Topical Corticosteroids Decrease IL-25 Expression by Immunohistochemistry.

BACKGROUND: Interleukin-25 (IL-25) is an important contributing factor in the pathogenesis of allergic rhinitis. It leads to increasing peripheral and infiltrating eosinophilia as well as serum IgE, IgG, and Th2 cytokines (IL-4, IL-5, IL-13), which are responsible for the allergic symptoms. Intranasal steroids (INS) are effective in treating allergic rhinitis, but their effect on IL-25 release has not been studied. We aimed to study the link between IL-25 and the pathophysiology of allergic rhinitis as well as the effect of INS on its release. METHODOLOGY: This was a cohort, prospective, nonrandomized study that included 60 patients, 35 allergic rhinitis patients and 25 controls. We studied the effect of INS on IL-25 release. RESULTS: Of allergic rhinitis patients 68.6% had strong cytoplasmic stain of IL-25 in the epithelial layer, while 25.7% had intermediate stain. INS caused significantly reduced IL-25 stain as only 14.3% of patients had intermediate stain and 85.7% had weak stain. Moreover, a correlation was found between nasal smear eosinophilia and the degree of IL-25 staining in the epithelial layer. CONCLUSION: Intranasal corticosteroids appear to be effective in the downregulation of IL-25, which may explain some of the utility of intranasal corticosteroid treatment in improving allergic rhinitis symptoms.

Chronic Mastitis in Egypt and Morocco: Differentiating between Idiopathic Granulomatous Mastitis and IgG4-Related Disease.

Idiopathic granulomatous mastitis (IGM) is a benign, frequently severe chronic inflammatory lesion of the breast. Its etiology remains unknown and reported cases vary in their presentation and histologic findings with an optimal treatment algorithm yet to be described owing mainly to the disease's heterogeneity. IgG4-related disease (IgG4-RD) is a newly recognized systemic fibroinflammatory condition characterized by a dense lymphoplasmacytic infiltrate with many IgG4-positive plasma cells, storiform fibrosis, and obliterative phlebitis. Immunosuppressive therapy is considered to be an effective first-line therapy for IgG4-RD. We sought to clarify and classify chronic mastitis according to the histologic findings of IgG4-RD mastitis with respect to IGM and to develop a robust diagnostic framework to help select patients for optimal treatment strategies. Using the largest collection to date (43 cases from Egypt and Morocco), we show that despite sharing many features, IGM and IgG4-RD mastitis are separate diseases. To diagnostically separate the diseases, we created a classification schema-termed the Michigan Classification-based upon our large series of cases, the consensus statement on IgG4-RD, and the histologic description of IGM in the literature. Using our classification, we discerned 17 cases of IgG4-RD and 8 cases of IGM among the 43 chronic mastitis cases, with 18 indeterminate cases. Thus, our Michigan Classification can form the basis of rational stratification of chronic mastitis patients between these two clinically and histopathologically heterogeneous diseases.

Lymphatic obstruction: a novel etiologic factor in the formation of antrochoanal polyps.

OBJECTIVES: Antrochoanal polyps (ACPs) originate from the inner wall of the maxillary sinus and either pass through the natural sinus ostia or cause pressure-induced destruction of the medial sinus wall. Eventually, they extend into the choanae and nasopharynx. Most authors who have studied the microstructure of ACPs, including the component stromal cells and surface epithelium, have not examined the transitional area between the sinus mucosa and the pedicle of the polyp. No explanation has been given for the absence of a cystic intrasinus portion of the polyp, in many cases refuting the therapy (most accepted) that polyps are caused by a mucous gland with a blocked acinus. We noted during endoscopic removal of the ACPs that the antral part of the polyp was cystic in only 5% of patients, and polypoid in 95%. The cystic intrasinus portion of the polyp is a cornerstone of the pathophysiology of ACPs, whether caused by inflammation, cicatrization, or allergy. This finding prompted us to examine the transitional area between the sinus mucosa and the pedicle of the polyp to verify the possibility that lymphatic obstruction--whether primary (areas of higher tissue pressure) or secondary (cicatrization or inflammation)-could be an etiologic factor in the formation of ACPs. METHODS: The study material consisted of 25 ACPs and 25 chronic maxillary sinusitis mucosal biopsy specimens (control group). The detection of lymphatic vessels was based on the identification of lymph vessel endothelial hyaluronic acid receptor I (LYVE-I) in the endothelial cells of the lymphatic capillaries. This was the first lymph-specific hyaluronic acid receptor to be characterized, and is a uniquely powerful marker for lymph vessels, differentiating them from (blood) capillaries. RESULTS: The density of the lymphatic vessels was marked in 22 of the 25 ACP specimens, ie, 88% of the ACP cases, compared with 16% of the control group. CONCLUSIONS: This study resulted in two main findings. The first was the absence of intramaxillary cysts in the ACPs in 23 cases (92%). The second was the markedly high density of lymphatic vessels in the transitional area between the sinus mucosa and the pedicle of the ACPs, in comparison with the density in the control group. These two findings refute the "blocked acinus theory" and indicate that lymphatic obstruction, whether primary or secondary to chronic sinus infection, might play a leading role in the formation and further growth of ACPs.

Prevalence of extramucosal fungal elements in sinonasal polyposis: a mycological and pathologic study in an Egyptian population.

OBJECTIVE AND HYPOTHESIS: The objective of the study was to define the true incidence of fungal elements in the nasal and sinus mucous in cases of chronic rhinosinusitis (CRS) with bilateral polyposis compared with normal controls-in an Egyptian African population-via mycological and histologic techniques. STUDY DESIGN: This study was conducted prospectively on 100 patients with the clinical diagnosis of CRS with bilateral nasal polyposis. Fifty volunteers with no history of nasal or paranasal sinus disease served as a control group. RESULTS AND CONCLUSION: The postulated criteria for the diagnosis of allergic fungal sinusitis were present in 92% of CRS with polyposis, suggesting that fungi are involved in the disease process of most CRS patients.

Immunohistochemical Study of Ezrin Expression in Colorectal Carcinoma: A Comparative Study between Objective Method and Digital Quantitative Assessment.

BACKGROUND: Colorectal cancer is one of the leading causes of cancer death in both developed and developing nations. It is the third most common type of cancer and the fourth leading cause of cancer-related deaths worldwide. Ezrin is involved in maintaining cell structure and cell motility. Expression levels of the ezrin gene correlate with numerous human malignancies. MATERIAL AND METHODS: Ezrin expression was evaluated in fifty one cases of colorectal carcinoma by using two methods; objective and quantitative method to determine the statistical relation between ezrin objective analysis score and clinicopathological parameters and to do a comparative study between both methods of analysis. RESULTS: Ezrin was expressed in 92.2% of cases, and it showed a statistical significant relation with tumor grade. A statistically significant relation was found between ezrin objective analysis score and ezrin quantitative analysis score (P-value <0.05). A strong positive Pearson correlation exists between both methods of analysis (R=0.868). CONCLUSION: Ezrin has a role in colorectal cancer progression and it might provide clinically valuable information in predicting the behavior of colorectal cancer. Digital pathology offers the potential for improvements in quality, efficacy and safety. It will be necessary to carry out similar studies on a larger sample size in order to elucidate the possible prognostic significance of ezrin in colorectal carcinoma and ensure the ability of digital pathology to transform the practice of diagnostic pathology. 
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Ki 67 assessment in breast cancer in an Egyptian population: a comparative study between manual assessment on optical microscopy and digital quantitative assessment.

BACKGROUND: Breast cancer is by far the most frequent cancer among women. The proliferative index, Ki-67, is more and more taken into consideration for treatment decisions. However, the reliability of the established Ki-67 scoring is limited. Digital pathology is currently suggested to be a potential solution to Ki 67 assessment problems. METHODS: This is a retrospective and prospective study including 100 patients diagnosed with invasive breast cancer. Three senior pathologists have been asked to estimate the Ki-67 proliferative index for each of the 100 cases by examining the whole glass slides on optical microscope and providing a continuous score then a categorical score ('high' and 'low' Ki 67 index) using once 14%, once 20% as threshold indicative of high Ki67 status. Finally, a digital quantitative assessment of Ki67 was performed. RESULTS: A high inter-observer agreement was found when using optical microscopy for Ki 67 assessment, with correlation coefficient (CC) estimated at 0.878 (p value < 0.01). The overall agreement between manual and automated evaluation of Ki 67 was only substantial (CC estimated at 0.745 (p value < 0.01)). When using categorical scores, the inter-observers concordance was substantial using both cutoff points with kappa value estimated at 0.796 ([0.696-0.925] while using 14% as a cut off point and at 0.766 ([0.672-0.938] while using 20% as a cutoff point (p value < 0). The inter-observers agreement was better while using 14% as cutoff point. Agreement between manual and automated assessment of Ki 67 indices using both cutoff points was only substantial (Kappa estimated at 0.623, p value < 0.01). In comparison to automated assessment of Ki 67 index, while using 14% as a cutoff point, the overall tendency of all observers was to overestimate the Ki 67 values but to underestimate the proliferation index while using 20% as a cutoff point. CONCLUSION: Automated assessment of Ki 67 value would appear to be comparable to visual Ki 67 assessment on optical microscopy. Such study would help define the role of digital pathology as a potential easy-to use tool for a robust and standardized fully automated Ki 67 scoring.

A comparative study between ciliary count and the degree of opacity of paranasal sinus CT scans in chronic sinusitis pre and post FESS.

OBJECTIVE: To investigate the relationship between the extent of sinus disease in chronic sinusitis as detected radiologically by computed tomography (CT) scan and the population of cilia (ciliary area) both before and after functional endoscopic sinus surgery (FESS). In a simple way this is a trial to statistically prove that the CT scan could be a valid indicator and a mirror of the histological status of the sinus mucosa. DESIGN: Twenty adult patients were enrolled in this study. Radiological extension of the sinus disease was quantitated using the classification proposed by Kennedy in 1992 and the ciliary population was studied using scanning electron microscopy and image analysis softwares. RESULTS AND CONCLUSION: The more advanced the sinusitis, as evidenced by CT scans, the more the expected reduction in the ciliary area (CA) and in the ciliary count. But after FESS the degree of ciliary regeneration does not depend statistically on the radiological condition of the sinuses and the degree of opacity prior to intervention, i.e. a statistically valid inverse relationship exists between the radiological stage of sinusitis and the ciliary population pre-operatively but the same relation does not extend to the ciliary population post-operatively.

Comparative study between quantitative digital image analysis and fluorescence in situ hybridization of breast cancer equivocal human epidermal growth factor receptors 2 score 2(+) cases.

BACKGROUND: Optimization of workflow for breast cancer samples with equivocal human epidermal growth factor receptors 2 (HER2)/neu score 2(+) results in routine practice, remains to be a central focus of the on-going efforts to assess HER2 status. According to the College of American Pathologists/American Society of Clinical Oncology guidelines equivocal HER2/neu score 2(+) cases are subject for further testing, usually by fluorescence in situ hybridization (FISH) investigations. It still remains on open question, whether quantitative digital image analysis of HER2 immunohistochemistry (IHC) stained slides can assist in further refining the HER2 score 2(+). AIM OF THIS WORK: To assess utility of quantitative digital analysis of IHC stained slides and compare its performance to FISH in cases of breast cancer with equivocal HER2 score 2(+). MATERIALS AND METHODS: Fifteen specimens (previously diagnosed as breast cancer and was evaluated as HER 2(-) score 2(+)) represented the study population. Contemporary new cuts were prepared for re-evaluation of HER2 immunohistochemical studies and FISH examination. All the cases were digitally scanned by iScan (Produced by BioImagene [Now Roche-Ventana]). The IHC signals of HER2 were measured using an automated image analyzing system (MECES, www.Diagnomx.eu/meces). Finally, a comparative study was done between the results of the FISH and the quantitative analysis of the virtual slides. RESULTS: Three out of the 15 cases with equivocal HER2 score 2(+), turned out to be positive (3(+)) by quantitative digital analysis, and 12 were found to be negative in FISH too. Two of these three positive cases proved to be positive with FISH, and only one was negative. CONCLUSIONS: Quantitative digital analysis is highly sensitive and relatively specific when compared to FISH in detecting HER2/neu overexpression. Therefore, it represents a potential reliable substitute for FISH in breast cancer cases, which desire further refinement of equivocal IHC results.

Ciliary count in chronic suppurative otitis media: comparative quantitative study between mucosal and squamous types using scanning electron microscopy and image analysis.

The objective of this study was to prove ciliary destruction in the middle-ear mucous membrane in cases of chronic suppurative otitis media (CSOM) and to compare both types of chronic suppurative otitis media with regard to the degree of ciliary destruction and ciliary count using objective quantitative techniques. The mucosa of the anterior mesotympanum over the promontory was sampled in 10 patients with mucosal CSOM and in another 10 patients with squamous type CSOM. Specimens were examined by scanning electron microscopy in combination with image analysis software techniques in order to study the cilia under higher magnifications and to calculate the ciliary area. Five patients with otosclerosis, no history suggestive of otitis media and normal ear drum appearance served as controls. Samples were taken and studied at the Faculty of Medicine of Cairo University. CSOM was found to be associated with significant ciliary destruction and this was more evident in the squamous type than in the mucosal type.

Ultrastructural ciliary changes of maxillary sinus mucosa following functional endoscopic sinus surgery: an image analysis quantitative study.

This was a study of the effect of functional endoscopic sinus surgery (FESS) on the ciliary regeneration of maxillary sinus mucosa in patients with chronic maxillary sinusitis, using objective quantitative methods. Twenty specimens from the mucosa of both the superolateral wall and the ostium of the maxillary sinus were sampled during FESS and then six to 12 months later. They were light examined first by light microscopy and then by scanning electron microscopy in combination with image analysis software in order to study the cilia under higher magnification and to calculate proportion of the field that was ciliated. Samples were taken and studied at Cairo University hospital. This study showed that the maxillary sinus mucosa in chronic sinusitis is capable of regeneration and could return towards normal with the improvement of ventilation and drainage of the maxillary sinus following FESS. There were no significant changes in the degree of glandular hyperplasia, goblet cells or pathological glands after surgery.

Virtual microscopy beyond the pyramids, applications of WSI in Cairo University for E-education & telepathology.

BACKGROUND: Telepathology, the practice of pathology at a long distance, has advanced continuously since 1986. The progress of telepathology passed through four stages: Static, Dynamic, Hybrid & Whole Slide Imaging. MATERIALS AND METHODS: A pilot project between the Italian Hospital in Cairo & the Civico Hospital in Palermo was completed successfully, applying the static & dynamic techniques of telepathology. This project began in 2003 and continued till now. In 2004, centers in Venice, London and Pittsburgh participated actively in our project. RESULTS: Over eight years we consulted on many problematic pathological cases with specialized pathological centers in Italy, U.K. & U.S.A. In addition to the highly specialized scientific value, we saved a lot of time and money. CONCLUSION: We concluded from our experience that telepathology is a very useful and applicable tool for additional consulting on difficult pathological cases especially for emerging countries. In view of this success we have already established our Digital Telepathology Unit in Cairo University, using the WSI technique in teaching which was greatly successful and encouraged us to build a huge digital pathology library which will expand our telepathology & E-learning programs to cover staff and students in Egypt and Eastern Mediterranean.

Virtual telepathology in Egypt, applications of WSI in Cairo University.

Telepathology, the practice of pathology at a long distance, has advanced continuously since 1986. Today, fourth-generation telepathology systems, so-called virtual slide telepathology systems, are being used for education applications. Both conventional and innovative surgical pathology diagnostic services are being designed and implemented as well. We have a successful experience in Egypt in applying the static & dynamic techniques in a pilot project between the Italian Hospital in Cairo (NPO) and the Civico Hospital in Palermo This project began in 2003 and continued till now. In 2004, centers in Venice, London and Pittsburgh participated actively in our project. During the past seven years we consulted on many problematic pathological cases with these different specialized pathological centers in Italy, UK & USA. In addition to the highly specialized scientific value of consulting on the cases and exchanging knowledge, we saved a lot of time and money and succeeded in providing our patients with a better medical service. In view of this success we have already established a new Digital Telepathology unit (DTU) in the pathology department, Cairo University, using the latest technique of telepathology which is Whole Slide Imaging (WSI) since one year. This unit is considered the first Digital pathology unit in all the universities of the whole Middle East. During the passed year we created a digital pathology library for the under graduate students using the WSI technique and changed the teaching method of the histopathology slides to be completely digital. We are building another digital pathology library (for post graduate candidates) which will be available to all pathology candidates in Egyptian universities & universities in the surrounding Arabic countries. We are also creating a digital pathology network between pathology centers in the Middle East for exchanging knowledge & telepathology.

Telepathology in emerging countries pilot project between Italy and Egypt.

Pathological examination includes gross & microscopic examinations at different magnification. Through the steps of examination, we obtain many images that can be used for telepathology. Telepathology is the practice of pathology at a distance, viewing images on a monitor rather than directly through a light microscope. It can be used for primary diagnosis, second opinion, quality assurance and distance learning. Telepathology is classified into Static, Dynamic, Hybrid and Whole Slide Imaging (WSI). We have a successful experience in Egypt in applying the static & dynamic techniques in a pilot project between the Italian Hospital in Cairo (NPO) and the Civico Hospital in Palermo. This project began in 2003 and continued till now. From the second year 2004, Ospedale S. Giovanni e Paolo Hospital in Venice, Charing Cross Hospital in London and the University of Pittsburgh Medical Center Health System (UPMC) in the USA participated actively in our project. During the past five years we consulted on many problematic pathological cases with these different specialized pathological centers in Italy, UK & USA. In addition to the highly specialized scientific value of consulting on the cases and exchanging knowledge, we saved a lot of time and money and succeeded in providing our patients with a better medical service.We are now in the process of establishing a Digital Telepathology Center (DTC) in the pathology department, Cairo University, using the latest technique of telepathology which is Whole Slide Imaging (WSI). We believe that it will help us to improve and extend diagnosis for our difficult pathological cases and will facilitate increased E-learning opportunities for staff and students both in Egypt and in the longer term in the wider Eastern Mediterranean.

Quantitative analysis of uvular muscles in cases of simple snoring and obstructive sleep apnea: an image analysis study.

Studies on the histopathological changes of the palatine muscles in cases of obstructive sleep apnea (OSA) and simple snoring are controversial, while some authors confirm the presence of muscle hypertrophy and increase in total muscle bulk (obstructive theory), others deny this confirming the presence of muscle atrophy and decrease in the muscle bulk (neurogenic theory), but all these studies depended on subjective observer dependent methods to calculate the muscle bulk. We are carrying a unique study to calculate the muscle bulk in uvular specimens in ten cases of OSA comparing it to ten cases with simple snoring and controls using digital computer dependent software (image analysis). Cases of OSA are associated with definite increase in the total muscle bulk of the palatine muscles when compared to cases of simple snoring and controls. Uvular muscular hypertrophy and the obstructive theory seem to explain the pathophysiology of OSA.