BRCA1 mutation carriers have a high rate of both breast and ovarian cancer. Tamoxifen is a selective estrogen receptor modulator (SERM), which is used for the treatment of primary breast cancer and for the prevention of contralateral breast cancer. Our objective is to assess if tamoxifen treatment is associated with an increase in the subsequent risk of ovarian cancer among women with a BRCA1 mutation.
A matched case-control study was performed. Cases were 154 women with ovarian cancer and a previous history of breast cancer. Controls were 560 women with no ovarian cancer and a history of breast cancer. All cases and controls carry a deleterious BRCA1 mutation. Cases and controls were matched for year of birth, age at diagnosis of breast cancer and country of residence. The effect of tamoxifen treatment on the risk of subsequent ovarian cancer was estimated using conditional logistic regression.
The unadjusted odds ratio for ovarian cancer, given previous tamoxifen treatment was 0.89 (95% CI 0.54–1.49, p = 0.66). After adjusting for other treatments, the odds ratio was 0.78 (95% CI 0.46–1.33, p = 0.36).
Tamoxifen treatment for breast cancer does not appear to increase the risk of ovarian cancer in BRCA1 mutation carriers.
Ovarian cancer; Tamoxifen; BRCA1 mutation
Alcohol consumption increases the risk of breast cancer among women in the general population, but its effect on women who carry a BRCA gene mutation is unclear. We conducted a case-control study of 1925 matched pairs of predominantly premenopausal women who carry a BRCA1 or a BRCA2 mutation. Information on current alcohol consumption was obtained from a questionnaire administered during the course of genetic counselling or at the time of enrolment. A modest inverse association between breast cancer and reported current alcohol consumption was observed among women with a BRCA1 mutation (OR = 0.82, 95% CI 0.70–0.96), but not among women with a BRCA2 mutation (OR = 1.00; 95% CI 0.71–1.41). Compared to non-drinkers, exclusive consumption of wine was associated with a significant reduction in the risk of breast cancer among BRCA1 carriers (p-trend = 0.01). Alcohol consumption does not appear to increase breast cancer risk in women carrying a BRCA gene mutation.
BRCA1; BRCA2; Alcohol; Breast cancer; Case-control; Wine
Dll4/Notch and HIF-1a-VEGF have been shown to play an important role during angiogenesis, but there are no data about their roles and association in missed abortion. In this study, we investigated the association of Dll4/Notch and HIF-1a-VEGF signaling in missed abortion.
Women with missed abortion (n = 27) and healthy controls (n = 26) were included in the study. Real-time Reverse Transcription-PCR Analyses (RT-PCR) was used to analyze the mRNA levels of Dll4/Notch and HIF-1a-VEGF signaling molecules. The protein level for Dll4 was measured by immunohistochemistry.
Compared with induced abortion, the expression of VEGF was statistically reduced while the level of VEGFR1 and Notch1 was significantly up-regulated in missed abortion. Though other molecules (VEGFR2 and Dll4) were marginally higher in missed abortion, no statistical difference was observed. The expression of HIF-1a was significantly up-regulated, and close negatively correlated with VEGF in missed abortion. Both in induced abortion and missed abortion, Dll4 was positively correlated with Notch1.
The early pregnancy is in a hypoxic environment, this may encourage the angiogenesis, but severe hypoxic may inhibit the angiogenesis. Aberrant Dll4/Notch and HIF-1a-VEGF signaling may have a role in missed abortion.
In the title molecule, C24H26N4, the pyrazoline ring assumes an envelope conformation with the aniline-bearing C atom at the flap position. The benzene ring and the pyridine ring form with the pyrazoline ring dihedral angles of 4.53 (1) and 6.26 (1)°, respectively. In turn, the aniline group is nearly perpendicular to the pyrazoline ring [dihedral angle = 79.96 (1)°]. The ethyl groups of the diethylamine substituent are disordered over two sets of sites, with an occupancy ratio of 0.624 (8):0.376 (8).
The current article reports a large scale study of the prediction of marijuana use cessation among individuals attending alternative high schools who were regular users at baseline. Based on the Triadic Influence Theory, predictors of marijuana use cessation at 1-year follow-up were organized by type of influence (e.g., interpersonal, cultural and attitudinal, and intrapersonal) and level of influence (e.g., distal and ultimate). Among the 522 students who were past 30-day marijuana users at baseline, quitting was defined as having not used marijuana in the last 30 days at 1-year follow-up (43% of baseline users). To account for the level of influence we employed a theory-based analytic strategy, hierarchical regression. In the final multivariate model, lower level of baseline marijuana use and less of a likelihood to endorse pro-drug-use myths remained predictors of marijuana use cessation 1-year later. Implications of these findings include the need to develop cessation programs that reduce psychological dependence on marijuana use, and correct cognitive misperceptions about drug use in order to help adolescents make decisions that lead to health-promoting behaviors.
marijuana; cessation; adolescents; youth; cannabis; self-initiated; predictors
The present study tested the efficacy of motivational interviewing-based booster sessions for Project Towards No Drug Abuse (TND), a 12-session school-based curriculum targeting youth at risk for drug abuse. In addition, generalization of effects to risky sexual behavior was assessed. The one-year outcomes evaluation of the project is presented.
A total of 24 schools were randomized to one of three conditions: Standard Care Control (SCC), TND classroom program only (TND-only), and TND plus Motivational Interviewing booster (TND+MI). A total of 1186 participants completed baseline and one-year follow-up surveys. Following the classroom program, youth in the TND+MI condition received up to three sessions of MI in person or by telephone. Effects were examined on 30-day cigarette, alcohol, marijuana, and hard drug use, as well as measures of risky sexual behavior (number of sex partners, condom use, having sex while using drugs or alcohol).
Collapsed across the two program conditions, results showed significant reductions in alcohol, hard drug use, and cigarette smoking, relative to controls. These effects held for an overall substance use index. The MI booster component failed to achieve significant incremental effects above and beyond the TND classroom program. No effects were found on risky sexual behavior.
While the program effects of previous studies were replicated, the study failed to demonstrate that an adequately implemented MI booster was of incremental value at one-year follow-up.
one-year follow-up; drug prevention; continuation high schools; Motivational Interviewing; boosters
Women with a BRCA1 mutation face a high lifetime risk of breast cancer. It is unknown to what extent environmental factors modify the inherent genetic risk. If women from different countries, but with similar mutations, experience different levels of cancer risk, non-genetic risk modifiers are likely to be present. Study subjects were a cohort of 1477 women with a BRCA1 mutation, from Canada (n = 358), the United States (n = 256) and Poland (n = 863). The women were followed for a mean of 4.3 years and 130 incident cases of breast cancer were recorded. Annual cancer incidence rates were calculated, and based on these, penetrance curves were constructed for women from North America and Poland. In a Cox proportional hazards model, residence in Poland, versus North America, was associated with an adjusted hazard ratio of 0.54 (95% CI 0.34-0.86; p = 0.01). The risk of breast cancer to age 70 was estimated to be 49% for women from Poland and 72% for women from North America. Among women with BRCA1 mutations, the risk of breast cancer in women who reside in Poland is less than that of women who reside in North America. The reasons for the difference are unknown, but this observation suggests that environmental factors or genetic modifiers are important in determining risk.
BRCA1; breast cancer; penetrance
Anhedonia—diminished capacity to experience pleasure—is associated with tobacco dependence and smoking cessation failure. However, the mechanisms linking anhedonia and smoking are unclear.
This study examined whether trait anhedonia predicted cognitive processing of emotional faces during experimentally-manipulated acute tobacco deprivation in smokers. Because nicotine may offset reward processing deficits in anhedonia and these deficits may become expressed during abstinence, we hypothesized that anhedonia would predict diminished cognitive processing of happy (vs. neutral) facial expressions in nicotine deprived but not nondeprived states.
Smokers not attempting to quit (n=75; 10+cig/day) completed anhedonia questionnaires in a baseline session. Participants then attended two counterbalanced experimental sessions: one following 18-hours of tobacco abstinence and one after unrestricted smoking. At both sessions, they completed a computer-based measure of attentional interference induced by emotional facial expressions.
The extent to which anhedonia predicted Happiness interference differed as a function of deprivation status (ps ≤ .04, ηp
2s > .06). Anhedonia predicted lower interference by happy (vs. neutral) faces in the deprived condition (r=−.28, p=.02) but not in the nondeprived condition (r=.08, p=.51). Analyses of a secondary measure of anhedonia found marginally-significant effects in the same direction.
These findings indicate that disrupted processing of positively-valenced social cues occurs upon abstinence in high-anhedonia individuals. This alteration may motivate reinstatement of smoking in order to remediate these deficits. More broadly, these results suggest that the neuropharmacological pathways affected by nicotine may underlie disrupted emotional processing in anhedonia—a prominent feature in several psychiatric disorders.
Anhedonia; Smoking; Nicotine Dependence; Nicotine Withdrawal; Emotional Processing; Facial expressions
To evaluate the effect of the cumulative number of ovulatory cycles and its contributing components on the risk of breast cancer among BRCA mutation carriers.
We conducted a matched case-control study on 2,854 pairs of women with a BRCA1 or BRCA2 mutation. Conditional logistic regression was used to estimate the association between the number of ovulatory cycles and various exposures and the risk of breast cancer. Information from a subset of these women enrolled in a prospective cohort study was used to calculate age-specific breast cancer rates.
The annual risk of breast cancer decreased with the number of ovulatory cycles experienced (ρ = −0.69; P = 0.03). Age at menarche and duration of breastfeeding were inversely related with risk of breast cancer among BRCA1 (P-trend < 0.0001) but not among BRCA2 (P-trend ≥ 0.28) mutation carriers. The reduction in breast cancer risk associated with surgical menopause (OR = 0.52; 95%CI 0.40–0.66; P-trend < 0.0001) was greater than that associated with natural menopause (OR = 0.81; 95%CI 0.62–1.07; P-trend = 0.14). There was a highly significant reduction in breast cancer risk among women who had an oophorectomy after natural menopause (OR = 0.13; 95%CI 0.02–0.54; P = 0.006).
These data challenge the hypothesis that breast cancer risk can be predicted by the lifetime number of ovulatory cycles in women with a BRCA mutation. Both pre- and post-menopausal oophorectomy protect against breast cancer.
Understanding the basis for the protective effect of oophorectomy has important implications for chemoprevention.
BRCA1; ovulatory cycles; breast cancer; oophorectomy
Formaldehyde can induce misfolding and aggregation of Tau protein and β amyloid protein, which are characteristic pathological features of Alzheimer’s disease (AD). An increase in endogenous formaldehyde concentration in the brain is closely related to dementia in aging people. Therefore, the discovery of effective drugs to counteract the adverse impact of formaldehyde on neuronal cells is beneficial for the development of appropriate treatments for age-associated cognitive decline.
In this study, we assessed the neuroprotective properties of TongLuoJiuNao (TLJN), a traditional Chinese medicine preparation, against formaldehyde stress in human neuroblastoma cells (SH-SY5Y cell line). The effect of TLJN and its main ingredients (geniposide and ginsenoside Rg1) on cell viability, apoptosis, intracellular antioxidant activity and the expression of apoptotic-related genes in the presence of formaldehyde were monitored.
Cell counting studies showed that in the presence of TLJN, the viability of formaldehyde-treated SH-SY5Y cells significantly recovered. Laser scanning confocal microscopy revealed that the morphology of formaldehyde-injured cells was rescued by TLJN and geniposide, an effective ingredient of TLJN. Moreover, the inhibitory effect of geniposide on formaldehyde-induced apoptosis was dose-dependent. The activity of intracellular antioxidants (superoxide dismutase and glutathione peroxidase) increased, as did mRNA and protein levels of the antiapoptotic gene Bcl-2 after the addition of geniposide. In contrast, the expression of the apoptotic-related gene - P53, apoptotic executer - caspase 3 and apoptotic initiator - caspase 9 were downregulated after geniposide treatment.
Our results indicate that geniposide can protect SH-SY5Y cells against formaldehyde stress through modulating the expression of Bcl-2, P53, caspase 3 and caspase 9, and by increasing the activity of intracellular superoxide dismutase and glutathione peroxidase.
Formaldehyde impairment; Geniposide; Neuroprotection
It has been suggested that selenium deficiency is a risk factor for several cancer types. We conducted a case-control study in Szczecin, a region of northwestern Poland, on 95 cases of lung cancer, 113 cases of laryngeal cancer and corresponding healthy controls.
We measured the serum level of selenium and established genotypes for four variants in four selenoprotein genes (GPX1, GPX4, TXNRD2 and SEP15). Selenium levels in the cases were measured after diagnosis but before treatment. We calculated the odds of being diagnosed with lung or laryngeal cancer, conditional on selenium level and genotype.
Among lung cancer cases, the mean selenium level was 63.2 µg/l, compared to a mean level of 74.6 µg/l for their matched controls (p<0.0001). Among laryngeal cancer cases, the mean selenium level was 64.8 µg/l, compared to a mean level of 77.1 µg/l for their matched controls (p<0.0001). Compared to a serum selenium value below 60 µg/l, a selenium level above 80 µg/l was associated with an odds ratio of 0.10 (95% CI 0.03 to 0.34; p = 0.0002) for lung cancer and 0.23 (95% CI 0. 09 to 0.56; p = 0.001) for laryngeal cancer. In analysis of four selenoprotein genes we found a modest evidence of association of genetic variant in GPX1 with the risk of lung and laryngeal cancers.
A selenium level below 60 µg/l is associated with a high risk of both lung and laryngeal cancer.
Understanding the relationship between Posttraumatic stress disorder (PTSD) and cigarette smoking has been difficult due to PTSD’s symptomatic heterogeneity. This study examined common and unique lifetime cross-sectional relationships between PTSD symptom clusters (Re-experiencing [intrusive thoughts and nightmares about the trauma], Avoidance [avoidance of trauma-associated memories or stimuli], Emotional Numbing [loss of interest, interpersonal detachment, restricted positive affect], and Hyperarousal [irritability, difficulty concentrating, hypervigilance, insomnia]) and three indicators of smoking behavior: (1) smoking status; (2) cigarettes per day; and (3) nicotine dependence. Participants were adult respondents in the National Epidemiologic Survey of Alcohol and Related Conditions with a trauma history (N=23,635). All four symptom clusters associated with each smoking outcome in single-predictor models (ps<.0001). In multivariate models including all of the symptom clusters as simultaneous predictors, Emotional Numbing was the only cluster to retain a significant association with lifetime smoking over and above the other clusters, demographics, and Axis-I comorbidity (OR=1.30, p<.01). While Avoidance uniquely associated with smoking status and nicotine dependence in multivariate models, these relations fellow below significance after adjusting for demographics and comorbidity. No clusters uniquely associated with cigarettes per day. Hyperarousal uniquely related with nicotine dependence over and above the other clusters, demographics, and Axis-I comorbidity (OR=1.51, p<.001). These results suggest that: (a) common variance across PTSD symptom clusters contribute to PTSD’s linkage with smoking in the American population; and (b) certain PTSD symptom clusters may uniquely associate with particular indicators of smoking behavior. These findings may clarify the underpinnings of PTSD-smoking comorbidity and inform smoking interventions for trauma-exposed individuals.
Posttraumatic Stress Disorder; Smoking; Comorbidity; Nicotine Dependence; Posttraumatic Stress Disorder Symptom Clusters
The aim of this study was to detect the expression of proliferatng cell nuclear antigen (PCNA) and c-myc in Epstein-Barr virus (EBV)-associated gastric carcinoma (EBVaGC) and EBV-negative gastric carcinoma (EBVnGC), as well as the expression of EBV-encoded proteins in EBVaGC and their effect on carcinogenesis and the development of gastric cancer. The PCNA and c-myc protein levels were assessed by immunohistochemistry in 13 EBVaGC and 45 EBVnGC specimens. The expression of related genes of EBV, including EB nuclear antigen (NA)-1 and EBNA2 genes, latent membrane protein 1 (LMP1) and early genes BARF1 and BHRF1 were tested by reverse transcription-polymerase chain reaction (RT-PCR) and southern blotting. The PCNA labeling index (LI) of EBVaGCs, EBVnGCs and the corresponding adjacent tissues of EBVaGCs were 49.3768±12.1832, 14.839±7.1847, 35.613±8.3831 and 24.2735±10.1332, respectively. The PCNA LI was significantly different between EBVaGC and EBVnGC of EBVaGC (t=4.686, P<0.01). The difference between EBVaGC and corresponding adjacent tissues of EBVaGC was also significant (t=8.805, P<0.01). The expression of c-myc protein was detected in 33 of 58 (55.39%) gastric carcinomas and in 21 of 58 (36.21%) adjacent tissues. There was a significant difference between the two groups (χ2=4.989, P<0.05). The expression of the c-myc protein was detected in 8 of 13 (61.54%) EBVaGCs and in 25 of 45 (55.56%) EBVnGCs. The difference between the two groups was not significant (χ2=0.147, P>0.05). EBNA1 mRNA was detected in all 13 EBVaGC cases, while EBNA2 and LMP1 mRNA was not detected in these cases. Of the 13 EBV-positive samples, 6 exhibited BARF1 transcripts and 2 exhibited BHRF1 transcripts. c-myc expression did not correlate with the presence of EBV in EBVaGC. EBV infection may induce PCNA expression. The lack of EBNA2 and LMP1 protein expression in EBVaGC suggests that EBNA2 and LMP1 do not correlate with cell apoptosis and c-myc expression. Early genes BARF1 and BHRF1 may play an important role in the development and progression of gastric carcinomas by immortalizing epithelial cells.
stomach neoplasm; Epstein-Barr virus; c-myc; proliferating cell nuclear antigen; reverse transcription-polymerase chain reaction; immunohistochemistry; progressive genes
To advance methods for the estimation of hospital performance based upon mortality ratios.
Observational study estimating trust performance in a year derived according to comparative standards from a 3-year period, accounting for patient-level case-mix and overdispersion (unexplained variability).
23 363 630 admissions to the English National Health Service (NHS) by NHS Trust.
Main outcome measures
Number of SDs (QUality and Outcomes Research Unit Measure, QUORUM banding) and comparative odds of hospital mortality difference from mean performance by trust compared for 2010/2011, 2008/2009 and 2009/2010, accounting for patient-level case-mix.
The model was highly predictive of mortality (C statistic=0.93), and well calibrated by risk stratum. There was substantial overdispersion. No trusts were more than 3 SDs above the mean, and only one trust was more than 2 SDs above the mean for 2010/2011.
QUORUM is highly predictive of patient mortality in hospital or up to 30 days after admission. However, like the Summary Hospital Mortality Indicator (SHMI), QUORUM is subjected to considerable remaining legitimate but unexplained variation. It is unlikely that measures like QUORUM and SHMI will be useful beyond identifying a very small number of trusts as potential outliers.
Public Health; Education & Training (See Medical Education & Training); Epidemiology
Electrical stimulation of visual cortex can produce a visual percept (phosphene). We electrically stimulated visual cortex in human patients implanted with subdural electrodes while recording from other brain sites. Across experimental manipulations, we found that phosphene perception occurred only if stimulation evoked high-frequency gamma oscillations in the temporoparietal junction (TPJ), a brain region associated with visual extinction and neglect. Electrical stimulation of TPJ modified detectability of low-contrast visual stimuli.
PTPRM has been shown to exhibit homophilic binding and confer cell-cell adhesion in cells including epithelial and cancer cells. The present study investigated the expression of PTPRM in breast cancer and the biological impact of PTPRM on breast cancer cells.
Expression of PTPRM protein and gene transcript was examined in a cohort of breast cancer patients. Knockdown of PTPRM in breast cancer cells was performed using a specific anti-PTPRM transgene. The impact of PTPRM knockdown on breast cancer was evaluated using in vitro cell models.
A significant decrease of PTPRM transcripts was seen in poorly differentiated and moderately differentiated tumours compared with well differentiated tumours. Patients with lower expression of PTPRM had shorter survival compared with those which had a higher level of PTPRM expression. Knockdown of PTPRM increased proliferation, adhesion, invasion and migration of breast cancer cells. Furthermore, knockdown of PTPRM in MDA-MB-231 cells resulted in increased cell migration and invasion via regulation of the tyrosine phosphorylation of ERK and JNK.
Decreased expression of PTPRM in breast cancer is correlated with poor prognosis and inversely correlated with disease free survival. PTPRM coordinated cell migration and invasion through the regulation of tyrosine phosphorylation of ERK and JNK.
The primary aim of this study was to test the hypothesis that adolescent binge drinkers, but not lighter drinkers, would show signs of impairment on tasks of affective decision-making as measured by the Iowa Gambling Test (IGT), when compared to adolescents who never drank.
We tested 207 10th grade adolescents in Chengdu City, China, using two versions of the IGT, the original and a variant, in which the reward/punishment contingencies were reversed. This enables one to distinguish among different possibilities of impaired decision-making, such as insensitivity to long-term consequences, or hypersensitivity to reward. Furthermore, we tested working memory capacity using the Self-ordered Pointing Test (SOPT). Paper and pencil questionnaires were used to assess drinking behaviors and school academic performance.
Results indicated that relative to never-drinkers, adolescent binge drinkers, but not other (ever, past 30-day) drinkers, showed significantly lower net scores on the original version of the IGT especially in the latter trials. Furthermore, the profiles of behavioral performance from the original and variant versions of the IGT were consistent with a decision-making impairment attributed to hypersensitivity to reward. In addition, working memory and school academic performance revealed no differences between drinkers (at all levels) and never-drinkers. Logistic regression analysis showed that after controlling for demographic variables, working memory, and school academic performance, the IGT significantly predicted binge-drinking.
These findings suggest that a “myopia” for future consequences linked to hypersensitivity to reward is a key characteristic of adolescents with binge-drinking behavior, and that underlying neural mechanisms for this “myopia” for future consequences may serve as a predisposing factor that renders some adolescents more susceptible to future addictive behaviors.
Executive function; Affective control; Reward; Working memory; Adolescent drinking; Iowa Gambling Test
A brief motivational interviewing (MI) intervention may be a viable adjunct to school-based substance abuse prevention programs. This article describes the development and implementation of a brief MI intervention with 573 adolescents (mean age 16.8; 40.3% female, 68% Latino) enrolled in eight continuation high schools in Southern California. Study participants were assigned to the MI condition in a randomized controlled trial of Project Toward No Drug Abuse. Data are provided on dosage, topics discussed, and quality of MI determined with the Motivational Interviewing Skill Code (MISC). Results suggest that the protocol was feasible and implemented with adequate fidelity. The study’s limitations are noted.
adolescent; motivational interviewing; substance use; prevention; intervention; telephone; school-based; booster
The catalytic subunit of telomerase, human telomerase reverse transcriptase (hTERT), is highly active in immortalized cells and more than 90% of human cancer cells, but is quiescent in the majority of normal somatic cells. Thus, the hTERT promoter has been extensively used in targeted cancer gene therapy. Vesicular stomatitis virus (VSV) matrix protein (MP) induces the apoptosis of tumor cells in the absence of other viral components. In our previous studies, we successfully constructed the pVAX-M plasmid from the pVAX plasmid, which expressed wild-type VSV MP (VSV MP is under the control of the CMV promoter) and demonstrated that pVAX-M efficiently suppresses the growth of malignant tumors via the induction of apoptosis in vitro and in vivo. The present study was designed to construct the plasmid phTERTM (VSV MP is under the control of the hTERT promoter) and investigate whether it had a targeted antitumor effect in nude mice bearing human lung adenocarcinoma. In vitro, A549 human lung adenocarcinoma cells were treated with NS, Lip-null, etoposide, Lip-pVAX-M or Lip-phTERT-M, and examined for cell viability through MTT assays or for apoptosis by flow cytometry and TUNEL assays. In vivo, A549 human lung carcinoma models in nude mice were established. Mice were treated with 10 4-weekly intravenous administrations of NS, Lip-null, etoposide (2 mg/kg), Lip-pVAX-M or Lip-phTERT-M. Subsequently, Lip-phTERT-M was found to be the most efficient inhibitor of tumor growth and inducer of tumor cell apoptosis when compared with the other groups in vivo and in vitro (P<0.05). Notably, immunohistochemical staining showed that Lip-phTERT-M significantly limited the overexpression of VSV MP to the tumor tissues and reduced VSV MP expression in other organs in comparison with Lip-pVAX-M (P<0.05). Therefore, it can be concluded that phTERT-M demonstrates a targeted antitumor effect on A549 human lung adenocarcinoma cells. These observations suggest that phTERT-M gene therapy may be a novel and potent strategy for targeting human lung adenocarcinoma.
vesicular stomatitis virus matrix protein; phTERT-M; pVAX-M; apoptosis; targeted antitumor effect
Persistent polyclonal B-cell lymphocytosis (PPBL) is rare and intriguing hematological disorder predominantly reported in young to middle- aged smoking women. It is characterized by persistent moderate polyclonal B-cell lymphocytosis with circulating hallmark binucleated lymphocytes and elevated polyclonal serum IgM. Most patients have benign clinical course on long-term follow-up. Some pathologic features of PPBL may resemble malignant lymphoma, including morphology as well as frequent cytogenetic and molecular abnormalities. Significant symptomatic splenomegaly requiring splenectomy is very unusual for this disorder; therefore there is a lack of descriptions of the morphologic features of the spleen in the literature. We present here one of the first detailed descriptions of the morphologic and immunohistochemical features of the spleen from a young female with PPBL who developed massive splenomegaly during 6-year follow up. Splenectomy was performed for symptomatic relief and suspicion of malignant process. The morphological and immunohistochemical features of the spleen closely mimicked involvement by B-cell lymphoma, however there was no monotypic surface light chain restriction seen by flow cytometry and no clonal rearrangement of IgH gene was detected by molecular analysis. Evaluating a splenectomy sample in cases like this may present a diagnostic challenge to pathologists. Therefore, correlation with B cell clonality studies (by flow cytometry and molecular analysis), clinical findings and peripheral blood morphology searching for characteristic binucleated lymphocytes is essential to avoid misdiagnosing this benign process as B-cell lymphoma. We also present here a literature review on pathogenesis of PPBL.
The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/5329558967545656
Persistent polyclonal B cell lymphocytosis; Splenomegaly; Lymphoma; Binucleated lymphocytes
Hyperinsulinemia and the metabolic syndrome are both risk factors for breast cancer. It is not clear if diabetes is associated with the risk of breast cancer in women with a BRCA1 or BRCA2 mutation.
The authors reviewed the medical histories of 6052 women with a BRCA1 or BRCA2 mutation, half of whom had been diagnosed with breast cancer. They estimated the odds ratio for breast cancer, given a self-report of diabetes. They then estimated the hazard ratio for a new diagnosis of diabetes associated with a history of breast cancer.
There was no excess of diabetes in the period before the diagnosis of breast cancer, compared with controls with no diagnosis of breast cancer. The risk of diabetes was doubled among BRCA carriers in the 15-year period after the diagnosis of breast cancer (relative risk, 2.0; 95% confidence interval [CI], 1.4–2.8; P = .0001), compared with carriers without cancer. The risk was particularly high for women with a body mass index (BMI) >25.0 kg/m2 (odds ratio, 5.8; 95% CI, 4.0–8.6; P = .0001).
After a diagnosis of breast cancer, women with a BRCA1 or BRCA2 mutation face a 2-fold increase in the risk of diabetes, which is exacerbated by a high BMI.
BRCA1; BRCA2; breast cancer; diabetes