Saba Kiremitci

Pauci-immune necrotizing crescentic glomerulonephritis with crescentic and full moon extracapillary proliferation: clinico-pathologic correlation and follow-up study.

The prognostic value of the type and extent of extracapillary proliferation (ECP) in pauci-immune necrotizing crescentic glomerulonephitis (PIGN) was evaluated in this study. In 141 PIGN cases, all glomeruli with ECP were grouped according to type (cellular, fibrocellular and fibrous) and extent of the lesions in Bowmans space; (segmental, semicircumferential and circumferential, which might be termed full moon-FM). Cases with cellular and fibrous lesions involving ≥ 50% of glomeruli with ECP were classified as cellular and fibrous groups, respectively, while the remaining cases were classified as fibrocellular. Cases with segmental and circumferential (FM glomerulus) lesions involving ≥ 50% of glomeruli with ECP were classified as ECPI and ECPIII (FM) groups, respectively, while the rest were classified as ECPII. All the cases were classified according to Berden et al. Significant results were only nearly obtained for the FM group, including the need for dialysis. The Cox regression model revealed a 2.6-fold risk for FM cases regarding dialysis requirement. We propose that the percentage of FM glomeruli should be noted in the pathology report, and cases with more than 50% of FM glomeruli (FM group) should be identified in the group with increased risk of dialysis requirement. Our series also suggests that classification according to Berden et al. is of clinical relevance.

Classifying Lupus Nephritis: An Ongoing Story

The role of the renal biopsy in lupus nephritis is to provide the diagnosis and to define the parameters of prognostic and therapeutic significance for an effective clinicopathological correlation. Various classification schemas initiated by World Health Organization in 1974 have been proposed until the most recent update by International Society of Nephrology/Renal Pathology Society in 2004. In this paper, we reviewed the new classification system with the associated literature to highlight the benefits and the weak points that emerged so far. The great advantage of the classification emerged to provide a uniform reporting for lupus nephritis all over the world. It has provided more reproducible results from different centers. However, the studies indicated that the presence of glomerular necrotizing lesion was no longer significant to determine the classes of lupus nephritis leading to loss of pathogenetic diversity of the classes. Another weakness of the classification that also emerged in time was the lack of discussions related to the prognostic significance of tubulointerstitial involvement which was not included in the classification. Therefore, the pathogenetic diversity of the classification still needs to be clarified by additional studies, and it needs to be improved by the inclusion of the tubulointerstitial lesions related to prognosis.

Gelsolin, NF-κB, and p53 expression in clear cell renal cell carcinoma: Impact on outcome

OBJECTIVES To examine the prognostic significance of Gelsolin, NF-κB, and p53 in clear cell renal cell carcinoma (CRCC), which has an unpredictable behavior and tendency for recurrence and metastasis. MATERIALS AND METHODS Immunohistochemistry was performed on 100 consecutive cases of CRCC using antibodies against Gelsolin, NF-κB, and p53. Tumors were grouped by nuclear grade (NG) as low NG (NG1, 2) or high NG (NG3, 4), and by pathological stage as localized (pT1, 2) or locally invasive (pT3, 4). Clinical stage was grouped as early stage (stage I, II) or late stage (stage III, IV). Evaluation was based on cytoplasmic (NF-κB(Cyt)) and nuclear (NF-κB(Nuc)) expression for NF-κB, nuclear expression for p53, membranous and cytoplasmic expression for Gelsolin. RESULTS Gelsolin expression correlated with high NG (p = 0.001), metastasis (p = 0.003), late stage (p = 0.008), and cancer death (p = 0.001). NF-κB(Cyt) expression correlated with high NG (p = 0.002), perirenal invasion (p = 0.010), local invasion (p = 0.020), and late stage (p= 0.003). NF-κB(Nuc) expression failed to predict the prognosis of CRCC. p53 expression correlated with high NG (p = 0.045), lymphovascular invasion (p = 0.05), metastasis (p = 0.001), late stage (p = 0.028), and cancer death (p = 0.034). However, only Gelsolin was found to correlate with disease-specific survival, (p = 0.006), and neither NF-κB nor p53 showed such relation. CONCLUSION Expressions of Gelsolin, NF-κB(Cyt), and p53 associated with aggressive behavior of CRCC, while Gelsolin expression specifically indicated poor disease-specific survival. The results of the present study served to determine biomarkers for predicting high-risk patients with CRCC, expected to show aggressive phenotype.

Roles of E-cadherin and cyclooxygenase enzymes in predicting different survival patterns of optimally cytoreduced serous ovarian cancer patients.

The relation between cyclooxygenase enzymes and E-cadherin, along with the roles of these markers in the prediction of survival in optimally cytoreduced serous ovarian cancer patients was investigated. Individuals who underwent primary staging surgery and achieved optimal cytoreduction (largest residual tumor volume<1 cm) constituted the study population. Specimens of 32 cases were immunohistochemically examined for cyclooxygenase-1, cyclooxygenase-2, and E-cadherin. Two could not be evaluated for E-cadherin and cyclooxygenase-1. Overall, 14/30, 19/30, and 15/32 cases were positive for E-cadherin, cyclooxygenase-1, and cyclooxygenase-2, respectively. The expressions of E-cadherin and cyclooxygenase-2 were inversely correlated (p:0.02). E-cadherin expression was related with favorable survival (p<0.001). The relation between the expression of cyclooxygenase enzymes and poor survival did not reach statistical significance. On multivariate analysis, E-cadherin appeared as an independent prognostic factor for survival. In conclusion, E-cadherin expression is strongly linked with favorable survival. E-cadherin and cyclooxygenase 2 may interact with each other during the carcinogenesis-invasion process. Further studies clarifying the relation between E-cadherin and cyclooxygenase enzymes may lead to new preventive and therapeutic targets in ovarian cancer.

Pathologist's puzzle: Membranoproliferative glomerulonephritis-like features in cryoglobulinemic glomerulonephritis

Mixed cryoglobulinemia is commonly related to chronic HCV infection, and renal complications occur frequently. Typical renal involvement presents with diffuse proliferative glomerular pathology, similar to membranoproliferative glomerulonephritis, with necrotizing arteritis of medium-sized vessels, referred to as cryoglobulinemic glomerulonephritis. However, the histological appearance may vary according to the clinical presentation and treatment applied. Not only membranoproliferative glomerulonephritis but also certain types of systemic vasculitis (Systemic Lupus Erythematosus, Polyarteritis Nodosa), thrombotic microangiopathy, and Waldenstroms Macroglobulinemia may exhibit similar histopathological findings in the biopsy with cryoglobulinemic glomerulonephritis. For an optimal differential diagnosis, clinicopathological correlation and serological findings should accompany the pathological findings. We present a case of cryoglobulinemic glomerulonephritis, and discuss the differential diagnosis in detail.

Kidney biopsy in AA amyloidosis: impact of histopathology on prognosis

Abstract In AA amyloidosis, while kidney biopsy is widely considered for diagnosis by clinicians, there is no evidence that the detailed investigation of renal histopathology can be utilized for the prognosis and clinical outcomes. In this study, we aimed to obtain whether histopathologic findings in kidney biopsy of AA amyloidosis might have prognostic and clinical value. This is a retrospective cohort study that included 38 patients who were diagnosed with AA amyloidosis by kidney biopsy between 2005 and 2013.The kidney biopsy specimens of patients were evaluated and graded for several characteristics of histopathological lesions and their relationship with renal outcomes. Segmental amyloid deposition in the kidney biopsy was seen in 29%, global amyloid deposition in 71, diffuse involvement of glomeruli in 84.2%, focal involvement in 7%, glomerular enlargement in 53%, tubular atrophy in 75% and interstitial fibrosis in 78% of patients. Histopathologically, glomerular enlargement, interstitial fibrosis, tubular atrophy, interstitial inflammation and global amyloid deposition were significantly associated with lower estimated glomerular filtration rate (eGFR) (p = .02, p < .001, p = .001, p = .009, p = .002, respectively) in univariate analysis. In multivariate analysis, tubular atrophy was the only predictor of eGFR (p = .019 B = −20.573). In the follow-up at an average of 27 months, 18 patients developed end-stage renal disease (ESRD). Among them, global amyloid deposition was the only risk factor for the development of ESRD (p = .01, OR = 18.750, %95 CI= 2.021–173.942). This is the first study showing that the histopathological findings in kidney biopsy of AA amyloidosis might have a prognostic and clinical value for renal outcomes.

De novo amyloidosis in a renal transplant patient.

Systemic AA amyloidosis is a serious complication of many chronic inflammatory disorders and chronic infections. Renal involvement is seen in the majority of the patients and can lead to end‐stage renal disease. Renal transplantation can be performed in these patients; however, amyloidosis can recur in the transplanted kidneys. On the other hand, de novo AA amyloidosis in renal transplant patients has been rarely reported. We report a 17‐yr‐old patient with end‐stage renal disease due to genitourinary anomalies who developed recurrent pyelonephritis after transplantation. Three yr after transplantation, renal biopsy was performed for proteinuria and AA amyloidosis was identified in the renal allograft. Although rare, chronic infections might cause de novo amyloidosis in renal transplant patients. Therefore, amyloidosis should be kept in mind in those types of patients who present with proteinuria.

C3 glomerulopathy in NLRP12-related autoinflammatory disorder: case-based review

Autoinflammatory diseases (AIDs) are a recently described group of conditions caused by mutations in multiple genes that code for proteins of the innate immune system. Cryopyrin-associated periodic syndromes (CAPS) are autoinflammatory diseases comprising three clinically overlapping disorders: familial cold urticarial syndrome (FCAS), Muckle–Wells syndrome (MWS), and neonatal-onset multisystem inflammatory disease (NOMID). CAPS have been associated with gain-of-function variations in NLRP3 (NOD-like receptor family, pyrin containing domain-3). However, a new class of autoinflammatory disease resembling FCAS or MWS has been described in patients with NLRP12 mutations. Here, we report a 6-year-old boy diagnosed with AID who developed an unexpected C3 glomerulopathy during attacks and carried a novel variation in NLRP12. Following treatment with IL (interleukin) 1 targeting agents, all symptoms and inflammation resolved. This is the first case in the literature affected by both autoinflammatory disease and C3 glomerulopathy.

Non-Diabetic Kidney Disease in Type 2 Diabetic Patients: Prevalence, Clinical Predictors and Outcomes

Background/Aims: Diabetic kidney disease (DKD) is one of the most frequent microvascular complications of diabetes and is the leading cause of end-stage kidney disease worldwide. In patients with diabetes, non-diabetic kidney disease (NDKD) can also occur. NDKD can be either alone or superimposed with the DKD. In this study, we aimed to investigate the utility of kidney biopsy in patients with type 2 diabetes mellitus (T2DM) and the predictability of diagnosing DKD versus NDKD from clinical and laboratory data. We also evaluated the prevalence and etiology of NDKD in patients with T2DM. Methods: We retrospectively reviewed type 2 diabetic patients who had kidney biopsy in the last 10 years for diagnosing possible NDKD in our center. In all patients kidney biopsies were performed because of atypical clinical features and biopsy samples were examined by light and immunofluorescence microscopy. Clinical parameters, laboratory workup and office blood pressures were recorded for each patient at the time of biopsy. Results: Eight patients were excluded due to missing data. A total of 48 patients (female/male: 26/22 and mean age: 59±8 years) were included in the study. According to the biopsy findings, 24 (50%) patients had NDKD alone, 20 (41.7%) had DKD alone and 4 (8.3%) had coexisting DKD and NDKD. The most common NDKD diagnoses were membranous nephropathy (29.2%), tubulointerstitial nephritis (20.8%) and IgA nephropathy (12.5%). There were no significant differences in three groups with respect to the duration of diabetes, proteinuria, hematuria and glycated hemoglobin A1c levels. Diabetic retinopathy (DR) was the most significant finding, which was associated with DKD. Positive and negative predictive values of DR for DKD were 88 and 81%, respectively. Conclusion: This study demonstrated a high prevalence of NDKD in patients with T2DM. The absence of DR strongly predicted NDKD. Clinical decision alone can lead to wrong diagnosis and delay in appropriate therapy. Clinicians should consider the kidney biopsy more liberally when there is uncertainty on the exact etiology of the kidney disease. However, prospective multicenter studies are needed to clarify the prognosis and outcomes of patients with diabetics.

Prognostic impact of epidermal growth factor receptor on clear cell renal cell carcinoma: Does it change with different expression patterns?

Introduction: The aim of this study was to assess whether epidermal growth factor receptor (EGFR) overexpression was a significant prognostic factor in clear cell renal cell carcinoma (CRCC) and whether its prognostic significance was affected by immunohistochemical expression patterns. Materials and Methods: Immunohistochemistry was performed on 100 cases of CRCC using an antibody against EGFR. Tumors were grouped by nuclear grade (NG) as low-NG (NG1, 2) or high NG (NG3, 4), and by pathological stage as localized (pT1, 2), or locally invasive (pT3, 4). Clinical disease was grouped by clinical stage as early stage (stage I, II), or late stage (stage III, IV). Evaluation of the EGFR overexpression was based on cytoplasmic (EGFR Cyt ), and membranous (EGFR Mem ) staining. Results: EGFR Cyt correlated with high NG (P = 0.001), lymphovascular invasion (P = 0.028), regional lymph node involvement (P = 0.027), metastasis (P = 0.001), late stage (P = 0.003), cancer-specific death (P = 0.036), and was a predictor for disease-specific survival (P = 0.012) whereas EGFR Mem correlated with only local invasion (P = 0.021) and perirenal invasion (P = 0.009) and did not show any correlation with cancer-specific death or disease specific survival. Conclusion: Our findings suggest that EGFR overexpression is an important prognostic factor in CRCC, and its prognostic value differs significantly with respect to the location of EGFR immunostaining. This prognostic difference may give direction on the management and treatment of CRCC patients.