Histomorphological and clinical characteristics of patients with thin glomerular basement membrane nephropathy.

BACKGROUND: Thin basement membrane nephropathy (TBMN) is a disorder characterized by ultrastructural abnormalities of the glomerular basement membrane (GBM), representing a spectrum of genetic and clinical phenotypes ranging from benign hematuria to proteinuria and chronic kidney disease. Recent studies have shown that a significant percentage of patients who initially present with hematuria later develop proteinuria and worsening renal function. MATERIALS AND METHODS: We retrospectively analyzed records of patients diagnosed with TBMN, including their clinical, laboratory, and histological features, in Slovenia from 2015 to 2020. RESULTS: TBMN was the main diagnosis at kidney biopsy in 34 (65%) of 52 included patients, while in 18 patients (35%) TBMN was diagnosed in addition to other renal diseases. In the isolated TBMN group, 29 of 34 patients had glomerulosclerosis (global, global and segmental, segmental only) accompanied by interstitial fibrosis/tubular atrophy of varying degrees. 13 patients with isolated TBMN had signs of advanced chronic kidney disease at the time of diagnosis, with estimated glomerular filtration rate < 60 mL/min/1.73m2. 29 patients had proteinuria, which exceeded 3 g/day in 4 patients. TBMN represents a proportion of patients with focal segmental glomerulosclerosis (FSGS) that have often been classified in the past as etiologically indeterminate FSGS. CONCLUSION: Ultrastructural examination showing diffuse thinning of the GBM is crucial for the TBMN diagnosis. TBMN was the main diagnosis of kidney biopsy in 2/3 of our patients, while it was accompanied by other renal diseases in 1/3. Up to 1/3 of patients with isolated TBMN had evidence of advanced chronic kidney disease at the time of diagnosis.

Glomerular and tubulointerstitial foscarnet nephropathy of kidney allograft with emphasis on ultrastructural findings: A case report.

INTRODUCTION: Foscarnet (trisodium phosphonoformate hexahydrate) is standard treatment for ganciclovir-resistant cytomegalovirus (CMV) infections. In the kidney, foscarnet-induced injury may be attributed to reversible tubulointerstitial lesions, but foscarnet crystals have also been observed within glomerular capillaries, suggesting that foscarnet can lead to glomerular lesions such as crescentic glomerulonephritis. We present biopsy and autopsy findings of foscarnet induced nephropathy in a transplanted kidney, with a particular emphasis on the histopathology and electron micrographic peculiarities of drug crystal deposits. CASE PRESENTATION: A 72-year-old Caucasian male patient with a deceased donor kidney was treated with several foscarnet applications due to ganciclovir-resistant CMV infection. Transplant kidney biopsy revealed massive glomerular crystalline precipitates, resulting in crescentic glomerulonephritis and tubular damage. The last foscarnet application was complicated with several infections and kidney graft failure. Autopsy revealed multi-organ damage due to foscarnet crystal precipitations associated with systemic CMV and fungal infection. On autopsy of kidney specimens, we succeeded in preserving the rectangular flat plate-like foscarnet crystals in stacks detected by transmission electron microscopy (TEM) after 100% alcohol fixation. The chemical composition of the crystals was confirmed by attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy. CONCLUSION: Transplant kidney biopsy remains the gold standard in distinguishing between foscarnet crystalline glomerular and/or tubulointerstitial lesions, and various forms of rejection and other causes of impaired renal function in transplant kidney.

Just Seeing Is Not Enough for Believing: Immunolabelling as Indisputable Proof of SARS-CoV-2 Virions in Infected Tissue.

BACKGROUND: There is increasing evidence that identification of SARS-CoV-2 virions by transmission electron microscopy could be misleading due to the similar morphology of virions and ubiquitous cell structures. This study thus aimed to establish methods for indisputable proof of the presence of SARS-CoV-2 virions in the observed tissue. METHODS: We developed a variant of the correlative microscopy approach for SARS-CoV-2 protein identification using immunohistochemical labelling of SARS-CoV-2 proteins on light and electron microscopy levels. We also performed immunogold labelling of SARS-CoV-2 virions. RESULTS: Immunohistochemistry (IHC) of SARS-CoV-2 nucleocapsid proteins and subsequent correlative microscopy undoubtedly proved the presence of SARS-CoV-2 virions in the analysed human nasopharyngeal tissue. The presence of SARS-CoV-2 virions was also confirmed by immunogold labelling for the first time. CONCLUSIONS: Immunoelectron microscopy is the most reliable method for distinguishing intracellular viral particles from normal cell structures of similar morphology and size as virions. Furthermore, we developed a variant of correlative microscopy that allows pathologists to check the results of IHC performed first on routinely used paraffin-embedded samples, followed by semithin, and finally by ultrathin sections. Both methodological approaches indisputably proved the presence of SARS-CoV-2 virions in cells.

Exploring the role of the complement system, endothelial injury, and microRNAs in thrombotic microangiopathy after kidney transplantation.

OBJECTIVE: We investigated whether the recipient's complement system function, kidney graft endothelial ultrastructural injury, and microRNA (miRNA) expression before transplantation may be associated with the risk of posttransplant de novo thrombotic microangiopathy (TMA). METHODS: Complement system function assessment, histological and ultrastructural examination of preimplantation and kidney graft biopsies, and microRNA assessment were performed on kidney transplant recipients (KTRs) with de novo TMA. RESULTS: On the basis of the clinical course, histological findings, and miRNA patterns, the following two de novo TMA phenotypes were observed: a self-limiting disease that was localized to the kidney graft and a systemic disease that progressed to graft failure without timely treatment. Decreased alternative complement pathway activity and ultrastructural endothelial injury before transplantation were confirmed in all five KTRs and four of five KTRs, respectively, but they did not correlate with de novo TMA severity. CONCLUSIONS: Alternative complement pathway abnormalities in KTRs and endothelial ultrastructural injury on preimplantation biopsy might be associated with de novo posttransplant TMA, although they did not predict posttransplant TMA severity (localized vs. systemic). The specific miRNA expression patterns in preimplantation kidney graft biopsies demonstrated a borderline statistically significant difference and might provide more accurate information on posttransplant TMA severity.

Pigmented (melanotic) myoepithelial tumor of soft tissue with EWSR1-KLF17 fusion.

Myoepithelial tumors of soft tissue are rare, morphologically and biologically heterogeneous tumors. EWSR1 fusion is found in about half of the cases, followed by PLAG1 and FUS fusions. EWSR1-KLF17 fusion has so far been reported in one benign myoepithelial tumor. Using next generation sequencing we identified another myoepithelial tumor of soft tissue with EWSR1-KLF17 fusion, located on the foot in a 55-year-old male. It was composed predominantly of spindle cells with multiple small areas of epithelioid and multinucleated cells in myxohyaline stroma and areas of melanin pigment in the cytoplasm of tumor cells. The pigmented tumor cells were positive for HMB45 and, ultrastructurally, melanosomes were identified in their cytoplasm. Melanin production has not been previously documented in myoepithelial tumors of soft tissue. Our case extends the spectrum of myoepithelial tumors of soft tissue and emphasizes the importance of molecular characterization of fusions, including determination of fusion partners in myoepithelial tumors and their mimics.