Punctate IgG staining particles localize in the budding ballooning clusters of reactive foot processes in minimal change disease.

The etiology of minimal change disease (MCD) remains a mystery as the only characteristic findings are the diffuse effacement of foot processes seen on electron microscopy (EM). Punctate IgG staining found floating outside glomerular capillary loops in MCD cases was recently identified as autoimmune antibodies against nephrin of podocytes. We hypothesized that the punctate IgG staining is located on budding ballooning clusters (BBC) of reactive foot processes in Bowman's space found on EM. We identified seven patients with MCD cases showing IgG staining that were subsequently evaluated for BBC on EM. We concurrently examined 12 negative controls, either unremarkable cases or tubulointerstitial diseases, by EM. Immunogold labeling was performed to confirm the presence of IgG and determine localization. In seven MCD cases, there were positive punctate IgG staining particles outside of the glomerular basement membranes (GBM) along with concurrent punctate staining for C3, kappa, and lambda. By EM, all seven (100%) MCD cases revealed BBC that was characterized by ballooning foot processes ranging from 1 to 6 µm and was either budding or detached from the GBM in 3-7 clusters; no electron-dense materials were seen in BBC. BBC was also seen in only 1 of 12 (8%) negative controls. Immunogold labeling identified IgG particles within BBC of MCD by EM, but not in the negative control. Our data suggest that BBC are EM structures of reactive foot processes that are most likely correlated with punctate IgG staining seen in cases of MCD, supported by immunogold labeling for IgG.

Myeloperoxidase Staining Identifies Endothelial Injury of Peritubular Capillaries and Glomeruli in Renal Antibody-Mediated Rejection.

OBJECTIVE: It remains unclear if C4d staining is related to any peritubular and glomerular injury during antibody mediated rejection (ABMR). The goal of this study was to determine if myeloperoxidase (MPO) staining can highlight endothelial injury in peritubular capillaries (PTC) and glomeruli. METHODS: The study included 12 native negative controls, 19 transplant biopsies with borderline changes (BC) as transplant controls, and one group of renal transplant biopsies with ABMR as the study group (acute/chronic, n=22). All three groups were stained for MPO immunohistochemically, and the MPO expressions in the endothelium of PTC and glomeruli were evaluated and correlated with serum creatinine (SCr). In addition, the ultrastructural layers of the PTC (an index for chronic allograft rejection) were correlated with MPO indices in PTC. RESULTS: The negative control group and the transplant controls showed no MPO expression in the endothelium of glomeruli and PTC. However, in the biopsies with ABMR, there were MPO-positive stains in the endothelial cells of glomeruli (15/21 cases, 71.4 %) and PTC (16/22 cases, 72.7 %). There were significant correlations between the peritubular MPO staining versus SCr (r=0.355 and p=0.0106) and glomerular MPO staining versus SCr (r=0.365 and p=0.0092). Furthermore, the layers of PTC by electron microscopy were significantly correlated with MPO scores in PTC (r=0.696, p=0.0001). CONCLUSION: Our data suggest that the MPO-positive endothelial injuries are most likely the cause leading to renal graft dysfunction following ABMR.

Resolving primary membranous glomerulopathy (MGN) reveals a dynamically metabolic pathway from sub-epithelium to glomerular basement membranes.

In idiopathic (primary) membranous glomerulopathy (MGN), there is a phenomenon of subepithelial deposits (stages 1 and 2) transitioned to intramembranous deposits, with lucent resolving features (stages 3 and 4). This phenomenon has not been described in other types of immune complex mediated glomerulonephritis with either subendothelial or mesangial deposits. The goal of this study was to evaluate what unique immunostaining pattern could occur in primary MGNs with intramembranous resolving features. PLA2R and IgG4 immunostains were performed in 50 primary MGNs, and 39 secondary MGNs after the clinical history was reviewed. Primary MGNs with resolving features were further evaluated in detail. A total of 84% (42/50) of primary MGN cases had diffuse positive immunostaining for IgG4 in the glomeruli, and most of them were also positive for PLA2R staining. Eight of the remaining primary MGN cases (8/50) with positive PLA2R but negative IgG4 staining in the glomeruli had diffuse resolving features as observed by electron microscopy. All secondary MGNs were stained negatively for both IgG4 and PLA2R except for one case with positive IgG4 staining but negative staining for PLA2R. Our data indicate that IgG4 staining on paraffin tissue is a very reliable screening tool to confirm the presence of primary MGN. Primary MGN with PLA2R+/IgG4- stains were seen in those with intramembranous resolving features. This finding is consistent with the known weak-binding capacity of IgG4 to the glomerular basement membranes. The transitional phenomenon from PLA2R+/IgG4+ subepithelial deposits to PLA2R+/IgG4- intramembranous resolving deposits in primary MGN implies that there may be a continuous metabolic activity from podocyte to glomerular basement membrane.

A Report of Ovarian Sertoli-Leydig Cell Tumors With Heterologous Intestinal-type Glands and Alpha Fetoprotein Elevation and Review of the Literature.

Ovarian Sertoli-Leydig cell tumors (SLCTs) are uncommon neoplasms that are occasionally associated with an elevated level of serum alpha fetoprotein (AFP), a marker of germ cell neoplasms, particularly yolk sac tumor (YST). We report 7 cases of ovarian SLCT (3 moderately differentiated, 2 poorly differentiated, 2 retiform) with heterologous intestinal-type glands, 6 of which were associated with elevated serum AFP. The intestinal-type mucinous glands were immunoreactive for SALL4 (4 cases), AFP (4 cases), glypican 3 (1 case), CDX2 (6 cases), and villin (7 cases), markers that are commonly expressed in YSTs, although the latter 2 markers would be expected to be positive in intestinal-type glands. We show that heterologous intestinal-type glands in ovarian SLCTs often have an endodermal sinus-like (YST-like) immunophenotype and stress that these should not be misinterpreted as microscopic foci of endodermal-type YST. Cases of ovarian SLCT with elevated serum AFP should be sampled extensively to look for foci of intestinal-type glands, the likely source of the AFP elevation in some of these neoplasms.

Choroidal Metastasis as an Unusual Initial Presentation of Transitional Cell Carcinoma of the Kidney.

Metastases of transitional cell carcinoma (TCC) of the renal pelvis to the eye is a very rare event, as only one previous case has been described in the literature. We present a patient with choroidal metastasis secondary to TCC of the renal pelvis, with a review of the relevant literature. A 61-year-old male presented with sudden-onset loss of vision of the left eye. Upon evaluation and assessment, the patient was found to have unilateral choroidal metastasis secondary to TCC of the renal pelvis. He is currently on palliative chemotherapy with carboplatin and gemcitabine. External beam radiation therapy is a common mode of treatment and will be considered accordingly.