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BACKGROUND: The need for extending pathology diagnostic expertise to more areas is now being met by the maturation of technology that can effectively deliver this level of care. The experience and lessons learned from our successfully deployed International Telepathology Service (ITS) to a hospital system in China guided us in starting a domestic telepathology network, the California Telepathology Service (CTS). Many of the lessons learned from the ITS project informed our decision-making for the CTS. New challenges were recognized and overcome, such as addressing the complexity and cost-benefit tradeoffs involved in setting up a digital consultation system that competes with an established conventional glass slide delivery system. METHODS: The CTS is based on a hub-and-spoke telepathology network using Leica Biosystems whole-slide image scanners and the eSlide Manager (eSM Version 12.3.3.7055, Leica Biosystems) digital image management software solution. The service currently comprises six spoke sites (UC San Diego [UCSD], UC Irvine [UCI], UC Davis, Northridge Hospital Medical Center [NHMC], Olive View Medical Center [OVMC], and Children's Hospital Los Angeles) and one central hub site (UCLA Medical Center). So far, five sites have been validated for telepathology case consultations following established practice guidelines, and four sites (UCI, UCSD, NHMC, and OVMC) have activated the service. RESULTS: For the active spoke sites, we reviewed the volume, turnaround time (TAT), and case types and evaluated for utility and value. From May 2017 to July 2018, a total of 165 cases were submitted. Of note, digital consultations were particularly advantageous for preliminary kidney biopsy diagnoses (avg TAT 0.7 day). CONCLUSION: For spoke sites, telepathology provided shortened TAT and significant financial savings over hiring faculty with expertise to support a potentially low-volume service. For the hub site, the value includes exposure to educationally valuable cases, additional caseload volume to support specialized services, and improved communication with referring facilities over traditional carrier mail. The creation of a hub-and-spoke telepathology network is an expensive undertaking, and careful consideration needs to be given to support the needs of the clinical services, acquisition and effective deployment of the appropriate equipment, network requirements, and laboratory workflows to ensure a successful and cost-effective system.
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Pheochromocytomatosis, a very rare form of pheochromocytoma recurrence, refers to new, multiple, and often small pheochromocytomas growing in and around the surgical resection bed of a previous adrenalectomy for a solitary pheochromocytoma. We here report a case of pheochromocytomatosis in a 70-year-old female. At age 64 years, she was diagnosed with a 6-cm right pheochromocytoma. She underwent laparoscopic right adrenalectomy, during which the tumor capsule was ruptured. At age 67 years, CT of abdomen did not detect recurrence. At age 69 years, she began experiencing episodes of headache and diaphoresis. At age 70 years, biochemical markers of pheochromocytoma became elevated with normal calcitonin level. CT revealed multiple nodules of various sizes in the right adrenal fossa, some of which were positive on metaiodobenzylguanidine (MIBG) scan. She underwent open resection of pheochromocytomatosis. Histological examination confirmed numerous pheochromocytomas ranging 0.1-1.2 cm in size. Next-generation sequencing of a panel of genes found a novel heterozygous germline c.570delC mutation in TMEM127, one of the genes that, if mutated, confers susceptibility to syndromic pheochromocytoma. Molecular analysis showed that the c.570delC mutation is likely pathogenic. Our case highlights the typical presentation of pheochromocytomatosis, a rare complication of adrenalectomy for pheochromocytoma. Previous cases and ours collectively demonstrate that tumor capsule rupture during adrenalectomy is a risk factor for pheochromocytomatosis. We also report a novel TMEM127 mutation in this case. LEARNING POINTS: Pheochromocytomatosis is a very rare form of pheochromocytoma recurrence.Pheochromocytomatosis refers to new, multiple and often small pheochromocytomas growing in and around the surgical resection bed of a previous adrenalectomy for a solitary pheochromocytoma.Tumor capsule rupture during adrenalectomy predisposes a patient to develop pheochromocytomatosis.Surgical resection of the multiple tumors of pheochromocytomatosis is recommended.Pheochromocytoma recurrence should prompt genetic testing for syndromic pheochromocytoma.
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OBJECTIVE: Lupus nephritis depends on autoantibody deposition and activation of multiple immune cell types that promote kidney inflammation, including lymphocytes and monocyte/macrophages. Laquinimod, currently in clinical trials for multiple sclerosis and lupus nephritis, reduces infiltration of inflammatory cells into the spinal cord in experimental autoimmune encephalomyelitis. Activated monocyte/macrophages infiltrate the kidneys during nephritis in systemic lupus erythematosus (SLE). We undertook this study to determine whether using laquinimod to reduce monocyte/macrophage-driven tissue damage as well as to alter lymphocytes in SLE nephritis could have greater therapeutic benefit than current treatments that primarily affect lymphocytes, such as mycophenolate mofetil (MMF). METHODS: To test laquinimod efficacy, we used the (NZB × NZW)F1 mouse model of SLE, in which disease manifests as nephritis. Preventive and therapeutic studies were performed to determine whether laquinimod could prevent or delay nephritis, as measured by proteinuria, serum creatinine, survival, and renal pathology. Spleen and kidney leukocyte populations and suppression assays were analyzed by flow cytometry. RESULTS: Laquinimod prevented or delayed lupus manifestations at levels equal to or better than MMF. Laquinimod treatment was associated with reduced numbers of monocyte/macrophages, dendritic cells, and lymphocytes, as well as with induction of myeloid-derived suppressor cells in spleens and kidneys. Laquinimod suppressed macrophage-secreted tumor necrosis factor α and induced production of interleukin-10 (IL-10). In addition, laquinimod suppressed interferon-γ and IL-17 production by lymphocytes and down-regulated expression of activation/costimulatory markers on antigen-presenting cells. CONCLUSION: The effects of laquinimod on myeloid and lymphoid cells may contribute to improvements in (NZB × NZW)F1 mouse survival, proteinuria, and glomerulonephritis. Future development of laquinimod as a therapeutic agent for lupus nephritis is promising.