Despite the current classification of high-grade serous carcinoma (HGSCA) and low-grade serous carcinoma (LGSCA) as mutually exclusive diseases based on morphology and molecular pathogenesis, cases ...with mixed morphologic features of HGSCA and LGSCA have been reported. Herein we assess the clinicopathologic, immunohistochemical (IHC), and molecular genetic characteristics of a group of these cases, which we termed indeterminate grade serous carcinoma (IGSCA) in comparison with groups of HGSCA and LGSCA. Using the World Health Organization (WHO) classification criteria, we selected 27 LGSCA and 19 IGSCA for detailed morphologic study. Thirteen classic HGSCA, 19 classic LGSCA, and 19 IGSCA were selected for p53 and BRAF V600E IHC and molecular genetic testing by next-generation sequencing. IGSCA showed the architectural patterns of invasion of LGSCA, but with higher grade nuclear features focally and a mitotic index intermediate between LGSCA and HGSCA. Few cases in the IGSCA group showed mutant TP53 by IHC or sequencing (4/18, 22.2%), 1 case had mutant BRAF non-V600E by sequencing, and 1 had an NRAS mutation. When present, the mutations were identical in the low-grade and high-grade areas. The IGSCA group had a long-term survival similar to the classic HGSCA group. IGSCA with mixed morphologic features of HGSCA and LGSCA is a rare and potentially clinically aggressive variant of serous carcinoma. Their distinct morphologic, but heterogenous molecular features, including low frequency of TP53 and BRAF mutations suggest that these rare tumors may have a different pathogenesis pathway compared with classic HGSCA and classic LGSCA.
Glomus tumors are rare mesenchymal neoplasms with a phenotype akin to the modified smooth muscle cells of the glomus body. Most are benign, but rare examples show malignant histologic characteristics ...and aggressive behavior. We recently encountered a malignant glomus tumor with BRAF V600E mutation. We sought to study a large cohort for this mutation, with particular attention to associated malignant histologic characteristics. Tumors were classified based on WHO criteria as benign, uncertain malignant potential (glomus tumors of uncertain malignant potential—GT-UMP), or malignant. Tumors were screened for BRAF V600E by immunohistochemistry, and positive staining was evaluated further by Sanger sequencing. A total of 102 glomus tumors were included and classified as benign (57, 56%), GT-UMP (15, 15%) and malignant (30, 29%). Tumors occurred in patients aged 8 to 89.9 years (median50.2), without sex predilection (55% men). Most occurred in the superficial soft tissue (84%) and upper extremities (55%). Six of 95 tested cases had BRAF V600E mutation (6%), including 0 of 57 benign tumors, 3 of 14 GT-UMP (21%), and 3 of 24 malignant tumors (12%). Follow-up was obtained for 59 cases (median75.7 mo, range7.8 to 268.5). Three of 11 malignant tumors (27%) had progressive disease1 with metastasis to brain and heart, 1 with enlarging residual disease, and 1 with recurrence. Two of 4 GT-UMP (50%) had progressive disease1 with metastasis to lung, and 1 with local recurrence (50%). Three of 44 benign tumors (7%) had local recurrence. Two of 5 patients with BRAF V600E had progression, including 1 GT-UMP with local recurrence and 1 malignant tumor with enlarging residual disease. In summary, BRAF V600E mutation was detected in 6% of glomus tumors, all of which were malignant or GT-UMP. This mutation may be associated with a malignant phenotype, although study of additional cases is needed. In patients with progressive disease, BRAF could be a promising therapeutic target.
Background Limited data exist regarding temporal trends in permanent pacemaker (PPM) implantation. To describe trends in incidence and comorbidities of PPM recipients, we conducted a retrospective ...population-based cohort study over a 30-year period. Methods All 1291 adult residents of Olmsted County, Minnesota, undergoing PPM implantation between 1975 and 2004 were included in the study. Trends in PPM implantation incidence, pacing mode and indication, and comorbidities (via Charlson Comorbidity Index CCI) were assessed through the Rochester Epidemiology Project. Permanent pacemaker recipients were compared with age- and sex-matched PPM-free controls from the population. Results Adjusted implantation incidence rates increased from 36.6 per 100 000 person-years during 1975 to 1979 to 99 per 100 000 person-years during 2000 to 2004 ( P < .0001). After adjusting for age (hazard ratio HR 1.06 per year), male sex (HR 1.28), and implant year (HR 0.98), the HR for death among PPM recipients by CCI quartiles was 1.0, 1.79, 2.29, and 3.91 for CCI of 0 to 1 (reference), 2 to 3, 4 to 6, and ≥7, respectively ( P < .0001). Overall, PPM recipients had higher CCI than the population-based controls ( P = .04), with higher mean CCI noted since 1990. Mean age-adjusted CCI increased from 3.15 to 4.60 among the cases ( P < .0001) and from 3.06 to 3.54 among the age- and sex-matched controls ( P = .047). Conclusions There have been significant increases in incidence of PPM implantation over 30 years, and PPM recipients have had an age-independent increase in comorbidities relative to the underlying population, especially over the past 15 years.
As food technology continues to advance, the potential for new food products to enter the food market grows, attracting considerable media interest. Whilst previous research has explored public ...perceptions of food-related hazards, much of this took place over 10 years ago. Continued technological developments have yielded new food products, for which there is no extant research on public perceptions. In light of this, there is a pressing need to update and extend research exploring public perceptions of food-related hazards. Using a psychometric approach, a nationally representative UK sample (n = 907) provided ratings of 11 old and new food hazards on a total of 12 risk characteristics (identified from previous research). Principal components analysis identified two main components: 'dread' and 'knowledge', which explained 80.8% of the variance in perceptions, consistent with past findings. Additives were perceived as the least dreaded and most known of the hazards considered, whereas ractopamine pork, atrazine corn and hormone beef were dreaded the most. 3D printed food and lab-grown meat were perceived as the least known. Our results highlight the importance of knowledge in shaping risk perceptions and have implications for risk management. An understanding of the factors which determine risk perceptions is vital for the development of effective risk management and risk communication strategies.
Objective: Understanding gender differences in self-perception of health (SPH) and self-efficacy can inform the design of tailored programs to improve health behaviors. We aimed to assess ...gender-specific differences in SPH and self-efficacy for maintaining wellness habits at
a work-place wellness center. Methods: A workplace wellness center member survey was conducted in 2016. Information about SPH and self-efficacy to maintain wellness habits was assessed. Data were analyzed to assess gender differences in SPH and self-efficacy. Results: The survey
was completed by 2784 members (mean age, 49.2 years; 68.2% women). SPH was similar between genders despite more men reporting health problems such as hypertension, diabetes, high cholesterol, and cigarette smoking. Women had higher self-efficacy about maintaining healthy diet, but the difference
was not clinically meaningful. Women had lower self-efficacy in their ability to maintain physical activity. Conclusions: In this large cohort of worksite wellness center members, men and women had similar self-perception of health despite higher disease burden among men. Women had
lower self-efficacy in their ability to maintain physical activity level but similar self-efficacy for maintaining healthy diet. These differences may inform the design of tailored wellness programs to meet the needs of both genders.
Abstract Risk assessments are common in multiple domains, from finance to medicine. They require evaluating an event’s potential severity and likelihood. We investigate the possible dependence of ...likelihood and severity within the domain of impact-based weather forecasting (IBF), following predictions derived from considering asymmetric loss functions. In a collaboration between UK psychologists and partners from four meteorological organisations in Southeast Asia, we conducted two studies ( N = 363) eliciting weather warnings from forecasters. Forecasters provided warnings denoting higher likelihoods for high severity impacts than low severity impacts, despite these impacts being described as having the same explicit numerical likelihood of occurrence. This ‘Severity effect’ is pervasive, and we find it can have a continued influence even for an updated forecast. It is additionally observed when translating warnings made on a risk matrix to numerical probabilities.
Abstract
Context
Historical outcomes in anaplastic thyroid cancer (ATC) have been dismal.
Objective
To determine whether an initial intensive multimodal therapy (MMT) is associated with improved ATC ...survival.
Design
MMT was offered to all patients with newly diagnosed ATC treated at the Mayo Clinic from 2003 through 2015; MMT vs care with palliative intent (PI) was individualized considering clinical status and patient preferences. Outcomes were retrospectively analyzed by American Joint Committee on Cancer stage and treatments compared with patient cohort data from 1949 through 1999.
Patients
Forty-eight patients (60% male; median age, 62 years); 18 treated with PI, 30 with MMT.
Main Outcome Measure
Overall survival (OS) and progression-free survival determined by Kaplan-Meier method.
Results
Median OS and 1-year survival for the later cohort were 9 months 95% confidence interval (CI), 4 to 22 months and 42% (95% CI, 28% to 56%) vs 3 months and 10% for the earlier cohort. Median OS was 21 months compared with 3.9 months in the pooled MMT vs PI groups for the later cohort hazard ratio (HR), 0.32; P = 0.0006. Among only patients in the later cohort who had stage IVB disease, median OS was 22.4 vs 4 months (HR, 0.12; 95% CI, 0.03 to 0.44; P = 0.0001), with 68% vs 0% alive at 1 year (MMT vs PI). Among patients with stage IVC cancer, OS did not differ by therapy.
Conclusion
MMT appears to convey longer survival in ATC among patients with stage IVA/B disease.
Intensive multimodal therapy appears to convey improved survival among patients with stage IVA/B ATC and should be considered among those accepting of substantial therapy-related toxicities.
Purpose of review
To explore the role of the tumor microenvironment (TME) in breast cancer, identify the changes that occur in the TME during breast cancer progression, and explore the possibility of ...modifying the TME to improve immune checkpoint inhibitor responses.
Recent findings
Emerging evidence shows the TME may be shaped by internal and external factors. Preclinical data suggests it may be possible to shift the TME to allow for better immune infiltration. In this review, we summarize emerging evidence of changes in the TME and how it can affect prognosis and responses to therapy. We also examine pre-clinical and clinical research aiming at modulating TME to increase proportion of patients who benefit from immune checkpoint inhibitors.
Summary
The composition of the TME in breast cancer is likely dynamic and may be altered. These changes may lead to more or less responses to immunotherapy.
Clustering of neural autoantibodies in patients with paraneoplastic neurologic disorders may predict tumor type. A mathematical analysis of neural autoantibody clusters was performed in 78,889 ...patients undergoing evaluation for a suspected paraneoplastic autoimmune neurologic disorder. Tumor predictive autoantibody profiles were confirmed in sera from patients with histologically proven tonsillar cancer, thymoma, and lung cancer.
Of note, 78,889 patient sera were tested for 15 defined neural autoantibodies (1.2 million tests). The observed and hypothesized frequencies of autoantibody clusters were compared and their tumor associations defined. A tumor validation study comprised serum from 368 patients with a variety of tumors (thymoma, lung, or tonsil).
Informative oncological associations included (i) thymoma in 85% of patients with muscle striational, acetylcholine receptor antibodies plus CRMP5 autoantibodies; (ii) lung carcinoma in 80% with both P/Q-type and N-type calcium channel antibodies plus SOX1-IgG; and (iii) in men, prostate carcinoma frequency more than doubled when striational and muscle AChR specificities were accompanied by ganglionic AChR antibody. In women, amphiphysin-IgG alone was associated commonly with breast carcinoma, but amphiphysin-IgG, coexisting with antineuronal nuclear autoantibody-type 1 or CRMP5-IgG, was associated with lung cancer (P < 0.0001). In the validation cohorts, many tumor-associated profiles were encountered that matched the clusters identified in the screening study (e.g., 15% of thymoma patients had striational, acetylcholine receptor antibodies plus collapsin response-mediator protein-5 autoantibodies).
Neural autoantibodies commonly coexist in specific clusters that are identifiable by comprehensive screening. Signature autoantibody clusters may predict a patient's cancer risk and type.
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