodium glutamate administration. Pathological analysis revealed the deposition of many lipid droplets in hepatocytes and sinusoidal dilatation in obese mice. Scanning electron microscopic analysis revealed the presence of sinusoidal dilatation, and the fenestrations of the sinusoid were significantly swollen in obese mice. These results suggest that a dysfunction of the sinusoidal endothelium occurs in chronic obesity.     

Intertubular Capillary Changes in Kidney Allografts: An Ultrastructural Study in Patients with Transplant Glomerulopathy

Fifteen kidney allograft specimens from 14 patients with transplant glomerulopathy were investigated by electron microscopy. Intertubular capillaries of all patients showed splitting and multilayering of the basement membranes, a change recalling that observed in the glomerular basement membranes in transplant glomerulopathy. Although the severity of the lesions varied from case to case, it was, to a certain extent, constant in each specimen and correlated well with the severity of the glomerular basement membrane changes in the same patient. The similarity of the two lesions suggests a possible common pathogenetic mechanism. The constant finding of intertubular capillary splitting and multilayering in patients with transplant glomerulopathy leads to the suspicion of this condition when such changes are found in kidney samples in which glomeruli are lacking. Therefore electron microscopy could achieve a specific diagnostic relevance in this field of nephropathology.     

Elevated Erythrocyte Sedimentation Rate Is Predictive of Interstitial Lung Disease and Mortality in Dermatomyositis: a Korean Retrospective Cohort Study

Interstitial lung disease (ILD) is a major cause of death in patients with dermatomyositis (DM). This study was aimed to examine the utility of the erythrocyte sedimentation rate (ESR) as a predictor of ILD and prognostic marker of mortality in patients with DM. One hundred-and-fourteen patients with DM were examined, including 28 with clinically amyopathic DM (CADM). A diagnosis of ILD was made based on high resolution computed tomography (HRCT) scans. The association between elevated ESR and pulmonary impairment and mortality was then examined. ILD was diagnosed in 53 (46.5%) of 114 DM patients. Cancer was diagnosed in 2 (3.8%) of 53 DM patients with ILD and in 24 (92.3%) of those without ILD (P < 0.001). The median ESR (50.0 mm/hour) in patients with ILD was significantly higher than that in patients without ILD (29.0 mm/hour; P < 0.001). ESR was inversely correlated with forced vital capacity (Spearman ρ = - 0.303; P = 0.007) and carbon monoxide diffusing capacity (ρ = - 0.319; P = 0.006). DM patients with baseline ESR ≥ 30 mm/hour had significantly higher mortality than those with ESR < 30 mm/hour (P = 0.002, log-rank test). Patients with a persistently high ESR despite immunosuppressive therapy was associated with higher mortality than those with a normalized ESR (P = 0.039, log-rank test). Elevated ESR is associated with increased mortality in patients with DM due to respiratory failure. Thus, monitoring ESR should be an integral part of the clinical care of DM patients.     

Cell and Tissue Interactions of Treponema pallidum in Primary and Secondary Syphilitic Skin Lesions: An Ultrastructural Study of Serial Sections

There are limited reports on the ultrastructure of syphilis skin lesions. The aim of this study has been to perform an electron microscopic investigation of the morphology and the tissue distribution of treponemes in primary and secondary cutaneous lesions. Three cases of primary syphilitic chancre and one case of secondary syphilis were included. Prominent epidermal abnormalities in the primary chancre and a perivascular inflammatory infiltrate in the secondary lesion were found by light microscopy. Ultrastructurally, spirochetes were located mainly in the blood vessel walls and dermal tissue of the chancre lesions. In the secondary syphilis case, spirochetes were more abundant between epidermal keratinocytes. Most of them adjusted to the intercellular spaces. Occasionally, the electron microscopy images were highly suggestive of an intracellular location. Both the ultrastructural and immunohistochemical examination of the primary and secondary syphilis lesions showed a paradoxical distribution of the causative microorganisms compared to the light microscopic changes. In addition, the ultrastructural findings strongly suggest that Treponema pallidum subspecies pallidum invades tissues, not only through an intercellular, but also through a transcellular pathway.