Superiority of virtual microscopy versus light microscopy in transplantation pathology.

Virtual microscopy has begun to change conventional pathology practice. We tested the reliability of this new technology in transplantation pathology. We studied 40 kidney transplant biopsies for cause and compared reproducibility of Banff scores using virtual slides versus glass slides. Three glass slides per biopsy were scanned as high-resolution digital slides using Aperio ScanScope. Three pathologists independently reviewed the biopsies: twice by glass slides and twice by virtual slides. Eleven histopathological lesions were scored and used to construct diagnosis according to Banff criteria. The intra-observer reproducibility of Banff scores was substantially good using either virtual slides or glass slides (mean κ: 0.69 vs. 0.64, p>0.05). The inter-observer reproducibility of Banff scores was better in virtual slides than in glass slides (mean κ: 0.42 vs. 0.28, p<0.001). Among the lesions, transplant glomerulopathy scoring by virtual slides showed the highest inter-observer reproducibility, with a similar accuracy to glass slides. The agreement for acute rejection between virtual and glass slides was not different from the agreement between two readings of glass slides. Thus, virtual microscopy is a reliable and more reproducible technology and has several advantages over glass slides, e.g., accessibility via internet, no fading. We recommend virtual microscopy for transplant diagnostics, including utilization for clinical trials.

Periadventitial tissue examination in temporal artery biopsies for suspected giant cell arteritis: a case series and literature review.

OBJECTIVE: Giant cell arteritis (GCA) is a systemic vasculitis, affecting medium- and large-sized vessels. Temporal artery biopsies (TABs) are currently the benchmark for diagnosing suspected cases of GCA. Often, the temporal artery is "skeletonized," and surrounding soft tissue is discarded at the time of biopsy. The purpose of this study was to identify cases in which diagnoses were made through examination of periadventitial soft tissue in nonskeletonized TABs. DESIGN: Retrospective observational case series and literature review. PARTICIPANTS: Six patients were recruited on a case-by-case basis. INCLUSION CRITERIA: bilateral TABs for suspected GCA and periadventitial findings leading to appropriate diagnosis. EXCLUSION CRITERIA: none. METHODS: A retrospective chart review was performed to collect patient demographics and clinical information in 2 academic institutions in Ontario, Canada. The primary outcome measure was identification of histopathological diagnoses made through examination of periadventitial soft tissue in TABs performed for suspected GCA. RESULTS: Two patients were diagnosed with GCA, one of which had a concurrent diagnosis of chronic lymphocytic leukemia. Four patients were diagnosed with small vessel vasculitis, 3 of which were antineutrophil cytoplasmic antibody-related vasculitides. All patients had evidence of a disease limited to the periadventitial tissue of the TAB. The results are limited by the study's size. CONCLUSIONS: This case series demonstrates that other serious conditions may declare themselves with symptoms similar to that of GCA. We recommend that surgeons perform a nonskeletonized TAB in all cases of suspected GCA and that pathologists adequately examine the periadventitial tissue in these biopsies to ensure appropriate diagnosis.

Cognitive biases in orbital mass lesions - Lessons learned.

PURPOSE: A patient's presentation and clinical diagnosis can at times be clouded by their past medical history. Clinicians' anchoring bias towards initial information, such as a history of cancer, may lead them astray when creating a differential diagnosis for a patient who presents with new signs and symptoms of a mass lesion, assuming metastatic disease without seeking tissue confirmation. METHODS: The presentation, workup, diagnosis, and treatment of two patients who presented with orbital masses in the context of a primary prostate cancer are presented in this report. RESULTS: In both cases, prostate cancer metastasis to the orbit was top on the differential. Ultimately, histopathological examination of biopsies taken from the orbital masses revealed orbital lymphoma in both patients. CONCLUSION: With mounting rates of patients who have survived a previous cancer, multiple primary cancers within one patient are becoming increasingly common. While prostate cancer metastasis to the orbit is a relatively rare event, orbital lymphoma is a more common diagnosis in orbital masses. Therefore, when patients present with orbital masses in the context of prostate cancer, the conclusion should not immediately be metastasis and a tissue diagnosis should be sought; especially given that the treatment of these entities is different.

Characterization of ocular and metastatic uveal melanoma in an animal model.

PURPOSE: To characterize, in detail, tumor development, malignant cell dissemination, and metastasis in a 10-week animal model of uveal melanoma. METHODS: One million 92.1 human primary uveal melanoma cells were injected into the suprachoroidal space of the right eye of 27 immunosuppressed albino rabbits. Intraocular tumor growth was monitored weekly by fundoscopy and by ultrasonography at the end of the experiment. To document the progression of the disease, one animal per week was killed. The enucleated eyes, lungs, and livers were macroscopically examined and histopathologically studied by hematoxylin and eosin, periodic acid-Schiff, and immunohistochemistry. Mononuclear layers isolated from the rabbits' blood samples were cultured. RESULTS: Histopathology showed intraocular tumors in 89% of the animals. Tumor growth was found 1 week after cell inoculation, and by the end of the experiment large tumor masses were observed. Microscopic pulmonary metastatic foci were first observed 4 weeks after cell injection. By the end of the experiment, all the animals had metastasis to the lungs. Interestingly, 18% of the animals also had micrometastasis to the liver. Viable adherent uveal melanoma cells were successfully isolated from peripheral blood and grown in vitro. CONCLUSIONS: In this study, most rabbits developed intraocular tumors followed by lung metastasis, and some of these rabbits later developed liver micrometastases. This novel source of research material warrants a follow-up longer than 10 weeks to further explore the pathophysiologic bases of liver involvement commonly encountered in humans. The success in the isolation and culture of circulating malignant cells in this animal model suggests that it might be worthwhile to explore the application of this technique to the management of patients with primary uveal melanoma.

Experimental models of uveal melanoma.

Over the past several decades, considerable effort has been directed toward developing suitable experimental models for the study of uveal melanoma. Animal models of uveal melanoma have undergone many improvements, leading to the development of experimental systems that better represent the disease in human beings. A major advance has come from the use of human uveal melanoma cell lines capable of inducing tumour growth and metastatic disease in immunodeficient hosts. Knowledge gained from the use of experimental models will ultimately be translated into better diagnostic and therapeutic strategies for patients with uveal melanoma. In this review the authors describe the current state-of-the-art designs of experimental models of uveal melanoma, highlighting the advantages and disadvantages of the available models. Novel findings from a rabbit model of uveal melanoma are also presented.

Current and emerging treatment options for uveal melanoma.

Uveal melanoma (UM) is the most common primary malignant intraocular tumor in adults, with a 10-year cumulative metastatic rate of 34%. The most common site of metastasis is the liver (95%). Unfortunately, the current treatment of metastatic UM is limited by the lack of effective systemic therapy. Options for the management of the primary intraocular tumor include radical surgery as well as conservative treatments in order to preserve visual acuity. For metastatic disease, several approaches have been described with no standard method. Nevertheless, median survival after liver metastasis is poor, being around 4-6 months, with a 1-year survival of 10%-15%. In this review, the authors summarize current and promising new treatments for UM.

Uveal melanoma dormancy: an acceptable clinical endpoint?

Uveal melanoma is a rare but life-threatening malignancy. Over the past decades, the morbidity of uveal melanoma has been markedly reduced as a result of advances in the diagnostic ability to detect smaller tumors at an earlier stage. This has allowed for the use of more conservative treatments, avoiding enucleation. Mortality, however, has remained unchanged. This indicates that life expectancy is independent of local tumor control. Metastatic disease, the leading cause of death, is usually diagnosed many years later, despite successful treatment of the primary tumor, and at a late stage, when no effective therapy is available. These observations suggest that the disease was already disseminated at the time of tumor diagnosis. The detection of circulating malignant cells in the bloodstream of patients at different time points in the course of the disease supports this observation. Tumor dormancy has been considered as the leading theory for this intriguing delayed appearance of metastasis. Recent knowledge gained about the biological behavior of uveal melanoma as well as novel potential therapeutic targets are presented in this review.