Numerous small vesticles in a case of clear cell Leiomyoma of deep soft tissue: An Ultrastructural Study

Intestinal microvillous disorders are an uncommon cause of severe diarrhea, with very poor prognosis. The authors report the case of a female infant with Down syndrome, aganglionic megacolon, severe diarrhea, and jejunal biopsy with ultrastructural changes consistent with microvillous atrophy. The patient condition improved after a colostomy performed in the setting of the treatment of Hirschprung disease.     

Microvillous Inclusion Disease: Report of a Case with Atypical Features

Microvillous inclusion disease is a rare lethal disorder characterized by intractable, severe, watery diarrhea beginning in early infancy. The underlying defect is thought to be an autosomal recessive genetic abnormality resulting in defective brush-border assembly and differentiation. Normally, this diagnosis is easily established through the electron microscopic demonstration of characteristic microvilli-lined inclusions lying within the apical cytoplasm of surface enterocytes. In a small number of patients appearing to have microvillous inclusion disease it has not proven possible to demonstrate the typical inclusions. The existence of another entity, termed intestinal microvillous dystrophy, has been proposed to account for such occurrences. This assertion was founded in large part upon the observation that the few subjects studied all displayed a slightly atypical clinical presentation. The case now being presented exhibited the morphologic features ascribed to intestinal microvillous dystrophy but had a clinical presentation that was entirely typical of microvillous inclusion disease. It serves thus to conceptually unite intestinal microvillous dystrophy with microvillous inclusion disease.     

Microvillous Inclusion Disease: Report of a Case with Atypical Features

Microvillous inclusion disease is a rare lethal disorder characterized by intractable, severe, watery diarrhea beginning in early infancy. The underlying defect is thought to be an autosomal recessive genetic abnormality resulting in defective brush-border assembly and differentiation. Normally, this diagnosis is easily established through the electron microscopic demonstration of characteristic microvilli-lined inclusions lying within the apical cytoplasm of surface enterocytes. In a small number of patients appearing to have microvillous inclusion disease it has not proven possible to demonstrate the typical inclusions. The existence of another entity, termed intestinal microvillous dystrophy, has been proposed to account for such occurrences. This assertion was founded in large part upon the observation that the few subjects studied all displayed a slightly atypical clinical presentation. The case now being presented exhibited the morphologic features ascribed to intestinal microvillous dystrophy but had a clinical presentation that was entirely typical of microvillous inclusion disease. It serves thus to conceptually unite intestinal microvillous dystrophy with microvillous inclusion disease.     

Microvillous inclusion disease: report of a case with atypical features

Microvillous inclusion disease is a rare lethal disorder characterized by intractable, severe, watery diarrhea beginning in early infancy. The underlying defect is thought to be an autosomal recessive genetic abnormality resulting in defective brush-border assembly and differentiation. Normally, this diagnosis is easily established through the electron microscopic demonstration of characteristic microvilli-lined inclusions lying within the apical cytoplasm of surface enterocytes. In a small number of patients appearing to have microvillous inclusion disease it has not proven possible to demonstrate the typical inclusions. The existence of another entity, termed intestinal microvillous dystrophy, has been proposed to account for such occurrences. This assertion was founded in large part upon the observation that the few subjects studied all displayed a slightly atypical clinical presentation. The case now being presented exhibited the morphologic features ascribed to intestinal microvillous dystrophy but had a clinical presentation that was entirely typical of microvillous inclusion disease. It serves thus to conceptually unite intestinal microvillous dystrophy with microvillous inclusion disease.     

Microvillous Inclusion Disease: Report of a Case with Atypical Features

Microvillous inclusion disease is a rare lethal disorder characterized by intractable, severe, watery diarrhea beginning in early infancy. The underlying defect is thought to be an autosomal recessive genetic abnormality resulting in defective brush-border assembly and differentiation. Normally, this diagnosis is easily established through the electron microscopic demonstration of characteristic microvilli-lined inclusions lying within the apical cytoplasm of surface enterocytes. In a small number of patients appearing to have microvillous inclusion disease it has not proven possible to demonstrate the typical inclusions. The existence of another entity, termed intestinal microvillous dystrophy, has been proposed to account for such occurrences. This assertion was founded in large part upon the observation that the few subjects studied all displayed a slightly atypical clinical presentation. The case now being presented exhibited the morphologic features ascribed to intestinal microvillous dystrophy but had a clinical presentation that was entirely typical of microvillous inclusion disease. It serves thus to conceptually unite intestinal microvillous dystrophy with microvillous inclusion disease.     

Microvillous Inclusion Disease with Abundant Vermiform,Electron-Lucent Vesicles

A 3-month-old girl with congenital secretory diarrhea underwent a duodenal biopsy. Histologic study showed villous atrophy and large amounts of PAS-positive material within enterocyte cytoplasm. Despite a clinical suspicion of microvillous inclusion disease, 2 sessions of electron microscopy were unsuccessful in detecting the diagnostic inclusions. Instead, large aggregates of electron-lucent, vermiform membranous vesicles were observed in enterocyte cytoplasm, corresponding to the PAS-positive material. A third attempt at electron microscopy was successful in detecting small numbers of microvillous inclusions. These and other recently reported cases document an expanding spectrum of ultrastructural findings in this disease, including examples where the classic microvillous inclusions are overshadowed by other features.     

Microvillous inclusion disease with abundant vermiform, electron-lucent vesicles

A 3-month-old girl with congenital secretory diarrhea underwent a duodenal biopsy. Histologic study showed villous atrophy and large amounts of PAS-positive material within enterocyte cytoplasm. Despite a clinical suspicion of microvillous inclusion disease, 2 sessions of electron microscopy were unsuccessful in detecting the diagnostic inclusions. Instead, large aggregates of electron-lucent, vermiform membranous vesicles were observed in enterocyte cytoplasm, corresponding to the PAS-positive material. A third attempt at electron microscopy was successful in detecting small numbers of microvillous inclusions. These and other recently reported cases document an expanding spectrum of ultrastructural findings in this disease, including examples where the classic microvillous inclusions are overshadowed by other features.     

Microvillous inclusion disease--an ultrastructural diagnosis: with a review of the literature

Microvillous inclusion disease is a rare disorder of infancy associated with protracted diarrhea. This malady reveals distinct ultrastructural changes. The surface enterocytes of the duodenum show vesicles lined with microvilli and the surface microvilli are poorly formed. The authors present one case of microvillous inclusion disease with a review of the literature.     

CD10 expression in a case of microvillous inclusion disease

All over the causes of intractable diarrhea of infancy, microvillous inclusion disease is a rare congenital defect of intestinal brush border of unknown aetiology. An autosomal recessive inheritance is suggested by cases occurring in siblings and high incidence of consanguinity. The prognosis of the disease is extremely poor, as life can be sustained only by total parenteral nutrition. Combined bowel-liver or bowel transplantation is regarded as the only potentially life-saving therapy. We report a case of microvillous atrophy who undergone a combined bowel, colonic and liver transplantation, and discuss the tools allowing the light microscopic diagnosis.     

Protracted diarrhea: results of the five-year survey in a tertiary hospital in Korea.

The syndrome of protracted diarrhea (PD) includes several diseases with diverse etiologies. This study was conducted to characterize the spectrum of causes, clinical manifestations, and the outcomes of PD. A retrospective analysis of the clinical and pathological findings was performed on 25 patients with diarrhea starting within the first 2 yr of life and a requirement of parenteral nutrition (PN). According to the intestinal histopathology, patients were classified into four groups: immune enteropathy (12 cases), lymphangiectasia (6 cases), epithelial dysplasia (5 cases), and unclassified (2 cases). All patients with epithelial dysplasia had earlier onset of diarrhea and longer duration of PN than those in the other groups. Three patients (12%) had an evidence of a familial condition. Five patients (three with microvillous inclusion disease and two with immune enteropathy) died. Sixteen patients recovered, and three (two with primary lymphangiectasia and one with microvillous inclusion disease) still had diarrhea. One patient underwent intestinal transplantation for tufting enteropathy. In conclusion, infants with PD should be referred to specialized centers where advanced diagnostic and therapeutic facilities are available, because histological analysis is critical for the diagnosis of PD, and PN or intestinal transplantation is the only therapeutic option in a subset of cases.     

Unusual ultrastructural features in microvillous inclusion disease: a report of two cases

Microvillous Inclusion Disease (MID) is an inherited disorder characterized by intractable diarrhea in infancy. Ultrastructural detection of pathognomonic microvillous inclusions in the enterocytes is essential for diagnosis. The aim of this research is to contribute to the knowledge of MID studying enterocytes and goblet cells (gc). Samples of duodenal mucosa from two young infants with MID (aged 75 days and 3 months, respectively) were studied by light and electron microscopy. Detection in the intestinal villi of immature gc (with microvilli) in one of the cases led us to seek them in control samples. The total number of gc with microvilli (immature) and without microvilli (mature) were counted. In both MID specimens, light microscopy showed atrophy of villi and PAS-positive material in the enterocyte cytoplasm. The ultrastructure of villous enterocytes was characterized by brush-border abnormalities, microvillous inclusions, dense apical granules, and lysosomes. Intermediate structures between microvillous inclusions and lysosomes were also detected within a cell, as were rare microvilli on the lateral membrane of the enterocytes. In one MID specimen, immature gc were also identified in the absorptive compartment. Only mature gc were observed in the controls. The significance of the latter finding requires further studies.     

Microvillous inclusion disease: ultrastructural variability

Microvillous inclusion disease (MVID) is a congenital, usually neonatal, autosomal recessive condition manifested by severe, prolonged secretory diarrhea. Intestinal biopsies reveal extensive microvilli abnormalities, typical inclusions and vesicles mainly of the apical-luminal enterocytes and colonocytes. Although diagnosis can be suspected by special stains of the mucosa (PAS, CD10), the definitive diagnosis, recommended in view of potential intestinal transplantation, requires electron microscopy. In view of the marked variability of ultrastructural changes, extensive illustration is considered valuable for diagnosis. While the pathogenesis is still unknown, a number of images illustrate the suspected “arrested-trafficking” hypothesis of microvillous abnormalities. Others micrographs support the “engulfing” mechanism of inclusion formation. The electron micrographs should help ultrastructural diagnosis in this heterogeneous disease and can confirm diagnosis even in the absence of the typical inclusions.     

Microvillous Inclusion Disease: Ultrastructural Variability

Microvillous inclusion disease (MVID) is a congenital, usually neonatal, autosomal recessive condition manifested by severe, prolonged secretory diarrhea. Intestinal biopsies reveal extensive microvilli abnormalities, typical inclusions and vesicles mainly of the apical-luminal enterocytes and colonocytes. Although diagnosis can be suspected by special stains of the mucosa (PAS, CD10), the definitive diagnosis, recommended in view of potential intestinal transplantation, requires electron microscopy. In view of the marked variability of ultrastructural changes, extensive illustration is considered valuable for diagnosis. While the pathogenesis is still unknown, a number of images illustrate the suspected “arrested-trafficking” hypothesis of microvillous abnormalities. Others micrographs support the “engulfing” mechanism of inclusion formation. The electron micrographs should help ultrastructural diagnosis in this heterogeneous disease and can confirm diagnosis even in the absence of the typical inclusions.     

巴柳氮对结肠炎小鼠肠TNF-α、IFN-γ和黏膜通透性影响的研究

目的 探讨结肠炎小鼠肠黏膜中TNF-α和IFN-γ的含量与肠黏膜通透性的关系及抗结肠炎药物巴柳氮的影响.方法 将45只C57BL/6J小鼠,分成正常对照组、葡聚糖硫酸钠(dextran-sulfatesodium,DSS)模型组、巴柳氮不同剂量组(42、141、423 ms/ks),正常对照组自由饮水,其余各组自由饮用5%DSS溶液7 d.巴柳氮采用灌胃给药7 d.实验结束后取结肠进行HE染色评分,结肠匀浆检测髓过氧化物酶(myeloperoxidase,MPO)活性,小肠匀浆检测TNF-α和IFN-γ含量,小肠黏膜进行透射电镜检查.Evans-蓝方法检测小肠黏膜通透性.结果 DSS结肠炎组小鼠病理评分(histo-logical index,HI)增高(P<0.01),结肠黏膜MPO活性增高,小肠匀浆TNF-α和IFN-γ含量明显增高(P<0.05).透射电镜检查小肠黏膜绒毛变短、萎缩,细胞间连接复合体缩短、变宽,细胞间隙扩大;小肠组织中Evans-蓝含量增高,提示肠黏膜通透性增加.巴柳氮组小鼠HI降低(P<0.05),MPO活性减低,同时TNF-α和IFN-γ含量降低.小肠黏膜绒毛形态和细胞间隙接近正常,小肠组织中Evans-蓝含量明显减少.结论 DSS结肠炎小鼠中肠黏膜TNF-α和IFN-γ含量与肠黏膜通透性增加一致,巴柳氮在其抗结肠炎作用同时修复肠黏膜屏障.     

Microvillous anomalies induced by various conditions of stress in the small intestine of the rat

The ultrastructural effects of acute and chronic stress in vivo on jejunal microvilli were studied in rats, in order to investigate factors which control microvillous organization. Rats were subjected to one of the following six conditions of stress: ischemia (15 min), hypothermia (20 min), lactose-induced diarrhea (3 days), mecamylamine-induced malabsorption (3 days), protein malnutrition (3 wk), or protein-calorie malnutrition (3 wk). At the end of each period of stress, the jejunum was fixed and prepared for electron microscopy. All six agents caused the appearance of abnormal microvilli, defined as “twinned”, involving up to 9.1% of the mucosal surface. The twinned microvillus consists of two cytoplasmic projections stemming from a base which is continuous with the cortical cytoplasm of the absorptive epithelial cell. Longitudinal filaments run from the apex of each branch, through the base, to the terminal web. In addition, another type of microvillous anomaly was observed, which was defined as “composite.” In the composite microvillus, three or more filamentous axes from the terminal web come to lie within a single enlarged microvillus. Contact of filaments with the apical membrane did not correlate with the presence of subapical dense material in either type of anomaly. Both abnormalities probably represent a stage of suppression of the microvillous border, rather than its regeneration, since they were observed during the period of stress.     

Microvillous Inclusion Disease: A Clinicopathologic Study of 17 Cases from the UK

Background: Microvillous inclusion disease (MVID) is a rare congenital disease producing intractable secretory diarrhea in early infancy. It is characterized by diffuse intestinal villous atrophy with no inflammatory reaction. Ultrastructural identification of apical microvillous inclusions in the surface enterocytes is diagnostic. However, there is difficulty in the diagnosis of MVID due to the existence of variants (e.g., microvillous dystrophy), possible disease resolution, and tissue orientation for electron microscopy (EM). The authors analyzed materials from 4 patients with MVID from a single institution. The morphologic features, distribution of lesions, biomarkers, and complementary ultrastructural characteristics were studied. Design: Materials of MVID cases were collected from 6 different hospitals in the United Kingdom between 1990 and 2008. Epidemiological data, including age range, median, mode, sex ratios, and follow-up, were retrieved. All intestinal biopsy specimens were analyzed histologically, histochemically (for PAS, n = 17), immunohistochemically (for CD10, n = 2 and polyclonal CEA, n = 4), and ultrastructurally (n = 9). Results: Ultrastructurally, apical microvillous inclusions in surface enterocytes in duodenal biopsies were identified in all cases, while 1 case had variant morphology (microvillous dystrophy and very occasionally atypical microvillous inclusions). Tissue orientation for EM was supportive for identification of inclusions in apical enterocytes. Morphologically, a bubbly vacuolated appearance of the apical cytoplasm with extensive or patchy absence of the brush border with occasional cytoplasm inclusions was observed in the enterocytes. Some of these changes vaguely resembled gastric mucin cell metaplasia. Architecturally, villous blunting with either crypt hypoplasia or hyperplasia and absence of inflammation were common findings. The epithelial changes were also found in colon biopsies. PAS, CD10, and p-CEA showed a bright apical cytoplasmic blush/staining, which correlated ultrastructurally with apical granules with inclusions of variable electron density in all cases. These stains also highlighted the targetoid inclusions. Conclusion: Besides electron microscopy identification of inclusions, the light microscopic morphological features together with the biomarker studies highlighting the apical cytoplasmic blush are quite unique and diagnostic of MVID. Furthermore, it is the opinion of the authors that a diagnosis of MVID can be made without electron microscopy.     

Role of a 60-megadalton plasmid and Shiga-like toxins in the pathogenesis of infection caused by enterohemorrhagic Escherichia coli O157:H7 in gnotobiotic piglets.

Enterohemorrhagic Escherichia coli (EHEC) of serotype O157:H7 has two putative virulence factors: (i) a fimbrial adhesin, specified by a 60-megadalton (MDa) plasmid, and (ii) bacteriophage-specified cytotoxin(s), known as Shiga-like toxin (SLT) or verotoxin. The contribution of these factors to the pathogenesis of EHEC-induced disease in gnotobiotic piglets was examined. The bacterial strains included the following: two EHEC strains and their corresponding plasmid-cured derivatives; another EHEC isolate and its derivative which had spontaneously lost the ability to produce SLT; one E. coli K-12 transconjugatant containing a 60-MDa plasmid from an EHEC strain; two K-12 strains into which an SLT-producing phage had been transduced (one of these strains also carried a 60-MDa EHEC-derived plasmid); and the parent K-12 strain. Each strain was fed to four piglets, which were observed for diarrhea and examined for development of characteristic mucosal lesions 3 or 5 days after inoculation. All 24 piglets inoculated with the three EHEC strains and their respective derivatives (two plasmid cured and one SLT negative) showed the typical mucosal lesions of bacterial attachment: effacement of microvillous border and cell membrane dissolution culminating in destruction of surface and glandular epithelium in the cecum and colon. No such lesions were observed in 12 piglets inoculated with three strains of E. coli K-12, including the strain which carried both the 60-MDa plasmid and a phage which specified production of SLT. Moderate to severe diarrhea was observed in 16 piglets inoculated with two EHEC strains and their derivatives (one plasmid cured and one SLT negative). The third EHEC strain and its plasmid-cured derivative produced fewer typical mucosal lesions and no diarrhea. The reason for the reduced virulence of this strain was not clear. These results demonstrate that neither the 60-MDa plasmid nor the capacity to produce SLT is essential for expression of virulence by E. coli O157:H7 in gnotobiotic piglets.     

Cryptosporidiosis of the human small intestine: a light and electron microscopic study

Intestinal infection by the coccidian parasite Cryptosporidium is a well-recognized condition in immunocompromised hosts and in some normal persons. The authors studied a patient with acquired immunodeficiency syndrome and cryptosporidiosis of the small intestine. The parasite inhabits the microvillous brush border of the intestinal epithelium and must be carefully sought on light microscopic examination of intestinal biopsy specimens. Characteristic life cycle stages are observed on electron microscopy. The absence of significant light microscopic alterations of the villous architecture in this patient's biopsy specimen and in other cases suggests that other factors, such as toxin elaboration by cryptosporidia or other organisms, may be involved in the pathogenesis of diarrhea. Abnormal aggregation of lysosomes at the apices of intestinal epithelial cells may reflect ineffective host phagocytic mechanisms.     

The bat pituitary cleft: phasic production and release of secretory granules by microvillous cells

The ultrastructure of the two types of cells, ciliated and microvillous, lining the wall of the bat pituitary cleft was examined at different periods during the annual life cycle. Ciliated lining cells remained unchanged in structure throughout the yearly activity cycle. In contrast, microvillous lining cells exhibited striking cyclic morphological changes. Throughout the active phase of the life cycle and during most of the hibernating period, the structure of microvillous cells is unchanged. However, toward the end of hibernation, the cells produce and store large numbers of round to ovoid dense secretory granules. Just prior to arousal, the microvillous cells are packed with secretory granules. At arousal, the cells undergo marked degranulation; the granules appear to be discharged into the lumen of the cleft. Degranulation is followed by a period of proliferation of rough endoplasmic reticulum, the cavity of which is often filled with large paracrystalline inclusions. Within 1 month, microvillous cells return to a resting state and are devoid of secretory granules.     

Biotype, serotype, and pathogenicity of attaching and effacing enteropathogenic Escherichia coli strains isolated from diarrheic commercial rabbits.

A total of 568 strains of Escherichia coli isolated from healthy and diarrheic rabbits were separated into 11 different biotypes according to the fermentation patterns of four carbohydrates. Strains belonging to biotypes 1 to 3, 6, and 8 induced lesions characteristic for attaching and effacing E. coli (AEEC). They attached to the intestinal epithelium of the terminal small intestine and the large intestine of 5-week-old rabbits after experimental infection and caused effacement of the microvillous brush border. However, pathogenicity for weaned rabbits, as judged by diarrhea score, anorexia, and reduced weight gain, varied according to the biotypes of the strains. Strains belonging to biotypes 1 and 6 produced only discrete clinical signs, strains belonging to biotypes 2 and 3+ (motile) induced diarrhea and growth depression, whereas strains belonging to biotypes 3- (immotile) and 8 caused severe clinical signs and high mortality. This confirms evidence from the field. Biotypes 3- and 8, accounting for 35.5 and 7.1% of AEEC strains in weaned diarrheic rabbits, respectively, were not detected in weaned healthy rabbits, while biotype 2 was the predominant strain in weaned healthy rabbits (62.3%). Finally, serotyping showed a close relationship between biotype and serotype of the AEEC examined. Most strains of biotypes 1+ and 2+ tested were O109:K-:H2 and O132:K-:H2, respectively, whereas all strains tested of biotype 3- were O15:K-:H- and those of biotype 8 were O103:K-:H2. These data indicate that specific clones of AEEC might be involved in juvenile rabbit enteritis. It was concluded that determination of biotypes allows the screening of highly pathogenic AEEC in weaned rabbits (biotypes 3- and 8).