Abstract
Introduction/Objective
Uterine leiomyosarcoma is a malignant neoplasm with three distinct histologic subtypes: spindle, epithelioid, and myxoid. Distinguishing leiomyosarcoma from ...mesenchymal uterine neoplasms such as endometrial stromal sarcoma can be challenging as they may exhibit a similar histology and immunohistochemical profile. In such cases, molecular studies can help achieve the definitive diagnosis. It has been shown that ~25% of the uterine myxoid leiomyosarcomas harbor TRPS1-PLAG1 and RAD51B-PLAG1 gene fusions. To our knowledge, no uterine leiomyosarcoma with RAB2A-PLAG1 gene fusion has been previously reported in the English literature.
Methods/Case Report
An 80-year-old woman presented with abnormal uterine bleeding. A large necrotic uterine mass with no evident lymphadenopathy was detected on imaging. Endometrial curettage demonstrated a malignant mesenchymal neoplasm that was positive for CD10, desmin, and vimentin and lacked expression of SMA, SMMH, synaptophysin, and chromogranin. AE1/AE3 highlighted rare foci. The patient underwent total hysterectomy with bilateral salpingo-oophorectomy. The hysterectomy specimen was notable for a 10.8 cm rubbery focally calcified tan- white mass histologically composed of high-grade spindle and epithelioid cells with hypocellular and hyalinized areas. The mitotic activity was >25/10HPF. Immunohistochemically, the neoplastic cells expressed CD10, caldesmon, desmin (patchy), SMA (weak focal), and CAM5.2 (patchy) while they were negative for ER, PR, HMB45, AE1/AE3, WT1, cyclin D1, BCOR, myogenin, pan-NTRK, and ALK. P53 staining showed a wild type expression pattern.
Histology and immunohistochemistry could not definitively differentiate between leiomyosarcoma and high grade endometrial stromal sarcoma. RNA sequencing identified a RAB2A-PLAG1 gene fusion. In light of the histology and ancillary studies, a diagnosis of leiomyosarcoma was rendered.
Results (if a Case Study enter NA)
NA
Conclusion
This is the first case of a uterine leiomyosarcoma with RAB2A-PLAG1 gene fusion. Pathologists should be cognizant of the extensive morphologic and immunophenotypic overlap between various uterine mesenchymal neoplasms. In challenging cases, molecular analysis is crucial in allowing the pathologist to arrive at the final diagnosis.
Background: During the COVID-19 pandemic, social-distancing and confinement measures were implemented. These May affect the mental health of patients with mental disorders such as schizophrenia. This ...study examined the clinical course of patients with schizophrenia at a public hospital in Morocco during the COVID-19 pandemic.
Methods: This longitudinal observational study was conducted across three periods in 15 months: 1 April 2020 (start of strict home confinement) to 30 June 2020 (T1), 1 July 2020 to 31 January 2021 (corresponding to the Delta wave) T2, and 1 February 2021 to 30 June 2021 (corresponding to the Omicron wave) T3. Patients aged 18 to 65 years with a diagnosis of schizophrenia or schizoaffective disorder (based on DSM 5) made before the pandemic who presented to the Faculty of Medicine and Pharmacy of Rabat were invited to participate. Psychotic symptomatology was evaluated using the Positive and Negative Syndrome Scale (PANSS). Severity and improvement of mental disorder were evaluated using the Clinical Global Impression (CGI)-Severity and -Improvement subscales. Depressive symptoms were assessed using the Calgary Depression Scale (CDS). Adherence to treatments was assessed using the Medication Adherence Rating Scale (MARS). All assessments were made by psychiatrists or residents face-to-face (for T1) or via telephone (for T2 and T3).
Results: Of 146 patients recruited, 83 men and 19 women (mean age, 39 years) completed all three assessments. The CGI-Severity score was higher at T2 than T1 and T3 (3.24 vs 3.04 vs 3.08, p equivalent 0.041), and the MARS score was higher at T1 and T2 than T3 (6.80 vs 6.83 vs 6.35, p equivalent 0.033). Patient age was negatively correlated with CDS scores for depressive symptoms at T1 (Spearman's rho equivalent −0.239, p equivalent 0.016) and at T2 (Spearman's rho equivalent −0.231, p equivalent 0.019). The MARS score for adherence was higher in female than male patients at T1 (p equivalent 0.809), T2 (p equivalent 0.353), and T3 (p equivalent 0.004). Daily tobacco consumption was associated with the PANSS total score at T3 (p equivalent 0.005), the CGI-Severity score at T3 (p equivalent 0.021), and the MARS score at T3 (p equivalent 0.002). Patients with a history of attempted suicide had higher CDS scores than those without such a history at T1 (p equivalent 0.015) and T3 (p equivalent 0.018) but not at T2 (p equivalent 0.346). Conclusion: Home confinement during the COVID-19 pandemic had limited negative impact on the mental health of patients with schizophrenia in Morocco.
The utility of cancer whole genome and transcriptome sequencing (cWGTS) in oncology is increasingly recognized. However, implementation of cWGTS is challenged by the need to deliver results within ...clinically relevant timeframes, concerns about assay sensitivity, reporting and prioritization of findings. In a prospective research study we develop a workflow that reports comprehensive cWGTS results in 9 days. Comparison of cWGTS to diagnostic panel assays demonstrates the potential of cWGTS to capture all clinically reported mutations with comparable sensitivity in a single workflow. Benchmarking identifies a minimum of 80× as optimal depth for clinical WGS sequencing. Integration of germline, somatic DNA and RNA-seq data enable data-driven variant prioritization and reporting, with oncogenic findings reported in 54% more patients than standard of care. These results establish key technical considerations for the implementation of cWGTS as an integrated test in clinical oncology.
Toxins from animal venoms are small peptide molecules able to interact with a wide range of specific cellular targets in order to modulate their activity, which enables them to act in many ...physiological and pathological processes. Recently, structuralandpharmacologicalstudieshaveshown the involvement of these biological agents in the pathogenesis of many diseases like diabetes, cancer paralysis, autoimmune diseases or neurological disorders. Nevertheless, the only punfication from scorpion venoms of theses peptides still doesn't offer sufficient quantities to allow conducting the pharmacological and structure-function studies. The solid phases peptide synthesis (SPPS) is a methodology that allows us to produce non-limited quantities of structural analogsfrom these peptides-toxins in. In this paper; we will try to highlight the importance of this methodology, and peptide engineering in general, in obtaining peptides of interest. We are also going to elucidate the problems encountered during the chemical synthesis of some betides and explain how to overcome them.
Fusions involving CRAF (RAF1) are infrequent oncogenic drivers in pediatric low‐grade gliomas, rarely identified in tumors bearing features of pilocytic astrocytoma, and involving a limited number of ...known fusion partners. We describe recurrent TRAK1::RAF1 fusions, previously unreported in brain tumors, in three pediatric patients with low‐grade glial‐glioneuronal tumors. We present the associated clinical, histopathologic and molecular features. Patients were all female, aged 8 years, 15 months, and 10 months at diagnosis. All tumors were located in the cerebral hemispheres and predominantly cortical, with leptomeningeal involvement in 2/3 patients. Similar to previously described activating RAF1 fusions, the breakpoints in RAF1 all occurred 5′ of the kinase domain, while the breakpoints in the 3′ partner preserved the N‐terminal kinesin‐interacting domain and coiled‐coil motifs of TRAK1. Two of the three cases demonstrated methylation profiles (v12.5) compatible with desmoplastic infantile ganglioglioma (DIG)/desmoplastic infantile astrocytoma (DIA) and have remained clinically stable and without disease progression/recurrence after resection. The remaining tumor was non‐classifiable; with focal recurrence 14 months after initial resection; the patient remains symptom free and without further recurrence/progression (5 months post re‐resection and 19 months from initial diagnosis). Our report expands the landscape of oncogenic RAF1 fusions in pediatric gliomas, which will help to further refine tumor classification and guide management of patients with these alterations.
We describe recurrent TRAK1::RAF1 fusions, previously unreported in brain tumors, in three pediatric patients with low‐grade glial‐glioneuronal tumors. We present the associated clinical, histopathologic and molecular features.
Abstract
Circulating cell-free DNA from blood plasma of cancer patients can be used to non-invasively interrogate somatic tumor alterations. Here we develop MSK-ACCESS (Memorial Sloan Kettering - ...Analysis of Circulating cfDNA to Examine Somatic Status), an NGS assay for detection of very low frequency somatic alterations in 129 genes. Analytical validation demonstrated 92% sensitivity in de-novo mutation calling down to 0.5% allele frequency and 99% for a priori mutation profiling. To evaluate the performance of MSK-ACCESS, we report results from 681 prospective blood samples that underwent clinical analysis to guide patient management. Somatic alterations are detected in 73% of the samples, 56% of which have clinically actionable alterations. The utilization of matched normal sequencing allows retention of somatic alterations while removing over 10,000 germline and clonal hematopoiesis variants. Our experience illustrates the importance of analyzing matched normal samples when interpreting cfDNA results and highlights the importance of cfDNA as a genomic profiling source for cancer patients.
Abstract
Background
Safe sampling of central nervous system tumor tissue for diagnostic purposes may be difficult if not impossible, especially in pediatric patients, and an unmet need exists to ...develop less invasive diagnostic tests.
Methods
We report our clinical experience with minimally invasive molecular diagnostics using a clinically validated assay for sequencing of cerebrospinal fluid (CSF) cell-free DNA (cfDNA). All CSF samples were collected as part of clinical care, and results reported to both clinicians and patients/families.
Results
We analyzed 64 CSF samples from 45 pediatric, adolescent and young adult (AYA) patients (pediatric = 25; AYA = 20) with primary and recurrent brain tumors across 12 histopathological subtypes including high-grade glioma (n = 10), medulloblastoma (n = 10), pineoblastoma (n = 5), low-grade glioma (n = 4), diffuse leptomeningeal glioneuronal tumor (DLGNT) (n = 4), retinoblastoma (n = 4), ependymoma (n = 3), and other (n = 5). Somatic alterations were detected in 30/64 samples (46.9%) and in at least one sample per unique patient in 21/45 patients (46.6%). CSF cfDNA positivity was strongly associated with the presence of disseminated disease at the time of collection (81.5% of samples from patients with disseminated disease were positive). No association was seen between CSF cfDNA positivity and the timing of CSF collection during the patient’s disease course.
Conclusions
We identified three general categories where CSF cfDNA testing provided additional relevant diagnostic, prognostic, and/or therapeutic information, impacting clinical assessment and decision making: (1) diagnosis and/or identification of actionable alterations; (2) monitor response to therapy; and (3) tracking tumor evolution. Our findings support broader implementation of clinical CSF cfDNA testing in this population to improve care.
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