A unique case of progressive hemifacial microsomia or Parry-Romberg syndrome associated with limb and brain anomalies with normal neurological findings: A review of the literature.

In this report, we describe an unusual case of progressive hemifacial atrophy or Parry-Romberg syndrome in a 10-year-old girl with progressive hemifacial microsomia and limb anomalies who had brain magnetic resonance imaging (MRI) findings of white matter hyper-intensities. Patients typically present with neurological manifestations such as epilepsy, facial pain, and migraines and ophthalmological symptoms in conjunction with white matter lesions. The patient demonstrated normal cognition and psychomotor development despite the presence of white matter lesions in her frontal lobe that is commonly associated with neurological symptoms. This report brings attention to the complicated relationship between facial, limb and brain imaging findings in Parry-Romberg syndrome and differentiates it from hemifacial microsomia syndrome.

PD-1 inhibition and treatment of advanced melanoma-role of pembrolizumab.

Remarkable clinical responses have been seen in patients with metastatic melanoma with targeted therapy (BRAFi vemurafenib, MEKi) and with modern immune cell-based approaches such as TCR engineered adoptive cell transfer (ACT) and earlier experiences with high-dose IL-2. The proximal mediators of these immune therapies are tumor-reactive CTL. Various mechanisms of resistance to immune-mediated apoptotic signals have been described, including phenotypic changes, effector cell exhaustion, functional tolerance, deficiencies in Ag processing and presentation, and mutation or down-regulation of antigenic epitopes. The immune system and drugs eradicate tumors via apoptosis. Therefore, tumors' resistance to apoptosis may be a determining factor that limits the efficacy of immunotherapies. It is predicted that these therapies have limited efficacy in patients whose melanomas have developed resistance to targeted therapy such as vemurafenib. Upregulation of the immune checkpoint molecule CTLA-4 on activated T cells and its interaction with CD80/86 blocks T cell activation. The fully humanized mAb ipilimumab blocks this interaction, resulting in sustained T cell stimulation. Likewise, the programmed death receptor 1 (PD-1) is another member of the B7:CD28 family of costimulatory molecules that regulates T cell activation, whose ligand (PD-L1) is expressed on melanomas. The human anti-PD-1 mAb, Pembrolizumab, overcomes tolerance, has a favorable pharmacokinetics profile with minimal undesired toxic side effects and has shown remarkable improvement in melanoma therapy. This review focuses on recent advances in the development of various anti-PD-1 checkpoint blockade antibodies and will summarize recent clinical data using immune checkpoint blocking antibodies.