A morphological mimic: An NTRK3-rearranged spindle cell neoplasm presenting as a groin mass.

Neurotrophic receptor tyrosine kinase (NTRK)-rearranged spindle cell neoplasms are a recently described group of soft tissue tumors. They commonly present as a painless mass on the extremities of children and young adults. They are characterized microscopically by a heterogeneous spectrum of infiltrative spindle cell proliferations, which can morphologically mimic several other spindle cell neoplasms. Their identification is vital, as they may be amenable to treatment with tyrosine kinase-targeted therapy. This case report describes a rare NTRK3-rearranged spindle cell neoplasm in the groin of a 29-year-old female and provides further clinical and morphological features of this entity.

PIGA Mutations and Glycosylphosphatidylinositol Anchor Dysregulation in Polyposis-Associated Duodenal Tumorigenesis.

The pathogenesis of duodenal tumors in the inherited tumor syndromes familial adenomatous polyposis (FAP) and MUTYH-associated polyposis (MAP) is poorly understood. This study aimed to identify genes that are significantly mutated in these tumors and to explore the effects of these mutations. Whole exome and whole transcriptome sequencing identified recurrent somatic coding variants of phosphatidylinositol N-acetylglucosaminyltransferase subunit A (PIGA) in 19/70 (27%) FAP and MAP duodenal adenomas, and further confirmed the established driver roles for APC and KRAS. PIGA catalyzes the first step in glycosylphosphatidylinositol (GPI) anchor biosynthesis. Flow cytometry of PIGA-mutant adenoma-derived and CRISPR-edited duodenal organoids confirmed loss of GPI anchors in duodenal epithelial cells and transcriptional profiling of duodenal adenomas revealed transcriptional signatures associated with loss of PIGA. IMPLICATIONS: PIGA somatic mutation in duodenal tumors from patients with FAP and MAP and loss of membrane GPI-anchors may present new opportunities for understanding and intervention in duodenal tumorigenesis.

Malignant glomus tumor arising in association with a fumarate hydratase-deficient leiomyoma: An unusual collision tumor.

Collision tumors, defined as "two independent neoplasms that occur in close proximity to one another but maintain distinct boundaries," are quite rare. We report an exceptional collision tumor composed of a genetically confirmed malignant glomus tumor and a fumarate hydratase (FH)-deficient leiomyoma, presenting as a subcutaneous thigh mass in a 38-year-old male who was known to have hereditary leiomyomatosis and renal cell carcinoma syndrome. Microscopic examination identified a biphasic subcutaneous mass comprising sheets and nodules of glomus cells, with nuclear atypia and mitotic activity, and fascicles of mitotically inactive smooth muscle with variably pleomorphic nuclei and intracytoplasmic eosinophilic inclusions, features of FH-deficient leiomyoma. Immunohistochemistry demonstrated loss of FH and robust 2-succinocysteine expression in the smooth muscle, with a normal (FH-retained) expression pattern in the glomus tumor. Next-generation sequencing, performed on the glomus tumor component, identified CARMN::NOTCH2 fusion, characteristic of malignant glomus tumors. Awareness of the distinctive morphologic, immunohistochemical, and molecular genetic features of glomus tumors and FH-deficient leiomyomas is important for correct clinical management of patients with exceptional collision tumors of this type.

The Impact of Cybervictimization on the Self-Management of Chronic Conditions: Lived Experiences.

BACKGROUND: Cybervictimization of people with long-term conditions is a disturbing phenomenon with a documented impact on health and well-being. These experiences are primarily examined using quantitative methods, focusing on children and young people. However, research centered on the cybervictimization of adults with chronic conditions is scarce, with limited qualitative input from the victims as experts in their own experiences. OBJECTIVE: This study aims to understand the impact of cybervictimization on the self-management of long-term conditions among adults with chronic conditions and disabilities in the United Kingdom. METHODS: This paper reports the findings from the qualitative phase of a phenomenologically informed mixed methods study. The biographical disruption concept was used to conceptualize the study. In-depth semistructured interviews were conducted with 13 participants with chronic conditions who experienced cybervictimization. A codebook was developed, and a zigzag approach to thematic analysis was used to define and refine themes. Ethical considerations and risk assessment were ongoing during the research process because of the sensitivity of the topic and cases of harassment. RESULTS: Cybervictimization has direct and indirect impacts on the self-management of chronic conditions. This impact was verified across 6 overarching themes that emerged from this study. First, biomedical events included overall health deterioration because of existing conditions, new diagnoses, and subjective physical complaints. Second, the impact on mental health was perceived through psychological consequences and psychiatric disorders that developed after or during this traumatic experience. Third, the multilevel impact theme focused on disrupting the strategies for coping with health conditions and involved unplanned changes to victims' health management priorities. Fourth, the impact of complexity reflected the perceived uniqueness in each case, intersectionality, struggle to obtain formal support, and subsequent health complications. Fifth, social network involvement comprised the effects of social isolation, victim blaming, and deception. Finally, the disability discrimination theme focused on prejudice, issues on inclusion, and hostility in society, with subsequent effects on well-being. CONCLUSIONS: People with long-term conditions experienced different forms of cybervictimization, all disruptive with various effects on health. Disability discrimination was a prominent finding to be further investigated. This paper reports the impact as themes to guide further research and practice, with the recognition that long-term conditions and impairments are not a homogeneous group. Despite the devastating consequences, there are positive points that strengthen potential interventions. Awareness-raising campaigns, training of support channels, and multidisciplinary research are recommended to tackle this issue and initiate change.

Cybervictimization of Adults With Long-term Conditions: Cross-sectional Study.

BACKGROUND: People living with chronic conditions and disabilities experience harassment both offline and on the web. Cybervictimization is an umbrella term for negative web-based experiences. It has distressing consequences on physical health, mental well-being, and social relationships. These experiences have mostly been documented among children and adolescents. However, the scope of such experiences is not well documented among adults with long-term conditions, and the potential impact has not been examined from a public health perspective. OBJECTIVE: This study aimed to examine the scope of cybervictimization among adults living with long-term conditions in the United Kingdom and the perceived impact on self-management of chronic conditions. METHODS: This paper reports the findings of the quantitative phase of a mixed methods study in the United Kingdom. This cross-sectional study targeted adults aged ≥18 years with long-term conditions. Using a web-based link, the survey was shared on the web via 55 victim support groups, health support organizations, and social media accounts of nongovernmental organizations and activists such as journalists and disability campaigners. People with long-term conditions were asked about their health conditions, comorbidities, self-management, negative web-based experiences, their impact on them, and support sought to mitigate the experiences. The perceived impact of cybervictimization was measured using a set of questions on a Likert scale, frequency tables, and the Stanford Self-Efficacy for Managing Chronic Diseases Scale. Demographic data and the impact on self-management were cross-tabulated to identify the demographic characteristics of the targeted individuals and potential conditions with complications and highlight directions for future research. RESULTS: Data from 152 participants showed that almost 1 in every 2 adults with chronic conditions was cybervictimized (69/152, 45.4%). Most victims (53/69, 77%) had disabilities; the relationship between cybervictimization and disability was statistically significant (P=.03). The most common means of contacting the victims was Facebook (43/68, 63%), followed by personal email or SMS text messaging, each accounting for 40% (27/68). Some participants (9/68, 13%) were victimized in web-based health forums. Furthermore, 61% (33/54) of victims reported that experiencing cybervictimization had affected their health condition self-management plan. The highest impact was on lifestyle changes such as exercise, diet, avoiding triggers, and avoiding excessive smoking and alcohol consumption. This was followed by changes to medications and follow-ups with health care professionals. Most victims (38/55, 69%) perceived a worsened self-efficacy on the Self-Efficacy for Managing Chronic Diseases Scale. Formal support was generally rated as poor, with only 25% (13/53) of victims having disclosed this experience to their physicians. CONCLUSIONS: Cybervictimization of people with chronic conditions is a public health issue with worrying consequences. This triggered considerable fear and negatively influenced the self-management of different health conditions. Further context- and condition-specific research is needed. Global collaborations to address inconsistencies in research are recommended.

Metastatic melanoma involving a genetically confirmed angiofibroma of soft tissue: A previously unreported type of tumor-to-tumor metastasis.

Tumor-to-tumor metastases are an uncommon phenomenon and are very rare in the context of malignant melanoma. This case report describes a 73-year-old male who underwent an excision of a melanoma from his forehead. Six months later, he developed metastatic disease, including metastasis to a genetically confirmed angiofibroma of soft tissue of the abdominal wall. Angiofibroma of soft tissue is a relatively recently described benign fibrovascular soft tissue tumor, and there appear to be no previous reports of it being a recipient tumor for a metastasis. Awareness of the phenomenon of tumor-to-tumor metastasis and of the distinctive morphologic and molecular genetic features of angiofibroma are critical to avoid misdiagnosis of this very rare event as "dedifferentiated" melanoma.

Frontline Response: Exploring the Impact of COVID-19 on Stalking Behaviours.

COVID-19 pandemic lockdown changed the way in which we engage with others and our ability to enjoy free movement away from the confinement of our own homes. Whilst this dramatic change affected everyone, it constituted something much more threatening for victims of stalking, repeatedly targeted by those with an obsessive and fixated behaviour. Whilst we know more about the impact of lockdown stalking behaviour, very little is known about how the police and frontline workers are responding to this challenge. This research aims to increase an understanding of stalking in this context. Firstly, it presents a quantitative examination of recorded data on stalking offences provided by all 43 police forces across England and Wales. In addition, it explores the experiences of those working on the frontline who respond to reports of stalking made by victims. A total of 15 in-depth interviews were conducted with twelve police officers from three forces in England, as well as three advocates of victims from two national stalking services. Analyses show that stalking behaviour has increased and evolved to use accessible channels alongside the COVID restrictions. In conclusion, considerable pressure has been placed on frontline workers to adapt and respond not only to increased incidents but also the changes in the nature of stalking behaviour.

A Metastatic Well-differentiated Squamous Cell Carcinoma in a Patient with an Arteriovenous Fistula.

Patients receiving hemodialysis have an increased risk of developing nonmelanoma skin cancers, such as cutaneous squamous cell carcinoma (SCC). Management of SCC usually relies on complete surgical excision of the primary tumor and may require regional lymph node dissection due to lymphatic spread. An 81-year-old man with an arteriovenous fistula (AVF) presented with an unusually aggressive metastatic well-differentiated SCC, necessitating an axillary dissection for lymph node metastasis. He had been referred for radiotherapy to complete his oncological treatment following excision of the primary SCC on his forearm. An AVF site is subjected to significant changes in circulatory pressure, leading to reduced lymphatic drainage and likely focal immunosuppression. Increased lymphatic burden, combined with repeated trauma to the fistula in an immunosuppressed patient, potentially precipitated the development of an SCC on the affected limb. The individual risk factors for SCC such as sites of chronic inflammation and repeated trauma, host immunosuppression, and renal disease are well established. This patient demonstrates the perfect storm of all these risk factors, leading to a highly malignant metastatic SCC. As the standards of renal care improve and the number of patients with AVF increases, we must remain vigilant in the management of SCCs in these patients.

APC transcription studies and molecular diagnosis of familial adenomatous polyposis.

Familial adenomatous polyposis (FAP) is characterised by the development of hundreds to thousands of colorectal adenomas and results from inherited or somatic mosaic variants in the APC gene. Index patients with suspected FAP are usually investigated by APC coding region sequence and dosage analysis in a clinical diagnostic setting. The identification of an APC variant which is predicted to alter protein function enables predictive genetic testing to guide the management of family members. This report describes a 4-generation family with a phenotype consistent with FAP, but in which an APC variant had not been identified, despite testing. To explore this further, quantitative PCR (qPCR) was employed to assess APC transcription, demonstrating reduced levels of APC RNA. Next generation sequencing (NGS) identified the APC 5'UTR/ Exon 1 variant, c.-190 G>A, that had been reported previously in an another FAP family with APC allelic imbalance. Quantitative RNA studies and DNA sequencing of the APC promoters/ Exon 1 may be useful diagnostically for patients with suspected FAP when coding region variants cannot be identified.

Mitonuclear gene X environment effects on lifespan and health: How common, how big?

Mitochondrial genetic variation can have profound effects on fitness, and the mitotype must interact with both the nuclear genes and the environment. We used Drosophila to investigate the extent to which mitotype effects on lifespan and activity are modulated by nucleotype and environmental variation. When nucleotype is varied, mitochondrial effects on lifespan persisted but were relatively small, and still male biased. Varying food as well, mitotype had substantial effects on male climbing speed, modifiable by nucleotype but less so by diet. Finally, mitotype affected fly lifespan much more in a cage environment compared with a vial, also modifiable by nucleotype and diet. The cage may represent a stressful environment. Mitochondrial genotype may affect fitness much more in conditions of stress, which may have implications for human health.

Cyber-Victimization of People With Chronic Conditions and Disabilities: A Systematic Review of Scope and Impact.

The victimization of individuals with chronic conditions or disabilities is prevalent with severe impact at psychological and physiological levels. With the increasing use of technology these experiences were further reshaped. This systematic review aimed at scoping the experiences of cyber-victimization of people living with chronic conditions or disabilities and examine the documented impact on them. Following a four-stage search strategy in several databases including MEDLINE, Embase, PsychINFO, CINAHL, Cochrane and snowballing of references, a total of 2,922 studies were scanned and 10 studies were eventually included. Quality assessment was done in two phases using tools specific to observational studies and cyber-victimization research. A narrative synthesis of reported results covered a total of 3,070 people. Sample size ranged between 42 and 823 participants, and the age range was 6-71 years with a majority of White ethnic backgrounds. Most studies (n=9) were cross sectional. The prevalence range of cyber-victimization was 2%-41.7% based on variable definitions, duration and methods. Targeted conditions included physical impairments, intellectual disabilities and specific chronic diseases. The most common documented impact was psychological/psychiatric, mainly depression followed by anxiety and distress. Somatic health complaints and self-harm were also reported. We concluded that people with chronic conditions and disabilities were consistently at higher risk of victimization with devastating health complications. Research gaps were identified such as the need to address more conditions and acknowledge differences between heterogeneous health conditions. Other recommendations include allowing flexibility and accountability to patients/victims in research design, education on victimization and health consequences, and improving primary care.

Case Report: A rapidly growing cyst on the scalp.

Trichilemmal carcinoma is a rare tumour derived from the outer root sheath of hair follicles .  It can be difficult to distinguish both clinically and histologically from other skin lesions, particularly squamous cell carcinoma.  We present the case of a 62-year-old female with a 20-year history of three 1-cm cysts on her scalp.  Over a six-month period, a cyst overlying the occiput had become painful and grown in size.  The general practitioner and subsequently local emergency department suspected infection.  The lesion was incised, and the patient was treated with oral antibiotics.  At the time of surgical excision, the lesion measured 3 x 4 cm. Microscopic examination identified rounded dermal lobules of squamous epithelium with trichilemmal keratinization, in keeping with a pre-existing pilar cyst.  There were areas with nuclear pleomorphism, mitoses and an infiltrative architecture.  A diagnosis of trichilemmal carcinoma arising in a pilar cyst was made.  Trichilemmal carcinomas are considered to be a low-grade tumour, but they have the potential to spread to lymph nodes and to metastasise to distant sites in the body, therefore adequate excision and appropriate follow-up are required.

On Textual Analysis and Machine Learning for Cyberstalking Detection.

Cyber security has become a major concern for users and businesses alike. Cyberstalking and harassment have been identified as a growing anti-social problem. Besides detecting cyberstalking and harassment, there is the need to gather digital evidence, often by the victim. To this end, we provide an overview of and discuss relevant technological means, in particular coming from text analytics as well as machine learning, that are capable to address the above challenges. We present a framework for the detection of text-based cyberstalking and the role and challenges of some core techniques such as author identification, text classification and personalisation. We then discuss PAN, a network and evaluation initiative that focusses on digital text forensics, in particular author identification.

Inherited predisposition to colorectal cancer: towards a more complete picture.

Colorectal carcinoma (CRC) is the third most common cancer worldwide. Hereditary factors are important in 15%-35% of affected patients. This review provides an update on the genetic basis of inherited predisposition to CRC. Currently known genetic factors include a group of highly penetrant mutant genes associated with rare mendelian cancer syndromes and a group of common low-penetrance alleles that have been identified through genetic association studies. Additional mechanisms, which may underlie a predisposition to CRC, will be outlined, for example, variants in intermediate penetrance alleles. Recent findings, including mutations in POLE, POLD1 and NTHL1, will be highlighted, and we identify gaps in present knowledge and consider how these may be addressed through current and emerging genomic approaches. It is expected that identification of the missing heritable component of CRC will be resolved through evermore comprehensive cataloguing and phenotypic annotation of CRC-associated variants identified through sequencing approaches. This will have important clinical implications, particularly in areas such as risk stratification, public health and CRC prevention.

It's not what you say, it's how you say it: language use on Facebook impacts employability but not attractiveness.

The expansion and increasing diversity of the Internet has seen a growth in user-generated online content, and an escalation in incorrect and nonstandardized language use (e.g., text speak). This evolution has been exemplified by social networking sites such as Facebook. In our experiment, participants viewed six Facebook profiles whose walls contained status updates that were either spelled correctly, incorrectly, or using text speak, and then rated the profile owners on measures of attractiveness and employability. It was shown that language use had no impact on attractiveness, but users who used correct language were seen as more intelligent, competent, and employable. These results highlight the need to control language in this area of research by demonstrating the variables' seemingly elevated importance to employers compared to peers. The findings also pave the way for further exploration of the Warranting Theory of impression formation online and the role of language in social media-based identity statements and behavioral residue.

The impact of cyberstalking: the lived experience - a thematic analysis.

Cyberstalking (CS) can have major psychosocial impacts on individuals. Victims report a number of serious consequences of victimization such as increased suicidal ideation, fear, anger, depression, and post traumatic stress disorder (PTSD) symptomology. Research is largely limited to quantitative outcome research. This study examines the diversity of experiences reported by people who define themselves as having been cyberstalked. Thematic analysis was used to explore 100 CS victim narratives, gathered by means of an online survey questionnaire designed to capture structured text responses. Five emergent themes were evident in the data: control and intimidation; determined offender; development of harassment; negative consequences; and lack of support. Findings identify similarities and differences to traditional stalking, along with the necessity of support for victims and illustration of the negative impacts this form of harassment produces.

A case of ossifying papillary renal cell carcinoma.

Osseous metaplasia can occur in renal cell carcinomas. We report a case of a 52-year-old lady who presented with hematuria. Ossification associated with a renal cell carcinoma was demonstrated on computed tomography urography and confirmed by histopathologic examination.