Emad Raddaoui

LPS-responsive beige-like anchor (LRBA) gene mutation in a family with inflammatory bowel disease and combined immunodeficiency

BACKGROUND Clinical immunology has traditionally relied on accurate phenotyping of the patients immune dysfunction for the identification of a candidate gene or genes for sequencing and molecular confirmation. Although this is also true for other branches of medicine, the marked variability in immune-related phenotypes and the highly complex network of molecules that confer normal host immunity are challenges that clinical immunologists often face in their quest to establish a specific genetic diagnosis. OBJECTIVE We sought to identify the underlying genetic cause in a consanguineous family with chronic inflammatory bowel disease-like disorder and combined immunodeficiency. METHODS We performed exome sequencing followed by autozygome filtration. RESULTS A truncating mutation in LPS-responsive beige-like anchor (LRBA), which abolished protein expression, was identified as the most likely candidate variant in this family. CONCLUSION The combined exome sequencing and autozygosity mapping approach is a powerful tool in the study of atypical immune dysfunctions. We identify LRBA as a novel immunodeficiency candidate gene the precise role of which in the immune system requires future studies.

Clinical utility and diagnostic accuracy of endoscopic ultrasound-guided fine needle aspiration of pancreatic lesions: Saudi Arabian experience.

Background/Aims: Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) has emerged as a new and effective tool in the evaluation of pancreatic mass lesions. It has proven to be a safe, accurate, and reliable diagnostic procedure and should be performed in centers with experienced gastroenterologists and cytopathologists for optimum results. In this study, we elaborate on our experience of specimen adequacy criteria, overall efficiency of the technique, and the cytomorphologic features of various pancreatic lesions. Patients and Methods: EUS-FNA of the pancreas and subsequent surgical and/or clinical follow-up of all cases performed at King Khalid University Hospital, King Saud University, Riyadh, Saudi Arabia, from November 2006 to January 2010, were retrospectively reviewed. Diff-Quik and Papanicolaou staining methods were used. Immunohistochemistry stains on cell-block preparations were applied whenever available and required. A total of 43 aspirates from 42 patients were available for retrospective review, including 37 (86%) adequate/diagnostic and 6 (14%) inadequate/non-diagnostic cases. The diagnostic group included 17 (46%) malignant and 20 (54%) benign cases. Of the malignant category (17 cases), 11 (65%) were diagnosed as positive for adenocarcinoma, 4 (23%) as neuroendocrine tumor, 1 (6%) as solid pseudo-papillary neoplasm, and 1 (6%) as non-Hodgkin’s lymphoma. The benign category (20 cases) included 5 (25%) cysts/pseudo-cysts, 8 (40%) non-specific pancreatitis, 4 (20%) granulomatous/tuberculous pancreatitis, 1 (5%) benign neoplasm, and 2 (10%) benign not otherwise specified, both were proven to be false-negative cases. The sensitivity, specificity and accuracy rate for the diagnosis of cancers were 74, 100, and 86%, respectively. No false-positive results were reported. All malignant cases showed characteristic cytomorphologic features that were sufficient for their diagnosis. Conclusion: EUS-FNA in adequate samples is an efficient and accurate modality in the diagnosis of pancreatic lesions. Applying immunohistochemical studies on cell-block preparation can facilitate the final, definitive, and specific diagnosis of some difficult pancreatic neoplasms.

Abdominal Wall Endometriosis

Background Abdominal wall endometriosis is usually preceded by obstetric operations and occasionally can be spontaneous. The diagnosis can be suspected clinically when there is systemic endometriosis or cyclic pain; otherwise it is difficult to differentiate it from other abdominal tumors and nonneoplastic conditions. Fine needle aspiration is an extremely valuable and safe tool for preoperative evaluation of abdominal wall endometriosis as the disease usually presents as a cutaneous/subcutaneous mass. Cases Two cases of abdominal wall endometriosis occurred. One was associated with systemic endometriosis, and the second was spontaneous. The diagnosis was reached correctly and confirmed by the subsequent histologic examination. Conclusion The cytopathologic diagnosis of endometriosis is feasible, and we need to include endometriosis in the differential diagnosis of an abdominal wall mass in a females.

Asthma masquerading as chronic obstructive pulmonary disease: a study of smokers fulfilling the GOLD definition of chronic obstructive pulmonary disease.

Background: Irreversible airways obstruction in smokers is usually attributed to chronic obstructive pulmonary disease (COPD). We speculate that some of these are cases of asthma indistinguishable from COPD. Objectives: To determine the prevalence of asthma in a ‘COPD’ population and how to differentiate the two conditions. Methods: This was a prospective observational study of smokers fulfilling the Global Initiative for Chronic Obstructive Lung Disease definition of COPD [mean post-salbutamol forced expiratory volume in 1 s (FEV1) 66.9% predicted]. They were classified into 4 groups, as follows: (1) inhaled corticosteroid (ICS)-responsive asthma, defined by normalization of spirometry upon ICS treatment; (2) irreversible asthma, defined as airway obstruction for 1 year and bronchial biopsy indicating asthma; (3) COPD, in the presence of bilateral panlobular emphysema with bullae on high-resolution computed tomography, hypercapneic respiratory failure or bronchial biopsy indicating COPD, and (4) unclassified airflow limitation (AFL). Results: Eighty patients fulfilled the definition of COPD. The initial diagnosis was COPD in 57.5% and asthma in 42.5%. The final diagnosis was ICS-responsive asthma in 48 patients (60%), irreversible asthma in 8 (10%), COPD in 16 (20%) and unclassified AFL in 8 (10%). A normal transfer coefficient for carbon monoxide (KCO) and an FEV1 fluctuation ≧18% during 1 year of follow-up distinguished irreversible asthma and COPD. Seven of the 8 patients with irreversible asthma had improved FEV1 at the end of 1 year (median 320 ml compared with –29 ml in COPD). Five out of the 8 unclassified AFL cases had normal KCO and a large improvement in FEV1 suggestive of irreversible asthma. Conclusions: COPD, even in heavy smokers, includes cases of asthma. FEV1 fluctuation during 1 year is a novel concept which may distinguish irreversible asthma and COPD.

Abrupt withdrawal of inhaled corticosteroids does not result in spirometric deterioration in chronic obstructive pulmonary disease: Effect of phenotyping?

BACKGROUND AND OBJECTIVE: Some studies show a decline of FEV1 only one month after withdrawal of inhaled corticosteroids (ICS), while others show no decline. We speculate that the presence of an asthma phenotype in the Chronic Obstructive Pulmonary Disease (COPD) population, and that its exclusion may result in no spirometric deterioration. METHODS: We performed a prospective clinical observation study on 32 patients who fulfilled the Global Initiative for Chronic Obstructive lung disease definition of COPD (Grade II-IV). They were divided into two phenotypic groups. 1. Irreversible asthma (A and B) (n = 13): A. Asthma: Bronchial biopsy shows diffuse thickening of basement membrane (≥ 6.6 μm). B. Airflow limitation (AFL) likely to be asthma: KCO > 80% predicted if the patient refused biopsy. 2. COPD (A and B) (n = 19): A. COPD: hypercapneic respiratory failure with raised bicarbonate, panlobular emphysema with multiple bullas, or bronchial biopsy showing squamous metaplasia and epithelial/subepithelial inflammation without thickening of the basement membrane. B. AFL likely to be COPD: KCO < 80% predicted. RESULTS: The asthma phenotype was significantly younger, had a strong association with hypertrophy of nasal turbinates, and registered a significant improvement of FEV1 (350 ml) vs a decline of - 26.5 ml in the COPD phenotype following therapy with budesonide/formoterol for one year. Withdrawal of budesonide for 4 weeks in the COPD phenotype resulted in FEV1 + 1.33% (SD ± 5.71) and FVC + 1.24% (SD ± 5.32); a change of <12% in all patients. CONCLUSIONS: We recorded no spirometric deterioration after exclusion of the asthma phenotype from a COPD group.

Can computed tomography and carbon monoxide transfer coefficient diagnose an asthma-like phenotype in COPD?

Post‐mortem and computed tomography (CT) studies indicated that emphysema is a feature of COPD even in the ‘blue bloater/chronic bronchitis’ type. We aim to test the hypothesis that the non‐emphysematous patients are distinct from the main body of COPD and are more akin to asthmatic patients.

Sarcoidosis presenting with massive splenomegaly in a child with a history of iridocyclitis and sensorineural deafness.

Childhood sarcoidosis is a rare multisystemic disorder that can have variable clinical presentations. A triad of skin, eye, and joint involvement is common in children younger than 5 years; however, pulmonary disease is more common in older children, similar to adults. The authors report the case of a 10-year-old girl who presented solely with massive splenomegaly. Her history was significant for iridocyclitis and unilateral sensorineural deafness at 6 and 7 years of age, respectively. A gallium scan showed diffuse splenic uptake, and the pathology of the spleen was consistent with a noncaseating granuloma, with no evidence of malignancy. A work-up for infectious etiology was unremarkable. This case demonstrates that the challenge in diagnosing sarcoidosis in young children stems from its ability to present in several unique clinical scenarios. It also reinforces the importance of tissue evaluation and the exclusion of other differential diagnoses, such as lymphoma, to confirm the diagnosis of sarcoidosis.

Utility of endobronchial ultrasound-guided-fine-needle aspiration and additional value of cell block in the diagnosis of mediastinal granulomatous lymphadenopathy

Background: Endobronchial ultrasound-guided transbronchial fine-needle aspiration is a minimally invasive technique for diagnosis of mediastinal lesions. Although most studies have reported the utility of EBUS-FNA in malignancy, its use has been extended to the benign conditions as well. Objective: To evaluate the diagnostic yield and cytologic accuracy of endobronchial ultrasound-guided transbronchial fine-needle aspiration (EBUS-FNA) in cases of clinically and radiologically suspected granulomatous diseases. Patients and Method: From May 2010 to April 2015, 43 of 115 patients who underwent EBUS-FNA at one center for radiologically and clinically suspicious granulomatous lesions, and with no definite histological diagnosis, were included in this retrospective study. Results: When the histological diagnosis was taken as the gold standard, the sensitivity of EBUS-FNA was 85% and specificity was 100% with the positive predictive value of 100. The combined diagnostic sensitivity of EBUS-FNA and transbronchial lung biopsy was 100%. In 4 cases, cell block provided an exclusive morphological diagnosis of sarcoidosis which was noncontributory by EBUS-FNA. Conclusion: Our study supports the use of EBUS-FNA, by virtue of being a safe, minimally invasive, and an outpatient procedure, in the diagnosis of granulomatous mediastinal lymphadenopathy, thereby obviating more invasive testing in a significant number of patients. Also, cell block provides additional data in the diagnosis in these benign mediastinal diseases.

A 38‐YEAR OLD WOMAN WITH A DURAL BASED LESION

Isolated intracranial xanthogranulomas arising from the dura mater are extremely rare.We present a case of a symptomatic large right frontoparietal dura based intracranial xanthogranuloma in a 38-year-old female. Xanthogranulomas are benign non-Langerhans cell histiocytic lesions. They are frequently described in the skin of infants and children. Extracutaneous manifestations especially in the central nervous system are highly uncommon. Dural xanthogranulomas usually arise in association with familial hypercholesterolemia, with Erdheim Chester disease (ECD), and with Weber-Christian disease. Our case however, had no such associations. In this report, the authors describe the clinical, radiological and microscopic presentation of this case and the differential diagnoses of intracranial xanthogranuloma.

Hemangioendothelioma of the eyelid can mimic chalazion.

Hemangioendothelioma is an uncommon vascular lesion that usually occurs in the liver, bone, lung, skin, and other organs with unknown etiology. A rare form of this lesion has been reported in the eyelid. We report the case of a 27-year-old female with right lower eyelid mass simulating chalazion of 3 weeks duration. The histopathologic examination of the excised nodule confirmed the diagnosis. To our knowledge, this is the fourth case of eyelid epithelioid hemangioendothelioma reported in the English literature.