Evaluating the Implementation and Impact of BRAF Reflex Mutation Testing in Melanoma, Lung, and Colorectal Cancers.

Background: Reflex molecular testing, the process of profiling specimens at diagnosis, is emerging in oncology, allowing for prompt therapy initiation, and potentially improving outcomes. This study evaluates the impact of reflex BRAF testing on treatment timelines and outcomes in melanoma, lung and colorectal cancers at the McGill University Health Center (MUHC).

Methods: A retrospective chart review was conducted at the MUHC.

Clinical, Dermoscopic, and Molecular Features of Acantholytic Squamous Cell Carcinoma: A Systematic Review.

Introduction: Acantholytic squamous cell carcinoma (aSCC) is a rare clinicopathological subtype of cutaneous squamous cell carcinoma, accounting for approximately 4.9% of all SCC cases. However, there are currently no standardized criteria for the diagnosis of aSCC.

The Impact of Next-generation Sequencing on Interobserver Agreement and Diagnostic Accuracy of Desmoplastic Melanocytic Neoplasms.

Next-generation sequencing (NGS) is increasingly being utilized as an ancillary tool for diagnostically challenging melanocytic neoplasms. It is incumbent upon the pathology community to perform studies assessing the benefits and limitations of these tools in specific diagnostic scenarios. One of the most challenging diagnostic scenarios faced by skin pathologists involves accurate diagnosis of desmoplastic melanocytic neoplasms (DMNs).

Invariant surface glycoprotein 65 of Trypanosoma brucei is a complement C3 receptor.

African trypanosomes are extracellular pathogens of mammals and are exposed to the adaptive and innate immune systems. Trypanosomes evade the adaptive immune response through antigenic variation, but little is known about how they interact with components of the innate immune response, including complement. Here we demonstrate that an invariant surface glycoprotein, ISG65, is a receptor for complement component 3 (C3).

CAP-ACP Workload Model for Advanced Diagnostics in Precision Medicine.

Objectives: In precision medicine, where oncologic management is tailored to the individual's clinical and genetic profiles, advanced diagnostic testing provides prognostic information and guides management in a growing number of malignancies. There is a need to capture the work pathologists perform to meet this demand by providing medically relevant, timely, and accurate testing results. This work includes not only direct patient consults (interpretation of results and issuing reports) but the administrative and medical oversight as well as the research needed to provide the necessary quality assurance, quality control, direction, and framework for the laboratory.

Defining the Criteria for Reflex Testing for Mutations in Cutaneous Melanoma Patients.

Targeted therapy has been developed through an in-depth understanding of molecular pathways involved in the pathogenesis of melanoma. Approximately ~50% of patients with melanoma have tumors that harbor a mutation of the oncogene. Certain clinical features have been identified in -mutated melanomas (primary lesions located on the trunk, diagnosed in patients <50, visibly pigmented tumors and, at times, with ulceration or specific dermatoscopic features).

Narrowband ultraviolet B therapy for refractory immune-related lichenoid dermatitis on PD-1 therapy: a case report.

Treatment with programmed cell death 1 inhibitors is associated with a wide range of cutaneous immune-related adverse events, with lichenoid eruptions representing one of the major cutaneous toxicities. We describe the case of an 81-year-old man with metastatic melanoma treated with pembrolizumab who subsequently developed a delayed-onset generalized lichenoid dermatitis. After failing multiple lines of systemic immunosuppression, narrowband ultraviolet B (NBUVB) phototherapy three times per week for 17 sessions resulted in a significant clinical response in his cutaneous eruption and was well tolerated.

Metastatic Prostatic Adenocarcinoma in Patient With Muir-Torre Syndrome Misdiagnosed as Metastatic Sebaceous Carcinoma: Case Report and Systematic Literature Review.

Muir-Torre syndrome (MTS) is a rare autosomal dominant condition characterized by the presence of at least one cutaneous sebaceous tumor and one visceral malignancy, arising mostly from the gastrointestinal tract. We present the case of a 63-year-old man with several cutaneous and visceral neoplasias in the context of MTS, and a pelvic lymph node lesion diagnosed initially as metastatic sebaceous carcinoma, but later identified as metastasis from a newly diagnosed prostatic adenocarcinoma. Histological similarities between these 2 lesions are discussed.

BORIS/CTCFL promotes a switch from a proliferative towards an invasive phenotype in melanoma cells.

Melanoma is among the most aggressive cancers due to its tendency to metastasize early. Phenotype switching between a proliferative and an invasive state has been suggested as a critical process for metastasis, though the mechanisms that regulate state transitions are complex and remain poorly understood. Brother of Regulator of Imprinted Sites (BORIS), also known as CCCTC binding factor-Like (CTCFL), is a transcriptional modulator that becomes aberrantly expressed in melanoma.

The metastatic site does not influence PD-L1 expression in advanced non-small cell lung carcinoma.

Introduction: PD-L1 expression by immunohistochemistry (IHC) testing with Tumor Proportion Score (TPS) ≥50% and ≥1% is required to be eligible for first- and second-line Pembrolizumab treatment for metastatic non-small cell lung cancer (NSCLC) respectively. Stage IV NSCLC often presents with metastasis to multiple distant sites which are easily accessible for biopsy. Knowing whether PD-L1 IHC TPS can be indifferently measured from different metastatic site is therefore an important clinical question.

The protein phosphatase 2A regulatory subunit PR70 is a gonosomal melanoma tumor suppressor gene.

Male gender is independently and significantly associated with poor prognosis in melanoma of all clinical stages. The biological underpinnings of this sex difference remain largely unknown, but we hypothesized that gene expression from gonosomes (sex chromosomes) might play an important role. We demonstrate that loss of the inactivated X chromosome in melanomas arising in females is strongly associated with poor distant metastasis-free survival, suggesting a dosage benefit from two X chromosomes.

Curative pelvic exenteration for recurrent cervical carcinoma in the era of concurrent chemotherapy and radiation therapy. A systematic review.

Objective: Pelvic exenteration requires complete resection of the tumor with negative margins to be considered a curative surgery. The purpose of this review is to assess the optimal preoperative evaluation and surgical approach in patients with recurrent cervical cancer to increase the chances of achieving a curative surgery with decreased morbidity and mortality in the era of concurrent chemoradiotherapy.

Methods: Review of English publications pertaining to cervical cancer within the last 25 years were included using PubMed and Cochrane Library searches.

Molecular pathology of cutaneous melanoma.

Cutaneous melanoma is associated with strong prognostic phenotypic features, such as gender, Breslow's thickness and ulceration, although the biological significance of these variables is largely unknown. It is likely that these features are surrogates of important biological events rather than directly promoting cutaneous melanoma progression. In this article, we address the molecular mechanisms that drive these phenotypic changes.

Copeptin and arginine vasopressin at high altitude: relationship to plasma osmolality and perceived exertion.

Purpose: A diuresis is a key part of acclimatisation to high altitude (HA). Arginine vasopressin (AVP) is a hormone involved in salt and water balance and may potentially have a role in the development of altitude illness. ProAVP (copeptin) is more stable than AVP and is assayed by a straightforward, automated method.

Scoring system avoids Chlamydia trachomatis overscreening in women seeking surgical abortions.

Objective: To develop and validate a predictive score to avoid unnecessary screening and prophylactic antibiotic use in abortion clinics by identifying a group of women who are at very low risk for Chlamydia trachomatis (CT) infection.

Methods: This population-based retrospective study includes 1000 women who underwent surgical abortion between January and September 2010. The main outcome measure was the rate of CT infection among women seeking an induced abortion according to sociodemographic and clinical data.

TCF2/HNF-1beta mutations: 3 cases of fetal severe pancreatic agenesis or hypoplasia and multicystic renal dysplasia.

Objective: The aim of this study was to document the association between pancreatic agenesis or hypoplasia and multicystic renal dysplasia related to transcription factor 2 (TCF2) or hepatocyte nuclear factor 1 beta mutations.

Methodology: We describe the phenotype of the pancreas and the kidneys from three fetuses heterozygous for a mutation of TCF2.

Cases: Case 1 had bilateral hyperechogenic, multicystic kidneys, bilateral clubfoot and pancreatic agenesis.

Petechiae in hanging: a retrospective study of contributing variables.

Petechiae, one of the classic signs of asphyxia, are thought to be more frequently observed in cases of hanging where part of the body is supporting the victim's weight, ie, cases of incomplete hanging. However, there is very little evidence-based medicine to support this claim. The present study is intended to evaluate the relationship between petechiae and the type of hanging (complete vs.

The dual role of the X-linked FoxP3 gene in human cancers.

The FoxP3 (forkhead box P3) gene is an X-linked gene that is submitted to inactivation. It is an essential transcription factor in CD4(+)CD25(+)FoxP3 regulatory T cells, which are therapeutic targets in disseminated cutaneous melanoma. Moreover, FoxP3 is an important tumor suppressor gene in carcinomas and has putative cancer suppressor gene function in cutaneous melanoma as well.

Multi-centre observational study of spurious hyperkalaemia due to EDTA contamination.

Background: A multi-centre observational study investigating the prevalence of spurious hyperkalaemia due to potassium ethylenediaminetetraacetic acid (kEDTA) contamination.

Methods: Serum EDTA was measured in anonymised serum samples with a serum potassium > 6.0 mmol/L collected over a one month period in five different hospital laboratories.

Respiratory, circulatory, and neurological responses to hanging: a review of animal models.

The pathophysiology of hanging is still poorly understood. This article presents a review of eight animal models: four models of isolated occlusion of the vessels of the neck (group 1), one model of combined tracheal and vessel occlusion (group 2), and three models of true animal hanging (group 3). Occlusion of the airway passages in group 2 did not accelerate respiratory arrest compared to group 1.

Mechanism of death in hanging: a historical review of the evolution of pathophysiological hypotheses.

In cases of hanging, the exact mechanism leading to death has yet to be elucidated. Most of our contemporary knowledge is still based on writings from the end of the 19th and the beginning of the 20th century. This article reviews the historic experiments that shaped our current theories.