Dataset for the reporting of carcinoma of renal tubular origin:recommendations from the International Collaboration on Cancer Reporting (ICCR)

AIMS The International Collaboration on Cancer Reporting (ICCR) has provided detailed datasets based upon the published reporting protocols of the Royal College of Pathologists, The Royal College of Pathologists of Australasia and the College of American Pathologists. METHODS AND RESULTS The dataset for carcinomas of renal tubular origin treated by nephrectomy was developed to provide a minimum structured reporting template suitable for international use and incorporated recommendations from the 2012 Vancouver Consensus Conference of the International Society of Urological Pathology and the fourth edition of the World Health Organization Bluebook on tumours of the urinary and male genital systems published in 2016. Reporting elements were divided into those, which are Required and Recommended components of the report. Required elements are; specimen laterality, operative procedure, attached structures, tumour focality, tumour dimension, tumour type, WHO/ISUP grade, sarcomatoid/rhabdoid morphology, tumour necrosis, extent of invasion, lymph node status, surgical margin status, AJCC TNM staging and co-existing pathology. Recommended reporting elements are; pre-operative treatment, details of tissue removed for experimental purposes prior to submission, site of tumour(s) block identification key, extent of sarcomatoid and/or rhabdoid component, extent of necrosis, presence of tumour in renal vein wall, lymphovascular invasion and lymph node status (size of largest focus and extranodal extension). CONCLUSIONS It is anticipated that the implementation of this dataset in routine clinical practise will inform patient treatment as well as provide standardized information relating to outcome prediction. The harmonisation of data reporting should also facilitate international research collaborations. This article is protected by copyright. All rights reserved

Radiation Nephropathy: A Review

The marked radiosensitivity of renal tissue represents a limitation on the total radiotherapeutic dose that safely can be applied to treatment volumes that include the kidneys. Radiation nephropathy is characterized by a progressive reduction in renal hemodynamics associated with a severe anemia. The latter is often normochromic normocytic in character, but can progress to a microangiopathic hemolytic anemia. The pathogenic mechanisms responsible for the development of radiation nephropathy remain ill-defined. Experimental studies which allow serial determinations of functional, morphologic, and cell kinetic radiation-induced changes indicate that primarily glomerular but also tubular alterations occur in the primary stages of radiation nephropathy. Glomerular capillary endothelial cell loss is seen within several weeks of irradiation. Remaining endothelial cells exhibit increased permeability leading to a subendothelial transudate. Mesangiolysis also is observed. In contrast, podocytes appear to be relatively unaffected at this stage. The endothelial changes appear to resolve, but the mesangial lesions progress, with hypercellularity and/or hypertrophy, increased mesangial matrix, mesangial sclerosis, and ultimately, glomerulosclerosis. These mesangial changes are similar to those observed in other chronic glomerulopathies. Dietary protein restriction, corticosteroids, and ACE-inhibitors all can reduce the severity of experimental radiation nephropathy

Dense deposit disease is not a membranoproliferative glomerulonephritis

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CD74 in kidney disease

CD74 (invariant MHC class II) regulates protein trafficking and is a receptor for macrophage migration inhibitory factor (MIF) and d-dopachrome tautomerase (d-DT/MIF-2). CD74 expression is increased in tubular cells and/or glomerular podocytes and parietal cells in human metabolic nephropathies, polycystic kidney disease, graft rejection and kidney cancer and in experimental diabetic nephropathy and glomerulonephritis. Stressors like abnormal metabolite (glucose, lyso-Gb3) levels and inflammatory cytokines increase kidney cell CD74. MIF activates CD74 to increase inflammatory cytokines in podocytes and tubular cells and proliferation in glomerular parietal epithelial cells and cyst cells. MIF overexpression promotes while MIF targeting protects from experimental glomerular injury and kidney cysts, and interference with MIF/CD74 signaling or CD74 deficiency protected from crescentic glomerulonephritis. However, CD74 may protect from interstitial kidney fibrosis. Furthermore, CD74 expression by stressed kidney cells raises questions about the kidney safety of cancer therapy strategies delivering lethal immunoconjugates to CD74-expressing cells. Thus, understanding CD74 biology in kidney cells is relevant for kidney therapeuticsGrant support: ISCIII and FEDER funds CP14/00133, PI13/00047, Sociedad Española de Nefrologia, ISCIII-RETIC REDinREN/RD012/0021, Comunidad de Madrid CIFRA S2010/ BMD-2378. Salary support: FIS to LV-R, Miguel Servet to MS-N. Programa Intensificación Actividad Investigadora (ISCIII/ Agencia Laín-Entralgo/CM) to AO

Light Chain Proximal Tubulopathy: Expanding the Pathologic Spectrum with and without Deposition of Crystalline Inclusions

Light chain proximal tubulopathy (LCPT) is an uncommon form of renal disease associated with dysproteinemias. It is characterized by intracytoplasmic deposition of crystallized mostly kappa monoclonal light chains in proximal tubules (PTs). Crystals are located within lysosomes by electron microscopy (EM). Rare lambda LCPT cases without crystals by EM were described. Retrospectively, we reviewed clinical, light microscopic (LM), immunofluorescence (IF), and EM findings in 9 cases) (8 males, 1 female; mean age 57 years (38–81)) with multiple myeloma. LM showed abundant cytoplasmic droplets in PT cells in all cases. Droplets were also present in the podocytes, endothelial and parietal cells in one case. IF revealed staining of crystals with kappa in 3 and lambda in 6. EM showed electron dense rectangular, rhomboid, or needle shaped crystals in PT cells in 3 cases (33%), one of which had crystals in podocytes and interstitial cells. Six lambda LCPT cases showed no crystals by EM (67%). This may reflect differences in the physicochemical properties of light chains. The mechanisms of crystal accumulation in these cells and the significance of this finding are unknown.</jats:p

Renal Cell Carcinoma with Unusual Metastasis to the Small Intestine Manifesting as Extensive Polyposis: Successful Management with Intraoperative Therapeutic Endoscopy

We present here a rare clinical case of a 53-year-old gentleman with metastasis from renal cell carcinoma (RCC) to the small intestine presenting with extensive polyposis and massive gastrointestinal bleeding which was successfully managed with intraoperative endoscopic polypectomy and segmental small bowel resection. The patient presented with melena 2 weeks after right nephrectomy for RCC. Capsule endoscopy found extensive polyposis throughout the small bowel, and the histological features confirmed the diagnosis of metastatic RCC. The patient eventually underwent laparotomy with intraoperative endoscopy of the entire small bowel. Most of the polyps were removed by snare polypectomy. Three segments of the small bowel with extensive transmural involvement had to be resected with primary anastomosis. In the 2 months following his surgery, the patient had no further evidence of gastrointestinal bleeding. The decision of meticulously removing close to 100 polyps by intraoperative endoscopy prevented the patient from requiring total small bowel resection and lifelong dependence on parenteral nutrition. In conclusion, gastrointestinal bleeding in a patient with known RCC should always trigger full gastrointestinal work-up including capsule endoscopy and, if necessary, double balloon enteroscopy

Afferent arteriolopathy and glomerular collapse but not segmental sclerosis induce tubular atrophy in old spontaneously hypertensive rats

In chronic renal disease, the temporal and spatial relationship between vascular, glomerular and tubular changes is still unclear. Hypertension, an important cause of chronic renal failure, leads to afferent arteriolopathy, segmental glomerulosclerosis and tubular atrophy in the juxtamedullary cortex. We investigated the pathological changes of hypertensive renal disease in aged spontaneously hypertensive rats using a large number of serial sections, where we traced and analyzed afferent arteriole, glomerulus and proximal tubule of single nephrons. Our major finding was that both afferent arteriolopathy and glomerular capillary collapse were linked to tubular atrophy. Only nephrons with glomerular collapse (n = 13) showed tubules with reduced diameter indicating atrophy [21.66 ± 2.56 μm vs. tubules in normotensive Wistar Kyoto rats (WKY) 38.56 ± 0.56 μm, p < 0.05], as well as afferent arteriolar wall hypertrophy (diameter 32.74 ± 4.72 μm vs. afferent arterioles in WKY 19.24 ± 0.98 μm, p < 0.05). Nephrons with segmental sclerosis (n = 10) did not show tubular atrophy and tubular diameters were unchanged (35.60 ± 1.43 μm). Afferent arteriolar diameter negatively correlated with glomerular capillary volume fraction (r = −0.36) and proximal tubular diameter (r = −0.46) implying reduced glomerular and tubular flow. In line with this, chronically damaged tubules showed reduced staining for the ciliary protein inversin indicating changed ciliary signalling due to reduced urinary flow. This is the first morphological study on hypertensive renal disease making correlations between vascular, glomerular and tubular components of individual nephron units. Our data suggest that afferent arteriolopathy leads to glomerular collapse and reduced urinary flow with subsequent tubular atrophy