IDH2 mutations are frequent in angioimmunoblastic T-cell lymphoma

Mutations in isocitrate dehydrogenase 1 (IDH1) and isocitrate dehydrogenase 2 (IDH2) occur in most grade 2 and 3 gliomas, secondary glioblastomas, and a subset of acute myelogenous leukemias but have not been detected in other tumor types. The mutations occur at specific arginine residues and result in the acquisition of a novel enzymatic activity that converts 2-oxoglutarate to D-2-hydroxyglutarate. This study reports IDH1 and IDH2 genotyping results from a set of lymphomas, which included a large set of peripheral T-cell lymphomas. IDH2 mutations were identified in approximately 20% of angioimmunoblastic T-cell lymphomas (AITLs), but not in other peripheral T-cell lymphoma entities. These results were confirmed in an independent set of AITL patients, where the IDH2 mutation rate was approximately 45%. This is the second common genetic lesion identified in AITL after TET2 and extends the number of neoplastic diseases where IDH1 and IDH2 mutations may play a role.     

Histopathology of surgically treated renal tumours in young adults: a developing country perspective

Background  

There is no data on the histopathological characteristics of renal tumours in young adults in Pakistan.     

Acute-Onset Cerebellar Symptoms in Lhermitte–Duclos Disease: Case Report

Adult-onset Lhermitte–Duclos disease (LD), or dysplastic cerebellar gangliocytoma, is a hamartoma considered pathognomonic for Cowden disease. Classically, LD has a progressive and insidious onset of symptoms. In this case report, we present a patient having rapid neurological deterioration from acute-onset LD. There are only three reported cases of acute LD presentation. A 22-year-old female presented to the emergency department with diplopia, dysarthria, dysphagia, and gait instability which developed within 6 h. A non-contrast CT scan revealed diffuse attenuation in the left cerebellum and mild ventricular dilatation. LP revealed no organisms. Magnetic resonance imaging revealed salient “tiger stripe” appearance of the left cerebellar cortex and effacement of the fourth ventricle. The patient subsequently underwent suboccipital craniotomy and gross total resection of the lesion. The tumor histology showed distortion of normal cerebellar architecture with dysplastic ganglion cells, loss of Purkinje cells, atrophy of the white matter, and expansion of cerebellar folia. Findings were consistent with adult-onset Lhermitte–Duclos disease.     

Squamous variant of gallbladder cancer: is it different from adenocarcinoma?

Background

Literature on squamous variants of gallbladder cancer (GBC) is limited.

Methods

This was a retrospective analysis of GBC patients operated on between August 2009 and March 2012. Patients with adenosquamous carcinoma or squamous cell carcinoma were compared with adenocarcinoma for clinicopathologic features and surgical outcomes.

Results

Of the primary GBC patients resected with curative intent, 14 had adenosquamous carcinoma (10) or squamous cell carcinoma (4) (group A), whereas 122 had adenocarcinoma (group B). Abdominal pain was the most common symptom in both groups; however, presentation with vomiting and an abdominal lump was more common in group A (P = .04 and <.01, respectively). Group A had a significantly larger tumor size (7.9 vs 4.8 cm, P = .01) and a higher incidence of adjacent organ involvement requiring extended resections (85.7% vs 26.2%, P < .01). Despite the higher T stage, node-negative disease was significantly higher in group A (42.9% vs 17.2%, P = .03). There was no significant difference in the median survival after curative resection between the 2 groups (28 vs 31 months, P = .24).

Conclusions

The squamous variant of GBC presented at an advanced T stage; however, nodal involvement and distant metastasis were less common. Despite the higher T stage, curative resection could be achieved in the majority with a comparable survival.     

Oral health status in children with acute lymphoblastic leukemia

Leukemia is a malignancy of the bone marrow. Acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy and accounts for nearly 75% of all newly diagnosed leukemias and 25% of all malignancies in childhood. The aim of the present study was to review the oral health status in children with ALL. Databases were explored using various combinations of the following keywords: "acute lymphoblastic leukemia", "children", "inflammation", "pediatric", "periodontal disease" and "periodontitis". Oral inflammatory conditions including chelitis, gingivitis, herpetic gingivostomatitis, mucositis, oral candidiasis, periodontitis and ulcerations are common manifestations in children with ALL. RESULTS: Periodontal inflammatory conditions and oral mucositis were reported to be significantly higher in children with ALL as compared to healthy controls. Tooth morphological disorders including agenesis, microdontia, short roots and developmental defects in the enamel and dentin were more often observed in children with ALL as compared to healthy controls. Children with ALL have a reduced salivary flow rate, which makes them more susceptible to dental caries as compared to healthy children. Malocclusion due to microdontia may also trigger temporomandibular joint disorders in children with ALL; however, this relationship needs further investigations. CONCLUSION: Oral inflammatory conditions including mucositis and gingivitis are common in children with ALL as compared to healthy children. Tooth morphological disorders including microdontia and enamel and dentin are common manifestations in children with ALL.     

Update on aldosterone antagonists use in heart failure with reduced left ventricular ejection fraction. Heart Failure Society of America Guidelines Committee

Aldosterone antagonists (or mineralocorticoid receptor antagonists [MRAs]) are guideline-recommended therapy for patients with moderate to severe heart failure (HF) symptoms and reduced left ventricular ejection fraction (LVEF), and in postmyocardial infarction patients with HF. The Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure (EMPHASIS-HF) trial evaluated the MRA eplerenone in patients with mild HF symptoms. Eplerenone reduced the risk of the primary endpoint of cardiovascular death or HF hospitalization (hazard ratio [HR] 0.63, 95% confidence interval [CI] 0.54-0.74, P < .001) and all-cause mortality (adjusted HR 0.76, 95% CI 0.62-0.93, P < .008) after a median of 21 months. Based on EMPHASIS-HF, an MRA is recommended for patients with New York Heart Association (NYHA) Class II-IV symptoms and reduced LVEF (<35%) on standard therapy (Strength of Evidence A). Patients with NYHA Class II symptoms should have another high-risk feature to be consistent with the EMPHASIS-HF population (age >55 years, QRS duration >130 msec [if LVEF between 31% and 35%], HF hospitalization within 6 months or elevated B-type natriuretic peptide level). Renal function and serum potassium should be closely monitored. Dose selection should consider renal function, baseline potassium, and concomitant drug interactions. The efficacy of eplerenone in patients with mild HF symptoms translates into a unique opportunity to reduce morbidity and mortality earlier in the course of the disease.     

Indications for cardiac resynchronization therapy: 2011 update from the Heart Failure Society of America Guideline Committee

Cardiac resynchronization therapy (CRT) improves survival, symptoms, quality of life, exercise capacity, and cardiac structure and function in patients with New York Heart Association (NYHA) functional class II or ambulatory class IV heart failure (HF) with wide QRS complex. The totality of evidence supports the use of CRT in patients with less severe HF symptoms. CRT is recommended for patients in sinus rhythm with a widened QRS interval (≥150 ms) not due to right bundle branch block (RBBB) who have severe left ventricular (LV) systolic dysfunction and persistent NYHA functional class II-III symptoms despite optimal medical therapy (strength of evidence A). CRT may be considered for several other patient groups for whom evidence of benefit is clinically significant but less substantial, including patients with a QRS interval of ≥120 to <150 ms and severe LV systolic dysfunction who have persistent mild to severe HF despite optimal medical therapy (strength of evidence B), some patients with atrial fibrillation, and some with ambulatory class IV HF. Several evidence gaps remain that need to be addressed, including the ideal threshold for QRS duration, QRS morphology, lead placement, degree of myocardial scarring, and the modality for evaluating dyssynchrony. Recommendations will evolve over time as additional data emerge from completed and ongoing clinical trials.