Onycholemmal carcinoma: a morphologic comparison of 6 reported cases.

BACKGROUND: We report 6 new cases of onycholemmal carcinoma, a rare, often misdiagnosed, subcategory of squamous cell carcinoma. All reported cases to date have been treated with amputation of the affected digit. OBJECTIVE: The purpose of this study was to present the clinical and pathological features of each new case and to discuss treatment options that spare digit functionality. METHODS: Hematoxylin-eosin stains were performed on tumor sections and examined using light microscopy. In situ hybridization using probes against human papillomavirus were examined in 1 case. RESULTS: The female to male ratio was 1:1 with involvement of fingers in 3, thumb in 1, and toe in 1. Among the symptoms were onycholysis, periungual erythema, and pain; symptom duration ranged from 6 months to 2 years. Histologically, all cases showed a well-differentiated atypical infiltrative squamous proliferative lesion exhibiting a lobulated and cystic pattern of growth in the dermis. Abrupt keratinization reminiscent of trichilemmal keratinization was noted. Mohs micrographic surgery and radiation therapy were used as primary treatment modalities, maintaining digit functionality and achieving remission. LIMITATIONS: Limitations of this study included the small number of cases, the infrequency with which this tumor has been reported in the literature, and the inability to obtain follow-up on an older archival case. CONCLUSIONS: Onycholemmal carcinoma is a distinct type of squamous cell carcinoma arising from the nail isthmus; its natural clinical course is indolent. In this regard less aggressive digit-sparing treatment modalities such as radiation or Mohs micrographic surgery should be considered.

Whole slide images and digital media in pathology education, testing, and practice: the Oklahoma experience.

Examination of glass slides is of paramount importance in pathology training. Until the introduction of digitized whole slide images that could be accessed through computer networks, the sharing of pathology slides was a major logistic issue in pathology education and practice. With the help of whole slide images, our department has developed several online pathology education websites. Based on a modular architecture, this program provides online access to whole slide images, still images, case studies, quizzes and didactic text at different levels. Together with traditional lectures and hands-on experiences, it forms the back bone of our histology and pathology education system for residents and medical students. The use of digitized whole slide images has a.lso greatly improved the communication between clinicians and pathologist in our institute.

Digital slides and ACGME resident competencies in anatomic pathology: An altered paradigm for acquisition and assessment.

Whole slide digital imaging technology has matured considerably over the past decade. Applications in pathology education are widespread and are rapidly transforming the manner in which medical students learn pathology and histology, and they have a novel and significant impact on postgraduate continuing medical education. Whole slide digital images for use in pathology graduate education have been slower in adoption and remain much less widespread. Emphasis on professional competency by the Accreditation Council on Graduate Medical Education (ACGME) and credentialing organizations, however, appear poised to significantly increase. The convergence of these two forces is propitious for pathology training. This article examines the opportunities for the use of whole slide images (WSI) in pathology residency training along with the developing potential uses in each of the areas of competency, as categorized by the ACGME. Barriers to WSI adoption in the pathology community are identified along with potentially significant promoters for adoption in training and practice. Current literature and recent presentations are reviewed. Digital pathology coupled with emphasis on competency is a shift of tremendous magnitude that can dramatically improve our abilities to help trainees acquire, demonstrate, and maintain the skills to practice pathology in the generation ahead.

Gene expression profiling in neutrophils from children with polyarticular juvenile idiopathic arthritis.

OBJECTIVE: We have previously reported a defect in neutrophil activation in children with polyarticular juvenile idiopathic arthritis (JIA). The current study was undertaken to determine whether gene expression abnormalities persist in JIA in remission and to use systems biology analysis to elucidate pathologic pathways in polyarticular JIA. METHODS: We performed gene expression profiling on neutrophils from children with polyarticular JIA. Children were grouped according to disease status. We studied 14 children with active disease who were taking medication, 8 children with clinical remission of disease who were taking medication (CRM status), and 6 children with clinical remission of disease who were not taking medication (CR status). We also studied 13 healthy children whose age ranges overlapped those of the patients. RESULTS: Neutrophil abnormalities persisted in children with polyarticular JIA even after disease remission was achieved. Children with active disease and those with CRM status showed no differences in expression of specific genes, although they could be separated on cluster analysis. A comparison of children with CR status and healthy control children revealed networks of pro- and antiinflammatory genes that suggested that remission is a state of homeostasis and balance rather than a return to normal immune function. Furthermore, gene overexpression in patients with CR status supports the hypothesis that neutrophils play a role in regulating adaptive immunity in this disease. CONCLUSION: Neutrophil gene profiling in polyarticular JIA suggests important roles for neutrophils in disease pathogenesis. These findings suggest the presence of complex interactions between innate and adaptive immunity, that are not easily modeled in conventional, linear, reductionist systems.

Disease-associated pathophysiologic structures in pediatric rheumatic diseases show characteristics of scale-free networks seen in physiologic systems: implications for pathogenesis and treatment.

BACKGROUND: While standard reductionist approaches have provided some insights into specific gene polymorphisms and molecular pathways involved in disease pathogenesis, our understanding of complex traits such as atherosclerosis or type 2 diabetes remains incomplete. Gene expression profiling provides an unprecedented opportunity to understand complex human diseases by providing a global view of the multiple interactions across the genome that are likely to contribute to disease pathogenesis. Thus, the goal of gene expression profiling is not to generate lists of differentially expressed genes, but to identify the physiologic or pathogenic processes and structures represented in the expression profile. METHODS: RNA was separately extracted from peripheral blood neutrophils and mononuclear leukocytes, labeled, and hybridized to genome level microarrays to generate expression profiles of children with polyarticular juvenile idiopathic arthritis, juvenile dermatomyositis relative to childhood controls. Statistically significantly differentially expressed genes were identified from samples of each disease relative to controls. Functional network analysis identified interactions between products of these differentially expressed genes. RESULTS: In silico models of both diseases demonstrated similar features with properties of scale-free networks previously described in physiologic systems. These networks were observable in both cells of the innate immune system (neutrophils) and cells of the adaptive immune system (peripheral blood mononuclear cells). CONCLUSION: Genome-level transcriptional profiling from childhood onset rheumatic diseases suggested complex interactions in two arms of the immune system in both diseases. The disease associated networks showed scale-free network patterns similar to those reported in normal physiology. We postulate that these features have important implications for therapy as such networks are relatively resistant to perturbation.

The meaning of clinical remission in polyarticular juvenile idiopathic arthritis: gene expression profiling in peripheral blood mononuclear cells identifies distinct disease states.

OBJECTIVE: The development of biomarkers to predict response to therapy in polyarticular juvenile idiopathic arthritis (JIA) is an important issue in pediatric rheumatology. A critical step in this process is determining whether there is biologic meaning to clinically derived terms such as "active disease" and "remission." The aim of this study was to use a systems biology approach to address this question. METHODS: We performed gene transcriptional profiling on children who fulfilled the criteria for specific disease states as defined by the consensus criteria developed by Wallace and colleagues. The study group comprised children with active disease (n = 14), children with clinical remission on medication (CRM; n = 9), children with clinical remission off medication (CR; n = 6), and healthy control children (n = 13). Transcriptional profiles in peripheral blood mononuclear cells (PBMCs) were obtained using Affymetrix U133 Plus 2.0 arrays. RESULTS: Hierarchical cluster analysis and predictive modeling demonstrated that the clinically derived criteria represent biologically distinct states. Minimal differences were seen between children with active disease and those with disease in CRM. Thus, underlying immune/inflammatory abnormalities persist despite a response to therapy. The PBMC transcriptional profiles of children whose disease was in remission did not return to normal but revealed networks of proinflammatory and antiinflammatory genes, suggesting that remission is a state of homeostasis, not a return to a normal state. CONCLUSION: Gene transcriptional profiling of PBMCs revealed that clinically derived criteria for JIA disease states reflect underlying biology. We also demonstrated that neither CRM nor CR status results in resolution of the underlying inflammatory process, but that these conditions are more likely to be states of balanced homeostasis between proinflammatory and antiinflammatory mechanisms.