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Kimura disease (KD) is a chronic, inflammatory disorder with slowly developing subcutaneous tumor-like swellings, often occurring in the head and neck region. KD is diagnosed based on histology, elevated levels of immunoglobulin type E, and increased peripheral eosinophil granulocytes. KD may coexist with glomerular renal diseases, and this case report is based on a patient with KD-associated membranous nephropathy. Patients with membranous nephropathy without KD have demonstrated responsiveness to treatment with monoclonal anti-CD20 antibodies. This case report is the first to investigate the effect of rituximab treatment in a patient with KD-associated membranous nephropathy. A 30-year-old Italian man living in Denmark was diagnosed with Kimura's disease based on subcutaneous nodules with eosinophil angiolymphoid hyperplasia. The patient was admitted to the hospital due to nephrotic syndrome. Serology showed eosinophil granulocytosis and negative PLA2-receptor antibody. Renal biopsy showed membranous nephropathy, and the patient was treated with systemic methylprednisolone followed by cyclosporin and then cyclophosphamide with only partial remission. Ultimately, treatment with intravenous rituximab was initiated, which resulted in overall remission and no nephrotic relapses at 30 months of follow-up. Thus, intravenous rituximab effectively decreased proteinuria and prevented nephrotic relapses in a patient with treatment-refractory membranous nephropathy due to KD.

Previous studies suggest an increased cancer risk in hypertension. Patients with hypertensive nephropathy have not been studied. A national registry study was performed to assess the presence and size of this association. Clinical data and cancer diagnoses for all patients with biopsy-proven hypertensive nephropathy between 1985 and 2015 in Denmark were extracted from four national registries and compared with age- and sex-adjusted national cancer rates. The risk of cancer was twice the background population. It was raised for renal cancer (odds ratio 10.4), myeloma (13.2), skin cancer (7.9), and other/unspecified (1.8). No increase in incidence was seen until 1 year before renal biopsy and then rose rapidly. It was again normal 5 years after biopsy. Hypertensive nephropathy is associated with an increased risk of myeloma, skin, renal, and other cancers. Screening of patients with hypertensive nephropathy, in the presence of reduced renal function or significant proteinuria, may be indicated.

Background: The association of increased cancer risk with glomerulonephritis (GN) is well known, but controversy exists concerning which types of GN are involved, and the size of the association. A national registry survey was performed to assess the size of this association, and the temporal relationship of cancer diagnosis to GN diagnosis. Methods: All patients with biopsy-proven GN between 1985 and 2015 in Denmark were extracted from The Danish Renal Biopsy Registry and the National Pathology Data Bank. Incident cancer diagnoses between 10 years previous and 10 years subsequent to the GN diagnosis were extracted from the Danish Cancer Registry. Residence, birth and death data were obtained from the National Patient Register. Expected cancer incidence, classified according to cohort, age and sex were extracted from the Nordcan database. Results: Nine hundred eleven cancers were diagnosed in 5594 patients. Thirty five percent were prevalent at renal biopsy. Prevalence at biopsy was 5.5% (expected 3.1%), but incidence was not increased < 1 year before biopsy. Increased cancer rates were seen for GN forms: minimal change, endocapillary, focal segmental glomerulosclerosis, mesangioproliferative, membranous, focal segmental, membranoproliferative, proliferative, ANCA-associated vasculitis, lupus nephritis and unclassified. Increased cancer rates were seen for lung, prostate, renal, non-Hodgkin lymphoma, myeloma, leukaemia and skin. The increased incidence was mainly limited to - 1 to 1 year after biopsy, but skin cancer showed an increased risk over time. Some diagnoses showed an increase 5-10 years after biopsy. Incidence was raised for patients with uraemia and nephrosis, but less for proteinuria or haematuria. Cancers in patients < 45 years were rare. The risk of developing cancer 0-3 years after biopsy for patients 45-64 years varied from 7.3% (minimal change) to 15.8% (unclassified GN); > 64 years from 11.8 (endocapillary GN) to 20.3% (unclassified). T

Hypertension and renal injury are off-target effects of sunitinib, a tyrosine kinase receptor inhibitor used for the treatment of various tumor types. Importantly, these untoward effects are accompanied by activation of the endothelin system. Here, we set up a study to explore the dose dependency of these side effects. Normotensive Wistar Kyoto rats were exposed to 3 different doses of sunitinib or vehicle. After 8 days, rats were euthanized. Telemetrically measured blood pressure rose dose dependently, from 13 to 30 mm Hg. Proteinuria was present at all doses, but a rise in cystatin C occurred only at the intermediate and high doses. Compared with vehicle circulating endothelin-1 increased dose dependently, whereas 24-hour urinary endothelin excretion decreased. Light and electron microscopy revealed glomerular endotheliosis and ischemia with the intermediate and high doses of sunitinib but completely absent histological abnormalities with the low dose. Podocyte number per glomerular circumference did not change. Glomerular nephrin, Neph1, podocin, and endothelin-converting enzyme gene expression were downregulated in a dose-dependent manner. We conclude that the sunitinib-induced rise in blood pressure requires lower doses than its induction of renal function impairment and that functional changes in glomerular filtration barrier contribute to the occurrence of proteinuria, given the lack of histopathologic changes with the low dose of sunitinib.

A 77-year-old female, with proptosis, reduced eye motility and diplopia which had developed over two to three months and a 69-year-old female with proptosis, oedema of the eyelid, reduced motility and ptosis, which had developed over three weeks, are presented in the present study. Computed tomography scans revealed irregular lacrimal gland tumours in the two patients. The two patients had history of breast cancer. The first breast cancer metastasis in the lacrimal gland demonstrated a cribriform growth pattern containing ductal elements. The epithelial tumour cells stained positive for cytokeratin (1-8, 10, 14-16, 18 and 19), oestrogen receptor, epithelial membrane antigen (EMA), carcinoembryonic antigen (CEA) and gross cystic disease fluid protein 15 (GCDFP-15). The second metastatic tumour was positive for EMA and estrogen receptor, but variably positive for CEA and GCDFP-15. The metastasis in the lacrimal gland was a pleomorphic tumour. The tumour cells were positive for EMA and variably positive for oestrogen and CEA. Metastases to the lacrimal gland are extremely rare, and metastases to the lacrimal gland should be considered in the diagnoses of lacrimal gland tumours. The present study aimed to describe two such cases and draw attention to breast carcinomas as a differential diagnosis and the most frequent cause of lacrimal gland metastasis.

INTRODUCTION: To evaluate survival and engraftment of mesenchymal stromal cells (MSCs) in vivo, it is necessary to track implanted cells non-invasively with a method, which does not influence cellular ultrastructure and functional characteristics. Iron-oxide particles have been applied for cell tracking for years, but knowledge regarding possible cytotoxic ultrastructural changes subsequent to iron-oxide particle labeling is limited. Hence, the purpose of this study was to label MSCs with dextran-coated ultrasmall super-paramagnetic iron-oxide (USPIO) particles conjugated with the transduction sequence of trans-activator of transcription (TAT) (IODEX-TAT) and evaluate the effect of labeling on ultrastructure, viability, phenotype and proliferative capacity of the cells.MATERIALS AND METHODS: MSCs were labeled with 5 and 10 μg IODEX-TAT/10(5) cells for 2, 6 and 21 hours. IODEX-TAT uptake and cellular ultrastructure were determined by electron microscopy. Cell viability was determined by propidium iodide staining and cell proliferation capacity by 5-bromo-2-deoxyuridine (BrdU) incorporation. Maintenance of stem cell surface markers was determined by flow cytometry. Results. IODEX-TAT labeling for 2, 6 and 21 h did not influence cellular ultrastructure or viability. Moreover, neither stem cell surface markers nor cell proliferation capacity was affected by labeling with IODEX-TAT.CONCLUSION: Our results demonstrate that labeling of MSCs for 21 h with a clinically relevant dose of 10 μg IODEX-TAT/10(5) cells is feasible and does not affect MSC ultrastructure, viability, phenotype or proliferation capacity.

A 71-year-old female with a known history of primary hepatic neuroendocrine carcinoma, presented with a visual defect, proptosis and restricted eye movements of the right eye. Biopsies from the orbit and from the primary hepatic neuroendocrine carcinoma showed similar morphological and immunohistochemical features, and high-resolution, array-based comparative genomic hybridization demonstrated loss of one copy each of chromosomes 3 and 18, and gain of 1q both in the primary hepatic neuroendocrine carcinoma and in the orbital tumour. The orbital mass was diagnosed as a metastasis from the primary hepatic neuroendocrine carcinoma. Primary hepatic neuroendocrine tumours are extremely rare, and the orbit is an extremely rare location for a neuroendocrine carcinoma metastasis. This is the first reported case of an orbital metastasis with origin from a primary hepatic neuroendocrine carcinoma.

Carcinomas of unknown primary origin constitute 3% to 5% of all newly diagnosed metastatic cancers, with the primary source difficult to classify with current histological methods. Effective cancer treatment depends on early and accurate identification of the tumor; patients with metastases of unknown origin have poor prognosis and short survival. Because miRNA expression is highly tissue specific, the miRNA profile of a metastasis may be used to identify its origin. We therefore evaluated the potential of miRNA profiling to identify the primary tumor of known metastases. Two hundred eight formalin-fixed, paraffin-embedded samples, representing 15 different histologies, were profiled on a locked nucleic acid-enhanced microarray platform, which allows for highly sensitive and specific detection of miRNA. On the basis of these data, we developed and cross-validated a novel classification algorithm, least absolute shrinkage and selection operator, which had an overall accuracy of 85% (CI, 79%-89%). When the classifier was applied on an independent test set of 48 metastases, the primary site was correctly identified in 42 cases (88% accuracy; CI, 75%-94%). Our findings suggest that miRNA expression profiling on paraffin tissue can efficiently predict the primary origin of a tumor and may provide pathologists with a molecular diagnostic tool that can improve their capability to correctly identify the origin of hitherto unidentifiable metastatic tumors and, eventually, enable tailored therapy.

To investigate diagnostic accuracy of detection of prostate cancer by magnetic resonance: to evaluate the performance of T2WI, DCEMRI and CSI and to correlate the results with biopsy and radical prostatectomy histopathological data.