Pediatric Burkitt’s lymphoma: CT findings

Purpose To review and analyze all CT scans of the cases of Burkitt’s lymphoma (BL) in children diagnosed in our institution. Materials and methods A retrospective analysis of 33 children with BL between the years 2003 and 2005 seen in our institution was undertaken. Twenty-nine male and four female patients from age 3 to 16 years (with a mean age 5.9 years) were reviewed. Results The gastrointestinal tract was involved in 19 patients (57.5%), kidneys in 9 (27.2%), peritoneum in 8 (24.2%), liver in 4 (12.1%), spleen in 3 (9%), adrenals in 3 (9%), and pancreas in 1 patient (3%). Extra-nodal head and neck involvement was seen in eight patients (24.2%). Bone involvement in four (12.1%), lung in three (9%), heart in two (6%), skin in two (6%), and testis in one (3%) of these patients. Abdominal lymph nodes were enlarged in 21 children (63.6%), while cervical lymph nodes were enlarged in 8 (24.2%). Conclusion CT proved to be an invaluable tool in the characterization of the disease processes in these children. In addition, it provided us with useful information about the anatomical distribution, patterns of involvement, as well as complications of BL.     

Role of Fas and Treg Cells in Fracture Healing as Characterized in the Fas‐Deficient (lpr) Mouse Model of Lupus

Previous studies showed that loss of tumor necrosis factor α (TNFα) signaling delayed fracture healing by delaying chondrocyte apoptosis and cartilage resorption. Mechanistic studies showed that TNFα induced Fas expression within chondrocytes; however, the degree to which chondrocyte apoptosis is mediated by TNFα alone or dependent on the induction of Fas is unclear. This question was addressed by assessing fracture healing in Fas‐deficient B6.MRL/Fas^lpr/J mice. Loss of Fas delayed cartilage resorption but also lowered bone fraction in the calluses. The reduced bone fraction was related to elevated rates of coupled bone turnover in the B6.MRL/Fas^lpr/J calluses, as evidenced by higher osteoclast numbers and increased osteogenesis. Analysis of the apoptotic marker caspase 3 showed fewer positive chondrocytes and osteoclasts in calluses of B6.MRL/Fas^lpr/J mice. To determine if an active autoimmune state contributed to increased bone turnover, the levels of activated T cells and Treg cells were assessed. B6.MRL/Fas^lpr/J mice had elevated Treg cells in both spleens and bones of B6.MRL/Fas^lpr/J but decreased percentage of activated T cells in bone tissues. Fracture led to ～30% to 60% systemic increase in Treg cells in both wild‐type and B6.MRL/Fas^lpr/J bone tissues during the period of cartilage formation and resorption but either decreased (wild type) or left unchanged (B6.MRL/Fas^lpr/J) the numbers of activated T cells in bone. These results show that an active autoimmune state is inhibited during the period of cartilage resorption and suggest that iTreg cells play a functional role in this process. These data show that loss of Fas activity specifically in chondrocytes prolonged the life span of chondrocytes and that Fas synergized with TNFα signaling to mediate chondrocyte apoptosis. Conversely, loss of Fas systemically led to increased osteoclast numbers during later periods of fracture healing and increased osteogenesis. These findings suggest that retention of viable chondrocytes locally inhibits osteoclast activity or matrix proteolysis during cartilage resorption. © 2014 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research.     

Budesonide for the treatment of ulcerative colitis

Introduction: Budesonide is a synthetic corticosteroid characterized by enhanced topical potency and limited systemic bioavailability. Its use in ulcerative colitis (UC) was limited to rectal preparations until recently when the new oral budesonide formulation incorporating the multi-matrix system technology was introduced. The purpose of this review is to evaluate the current role of oral and rectal budesonide in managing UC patients

Areas covered: In this paper, we described the chemical structure and pharmacologic characteristics of the different oral and rectal budesonide preparations, provided a summary of the published trials that evaluated the efficacy and safety of budesonide in UC, and discussed the current status of its use in this population

Expert opinion: Budesonide is effective in inducing remission in a subset of patients with mild-moderate UC. Nevertheless, the current evidence suggests inferiority of oral budesonide to 5-aminosalisylates (5-ASA) and systemic steroids, whereas rectal applications are comparable to other rectal steroid preparations, but still inferior to rectal 5-ASA. In clinical practice, several issues need clarification including, its exact position in the line of induction agents; the role of combining budesonide and 5-ASAs; the role of combining oral and rectal budesonide; and the role of budesonide in maintenance therapy.     

Embryonal tumor with abundant neuropil and true rosettes: a report of three cases of a rare tumor,with an unusual case showing rhabdomyoblastic and melanocytic differentiation

Embryonal tumor with abundant neuropil and true rosettes (ETANTR) is an increasingly recognized entity that belongs to the family of embryonal tumors of the CNS. The authors present three cases of this rare tumor that were encountered at King Hussein Cancer Center, Amman, Jordan. Discussion of the clinicopathological findings is presented along with a recent literature review. Sixteen‐, 57‐ and 30‐month‐old children presented with tumors located in the pineal gland, the right fronto‐ parieto‐temporal region and the cerebellum, respectively. The findings of hypocellular neuropil as well as the characteristic ependymoblastic rosettes were seen. In addition the third case showed an abnormal combination of patterns including melanocytic and rhabdomyoblastic differentiation. The tumors stained positively for synaptophysin in the neuropil and small cell component, while the ependymoblastic rosettes stained for vimentin only. Epithelial membrane antigen and CD99 were negative in all components. One of the cases showed tetraploidy of chromosome 2. All cases exhibited an aggressive course. This is a rare and recently recognized tumor with dismal outcome, and reporting of additional new cases should help in gaining more knowledge about it.     

PTEN deletion and heme oxygenase-1 overexpression cooperate in prostate cancer progression and are associated with adverse clinical outcome

Overexpression of the pro-survival protein heme oxygenase-1 (HO-1) and loss of the pro-apoptotic tumour suppressor PTEN are common events in prostate cancer (PCA). We assessed the occurrence of both HO-1 expression and PTEN deletion in two cohorts of men with localized and castration-resistant prostate cancer (CRPC). The phenotypic cooperation of these markers was examined in preclinical and clinical models. Overall, there was a statistically significant difference in HO-1 epithelial expression between benign, high-grade prostatic intraepithelial neoplasia (HGPIN), localized PCA, and CRPC (p < 0.0001). The highest epithelial HO-1 expression was noted in CRPC (2.00 ± 0.89), followed by benign prostate tissue (1.49 ± 1.03) (p = 0.0003), localized PCA (1.20 ± 0.95), and HGPIN (1.07 ± 0.87) (p < 0.0001). However, the difference between HGPIN and PCA was not statistically significant (p = 0.21). PTEN deletions were observed in 35/55 (63.6%) versus 68/183 (37.1%) cases of CRPC and localized PCA, respectively. Although neither HO-1 overexpression nor PTEN deletions alone in localized PCA showed a statistically significant association with PSA relapse, the combined status of both markers correlated with disease progression (log-rank test, p = 0.01). In a preclinical model, inhibition of HO-1 by shRNA in PTEN-deficient PC3M cell line and their matched cells where PTEN is restored strongly reduced cell growth and invasion in vitro and inhibited tumour growth and lung metastasis formation in mice compared to cells where only HO-1 is inhibited or PTEN is restored. In summary, we provide clinical and experimental evidence for cooperation between epithelial HO-1 expression and PTEN deletions in relation to the PCA patient's outcome. These findings could potentially lead to the discovery of novel therapeutic modalities for advanced PCA.     

Cystic tumor in a 4 month old male

Cystic choroid plexus tumor is a rare variant of choroid plexus papilloma (CPP), reported mostly in infants. It is associated with the development of acute hydrocephalus in many cases. The presence of atypical CPP has recently been recognized by the WHO as a grade II tumor with increased mitotic activity. We are reporting a case of a 3.5 month infant who presented with seizures and features of increased intracranial pressure. He was found to have cystic atypical choroid plexus papilloma.     

Interactions and relationships of PTEN, ERG, SPINK1 and AR in castration-resistant prostate cancer

Bismar T A, Yoshimoto M, Duan Q, Liu S, Sircar K & Squire J A
(2012) Histopathology  60, 645–652
Interactions and relationships of PTEN, ERG, SPINK1 and AR in castration‐resistant prostate cancer Aims: Recently, ETS‐related gene (ERG) gene rearrangements, phosphatase tensin homologue (PTEN) deletions and serine protease inhibitor Kazal type 1 (SPINK1) overexpression were investigated as potential markers for molecularly subtyping prostate cancer (PCA). However, their incidence and co‐association in castration‐resistant PCA (CRPC) has not been characterized fully. Methods and results: A cohort of 59 CRPC patients was investigated for ERG rearrangements, PTEN deletions and androgen receptor (AR) amplification by fluorescence in‐situ hybridization. SPINK1 overexpression was assessed by immunohistochemistry. ERG rearrangements and PTEN deletions were detected in 22 of 53 (41.5%) and 35 of 55 (63.6%) of cases, with 15 of 22 (68.1%) of ERG rearrangements occurring through deletions. SPINK1 overexpression occurred in three of 51 (5.8%) of cases exclusively in non‐ERG rearranged and AR amplification was detected in 12 of 49 (24.4%) of cases. Only PTEN deletions showed intrafocal heterogeneity occurring in nine of 35 (25.7%) of cases. PTEN deletions were significantly associated with each of ERG rearrangements occurring by deletions only (P = 0.001), AR amplification (P = 0.002) and SPINK1 overexpression (P = 0.002). None of the SPINK1 overexpressing tumours showed AR amplification (P = 0.005) and all occurred in PTEN deleted foci (P = 0.002). Conclusion: The study supports the heterogeneous nature of CRPC and confirms a significant association between PTEN, ERG, AR and SPINK1. Characterizing combined markers will aid in defining PCA subgroups relevant to prognosis contributing to the design of improved therapeutic approaches for CRPC.     

Massive duodenal variceal bleed; complication of extra hepatic portal hypertension: Endoscopic management and literature review

Bleeding from duodenal varices is reported to be a catastrophic and often fatal event. Most of the cases in the literature involve patients with underlying cirrhosis. However, approximately one quarter of duodenal variceal bleeds is caused by extrahepatic portal hypertension and they represent a unique population given their lack of liver dysfunction. The authors present a case where a 61-year-old male with history of remote crush injury presented with bright red blood per rectum and was found to have bleeding from massive duodenal varices. Injection sclerotherapy with ethanolamine was performed and the patient experienced a favorable outcome with near resolution of his varices on endoscopic follow-up. The authors conclude that sclerotherapy is a reasonable first line therapy and review the literature surrounding the treatment of duodenal varices secondary to extrahepatic portal hypertension.