The diagnostic challenges of differentiating metastatic extramammary Paget disease and prostatic adenocarcinoma: A case report and review of the literature.

Extramammary Paget disease (EMPD) is a rare dermatologic malignancy with a high rate of recurrence and increased risk for developing secondary malignancies. We present a 74-year-old male with previously resected primary EMPD who presented with widespread PSMA-avid lesions without prostatic uptake, an elevated PSA >100, and a negative prostate biopsy. Based on this and immunohistological staining, recurrent EMPD was suspected.

Phase I Study of Fianlimab, a Human Lymphocyte Activation Gene-3 (LAG-3) Monoclonal Antibody, in Combination With Cemiplimab in Advanced Melanoma.

Purpose: Coblockade of lymphocyte activation gene-3 (LAG-3) and PD-1 receptors could provide significant clinical benefit for patients with advanced melanoma. Fianlimab and cemiplimab are high-affinity, human, hinge-stabilized IgG4 monoclonal antibodies, targeting LAG-3 and PD-1, respectively. We report results from a first-in-human phase-I study of fianlimab and cemiplimab safety and efficacy in various malignancies including advanced melanoma.

Cutaneous and Noncutaneous Adverse Effects in Patients with Advanced Melanoma Receiving Immunotherapy.

Relationships between cutaneous adverse effects (CAEs) and noncutaneous adverse effects (NCAEs) of melanoma immunotherapy may help identify patterns tied to distinct immunologic pathways. The objective of this study was to determine the associations between CAEs and NCAEs among patients with stages III-IV melanoma receiving immunotherapy and who were enrolled in a prospective cohort. Electronic medical record data were abstracted from the first immunotherapy infusion until 1 year later.

Case Report: Delayed Onset Multi-Organ Toxicities in a Melanoma Patient Achieving Complete Response to BRAF/MEK Inhibition.

Autoimmune toxicities, while common following treatment with cancer immunotherapies, are not well-characterized in patients treated with BRAF/MEK inhibitors. Emerging data suggest that autoimmune effects may be linked with superior responses to both treatment modalities; however, there is little evidence describing mechanisms of immune-related toxicity for patients on BRAF/MEK inhibitors. Here we describe the experience of a 59-year-old HLA-A2, A29, B27-positive male with recurrent/metastatic melanoma.

Effect of immunotherapy time-of-day infusion on overall survival among patients with advanced melanoma in the USA (MEMOIR): a propensity score-matched analysis of a single-centre, longitudinal study.

Background: The dependence of the adaptive immune system on circadian rhythm is an emerging field of study with potential therapeutic implications. We aimed to determine whether specific time-of-day patterns of immune checkpoint inhibitor infusions might alter melanoma treatment efficacy.

Methods: Melanoma Outcomes Following Immunotherapy (MEMOIR) is a longitudinal study of all patients with melanoma who received ipilimumab, nivolumab, or pembrolizumab, or a combination of these at a single tertiary cancer centre (Winship Cancer Institute of Emory University, Atlanta, GA, USA).

Clinical Correlation between Acute Exudative Polymorphous Paraneoplastic Vitelliform Maculopathy and Metastatic Melanoma Disease Activity: A 48-month Longitudinal Case Report.

Purpose: Longitudinal evaluation of acute exudative polymorphous paraneoplastic vitelliform maculopathy (AEPPVM) following diagnosis and treatment of metastatic melanoma.

Methods: Case report of a 47-year-old male with unknown primary metastatic melanoma and AEPPVM monitored before and during melanoma treatment using clinical exam, retinal imaging, and electroretinograms (ERG). Genetic testing and autoantibody panels were performed.

Changing Therapeutic Landscape for Melanoma With Multiple Brain Metastases.

Over 90 000 people are expected to be diagnosed with melanoma in the United States this year. The development of brain metastases is particularly difficult to manage. Over the past few years, melanoma patients with multiple unresectable brain metastases for which stereotactic surgery might also not be a viable option have fortunately experienced a dramatic expansion in available management options given improvements made to targeted agents, immunotherapy, and radiotherapy.

Chemokine receptor 4 targeted protein MRI contrast agent for early detection of liver metastases.

Liver metastases often progress from primary cancers including uveal melanoma (UM), breast, and colon cancer. Molecular biomarker imaging is a new non-invasive approach for detecting early stage tumors. Here, we report the elevated expression of chemokine receptor 4 (CXCR4) in liver metastases in UM patients and metastatic UM mouse models, and development of a CXCR4-targeted MRI contrast agent, ProCA32.

Surgical Considerations and Systemic Therapy of Melanoma.

Recent advances in effective medical therapies have markedly improved the prognosis for patients with advanced melanoma. This article aims to highlight the current era of integrated multidisciplinary care of patients with advanced melanoma by outlining current approved therapies, including immunotherapy, targeted therapy, radiation therapy, and other strategies used in both the adjuvant and the neoadjuvant setting as well as the evolving role of surgical intervention in the changing landscape of advanced melanoma.

Predictors of Overall and Progression-Free Survival in Patients with Ocular Melanoma Metastatic to the Liver Undergoing Y90 Radioembolization.

Purpose: To investigate predictors of overall survival (OS) and progression-free survival (PFS) in patients with ocular melanoma metastatic to the liver undergoing yttrium-90 (Y90) radioembolization, including the effect of concurrent immunotherapy.

Methods: An IRB-approved retrospective review of 24 patients with ocular melanoma metastatic to the liver who underwent Y-90 treatment between June 2003 and January 2018 was performed. Data regarding patients' performance status at the time of Y90, intra-/extrahepatic tumor burden, and treatment response were evaluated.

Approaches to High-Risk Resected Stage II and III Melanoma.

Over the last decade, several therapies, including both targeted and immune checkpoint inhibitors, have dramatically changed the treatment landscape for patients with metastatic melanoma. These same therapies are now being used in the adjuvant setting with the hope of delaying or preventing the development of metastatic disease. Although phase III trials have shown a clear benefit for patients with resected bulky nodal disease, treatment decisions for patients with earlier-stage (high-risk stage II and stage IIIA) melanoma in the adjuvant setting are less straightforward given the small number of patients studied so far.

Multiple keratin granulomata: A potential histologic clue to cutaneous squamous cell carcinoma responding to programmed cell death protein 1 inhibitor therapy.

We present histologic features of a locally advanced cutaneous squamous cell carcinoma (cSCC) treated with the programmed cell death protein-1 (PD-1) antagonist, pembrolizumab, with a partial response. This contributes to a growing body of literature supporting the efficacy of pembrolizumab in treatment of surgically unresectable cSCC. We also provide a detailed description of the histologic features, particularly keratin granulomata with adjacent lymphocytic aggregates and fibrosis, observed in cSCC under treatment with a PD-1 antagonist.

The importance of surgery in scalp angiosarcomas.

Background: Scalp angiosarcomas (SA) are rare, representing <1% of soft tissue sarcomas. The optimal management of these tumors is unknown, with management based on small case series. We sought to assess the impact of different therapies on overall survival (OS), the practice patterns nationally, and identify factors associated with OS for non-metastatic scalp angiosarcomas.

Systemic Therapy Options for Patients With Unresectable Melanoma.

There has been a therapeutic revolution in the treatment of metastatic melanoma over the past decade. Patients presenting with inoperable disease have several therapeutic options, which can include both targeted and immune therapy. Immune checkpoint inhibitors have demonstrated an improvement in overall survival and led to some durable responses.

Patient preferences regarding incidental genomic findings discovered during tumor profiling.

Background: During the process of tumor profiling, there is the potential to detect germline variants. To the authors' knowledge, there currently is no accepted standard of care for how to deal with these incidental findings. The goal of the current study was to assess disclosure preferences among patients with cancer regarding incidental genomic variants that may be discovered during tumor profiling.

Tumor profiling and the incidentalome: patient decisions and risks.

In recent years, the field of oncology has witnessed rapid advancements in genetic sequencing simultaneously with steeply declining costs of sequencing technology. As a result, genomics-driven cancer medicine and the use of tumor profiling are quickly becoming mainstays of cancer therapy. Oncology patients can benefit from tumor profiling by allowing the selection of targeted therapies tailored to their disease.

Advances in the systemic treatment of metastatic melanoma.

Prior to 2011, the only commercially available agents commonly used to treat metastatic melanoma-including dacarbazine, temozolomide (Temodar), fotemustine, carboplatin, paclitaxel, and interleukin-2-demonstrated limited efficacy, and no study involving these agents had shown an improvement in overall survival. The standard of care for the treatment of metastatic melanoma was radically changed by the subsequent approval of two agents, ipilimumab (Yervoy) and vemurafenib (Zelboraf), both of which improved survival in randomized phase III trials. Within the relatively short time that ipilimumab and vemurafenib have been commercially available, phase II data for the investigational agents nivolumab and MK-3475, for the combination of dabrafenib and trametinib, and for adoptive cell therapy strongly suggest even further improvements in treatment outcomes.

Understanding patients' attitudes toward communication about the cost of cancer care.

Purpose: Recent publications have promoted physician-patient communication on cost as a means of decreasing overall spending and minimizing patients' financial burden in oncology. No study has assessed patients' perspectives on cost communication in oncology. We sought to describe oncology patients' attitudes toward cost communication, explore potential predictors for patients' communication preferences, and assess how patients with cancer consider cost when making management decisions.

Regulation of neural progenitor cell fate by anandamide.

Exogenous application of neural progenitor cells (NPCs) has successful implications in treating brain disorders, and research is beginning to identify ways to mimic this exogenous application by activating endogenous stem cell compartments. The recent discovery of a functional endocannabinoid system in murine NPCs (mNPCs) represents one potential therapeutic means to influence endogenous stem cell compartments. High levels of the endogenous cannabinoids anandamide (AEA) and 2-arachidonoylglycerol (2-AG) persist during CNS inflammation and infection.

False positive reactivity of recombinant, diagnostic, glycoproteins produced in High Five insect cells: effect of glycosylation.

Baculovirus-mediated expression of recombinant proteins for use in diagnostic assays is commonplace. We expressed a diagnostic antigen for cysticercosis, GP50, caused by the larval stage of Taenia solium, in both High Five and Sf9 insect cells. Upon evaluation of the specificity of recombinant GP50 (rGP50) in a western blot assay, we observed that 12.

Characterization and cloning of T24, a Taenia solium antigen diagnostic for cysticercosis.

The third and final diagnostic antigen of the lentil lectin purified glycoproteins (LLGP) extracted from the larval stage of Taenia solium has been characterized, cloned, and expressed. T24 is an integral membrane protein that belongs to the tetraspanin superfamily. It migrates at a position corresponding to 24-kDa and as a homodimer at 42-kDa.