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Xanthogranulomatous epithelial tumor (XGET) is an extremely rare and recently described mesenchymal neoplasm characterized by a distinctive histological appearance and clinical presentation. This case report describes a unique case of XGET in a 66-year-old female patient who presented with a 5 cm mass in the dorsal distal left thigh. The clinical, radiological, and pathological findings, as well as the management and follow-up, are discussed. [ABSTRACT FROM AUTHOR]

Wu M, Arcaro A, Varga Z, Vogetseder A, Hir ML, Wuthrich RP, Serra AL. Pulse mTOR inhibitor treatment effectively controls cyst growth but leads to severe parenchymal and glomerular hypertrophy in rat polycystic kidney disease. Am J Physiol Renal Physiol 297: F1597-F1605, 2009. First published September 23, 2009; doi: 10.1152/ajprenal.00430.2009.--The efficacy of mammalian target of rapamycin (mTOR) inhibitors is currently tested in patients affected by autosomal dominant polycystic kidney disease. Treatment with mTOR inhibitors has been associated with numerous side effects. However, the renal-specific effect of mTOR inhibitor treatment cessation in polycystic kidney disease is currently unknown. Therefore, we compared pulse and continuous everolimus treatment in Han: SPRD rats. Four-week-old male heterozygous polycystic and wild-type rats were administered everolimus or vehicle by garage feeding for 5 wk, followed by 7 wk without treatment, or continuously for 12 wk. Cessation of everolimus did not result in the appearance of renal cysts up to 7 wk postwithdrawal despite the reemergence of S6 kinase activity coupled with an overall increase in cell proliferation. Pulse everolimus treatment resulted in striking noncystic renal parenchymal enlargement and glomerular hypertrophy that was not associated with compromised kidney function. Both treatment regimens ameliorated kidney function, preserved the glomerular-tubular connection, and reduced proteinuria. Pulse treatment at an early age delays cyst development but leads to striking glomerular and parenchymal hypertrophy. Our data might have an impact when long-term treatment using mTOR inhibitors in patients with autosomal dominant polycystic kidney disease is being considered. Han:SPRD; S6K; 4E-BP1 doi: 10.1152/ajprenal.00430.2009

We investigated the proliferative capacity of renal proximal tubular cells in healthy rats. Previously, we observed that tubular cells originate from differentiated cells. We now found 1) by application of bromo-deoxyuridine (BrdU) for 14 days and costaining for BrdU, and the [G.sub.1]-phase marker cyclin D1 that the bulk of cells in the S3 segment of juvenile rats were involved in proliferation; 2) that although the proliferation rate was about 10-fold higher in juvenile rats compared with adult rats, roughly 40% of S3 cells were in [G.sub.1] in both groups; 3) that after a strong mitotic stimulus (lead acetate), proliferation was similar in juveniles and adults; 4) that there was a high incidence of cyclin D1-positive cells also in the healthy human kidney; and 5) by labeling dividing cells with BrdU for 2 days before the application of lead acetate and subsequent costaining for BrdU and cell cycle markers, that, although a strong mitotic stimulus does not abolish the period of quiescence following division, it shortens it markedly. Thus the capacity of the proximal tubule to rapidly recruit cells into division relies on a large reserve pool of cells in [G.sub.1] and on the shortening of the obligatory period of quiescence that follows division. kidney; cyclin D1; bromodeoxyuridine; stem cells; regeneration

We searched for evidence for a contribution of stem cells in growth of the proximal S3 segments of healthy rats. According to the stem cell model, stem cells are undifferentiated and slow cycling; the bulk of cycling cells are transit amplifying, rapidly cycling cells. We show the following. 1) By continuous application of a thymidine analog (ThA) for 7 days, S3 proximal epithelial cells in healthy kidneys display a high-cycling rate. 2) Slow-cycling cells, identified by lack of ThA uptake during 14 days of continuous ThA application up to death and by expression of the cell cycle protein Ki67 at death, have the same degree of differentiation as quiescent cells. 3) To detect rapidly cycling cells, rats were killed at various time points after injection of a ThA. Double immunofluorescence for ThA and a cell cycle marker was performed, with colocalization indicating successive divisions. During one week after division, daughter cells display a very low proliferation rate, indicating the absence of rapidly cycling cells. 4) Labeling with cyclin D1 showed that this low proliferation rate is due to cycle arrest. 5) More than 50% of the S3 cells entered the cell cycle 36 h after a potent proliferative stimulus (lead acetate injection). We conclude that generation of new cells in the proximal tubule relies on division of differentiated, normally slow-cycling cells. These may rapidly enter the cycle under an adequate stimulus. immunohistochemistry; cell cycle; proliferation; renal stem cells; proximal tubule; renal epithelial cells

Cancer-testis antigens (CTAgs) play a major role in the immune response against cancer, but their biological functions in germ and cancer cells is still unclear. MAGE-C1 and MAGE-C2 are two CTAgs located at the Xq27 region of chromosome X and frequently expressed in multiple myeloma. Chromosomal rearrangements often occur in myeloma. We therefore investigated whether numerical and structural chromosomal aberrations correlate with their protein expression in primary multiple myelomas. To this aim, we designed new fluorescence in situ hybridization probes specific for the MAGE region in the Xq27 region and evaluated simultaneously aberrations of the X chromosome centromere. The comparison of MAGE copy number and chromosome X status revealed that MAGE copy number changes occurred in 6/43 (14%) cases, independent of concomitant X chromosome alterations. These numerical aberrations are less frequent than the expression of MAGE-C1 and MAGE-C2 (63% and 27% of patients, respectively) and do not always correlate with MAGE-C1 and MAGE-C2 expressions, suggesting alternative regulatory mechanisms in the expression of these genes. [ABSTRACT FROM AUTHOR]

Fibroblast specific protein 1 (FSP1)/S100A4 is a calcium binding protein which has been linked to epithelial-mesenchymal transition, tissue fibrosis, pulmonary vascular disease, metastatic tumour development, increased tumour cell motility and invasiveness. This protein is reported to be also expressed in newly formed and differentiated fibroblasts and has been used in various studies to demonstrate epithelial-mesenchymal transition (EMT). We aimed to characterize S100A4 positive cells in different human tissue compartments, with the focus on fibroblasts/myofibroblast. We found S100A4 expression in a wide range of cells. Fibroblasts/myofibroblasts showed a broad spectrum of staining intensity, ranging from negative to strong expression of S100A4, with the strongest expression in smooth muscle actin positive myofibroblasts. Cells of haematopoietic lineage, namely CD4 and CD8 positive T-lymphocytes, but not B-lymphocytes expressed S100A4. All investigated monocytes, macrophages and specialised histiocytes were positive for S100A4. Even some epithelial cells of the kidney and bladder were positive for S100A4. Expression was also found in the vasculature. Here, cells of the subendothelial space, tunica adventitia and some smooth muscle cells of the tunica media were positive for S100A4. In summary, S100A4 is expressed in various cell types of different lineage and is not, as originally believed, specific for fibroblasts (FSP). Results attained under the premise of specificity of FSP1/S100A4 for fibroblasts, like the founding research on EMT type 2 in kidney and liver, therefore need to be reinterpreted., (©The Author(s) 2023. Open Access. This article is licensed under a Creative Commons CC-BY International License.)

A Rare Cause of Hypercalcemia Abstract. Sarcoidosis is a rare cause of hypercalcemia, which is in most cases caused by primary hyperparathyroidism or a malignant tumor. Other rare causes include vitamin D intoxication, other granulomatous diseases (such as tuberculosis, or fungal infection) or mutiple myeloma. Because of the broad differential diagnosis, a systematic diagnostic approach is crucial to establish the correct diagnosis. Therapeutic measures include volume replacement and subsequent administration of bisphosphonates. If hypercalcemia is caused by sarcoidosis, therapy with systemic corticosteroids is indicated.