Three variants of cryoglobulinemic glomerulopathy are well known, however, the concurrent acute enteritis secondary to a mixed polyclonal cryoglobulin associated thrombotic vasculitis is rarely reported in the literature. We report a case of a 72-year-old man with medical history of hypertension, leukocytoclastic vasculitis, positive serum cryoglobulin, hepatitis C, and membranoproliferative pattern of glomerulonephritis diagnosed 4 years ago. This patient recently presented with abdominal pain for one week. Labs showed worsening renal function, monoclonal IgM-kappa, and positive cryoglobulin in his serum, but negative hepatitis C test. The second renal biopsy showed a membranoproliferative pattern of glomerulopathy with many hyaline thrombi in the glomerular capillary loops. A mixed monoclonal IgM and polyclonal IgG cryoglobulinemic glomerulonephritis (type 2) was diagnosed. His concurrent jejunal biopsy revealed infiltration of neutrophils into glands and submucosal thrombus consistent with ischemic acute jejunitis. The submucosal thrombus of the jejunal biopsy was morphologically similar to the hyaline-thrombi found in glomerular capillary loops. Therefore, we concluded that cryoglobulin associated hyaline thrombi were the most likely etiology for both of his renal disease and acute ischemic jejunitis in this patient. This patient's symptoms are due to simultaneous renal and intestinal thrombosis occurring in cryoglobulinemia. This concurrent thrombosis has not been well described in the literature.
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.
Abstract Introduction/Objective Only one prior case report indicates that mixed positive cryoglobulin in serum can be associated with intestinal vasculitis (Annals of Internal Medicine, 1974). Methods/Case Report We report a 63-year old man with history of positive serum cryoglobulin and hepatitis-C 4 years ago and membranoproliferative pattern of glomerulonephritis with possible cryoglobulin type of deposits by electron microscopy on renal biopsy. After treatment, his hepatitis C became negative. But he was recently found to have monoclonal IgM-kappa and positive cryoglobulin in his serum, and the concurrent renal biopsy showed membranoproliferative pattern of glomerulopathy with many hyaline-thrombi (eosinophilic vascular occlusions with no lamination, inflammatory cells or nuclear debris) in the glomerular capillary loops (Figure, left panel). Both immunofluorescent and electron microscopy confirmed a mixed IgG polyclonal and IgM monoclonal type 2 cryglobulinemic glomerulonephritis. The patient also developed abdominal pain and underwent intestinal endoscopy with biopsy. His jejunal biopsy revealed neutrophil infiltration into glands and surface epithelium, with superficial sloughed epithelial cells, consistent with acute jejunitis with features of ischemic etiology. In addition, hyaline-thrombi were identified in the submucosal vessels with surrounding vasculitis (Figure, right panel); the central part of thrombi was morphologically similar to that found in glomerular capillary loops. Therefore, we conclude that cryoglobulin associated hyaline-thrombi were the most likely etiology to cause the acute ischemic jejunitis in this patient. Results (if a Case Study enter NA) NA Conclusion NA
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.
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.
Abstract Introduction/Objective IgG4 related disease, a systemic autoimmune inflammatory disorders, can be identified by high% of IgG4 positive plasma cells, thus IgG4 staining in paraffin embedded tissue is widely available in the most of pathology labs. IgG4 staining has been found useful to identify primary MGN (PLA2R and/or THSD7A positive) by others and us. This study was to scrutinize the findings of primary vs secondary MGN needed for IgG4 staining as a screening tool in our renal pathology practice over pasts 5 years Methods/Case Report IgG4 staining in paraffin embedded tissue was performed in 45 primary MGN and 43 secondary MGN after the clinical history was reviewed and a possibility of primary MGN cannot be excluded. In addition, both groups of cases were also stained for PLA2R. Detail correlation with clinical history was analyzed. Results (if a Case Study enter NA) Totally 82 % (37/45) of primary MGN was found diffuse positive for IgG4 staining at 2+ intensity in the glomeruli. Seven out of eight remaining primary MGN cases with either negative or weak IgG4 stained MGN were found to have diffuse resolving features by electron microscopy but there was still positive PLA2R staining in the glomeruli. All secondary MGN were stained negatively for both IgG4 and PLA2R and we found that etiologies of the secondary MGN included membranous lupus nephritis, infection, GVHD, or variants of cancers. Conclusion Our data indicate that IgG4 staining along (without IgG1-3 staining) is a reliable screening tool to confirm the majority of primary MGN vs secondary MGN in paraffin embedded tissue. As both PLA2R+ and THSD7A+ primary MGN are both IgG4 related, the IgG4 staining may potentially represent a wider range of scope in identifying primary MGN. In addition, negative/weak IgG4 staining in PLA2R-positive MGN most likely represents a primary MGN with resolving features.
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.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.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).Our data suggest that the MPO-positive endothelial injuries are most likely the cause leading to renal graft dysfunction following ABMR.
Adult polycystic kidney disease (APKD) is a genetic disorder leading to premature renal dysfunction and failure. The prevalence of malignant renal tumors occurring in the APKD setting has been rarely reported.
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