Mucosal Pathology Research Articles

EvolutionaryDevelopmentsinInterpretingthe Gluten-InducedMucosalCeliacLesion:An ArchimedianHeuristic.

The evolving history of the small intestinal biopsy and its interpretation—and misinterpretations—are described in this paper. Certain interpretative errors in the technical approaches to histological assessment are highlighted—even though we may never be rid of them. For example, mucosal “flattening” does not reduce individual villi to their cores, as still seems to be widely believed. Neither is the mucosa undergoing an atrophic process—since it can recover structurally. Rather, the intestinal mucosa manifests a vast hypertrophic response resulting in the formation of large plateaus formed from partially reduced villi and their amalgamation with the now increased height and width of the inter-villous ridges: this is associated with considerable increases in crypt volumes. Sections through mosaic plateaus gives an erroneous impression of the presence of stunted, flat-topped villi which continues to encourage both the continued use of irrelevant “atrophy” terminologies and a marked failure to perceive what random sections through mosaic plateaus actually look like. While reviewing the extensive 40+ year literature on mucosal analysis, we extracted data on intraepithelial lymphocytes (IEL) counts from 607 biopsies, and applied receiver-operating characteristic (ROC)-curve analysis. From that perspective, it appears that counting IEL/100 enterocyte nuclei in routine haematoxylin and eosin (H&E) sections provides the most useful discriminator of celiac mucosae at histological level, with an effective cut-off of 27 IEL, and offering a very high sensitivity with few false negatives. ROC-curve analysis also revealed the somewhat lesser accuracies of either CD3+ or γδ+ IEL counts. Current official guidelines seem to be somewhat inadequate in clearly defining the spectrum of gluten-induced mucosal pathologies and how they could be optimally interpreted, as well as in promoting the ideal manner for physicians and pathologists to interact in interpreting intestinal mucosae submitted for analysis. Future trends should incorporate 3-D printing and computerised modelling in order to exemplify the subtle micro-anatomical features associated with the crypt-villus interzone. The latter needs precise delineation with use of mRNA in-section assays for brush border enzymes such as alkaline phosphate and esterase. Other additional approaches are needed to facilitate recognition and interpretation of the features of this important inter-zone, such as wells, basins and hypertrophic alterations in the size of inter-villous ridges. The 3-D computerised models could considerably expand our understandings of the microvasculature and its changes—in relation both to crypt hypertrophy, in addition to the partial attrition and subsequent regrowth of villi from the inter-villous ridges during the flattening and recovery processes, respectively.

Glucose diffusion in colorectal mucosa-a comparative study between normal and cancer tissues.

Colorectal carcinoma is a major health concern worldwide and its high incidence and mortality require accurate screening methods. Following endoscopic examination, polyps must be removed for histopathological characterization. Aiming to contribute to the improvement of current endoscopy methods of colorectal carcinoma screening or even for future development of laser treatment procedures, we studied the diffusion properties of glucose and water in colorectal healthy and pathological mucosa. These parameters characterize the tissue dehydration and the refractive index matching mechanisms of optical clearing (OC). We used ex vivo tissues to measure the collimated transmittance spectra and thickness during treatments with OC solutions containing glucose in different concentrations. These time dependencies allowed for estimating the diffusion time and diffusion coefficient values of glucose and water in both types of tissues. The measured diffusion times for glucose in healthy and pathological mucosa samples were 299.2 ± 4.7 ?? s and 320.6 ± 10.6 ?? s for 40% and 35% glucose concentrations, respectively. Such a difference indicates a slower glucose diffusion in cancer tissues, which originate from their ability to trap far more glucose than healthy tissues. We have also found a higher free water content in cancerous tissue that is estimated as 64.4% instead of 59.4% for healthy mucosa.

消化管病理からの鑑別診断

消化管病理からの鑑別診断

Wavelength dependence of the refractive index of human colorectal tissues: comparison between healthy mucosa and cancer

Biological tissues have individual optical properties that may be used as an identity card. The refractive index in particular, which can be measured directly, is very significant for the improvement or development of optical technologies in clinical practice. With the objective of verifying if healthy and pathological tissues can be discriminated from refractive index measurements, we have studied human colorectal mucosa. By using the total internal reflection method to measure the refractive index from healthy and pathological colorectal mucosa tissues at different wavelengths, it was possible to calculate the dispersion curves for both types of tissues. It was observed a decaying refractive index with wavelength, both for healthy and pathological tissues, which were fitted with curves described by Cornu’s equation for wavelengths between ultraviolet and near-infrared range. Experimental results show higher refractive index values for the pathological mucosa for all wavelengths. By performing measurements at wavelengths near 850 nm, we have detected non-monotonic behavior for the refractive index of both healthy and pathological tissues. Such abnormal wavelength dependence is evidence of lipids in both tissues. The acquired experimental data demonstrated that it is possible to discriminate between healthy and pathological tissues from refractive index measurements. Similar studies can be made for different biological tissues. By using lasers with different wavelengths it might be possible to identify other tissue components.

Pathogenesis of diverticulosis and diverticular disease.

Diverticulosis is defined by the presence of diverticula due to herniation of mucosa and muscularis mucosa through the muscularis propria at sites of vascular penetration in the colon and is asymptomatic in the vast majority affected. There are global differences of distribution, in Western industrialized societies, the most common site is in the left colon, but in Asia right sided diverticulosis predominates. Whilst present in 17.5% of a general population and 42% of all comers at endoscopy it is seen in 71% of those aged ≥80 years. Diverticular disease is defined as clinically significant and symptomatic diverticulosis, which may have an absence of macroscopically overt colitis and in true diverticulitis there is macroscopic inflammation of diverticula with related acute or chronic complications. Whilst overall, diverticulitis affects only 4% of those with diverticulosis, in younger patients (aged 40-49 years) this peaks at 11%. Diverticulosis is one of the most common chronic diseases, yet research in this field on pathogenesis has lagged behind other common conditions such as diabetes mellitus. However, in the last decade there have been major advances in taxonomy that can be used to relate to patients' outcome and treatment in both medicine and surgery. It has been shown there is an association with age, diet, drugs and smoking. Genetic studies have shown a familial association and a specific gene, TNFSF 15 may predict severity of disease. The role of the microbiome has been explored and microbial and metabolomic signatures are also important in predicting disease severity. That diverticulosis is a chronic disease is shown by mucosal pathology with subtle chronic inflammation present in those with asymptomatic diverticulosis and inflammation may lead to muscular hypertrophy, enteric nerve remodeling with disordered motility. The diverticulitis quality of life instrument shows that this condition impacts markedly on patients' well-being and prevention and amelioration of complications should be the aim of treatment and further research to attain this goal is needed.

Vγ1⁺ γδT Cells Are Correlated With Increasing Expression of Eosinophil Cationic Protein and Metalloproteinase-7 in Chronic Rhinosinusitis With Nasal Polyps Inducing the Formation of Edema.

PurposeWe have found that expression of γδT cells is increased in pathological mucosa of chronic rhinosinusitis with nasal polyps (CRSwNP) compared with normal nasal mucosa. This increase is correlated with the infiltration of eosinophils in CRSwNP. Here, we investigated the expression of γδT cells, inflammation and tissue remodeling factors as well as their probable relationships in different types of chronic rhinosinusitis (CRS) in China.MethodsA total of 76 surgical tissue samples that included 43 CRSwNP samples (15 eosinophilic and 28 non-eosinophilic), 17 CRS samples without nasal polyps (CRSsNP), and 16 controls were obtained. Quantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to measure the mRNA expression levels of Vγ1+ γδT cells, Vγ4+ γδT cells, eosinophil cationic protein (ECP), interleukin (IL)-8, transforming growth factor (TGF)-β2, metalloproteinase (MMP)-7, tissue inhibitor of metalloproteinase (TIMP)-4 and hypoxia-inducible factor (HIF)-1α. Enzyme linked immunosorbent assay (ELISA) was used to measure the protein level of ECP and MMP-7 in CRSwNP. The eosinophils were counted and the level of edema was analyzed with HE staining.ResultsThe mRNA expression levels of the Vγ1 subset, ECP and MMP-7 were significantly increased in CRSwNP with histological characteristics of eosinophilic infiltration and edema. The expression of the Vγ1 gene in CRSwNP correlated positively with the expression of both ECP and MMP-7. No significant decreases in the mRNA expression levels of TGF-β2, TIMP-4 or HIF-1α were observed in the CRSwNP samples. The expression levels of Vγ1 gene, ECP and MMP-7 were significantly increased in eosinophilic CRSwNP compared to non-eosinophilic CRSwNP.ConclusionsOur results suggest the associations between Vγ1+ γδT cells, ECP and MMP-7 in CRSwNP, indicating that Vγ1+ γδT cells can induce the eosinophilic inflammation, which has a further effect on the formation of edema.

Laryngopharyngeal reflux and herpes simplex virus type 2 are possible risk factors for adult-onset recurrent respiratory papillomatosis (prospective case-control study).

The human papillomavirus (HPV) causes recurrent respiratory papillomatosis (RRP). Although HPV prevalence is high, the incidence of papillomatosis is low. Thus, factors other than HPV infection probably contribute to RRP. This study investigated whether patients with papillomatosis are more often infected with herpes simplex virus type 2 and chlamydia trachomatis (ChT) and whether laryngopharyngeal reflux (LPR) occurs in this group of patients more often. Prospective case-control study. Department of Otorhinolaryngology of University Hospital. The study included 20 patients with adult-onset RRP and 20 adult patients with vocal cord cyst and no pathology of laryngeal mucosa (control group). Immunohistochemical analysis of pepsin, HPV, herpes simplex virus type 2 and ChT was performed in biopsy specimens of laryngeal papillomas and of healthy laryngeal mucosa (control group) obtained from medial part of removed vocal cord cyst during microlaryngoscopy procedures. Pathologic LPR (pepsin in tissue) was diagnosed in 8/20 (40.0%) patients with papillomatosis and in 0/20 control patients (P = .003). Herpes simplex virus type 2 was present in 9/20 (45.0%) patients with papillomatosis and in 0/20 control patients (P = .001). Five specimens were positive for both pepsin and herpes simplex virus type 2. No samples were positive for ChT. There were no significant differences between groups for age, body mass index, diabetes mellitus and gastrooesophageal reflux disease. Tobacco exposure was not more frequent in RRP group either (P = .01). Results show that LPR and herpes simplex virus type 2 are significantly more often present in patients with RRP. LPR and herpes simplex virus type 2 might activate latent HPV infection and thereby be possible risk factors for RRP.

Distribution of oral and maxillofacial lesions in pediatric patients from a Brazilian southeastern population

ObjectivesOral lesions affecting infants account for approximately 10% of all samples from diagnostic services and studies investigating the distribution of these lesions in pediatrics from different geographic areas are desired to improve the diagnostic knowledge of clinicians. Therefore, the aim of this study is to describe the distribution of oral lesions in a southeastern Brazilian population. MethodsThe oral pathology files of the University of Campinas was retrospectively reviewed for all cases diagnosed from 2000 to 2014 affecting patients 16-years-old and younger. Data on gender and diagnosis were retrieved from patients' oral pathology reports and included in a Microsoft Excel® database. ResultsOut of 34,138 cases, 2539 affected pediatric patients (7.4%) with a higher incidence in those with 13–16 years-old. Salivary gland disease was the most common group of lesions (37.1%), followed by mucosal pathology (13.6%) and odontogenic cysts (11.3%). Mucous extravasation cyst was the most common lesion (36.3%), followed by fibrous hyperplasia (5.6%) and dental follicle (5.2%). Dental lesions were uncommon (7.9%) and malignancies rare (0.4%). ConclusionsOur results were similar to previous studies and the small differences observed were more likely result of methodological variability and characteristics of the service of origin from where samples were collected.

Classification chaos in coeliac disease: Does it really matter?

The spectrum of mucosal pathology in coeliac disease (CD), initially defined by Marsh in 1992 has been subjected to several modifications in the following years by Oberhuber, then by Corazza and Villanaci, and finally by Ensari. The present study, aimed to end the ongoing confusion regarding the classification of mucosal pathology in CD by applying all the classifications proposed so far on a large series of cases. A total of 270 duodenal biopsies taken from the distal duodenum of patients with a diagnosis of CD were included in the study. All biopsies were classified according to Marsh, Oberhuber, Corazza Villanaci, and Ensari classification schemes. For statistical analyses cases were divided into three groups: Group 1 included type 1 lesions in Marsh, Ensari, and Oberhuber and grade A in Corazza Villanaci classifications. Group 2 comprised of type 2 lesions in Marsh and Ensari classifications together with type2, type 3a and 3b lesions in Oberhuber classification and grade B1 lesions in Corazza Villanaci classification. Group 3 included type 3 lesions in Marsh and Ensari classifications, and type 3c lesions in Oberhuber, and grade B2 lesions in Corazza Villanaci classifications. The kappa value was 1.00 (excellent) for group 1, 0.53 (fair) for group 2 and 0.78 (excellent) for group 3 (p<0.0001). These results suggest that any of the above classification system would serve similar purposes in the diagnosis of CD. Therefore, it is advisable that the pathologist should use the simplest reliable scheme.

324. Sensitivity and specificity of fractal analysis to distinguish between healthy and pathological rectal mucosa microvasculature seen during colonoscopy

324. Sensitivity and specificity of fractal analysis to distinguish between healthy and pathological rectal mucosa microvasculature seen during colonoscopy

The aging mouth: differentiating normal aging from disease.

Aging is the physiologic change that occurs over time. In humans, this change occurs at different rates and are related to lifestyle, environment and genetics. It can be challenging to differentiate normal aging from disease. In the oral cavity, with increasing age the teeth demonstrate wearing of the enamel, chipping and fracture lines, and a darker color. The pulp chamber and canals are reduced in size as a result of the deposition of secondary dentin. Coronal or root caries, however, represent disease. A limited amount of periodontal attachment loss occurs in association with aging, usually manifesting as recession on the buccal surface of teeth. Severe periodontitis occurs in 10.5-12% of the population, with the peak incidence being observed at 35-40years of age. Changes to the mucosal tissue that occur with age include reduced wound-healing capacity. However, environmental factors, such as smoking, dramatically increase the risk of mucosal pathology. Reduced salivary gland function is often seen in association with medication usage, as well as with disorders such as diabetes mellitus. Both medication use and chronic disorders are more common in older adults. Masticatory function is of particular importance for older adults. Maintenance of a nutritionally complete diet is important for avoiding sarcopenia and the frailty syndrome. Successful oral aging is associated with adequate function and comfort. A reduced, but functional, dentition of 20 teeth in occlusion has been proposed as a measure of successful oral aging. Healthy oral aging is important to healthy aging from both biological and social perspectives.

A Dynamic Rabbit Model of Sinus Barotrauma and Its Related Pathology.

This study was undertaken to establish a dynamic animal model of sinus barotrauma (SB). The right nasal cavities of 65 rabbits were filled with sponges to obstruct the right ostiomeatal complex (OMC), while in the left nasal cavities, the left OMC was kept clear. The rabbits were exposed to hypobaric chamber simulation. The right sinuses were assigned as the model group, randomly divided into 13 subgroups with 5 in each subgroup, while the left sinuses were assigned as the control group. The hypobaric chamber simulation involved 6 pairs of ascending/descending speeds (100 m · s(-1), 75 m · s(-1), 50 m · s(-1)) to 2 altitudes (13,123 ft or 6562 ft). The ascending/descending speed for Model Group 13 was 15 m · s(-1) to an altitude of 13,123 ft. The control group was not exposed to hypobaric chamber simulation or obstruction of the OMC. All rabbits were monitored for behavior and via nasal endoscopy, MRI, and mucosal pathology, and statistically analyzed. SB appeared at the ascending/descending speeds of 50 m · s(-1), 75 m · s(-1), and 100 m · s(-1). SB was more obvious at 100 m · s(-1) than at 50 m · s(-1) and 75 m · s(-1), and SB happened mainly at altitudes between 0-6562 ft. Based on behavior during hypobaric chamber simulation and the results of endoscopic morphology, imaging, and cell pathology, SB could be divided into mild, moderate, and severe. By obstructing the OMC and using hypobaric chamber simulation at high ascending/descending speeds and altitude, a dynamic rabbit model of SB at various degrees was established. The severity of SB was proportional to the ascending/descending speeds and mainly seen below 6562 ft.

Precancerous diseases in the structure of oral mucosa pathology

Precancerous diseases in the structure of oral mucosa pathology

Precancerous diseases in the structure of oral mucosa pathology

Precancerous diseases in the structure of oral mucosa pathology

Oral and maxillofacial pathology submitted to Rizgary Teaching Hospital: a 6-year retrospective study

The majority of surveys concerning oral pathology accessions have focused on specific pathological categories or particular age groups, and few studies have analysed the whole range of specimens submitted for histopathological examination. An analysis of all oral pathology submitted to the Department of Histopathology in Rizgary Teaching Hospital in Erbil, Iraq, during the 6-year period 2008-2013, was performed. Histopathology samples (excluding smears) from the maxillae, mandible, salivary glands, the lips and oral mucosa, the tongue, the hard and soft palate and uvula, and the pillars of the fauces were included. The specimens were grouped into six diagnostic categories: oral mucosal and skin pathology; benign neoplasms; malignant neoplasms; non-neoplastic salivary gland disorders; cysts; and miscellaneous pathology. The total number of oral and maxillofacial specimens was 616 of 20,571 specimens. One-third of the oral and maxillofacial specimens were in the mucosal and skin pathology category, followed by benign neoplasms (24.2%) - of which 26.8% were odontogenic tumours and 42.6% were salivary gland tumours - and malignant neoplasms (n = 100, 16.2%). Neoplastic (n = 62) and non-neoplastic (n = 41) salivary gland disorders accounted for 16.7% (n = 103) of the specimens submitted, whereas odontogenic cysts (n = 34) and tumours (n = 40) comprised 5.5% and 6.5% of all biopsies. Many of our findings are consistent with those reported in the literature. However, a relatively larger proportion of neoplastic lesions were found in our cohort and in other Iraqi centres. Of concern to practising clinicians in Iraq is that one in 10 biopsies submitted was a squamous cell carcinoma and three in 20 accessions were malignant.

The microbiota-derived metabolite indole decreases mucosal inflammation and injury in a murine model of NSAID enteropathy

ABSTRACTNon-steroidal anti-inflammatory drugs (NSAIDs) are one of the most frequently used classes of medications in the world. Unfortunately, NSAIDs induce an enteropathy associated with high morbidity and mortality. Although the pathophysiology of this condition involves the interaction of the gut epithelium, microbiota, and NSAIDs, the precise mechanisms by which microbiota influence NSAID enteropathy are unclear. One possible mechanism is that the microbiota may attenuate the severity of disease by specific metabolite-mediated regulation of host inflammation and injury. The microbiota-derived tryptophan-metabolite indole is abundant in the healthy mammalian gut and positively influences intestinal health. We thus examined the effects of indole administration on NSAID enteropathy. Mice (n = 5 per group) were treated once daily for 7 days with an NSAID (indomethacin; 5 mg/kg), indole (20 mg/kg), indomethacin plus indole, or vehicle only (control). Outcomes compared among groups included: microscopic pathology; fecal calprotectin concentration; proportion of neutrophils in the spleen and mesenteric lymph nodes; fecal microbiota composition and diversity; small intestinal mucosal transcriptome; and, fecal tryptophan metabolites. Co-administration of indole with indomethacin: significantly reduced mucosal pathology scores, fecal calprotectin concentrations, and neutrophilic infiltration of the spleen and mesenteric lymph nodes induced by indomethacin; modulated NSAID-induced perturbation of the microbiota, fecal metabolites, and inferred metagenome; and, abrogated a pro-inflammatory gene expression profile in the small intestinal mucosa induced by indomethacin. The microbiota-derived metabolite indole attenuated multiple deleterious effects of NSAID enteropathy, including modulating inflammation mediated by innate immune responses and altering indomethacin-induced shift of the microbiota.

Coeliac disease: to classify or not to classify - that is the question!

Coeliac disease: to classify or not to classify - that is the question!

Neutralization of pro-inflammatory monocytes by targeting TLR2 dimerization ameliorates colitis.

Monocytes have emerged as critical driving force of acute inflammation. Here, we show that inhibition of Toll-like receptor 2(TLR2) dimerization by a TLR2 transmembrane peptide (TLR2-p) ameliorated DSS-induced colitis by interfering specifically with the activation of Ly6C(+) monocytes without affecting their recruitment to the colon. We report that TLR2-p directly interacts with TLR2 within the membrane, leading to inhibition of TLR2-TLR6/1 assembly induced by natural ligands. This was associated with decreased levels of extracellular signal-regulated kinases (ERK) signaling and reduced secretion of pro-inflammatory cytokines, such as interleukin (IL)-6, IL-23, IL-12, and IL-1β. Altogether, our study provides insights into the essential role of TLR2 dimerization in the activation of pathogenic pro-inflammatory Ly6C(hi) monocytes and suggests that inhibition of this aggregation by TLR2-p might have therapeutic potential in the treatment of acute gut inflammation.

Prevalence of Oral Premalignant Lesions/Conditions and Mucosal Pathology in North Indian Population

Prevalence of Oral Premalignant Lesions/Conditions and Mucosal Pathology in North Indian Population

Benign Orofacial Lesions in Libyan Population: A 17 Years Retrospective Study.

Objectives:To analyze the frequency and type of benign orofacial lesions submitted for diagnosis at Tripoli Medical Centre over 17 years period (1997-2013).Materials and Methods:Entries for specimens from patients were retrieved and compiled into 9 diagnostic categories and 82 diagnoses.Results:During the 17 years period, a total of 975 specimens were evaluated, it comprised a male-female ratio of 0.76:1. The mean age of biopsied patients was 36.3±18.32 years. The diagnostic category with the highest number of specimens was skin and mucosal pathology (22.87%); and the most frequent diagnosis was pyogenic granuloma (14.05%).Conclusion:Pyogenic granuloma, lichen planus, radicular cyst and fibroepithelial polyp were found to be the most predominant diagnoses. Frequencies of most benign orofacial diseases were comparable to similar studies in the literature and to those reported from the eastern region of Libya. Further surveys are needed to define the epidemiology of orofacial diseases in Libyan population.