ABSTRACT
Focal segmental glomerulosclerosis (FSGS) is a common renal disorder, characterized by progressive segmental sclerosis of renal glomeruli and clinical symptoms corresponding to proteinuria. Classically, it is not considered to be an antibody-mediated disease, however, IgM and C3 deposition may be seen in a subset of cases of FSGS. The impact of this immune deposition on histopathological features in renal core biopsies, on the urinary biochemical parameters, and the clinical outcomes, has not been previously investigated in our population. The aim of this study is to analyze the aforementioned parameters in patients with primary FSGS having antibody deposition as compared to those who do not have any antibody deposition. Some 155 patients diagnosed with FSGS were retrospectively enrolled in our study. The renal biopsies were reviewed for histopathological features and immunofluorescence (IF) findings of IgM and C3 glomerular deposition. These histological features were then compared with the biochemical parameters as well as the clinical outcomes of patients. The patients were assigned to Groups 1 and 2 based on the IF findings. The IgM and/or C3 glomerular deposition had a low incidence in patients with primary FSGS in our study (28.3%). Patients having IgM and C3 co-deposition had a significantly longer time duration since the onset of their clinical symptoms; active disease duration (42 months vs 22 months, p=0.049). The mean pre-treatment serum creatinine of patients with IgM and C3 co-deposition was 6.00 mg/dL as compared to 3.29 mg/dL in patients with no immune deposition (p=0.037). The immune deposition was associated with higher rates of segmental and global glomerulosclerosis, but this finding along with other evaluated histological parameters did not show statistical significance. The number of patients having IgM and/or C3 deposition and with active steroid use/renal dialysis was similar to patients having no IgM and/or C3 deposition. The IgM and/or C3 deposition in FSGS has a low incidence within and is not associated with any significant differences in histological parameters on renal core biopsies of patients from the Pakistani population. IgM and/or C3 deposition is also associated with a significantly longer duration of active disease and these patients may present with higher pre-treatment serum creatinine. Other biochemical parameters and clinical outcomes appear comparable between the groups based on the available clinical data.
ABSTRACT
Gemistocytic differentiation is a rare histological feature seen in IDH mutant Astrocytomas. The 2021 World Health Organization (WHO) retains the diagnosis of IDH mutant Astrocytoma with its classical histology and tumors with the rare histological pattern of gemistocytic differentiation. Gemistocytic differentiation has historically been associated with a worse prognosis and shorter survival, and this prognostic difference has not been investigated in detail in our population. A population-based retrospective study included 56 patients with IDH mutant Astrocytoma with Gemistocytic differentiation and IDH mutant Astrocytoma diagnosed between 2010 and 2018 in our hospital. Demographic, histopathological, and clinical parameters were compared between the two groups. Gemistocyte percentage, perivascular lymphoid infiltrates, and Ki-67 proliferation index were also analyzed. A Kaplan-Meier analysis was done to analyze any prognostic difference in the overall survival time between the two groups. Patients with an IDH mutant Astrocytoma having gemistocytic differentiation had an average survival period of 2 years, while patients diagnosed with an IDH mutant Astrocytoma had an average survival time of approximately 6 years. There was a statistically significant decrease in survival time (p = 0.005) for patients with tumors with gemistocytic differentiation. The percentage of gemistocytes and the presence of perivascular lymphoid aggregates did not correlate with survival time (p = 0.303 and 0.602, respectively). Tumors with gemistocytic morphology had a higher mean Ki-67 proliferation index (4.4%) than IDH mutant Astrocytoma (2.0%, p = 0.005). Our data suggest that IDH mutant Astrocytoma with Gemistocytic differentiation is an aggressive variant of IDH mutant Astrocytoma associated with a shorter survival time and an overall worse prognosis. This data might be helpful to clinicians in the future management of IDH mutant Astrocytoma with Gesmistocytic differentiation as an aggressive tumor.
