Bilateral gluteal metastases from a misdiagnosed intrapelvic gastrointestinal stromal tumor

<p>Abstract</p> <p>Background</p> <p>The location of gastrointestinal stromal tumors (GIST) outside of the gastrointestinal system is a rare event.</p> <p>Case presentation</p> <p>A 56-year old woman presented with a GIST of the pelvis was misdiagnosed and treated as a uterine leiomyosarcoma. The diagnosis was made after the CD117 (KIT) positivity in the biopsy of the excised bowel mass four years from the first presentation. During this period she presented a bilateral muscle and subcutaneous metastasis in the gluteal area.</p> <p>Conclusion</p> <p>The correct diagnosis of the extra-gastrointestinal stromal tumor is a challenge even for experienced pathologists. CD117 (KIT) positivity is the most important immunohistochemical feature in the histological diagnosis. To our knowledge a metastatic EGIST (extra-gastrointestinal stromal tumor) to the skeletal muscle bilaterally has not been described previously in the English medical literature.</p

Primary biliary cirrhosis and autoimmune cholangitis are not associated with coeliac disease in Crete

BACKGROUND: An increased prevalence of coeliac disease in patients with primary biliary cirrhosis has been recently reported. However, in other studies the association has not been confirmed. There have been no formal attempts to systematically evaluate patients with autoimmune cholangitis for coeliac disease. METHODS: Sera from 62 patients with primary biliary cirrhosis, 17 with autoimmune cholangitis and 100 blood donors were screened for anti-gliadin, anti-endomysial, anti-reticulin, and IgA class antibodies to guinea pig liver-derived tissue transglutaminase. Eighteen untreated coeliacs served as methodological controls. Analyses were performed by using the χ(2) and Fischer's exact tests. RESULTS: Anti-gliadin antibodies were detected in 21% of patients with primary biliary cirrhosis, 35% of patients with autoimmune cholangitis, and 3% of controls (p < 0.001). IgA class gliadin antibodies positivity was more pronounced in patients with Scheuer's stage III-IV disease (p < 0.05). Anti-transglutaminase antibodies were detected in 10% and in 18% of patients with primary biliary cirrhosis and autoimmune cholangitis respectively (p < 0.001). Anti-reticulin and anti-endomysial antibodies were negative in all patients. Duodenal biopsies were performed in 59% and 71% of patients with primary biliary cirrhosis and autoimmune cholangitis respectively, tested positive for at least one antibody class. No histological features of coeliac disease were found. CONCLUSIONS: We were unable to demonstrate an increased risk of coeliac disease in patients with primary biliary cirrhosis and autoimmune cholangitis. Our results confirm the previously reported high prevalence of false-positive anti-gliadin and guinea pig liver-derived anti-tissue transglutaminase antibodies in patients with chronic liver disease

Polygenic Risk Scores for Prediction of Breast Cancer and Breast Cancer Subtypes

Stratification of women according to their risk of breast cancer based on polygenic risk scores (PRSs) could improve screening and prevention strategies. Our aim was to develop PRSs, optimized for prediction of estrogen receptor (ER)-specific disease, from the largest available genome-wide association dataset and to empirically validate the PRSs in prospective studies. The development dataset comprised 94,075 case subjects and 75,017 control subjects of European ancestry from 69 studies, divided into training and validation sets. Samples were genotyped using genome-wide arrays, and single-nucleotide polymorphisms (SNPs) were selected by stepwise regression or lasso penalized regression. The best performing PRSs were validated in an independent test set comprising 11,428 case subjects and 18,323 control subjects from 10 prospective studies and 190,040 women from UK Biobank (3,215 incident breast cancers). For the best PRSs (313 SNPs), the odds ratio for overall disease per 1 standard deviation in ten prospective studies was 1.61 (95%CI: 1.57-1.65) with area under receiver-operator curve (AUC) = 0.630 (95%CI: 0.628-0.651). The lifetime risk of overall breast cancer in the top centile of the PRSs was 32.6%. Compared with women in the middle quintile, those in the highest 1% of risk had 4.37- and 2.78-fold risks, and those in the lowest 1% of risk had 0.16- and 0.27-fold risks, of developing ER-positive and ER-negative disease, respectively. Goodness-of-fit tests indicated that this PRS was well calibrated and predicts disease risk accurately in the tails of the distribution. This PRS is a powerful and reliable predictor of breast cancer risk that may improve breast cancer prevention programs.NovartisEli Lilly and CompanyAstraZenecaAbbViePfizer UKCelgeneEisaiGenentechMerck Sharp and DohmeRocheCancer Research UKGovernment of CanadaArray BioPharmaGenome CanadaNational Institutes of HealthEuropean CommissionMinistère de l'Économie, de l’Innovation et des Exportations du QuébecSeventh Framework ProgrammeCanadian Institutes of Health Researc

Author Correction: Iron restriction inside macrophages regulates pulmonary host defense against Rhizopus species

The original version of this Article contained an error in the spelling of the author Emilien Etienne, which was incorrectly given as Emilien Ettiene. These errors have now been corrected in both the PDF and HTML versions of the Article

Iron restriction inside macrophages regulates pulmonary host defense against Rhizopus species.

Mucormycosis is a life-threatening respiratory fungal infection predominantly caused by Rhizopus species. Mucormycosis has incompletely understood pathogenesis, particularly how abnormalities in iron metabolism compromise immune responses. Here we show how, as opposed to other filamentous fungi, Rhizopus spp. establish intracellular persistence inside alveolar macrophages (AMs). Mechanistically, lack of intracellular swelling of Rhizopus conidia results in surface retention of melanin, which induces phagosome maturation arrest through inhibition of LC3-associated phagocytosis. Intracellular inhibition of Rhizopus is an important effector mechanism, as infection of immunocompetent mice with swollen conidia, which evade phagocytosis, results in acute lethality. Concordantly, AM depletion markedly increases susceptibility to mucormycosis. Host and pathogen transcriptomics, iron supplementation studies, and genetic manipulation of iron assimilation of fungal pathways demonstrate that iron restriction inside macrophages regulates immunity against Rhizopus. Our findings shed light on the pathogenetic mechanisms of mucormycosis and reveal the role of macrophage-mediated nutritional immunity against filamentous fungi

Author Correction: Iron restriction inside macrophages regulates pulmonary host defense against Rhizopus species.

The original version of this Article contained an error in the spelling of the author Emilien Etienne, which was incorrectly given as Emilien Ettiene. These errors have now been corrected in both the PDF and HTML versions of the Article

Low expression of p27 protein combined with altered p53 and Rb/p16 expression status is associated with increased expression of cyclin A and cyclin B1 in diffuse large B-cell lymphomas

The expression of the cyclin-dependent kinase inhibitor (CDKI) p27 protein was investigated in relation to (1) the expression of the cell cycle regulators p53, Rb and p16 and (2) the proliferation profile as determined by the expression of Ki67, cyclin A, and cyclin BI in 80 cases of de novo diffuse large B-cell lymphomas (DLBCL). P27 expression was low/null in large tumor cells in 58/80 cases and intermediate/high in 22/80 cases. Increased expression of p53 protein was observed in 39/80 cases. Decreased expression of Rb and p16 proteins was mutually exclusive and was observed in 5/80 and 14/80 cases, respectively. The analysis of the p27 expression status (low/null versus intermediate/high) with respect to the p53 and/or Rb/p16 expression status showed that low/null p27 expression was significantly correlated with increased p53 expression (P = .018) and showed a strong trend for correlation with concurrent increased p53 expression and decreased Rb or p16 expression (P = .050). These findings suggest a tendency for concurrent alterations of the cell cycle regulators p27, p53, and Rb or p16 in DLBCL, which might result in impaired tumor growth control. Indeed, the analysis of the combined p27/p53/Rb/p16 expression status with respect to the proliferation profile showed that (1) three alterations in the combined p27/p53/Rb/p16 status (i.e., low/null P27 expression, increased expression of p53, and decreased expression of Rb or p16) were significantly correlated with increased expression of cyclin B1 (P = .005) and (2) two or three alterations were significantly correlated with increased expression of cyclin A (P = .014). These findings suggest combined impairment of a complex cell-cycle control network involving the CDK inhibitor p27, the P53 pathway, and the Rbl pathway, which exerts a cooperative effect resulting in enhanced tumor cell proliferation