Feriyl Bhaijee

Molecular Analysis of Thyroid Tumors

Thyroid cancer is the most common endocrine malignancy, and its incidence is rising in the USA and other countries. Papillary and follicular thyroid carcinomas are the two most common types of thyroid cancer. Non-overlapping genetic alterations, including BRAF and RAS point mutations, and RET/PTC and PAX8/PPARγ rearrangements, are found in more than 70% of papillary and follicular thyroid carcinomas. These represent the most common genetic alterations in thyroid cancer, as well as molecular markers of diagnostic and prognostic significance. The use of these and other emerging molecular markers will likely improve the diagnosis of malignancy in thyroid nodules as well as facilitate more individualized operative and postoperative management. Herein, we provide a brief overview of the common genetic alterations in papillary and follicular thyroid carcinoma and discuss the diagnostic and prognostic significance thereof.

Human Immunodeficiency Virus-Associated Gastrointestinal Disease: Common Endoscopic Biopsy Diagnoses

The gastrointestinal (GI) tract is a major site of disease in HIV infection: almost half of HIV-infected patients present with GI symptoms, and almost all patients develop GI complications. GI symptoms such as anorexia, weight loss, dysphagia, odynophagia, abdominal pain, and diarrhea are frequent and usually nonspecific among these patients. Endoscopy is the diagnostic test of choice for most HIV-associated GI diseases, as endoscopic and histopathologic evaluation can render diagnoses in patients with non-specific symptoms. In the past three decades, studies have elucidated a variety of HIV-associated inflammatory, infectious, and neoplastic GI diseases, often with specific predilection for various sites. HIV-associated esophageal disease, for example, commonly includes candidiasis, cytomegalovirus (CMV) and herpes simplex virus (HSV) infection, Kaposis sarcoma (KS), and idiopathic ulceration. Gastric disease, though less common than esophageal disease, frequently involves CMV, Mycobacterium avium-intracellulare (MAI), and neoplasia (KS, lymphoma). Small bowel biopsies and intestinal aspirates from HIV-infected patients often show HIV enteropathy, MAI, protozoa (Giardia, Isospora, Cryptosporidia, amebae, Microsporidia), and helminths (Strongyloides stercoralis). Colorectal biopsies demonstrate viral (CMV, HSV), bacterial (Clostridia, Salmonella, Shigella, Campylobacter), fungal (cryptococcosis, histoplasmosis), and neoplastic (KS, lymphoma) processes. Herein, we review HIV-associated GI pathology, with emphasis on common endoscopic biopsy diagnoses.

Barriers to initiation of antiretrovirals during antituberculosis therapy in Africa

Background In the developing world, the principal cause of death among HIV-infected patients is tuberculosis (TB). The initiation of antiretroviral therapy (ART) during TB therapy significantly improves survival, however it is not known which barriers prevent eligible TB patients from initiating life-saving ART. Method Setting. A South African township clinic with integrated tuberculosis and HIV services. Design. Logistic regression analyses of a prospective cohort of HIV-1 infected adults (≥18 years) who commenced TB therapy, were eligible for ART, and were followed for 6 months. Findings Of 100 HIV-1 infected adults eligible for ART during TB therapy, 90 TB patients presented to an ART clinic for assessment, 66 TB patients initiated ART, and 15 TB patients died. 34% of eligible TB patients (95%CI: 25–43%) did not initiate ART. Male gender and younger age (<36 years) were associated with failure to initiate ART (adjusted odds ratios of 3.7 [95%CI: 1.25–10.95] and 3.3 [95%CI: 1.12–9.69], respectively). Death during TB therapy was associated with a CD4+ count <100 cells/µL. Conclusion In a clinic with integrated services for tuberculosis and HIV, one-third of eligible TB patients – particularly young men – did not initiate ART. Strategies are needed to promote ART initiation during TB therapy, especially among young men.

Muir-Torre syndrome.

Muir-Torre syndrome (MTS) is a rare autosomal-dominant genodermatosis characterized by sebaceous neoplasms and one or more visceral malignancies. Sebaceous tumors include sebaceous adenoma and carcinoma, which may be solitary or multiple. Visceral malignancies most often arise in the colorectum and endometrium. Because a subset of patients with phenotypic MTS will have germline mutations in the DNA mismatch repair genes hMSH2 and hMLH1, MTS is considered a phenotypic subtype of Lynch syndrome (also known as hereditary nonpolyposis colorectal cancer syndrome), in which inherited defects in DNA mismatch repair genes result in microsatellite instability. Pathologists have an important role in the early detection and initial diagnosis of MTS: identification of at-risk individuals allows appropriate screening and surveillance for visceral malignancies, thereby reducing morbidity and mortality. Herein, we describe the clinicopathologic features of MTS.

Squamous cell carcinoma of the renal pelvis

Primary squamous cell carcinoma (SCC) of the renal pelvis is rare because SCC represents only 0.5% to 0.8% of malignant renal tumors. Chronic irritation, inflammation, and infection induce squamous metaplasia of the renal collecting system, which may progress to dysplasia and carcinoma in most of affected individuals. Nephrolithiasis, especially formation of staghorn calculi, is the most common risk factor for SCC, which usually occurs in older adults (age 50-70 years) with no sex predilection. Clinical features include flank or abdominal mass, weight loss, hematuria, or paraneoplastic syndromes, such as hypercalcemia. Radiologically, SCC of the renal pelvis may appear as a solid mass, hydronephrosis, or calcifications. The radiologic differential diagnosis includes primary and secondary renal neoplasms and xanthogranulomatous pyelonephritis. Squamous cell carcinomas of the renal pelvis are usually large, necrotic, and ulcerated, with gross invasion of the renal parenchyma and perinephric soft tissue. Most SCCs of the renal pelvis are moderately or poorly differentiated and typically present at an advanced stage. Surgical resection and adjuvant chemoradiotherapy are rarely curative. The prognosis is dismal with a 5-year survival rate of less than 10%.

Clinical deterioration during antituberculosis treatment in Africa: Incidence, causes and risk factors

BackgroundHIV-1 and Mycobacterium tuberculosis cause substantial morbidity and mortality. Despite the availability of antiretroviral and antituberculosis treatment in Africa, clinical deterioration during antituberculosis treatment remains a frequent reason for hospital admission. We therefore determined the incidence, causes and risk factors for clinical deterioration.MethodsProspective cohort study of 292 adults who initiated antituberculosis treatment during a 3-month period. We evaluated those with clinical deterioration over the following 24 weeks of treatment.ResultsSeventy-one percent (209/292) of patients were HIV-1 infected (median CD4+: 129 cells/μL [IQR:62-277]). At tuberculosis diagnosis, 23% (34/145) of HIV-1 infected patients qualifying for antiretroviral treatment (ART) were receiving ART; 6 months later, 75% (109/145) had received ART. Within 24 weeks of initiating antituberculosis treatment, 40% (117/292) of patients experienced clinical deterioration due to co-morbid illness (n = 70), tuberculosis related illness (n = 47), non AIDS-defining HIV-1 related infection (n = 25) and AIDS-defining illness (n = 21). Using HIV-1 uninfected patients as the referent group, HIV-1 infected patients had an increasing risk of clinical deterioration as CD4+ counts decreased [CD4+>350 cells/μL: RR = 1.4, 95% CI = 0.7-2.9; CD4+:200-350 cells/μL: RR = 2.0, 95% CI = 1.1-3.6; CD4+<200 cells/μL: RR = 3.0, 95% CI = 1.9-4.7]. During follow-up, 26% (30/117) of patients with clinical deterioration required hospital admission and 15% (17/117) died. Fifteen deaths were in HIV-1 infected patients with a CD4+<200 cells/μL.ConclusionsIn multivariate analysis, HIV-1 infection and a low CD4+ count at tuberculosis diagnosis were significant risk factors for clinical deterioration and death. The initiation of ART at a CD4+ count of <350 cells/μL will likely reduce the high burden of clinical deterioration.

Pathogenesis, diagnosis, and management of gastric ischemia.

BACKGROUND & AIMS Gastric ischemia is infrequently reported in the medical literature and under-recognized clinically and histopathologically. Various medical terms are used to describe gastric ischemia. We define and review the pathogenesis, diagnosis, and management of gastric ischemia. METHODS We describe 6 cases of gastric ischemia. We discuss features of the gastric vascular supply and review literature on this disorder. RESULTS Gastric ischemia results from diffuse or localized vascular insufficiency caused by etiologies such as systemic hypotension, vasculitis, or disseminated thromboembolism. The disorder is managed by fluid resuscitation, nasogastric tube placement (for intermittent air and fluid aspiration, to prevent or reduce gastric distention), aggressive acid reduction (via intravenous administration of proton pump inhibitors), and selective use of broad-spectrum antibiotics for patients with sepsis or gastric pneumatosis. CONCLUSIONS Gastric ischemia has a poor prognosis. Early diagnosis is required for appropriate patient management.

Russell body gastroenteritis: an aberrant manifestation of chronic inflammation in gastrointestinal mucosa.

First described in 1998, Russell body gastritis is a rare chronic inflammatory condition characterized by abundant intramucosal polyclonal plasma cells, which contain intracytoplasmic eosinophilic globules of immunoglobulins (Russell bodies) that displace the nucleus, with an accompanying chronic inflammatory infiltrate. Russell bodies represent a cellular response to overstimulation of plasma cells, leading to the accumulation of abundant, nondegradable, condensed immunoglobulin in dilated rough endoplasmic reticulum cisternae. Russell body gastritis usually occurs in the gastric antrum, but two cases of Russell body duodenitis have been recently described. Herein, we report an unusual case of Barrett esophagus with prominent lymphoplasmacytic infiltration and Russell bodies, which expands the current spectrum of Russell body gastritis/duodenitis. Given the various anatomic locations in which Russell body gastritis may arise, we suggest that “Russell body gastroenteritis” may be a more appropriate designation for this uncommon reactive condition.

Endoscopic Mucosal Resection of an Epstein–Barr Virus-Associated Lymphoepithelioma-Like Gastric Carcinoma

Epstein–Barr virus (EBV) usually causes a life-long persistent infection of the B lymphocytes in 90 % of adults [1, 2]. EBV is oncogenic in the development of Burkitt lymphoma, immunosuppression-related lymphoma, Hodgkin’s lymphoma, and nasopharyngeal carcinoma. Recently, EBV-associated gastric carcinomas were found to have a prevalence of 8.7 % and they tend to be located in the gastric cardia and body [2]. Primary gastric lymphoepithelioma-like carcinoma (LLC) is rare and associated with latent EBV infection [2–4]. We report a case of EBVassociated primary gastric LLC diagnosed and completely removed by endoscopic mucosal resection (EMR).

Assessment at antiretroviral clinics during TB treatment reduces loss to follow-up among HIV-infected patients.

Setting A South African township clinic where loss to follow-up during TB treatment may prevent HIV-infected TB patients from receiving life-saving ART. Objective To determine factors associated with loss to follow-up during TB treatment. Design Regression analyses of a cohort of ART-eligible TB patients who commenced TB treatment and were followed for 24 weeks. Results Of 111 ART-eligible TB patients, 15 (14%) died in the ensuing 24 weeks. Of the remaining 96 TB patients, 11 (11%) were lost to follow-up. All TB patients lost to follow-up did not initiate ART. Of 85 TB patients in follow-up, 62 (73%) initiated ART 56 days after TB diagnosis (median, IQR 33–77 days) and 31 days after initial assessment at an ART clinic (median, IQR: 18–55 days). The median duration from TB diagnosis to initial assessment at an ART clinic was 19 days (IQR: 7–48 days). At 24 weeks, 6 of 85 (7%) TB patients who presented to an ART clinic for assessment were lost to follow-up, compared to 5 of 11 (45%) TB patients who did not present to an ART clinic for assessment. Logistic regression analysis (adjusted odds ratio  = 0.1, 95% confidence interval [95% CI]: 0.03–0.66) and our Cox proportional hazards model (hazard ratio  = 0.2, 95% CI: 0.04–0.68) confirmed that assessment at an ART clinic during TB treatment reduced loss to follow-up. Conclusion Assessment at antiretroviral clinics for HIV care by trained health-care providers reduces loss to follow-up among HIV-infected patients with TB.