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We describe a case of a melanocytic proliferation arising in a giant congenital melanocytic nevus CMN and outline the potential utility of an immunohistochemical study with PReferentially expressed Antigen in MElanoma PRAME in distinguishing benign proliferative nodules PN from melanoma in this context A 15dayold girl presented with a fibrotic nodule clinically suspicious for melanoma within a giant CMN Histopathological examination showed a predominantly intradermal melanocytic nevus with congenital features intermixing with an illdefined proliferation of larger melanocytes demonstrating mildtomoderate cytologic atypia and increased mitotic activity YAPTEAD Inhibitor 1 chemical structure AntiPRAME was diffusely positive within the congenital nevus while negative within the larger proliferating cells Chromosomal microarray analysis revealed whole chromosomal gains and losses only consistent with a PN arising in a giant CMN To our knowledge PRAME expression in giant CMN PN and pediatric melanomas has not been previously described Based on our experience with this case we propose that differential patterns of PRAME expression may be present in these three lesions allowing PRAME immunohistochemistry to potentially serve as a helpful adjunct diagnostic tool for laboratories that do not readily have access to molecular testing in rendering a diagnosis for atypical melanocytic proliferations arising in giant CMN Alzheimers Disease AD is characterised by extracellular deposition of amyloidβ Aβ in amyloid plaques and intracellular aggregation and accumulation of hyperphosphorylated tau in neurofibrillary tangles NFTs Although several kinases have been identified that contribute to the pathological phosphorylation of tau kinasetargeted therapies for AD have not been successful in clinical trials Critically the kinases responsible for numerous identified tau phosphorylation sites remain unknown G proteincoupled receptor GPCR kinases GRKs have recently been implicated in phosphorylation of nonGPCR substrates eg tubulin and αsynuclein and in neurological disorders including schizophrenia and Parkinsons disease Accordingly we investigated the involvement of GRKs in the pathophysiology of AD We performed a comprehensive immunohistochemical and biochemical analysis of the ubiquitously expressed GRKs namely GRK2 3 5 and 6 in postmortem human brain tissue of control subjects and AD patients GRKs display unique cell typespecific expression patterns in neurons astrocytes and microglia Levels of GRKs 2 5 and 6 are specifically decreased in the CA1 region of the AD hippocampus Biochemical evidence indicates that the GRKs differentially associate with total soluble and insoluble pools of tau in the AD brain Complementary immunohistochemical studies indicate that the GRKs differentially colocalise with total tau phosphorylated tau and NFTs Notably GRKs 3 and 5 also colocalise with amyloid plaques These studies establish a link between GRKs and the pathological phosphorylation and accumulation of tau and amyloid pathology in AD brains and suggest a novel role for these kinases in regulation of the pathological hallmarks of AD These studies establish a link between GRKs and the pathological phosphorylation and accumulation of tau and amyloid pathology in AD brains and suggest a novel role for these kinases in regulation of the pathological hallmarks of ADRare pathogenic variants in TOR1AIP1 OMIM 614512 coding the inner nuclear membrane protein laminassociated protein 1 LAP1 have been associated with a spectrum of disorders including limb girdle muscular dystrophy with cardiac involvement and a severe multisystem phenotype Recently Cossins et al reported two siblings with limb girdle muscular dystrophy and impaired transmission of the neuromuscular synapse demonstrating that defective LAP1 may lead to a congenital myasthenic syndrome Herein we describe the association of TOR1AIP1 deficiency with congenital myasthenic syndrome in three siblings Centric relation is a dental term that has undergone many alterations over the years which in turn have led to significant clinical controversies These continuing changes in the meaning of the term CR have not only led to confusion but they also have resulted in a variety of unnecessary diagnostic and therapeutic procedures Analysis of the dental literature reveals ongoing misunderstanding and disagreement regarding that term among both clinicians and academic dentists A search of the PubMed database was performed with the following search terms centric relation masticatory muscles maxillomandibular relationship and condylar position Relevant literature from the past 70years until the present day was meticulously scrutinised As expected the literature review on the topic of CR revealed a problematic pattern of changing definitions and clinical disagreements all of which have had a significant impact on the practice of dentistry There are semantic conceptual and practical reasons fby the maximum intercuspation of the teeth and should therefore be considered as biologically acceptable Primary cutaneous CD30 lymphoproliferative diseases are the second most common group of cutaneous Tcell lymphomas including lymphomatoid papulosis LyP primary cutaneous anaplastic largecell lymphoma pcALCL and borderline cases These diseases form a spectrum and may show overlapping histopathological phenotypic and genetic features In the 2016 WHO classification LyP with 6p253 rearrangement was introduced as a rare new subtype of LyP and showed distinctive clinicopathological features The striking biphasic histopathologic pattern presented with larger transformed lymphocytes diffusely infiltrating the dermis and smaller atypical cells infiltrating the epidermis as in pagetoid reticulosis Herein we report two cases of pcALCL with rearrangement involving the DUSP22IRF4 locus on 6p253 that show the same particular biphasic histopathologic pattern We review the literature regarding five similar reported cases and discuss the clinical pathologic immunotype and followup features Our findings suggest that the biphasic histopathologic pattern is not a unique characteristic of LyP with 6p25