SMARCB1 (INI1) Deficient Tumours of the Uterine Cervix: Report of Two Cases, Including One Associated With an NTRK Fusion.

Pathogenic variants (mutations) and other molecular events involving subunits of the SWItch/Sucrose Non-Fermentable chromatin remodelling complex are common in a wide variety of malignancies. Many of these neoplasms are characterized by undifferentiated morphology. They arise at a variety of sites in the female genital tract but have rarely been reported in the uterine cervix. We report 2 primary cervical neoplasms arising in young women (ages 28 and 29 yr) exhibiting loss of nuclear immunoreactivity with SMARCB1 (INI1). In one case, which had a mixture of epithelioid and spindle cells, molecular studies revealed no SMARCB1 pathogenic variant, but showed a SPECCL1::NTRK 3 fusion, in keeping with an NTRK fusion sarcoma. The second case exhibited rhabdoid morphology and molecular testing confirmed a SMARCB1 pathogenic variant (c.425 T>G:p.(Leu142Ter) which, interpreted in conjunction with the morphology and immunohistochemistry, resulted in classification as a proximal-type epithelioid sarcoma. To our knowledge, this is the first reported cervical neoplasm exhibiting a SMARCB1 pathogenic variant and the first NTRK fusion sarcoma showing SMARCB1 protein loss. We discuss the diagnostic challenges and complexities of the molecular findings.

Cervical Small Cell Variant of Paraganglioma With Sarcomatous Transformation: Report of a Unique Case.

We report a unique primary cervical neoplasm in a 44-yr-old woman which we believe, based on the morphology and immunophenotype, represents an extremely unusual small cell variant of paraganglioma. This represents the first report of a primary cervical paraganglioma. Following chemoradiation treatment, the tumor underwent malignant transformation into an S100 and SOX10 positive sarcoma, morphologically and immunohistochemically resembling a malignant peripheral nerve sheath tumor, which we believe represents a sarcoma derived from the sustentacular cells of the paraganglioma. Mutational analysis detected a nonsense mutation of NF1 gene in the sarcoma. This further supports the diagnosis as both somatic and germline NF1 mutations have been associated with paragangliomas and malignant peripheral nerve sheath tumors. Targeted RNA sequencing (ARCHER, expanded sarcoma panel) covering many known genes implicated in sarcoma development, did not reveal any other molecular alteration (fusion or internal tandem duplication).

Health research systems in change: the case of 'Push the Pace' in the National Institute for Health Research.

BACKGROUND: Those running well-organised health research systems are likely to be alert for ways in which they might increase the quality of the services they provide and address any problems identified. This is important because the efficiency of the research system can have a major impact on how long it takes for new treatments to be developed and reach patients. This opinion piece reflects on the experience and learning of the United Kingdom-based National Institute for Health Research (NIHR) when it implemented continuous improvement activity to improve its processes. DISCUSSION: This paper describes the structure and work of the NIHR and why, despite is successes as a health research system and ongoing local continuous improvement, it believed in the value of an organisation-wide continuous improvement activity. It did this by implementing an approach called 'Push the Pace'. Initially, the organisation focused on reducing the amount of time it took for research to transition from an early concept to evidence that changes lives. This scrutiny enabled the NIHR to realise further areas of improvement it could make - additional goals were increased transparency, process simplification, and improved customer and stakeholder experience. We discuss our experience of Push the Pace with reference to literature on continuous improvement. CONCLUSION: Continuous improvement is a cycle, an activity that is done constantly and over time, rather than an act or linear activity (such as Push the Pace). We believe that the work of Push the Pace has initiated a strong commitment to a culture of continuous improvement in the NIHR. This is significant because culture change is widely recognised as immensely challenging, particularly in such a large and distributed organisation. However, our biggest challenge will be to enable all staff and stakeholders of the NIHR to participate in the continuous improvement cycle.

The impact of concurrent HIV-infection on women with vulvar cancer: Comparison of clinical characteristics and outcome.

BACKGROUND: HPV-related vulvar cancer is increasing in prevalence, especially in women living with HIV. Treatment of vulva cancer is based on evidence from HPV-independent cancers, which affect older women. The impact of HIV on vulvar cancer characteristics and treatment outcomes needs to be elucidated. PATIENTS AND METHODS: A retrospective observational study compared the clinical characteristics, treatment, and outcomes of 92 HIV-positive and 131 HIV-negative women with vulvar cancer at our institution. Using descriptive statistics, HIV-positive and negative patients were compared and Cox regression models were tested for differences in mortality and recurrence. RESULTS: HIV-positive patients were 20 years younger than HIV-negative patients (p < 0.001). More than 50% of patients presented with advanced stage cancer, however this was independent of HIV-status. Although HIV infection was associated with poorer survival (p = 0.022); rates of cure (p = 0.933) and recurrence rates (p = 0.8) were similar in HIV-positive and negative women. CONCLUSIONS: Vulvar cancer occurs at a much younger age in women living with HIV. Awareness among HIV-positive women and health care providers would lead to diagnosis of vulvar cancer at an earlier stage. Treatment protocols for HPV-related vulvar cancer should not be altered due to HIV status and should take into consideration the young age of the patients.

Feline diabetes mellitus in the UK: the prevalence within an insured cat population and a questionnaire-based putative risk factor analysis.

Prevalence and risk factors for the development of diabetes mellitus (DM) in cats in the United Kingdom have not previously been reported. The prevalence of DM was evaluated in a large insured population and was found to be 1 in 230 cats. In this insured cat population Burmese cats were 3.7 times more likely to develop DM than non-pedigree cats. A convenience-sampling questionnaire-based study was used in order to identify putative risk factors for the development of DM. The univariate risk factor analysis identified being male, neutered, inactive, weighing >or=5 kg and having a history of corticosteroid treatment as significant risk factors for the development of DM in these cats. In addition, male cats treated with megestrol acetate had a significantly increased risk of developing DM compared to females. In contrast, there was no difference in DM occurrence between male and female Burmese cats. A multivariate classification tree-based model on the questionnaire data looking for interactions between risk factors, identified gender as the most important overall risk factor for the development of DM with low physical activity being the next most important risk factor for female cats and breed the next most important for male cats.

An audit of indications and complications associated with elective hysterectomy at a public service hospital in South Africa.

OBJECTIVE: To assess relationships between clinical indication for hysterectomy and postoperative histologic findings, and to audit complications of hysterectomy at the gynecologic surgical unit of a public-service hospital in South Africa. METHODS: Surgical indications and details, histologic findings, and postoperative course were reviewed and analyzed for 335 patients who underwent hysterectomy at Groote Schuur Hospital, Cape Town, South Africa, in 2007. RESULTS: Hysterectomy was performed abdominally in 265 patients (79.1%) and vaginally in 70 (20.9%) patients (5 of these procedures were laparoscopically assisted). The most common indication was fibroid-related menorrhagia (23%), followed by abnormal uterine bleeding (14.9%). The incidence of intraoperative complications was 6-fold greater among patients with malignant disease than among those with a benign condition (P=0.001). The incidence of postoperative complications was greater following abdominal rather than vaginal surgery, whether traditional or laparoscopic (P=0.02). CONCLUSION: Most hysterectomies were carried out abdominally rather than vaginally, in part because many patients presented with advanced cancer or other condition that warranted this approach. Because of resource constraints, patients with benign conditions were more likely to be offered surgery if they had a clearly defined condition.