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Background Lymphocytic gastritis (LG), characterized by marked intra-epithelial lymphocytosis in the gastric mucosa, has been frequently associated with both celiac disease (CD) and H. pylori gastritis. The aim of this study was to review and correlate the morphology of LG with the presence of CD and H. pylori. Materials and Methods Gastric biopsies diagnosed with LG from 1/1/2006 to 8/1/2013 at our institution and corresponding small bowel biopsies, when available, were reviewed for verification of the diagnosis and to assess for the presence of H. pylori and CD. Immunohistochemical (IHC) staining for H. pylori was performed on all gastric biopsies. Demographic, clinical, and laboratory data were obtained from the medical record. Results Fifty-four of the 56 cases that met inclusion criteria demonstrated significant intra-epithelial lymphocytosis as the predominant histologic abnormality; however, none were associated with H. pylori infection by IHC staining. Two cases that also showed a prominent intra-epithelial and lamina propria neutrophilic infiltrate were both positive for H. pylori and were excluded from further study. Of the 36 small bowel biopsies available, 19 (53%) showed changes in CD. Conclusions LG is not a distinct clinicopathologic entity, but a morphologic pattern of gastric injury that can be secondary to a variety of underlying etiologies. When restricted to cases with lymphocytosis alone, LG is strongly associated with CD and not with active H. pylori infection. However, cases that also show significant neutrophilic infiltrate should be regarded as “active chronic gastritis” and are often associated with H. pylori infection. A morphologic diagnosis of LG should prompt clinical and serologic workup to exclude underlying CD.

Eosinophilic esophagitis (EoE) is characterized clinically by dysphagia, chest pain, and food impaction, and morphologically by increased numbers of intraepithelial eosinophils and marked basal hyperplasia of the squamous mucosa. The consensus criteria for a diagnosis of EoE include the presence of ≥15 eosinophils/HPF in biopsies from both proximal and distal esophagus in the absence of other causes of esophageal eosinophilia, and the lack of clinical response to proton pump inhibitor therapy. Because of the variability in the distribution of intraepithelial eosinophils among biopsy fragments and the lack of standardized biopsy practices, we sought to determine the optimal number of esophageal biopsies from the mid and distal esophagus needed to reach the minimum morphologic criteria of ≥15 eosinophils/HPF.From 5 January 2009 to 26 September 2011, 771 patients were diagnosed with EoE at our institution. From that patient population, 102 sequential cases were chosen for further study, all of whom had biopsies taken from the mid and distal esophagus. Cases with only gastric mucosa present and biopsies taken from patients with a previous diagnosis of EoE were excluded. The original HE-stained slides were reviewed, and the number of biopsy fragments containing squamous mucosa was recorded. By using a × 40 objective and × 10 oculars (field diameter=0.52 mm, field area=0.21 mm(2)), the number of eosinophils per high power field (EOS/HPF) in up to three HPFs was counted in each biopsy fragment.The EOS/HPF were counted in 1,342 biopsy fragments. The number of biopsy fragments obtained from the mid esophagus ranged from 1 to 20 (mean 7; median 7) and those obtained from the distal esophagus ranged from 1 to 18 (mean 6; median 5). There was no significant difference between the mean number of EOS/HPF from the mid (26) and lower (25) esophagus or between the mean peak number of EOS/HPF from the mid (69.1) and lower (60.4) esophagus. The probability of one, four, five, and six biopsy fragments containing15 EOS/HPF was 0.63, 0.98, 0.99, and0.99, respectively.From these data, at least four biopsy fragments should be submitted from the mid and/or proximal esophagus to optimize the chances of a positive diagnosis of EoE in populations not known to have undergone previous proton pump inhibitor therapy. However, the yield is not increased beyond six biopsy fragments. In order to morphologically exclude a diagnosis of reflux esophagitis as the cause of intraepithelial eosinophilia, distal esophageal biopsies, if obtained, must be accompanied by more proximal biopsies (i.e., mid esophagus or higher).

Objectives: To calculate the incidence of nondiagnostic (ND) colorectal (CR) polyp cases in which deeper tissue sectioning rendered new diagnostic information—particularly adenomas—in 2 laboratories staffed by the same pathologists. Methods: After initial diagnosis, 100 ND CR polyps from each laboratory were reexamined with 3 deeper levels to establish rates of diagnostic conversion based on biopsy specimen location and original observation(s). Results: Deeper sectioning rendered new diagnostic information in 43 (21.5%) of 200 biopsy specimens and specifically adenomas in 16 (8.0%) of 200 biopsy specimens. Conclusions: These results support routine ordering of deeper levels on ND CR polyps to improve adenoma detection rates, especially those cases without any histologic abnormality. If another biopsy in the same case already is adenomatous, examination of deeper levels may not be necessary, as it may not have any significant effect on the clinical management of the patient.

Renal pathologists and nephrologists met on February 20, 2015 to establish an etiology/pathogenesis-based system for classification and diagnosis of GN, with a major aim of standardizing the kidney biopsy report of GN. On the basis of etiology/pathogenesis, GN is classified into the following five pathogenic types, each with specific disease entities: immune-complex GN, pauci-immune GN, antiglomerular basement membrane GN, monoclonal Ig GN, and C3 glomerulopathy. The pathogenesis-based classification forms the basis of the kidney biopsy report. To standardize the report, the diagnosis consists of a primary diagnosis and a secondary diagnosis. The primary diagnosis should include the disease entity/pathogenic type (if disease entity is not known) followed in order by pattern of injury (mixed patterns may be present); score/grade/class for disease entities, such as IgA nephropathy, lupus nephritis, and ANCA GN; and additional features as detailed herein. A pattern diagnosis as the sole primary diagnosis is not recommended. Secondary diagnoses should be reported separately and include coexisting lesions that do not form the primary diagnosis. Guidelines for the report format, light microscopy, immunofluorescence microscopy, electron microscopy, and ancillary studies are also provided. In summary, this consensus report emphasizes a pathogenesis-based classification of GN and provides guidelines for the standardized reporting of GN.

Dense deposit disease (DDD) is a rare glomerular disease that typically affects children, young adults, and much less commonly, older patients. The pathophysiologic process underlying DDD is uncontrolled activation of the alternative pathway (AP) of complement cascade, most frequently secondary to an autoantibody to C3 convertase called C3 nephritic factor, although mutations in factor H and autoantibodies to this protein can impair its function and also cause DDD. Since 1995, we have diagnosed DDD in 14 patients aged 49 years or older; 10 of these patients (71.4%) carry a concomitant diagnosis of monoclonal gammopathy of undetermined significance (MGUS). In 1 of these 10 patients, the index case described here, we evaluated the AP and showed low serum AP protein levels consistent with complement activity, heterozygosity for the H402 allele of factor H, and low levels of factor H autoantibodies, which can affect the ability of factor H to regulate AP activity. In aggregate, these findings suggest that in some adults with MGUS, DDD may develop as a result of autoantibodies to factor H (or other complement proteins) that on a permissive genetic background (the H402 allele of factor H) lead to dysregulation of the AP with subsequent glomerular damage. Thus, DDD in some older patients may be a distinct clinicopathologic entity that represents an uncommon complication of MGUS.

Summary Renal oncocytoma is a benign tumor occurring singly or as multiple synchronous lesions. The histologic features of renal oncocytoma may overlap with those of chromophobe renal cell carcinoma. Chromosomal translocations involving the CCND1 locus at 11q13 and overexpression of cyclin D1 occur in a subset of renal oncocytomas. We evaluated a series of 63 renal oncocytomas and 36 chromophobe renal cell carcinomas and assessed the clinical features, cyclin D1 overexpression by immunohistochemistry, and alterations of the CCND1 gene by fluorescence in situ hybridization. All 36 chromophobe renal cell carcinomas were negative for cyclin D1 overexpression and alterations of CCND1 . Of the 63 renal oncocytomas, 21 (33%) showed cyclin D1 overexpression. Of 21 renal oncocytomas with cyclin D1 overexpression, a CCND1 rearrangement was detected in 12 (57%). A CCND1 rearrangement was also identified in 1 (2%) of the 42 renal oncocytomas without cyclin D1 overexpression. Of 42 renal oncocytomas without cyclin D1 overexpression, 16 (38%) were from patients with multiple renal oncocytomas at nephrectomy. Of 21 renal oncocytomas with cyclin D1 overexpression, only 1 (5%) patient had multiple renal oncocytomas ( P = .006). Of the 25 patients whose original tumor showed no cyclin D1 overexpression, 8 (32%) developed a subsequent renal oncocytoma. None of 15 patients whose original tumor showed cyclin D1 overexpression had a subsequent renal oncocytoma ( P = .016). The findings of this study suggest that renal oncocytomas lacking cyclin D1 overexpression may be associated with the development of multiple renal oncocytomas and that these patients are more likely to develop subsequent renal oncocytomas suggesting the need for more frequent clinical for these patients and little need for follow-up in patients with renal oncocytomas overexpressing cyclin D1. The data also show that cyclin D1 overexpression and CCND1 rearrangements by fluorescence in situ hybridization are absent in chromophobe renal cell carcinoma, suggesting that these are useful when differentiating between renal oncocytoma and chromophobe renal cell carcinoma.

Background Bleeding is one of the most common complications after kidney biopsy. Amyloidosis is thought to be 1 of the risk factors, but this has not been confirmed in a large study. We performed this study to assess the risk of bleeding after kidney biopsy in patients with amyloidosis. Study Design Retrospective study. Settings & Participants 101 patients with and 188 patients without amyloidosis undergoing outpatient percutaneous kidney biopsy at a major medical center in the absence of abnormal partial thromboplastin time, prothrombin time international normalized ratio, or platelet count and/or uncontrolled hypertension. Predictor Clinical diagnosis of amyloidosis. Outcomes & Measurements Post–kidney biopsy bleeding confirmed by means of imaging. Bleeding was defined as major if it required blood transfusion, hospital admission, or other invasive procedures and minor if none of these interventions were needed. Results Post–kidney biopsy bleeding was observed in 9.9% of patients with amyloidosis and 10.6% of controls ( P = 0.8). Bleeding was major in 4% of patients with amyloidosis and 2.1% of controls ( P = 0.4). Three patients from each group required blood transfusions and selective renal angiography. All except 1 patient from the control group underwent embolization. Limitations Retrospective data analysis and overall low event rate did not allow for independent risk-factor analysis. Conclusions The present study suggests that in the absence of a hematostatic disorder and/or uncontrolled hypertension, bleeding risk during kidney biopsy is not increased in patients with systemic amyloidosis. Kidney biopsy can be performed safely using the same screening criteria as for patients without amyloidosis.

Warm antibody autoimmune hemolytic anemia usually is associated with extravascular hemolysis. We report a case of a 42-year-old man with sustained and moderately severe warm antibody autoimmune hemolytic anemia, hemoglobinuria, hemosiderinuria, and acute kidney injury. We show marked induction of heme oxygenase-1 and increased ferritin expression in renal tubules, along with increased iron deposition in renal proximal tubules. These findings in this clinical case thus recapitulate those observed in experimental models of heme protein-induced kidney injury in which a coupled induction of heme oxygenase-1 and ferritin occurs in the kidney. We discuss the pathobiological significance of these findings and suggest that this linked response confers cytoprotection to the kidney exposed to hemoglobin and mitigates the severity of acute kidney injury that may otherwise occur. Finally, this case report documents that nephrotic-range proteinuria can occur in patients with autoimmune hemolytic anemia complicated by hemoglobinuria.

Improvements in anti-HLA antibody detection and diagnostic criteria have increased recognition of antibody-mediated rejection (AMR) following renal transplantation. Therapy of acute AMR is directed toward rapidly lowering circulating donor-specific antibody (DSA) activity. Despite reversal of acute renal dysfunction, however, antibody-secreting plasma cells in spleen and bone marrow are not depleted by treatment and circulating DSA commonly remains detectable in peripheral blood. Sequential ultrastructural studies of renal allografts during acute AMR show progression of microvascular endothelial abnormalities from necrosis and apoptosis to glomerular and peritubular capillary basement membrane duplication, termed transplant glomerulopathy (TG), a manifestation of chronic AMR. Additionally, long-term exposure to anti-HLA antibodies (particularly against class II antigens) is associated with shortened allograft survival and TG even in the absence of documented acute AMR. The association of TG with prior acute AMR and with circulating DSA provides evidence that antibody-mediated allograft injury exists as a spectrum of renal injury. Although effective therapy is available for acute AMR, allografts remain at risk for chronic AMR and shortened survival. The optimum approach to treatment for chronic AMR remains to be determined.

The BK virus is a ubiquitous member of the group of human polyoma viruses that commonly is reactivated in the setting of immunosuppression related to renal transplantation, which results in tubulointerstitial nephritis and allograft dysfunction. BK virus-associated nephropathy occurring in association with human immunodeficiency virus infection and acquired immunodeficiency syndrome (AIDS) was reported only rarely. We describe the case of a 43-year-old man with AIDS presenting with nonoliguric renal failure. The renal biopsy specimen showed tubulointerstitial nephritis and renal tubular cell changes consistent with BK viral inclusions. Results of in situ hybridization for BK viral DNA were positive and showed tubular cell intranuclear inclusions. To our knowledge, this represents the third case of AIDS-associated BK virus-associated nephropathy diagnosed by means of biopsy.

Cigarette smoking is associated with vascular lesions and chronic renal failure. In this report, we describe clinical and kidney biopsy findings for a 66-year-old woman with a history of long-term heavy cigarette smoking who developed proteinuria and decreasing renal function. This study also describes clinical and kidney biopsy findings for 9 patients with a history of smoking. None of these patients had hypertension, diabetes mellitus, or other risk factors that might result in vascular injury. Renal biopsy specimens showed a range of long-term changes with varying degrees of focal segmental or focal global glomerulosclerosis, nodular glomerulosclerosis, ischemic glomeruli, interstitial fibrosis and tubular atrophy, and mild to moderate arterial sclerosis and arteriolar hyalinosis. Electron microscopy often showed glomerular capillary wall thickening caused by subendothelial expansion by cellular elements and new basement formation resulting in segments of double contours. These changes indicate endothelial injury and glomerular capillary wall remodeling; the lesions mimic those seen in patients with chronic hypertension and chronic or healed thrombotic microangiopathies.

Recent protocols have allowed successful positive crossmatch (+XM) and ABO incompatible (ABOI) kidney transplantation, although their long-term outcome is not clear. To begin to assess this issue we compared protocol biopsies performed 12 months posttransplant in 37 +XM, 24 ABOI and 198 conventional allografts. Although the majority in all three groups had only minimal histologic changes, transplant glomerulopathy (TG) was significantly increased in +XM (22% vs. 13% ABOI vs. 8% conventional, p = 0.015), and correlated with prior humoral rejection (HR) by multivariate analysis (odds ratio 17.5, p < or = 0.0001). Patients with a prior history of HR also had a significant increase in interstitial fibrosis (No HR 54% vs. HR 86%, p = 0.045). In the absence of HR no difference in histologic changes was seen between groups, although all three groups had a demonstrable mild increase in interstitial fibrosis from biopsies performed at the time of transplant. Thus, although HR is associated with an increase in TG, in its absence allograft histology is similar in +XM, ABOI and conventional allografts 1 year posttransplant.

Background. The aetiological and clinical associations of collapsing focal segmental glomerulosclerosis (cFSGS) following kidney transplantation (KTx) are poorly described. In this study, post-transplant cFSGS and non-collapsing FSGS (ncFSGS) were compared in recent KTx recipients. Evidence for intragraft viral infection was sought. Methods. Twenty-nine cases of post-KTx FSGS were identified and classified as cFSGS (n ¼ 10) or ncFSGS (n ¼ 19). Biopsies were scored using Banff ‘97 criteria and subjected to in situ hybridization (ISH) for parvovirus B19 (pvB19), simian virus 40 (SV40) and BK virus (BKV). Results. cFSGS and ncFSGS patients were comparable for age, gender, weight, delayed function, human leucocyte antigen (HLA) matching, acute rejection and median time to diagnosis. Deceased donor source was more common among cFSGS cases (70 vs 32%, P ¼ 0.05). FSGS was recurrent in 2/10 cFSGS cases compared with 8/19 ncFSGS (P ¼ NS). cFSGS was associated with more proteinuria (11.9 vs 7.2 g/day, P ¼ 0.05) and higher serum creatinine (4.2 vs 1.9 mg/dl, P ¼ 0.0001) at diagnosis. Plasmapheresis was used in two out of 10 cFSGS and seven out of 19 ncFSGS cases with treatment response in 0 of two and three of seven, respectively. Graft loss was more rapid with cFSGS compared with ncFSGS (P ¼ 0.02). Histologically, cFSGS was associated with more severe chronic vascular abnormalities. All biopsies were negative for pvB19, SV40 and BKV by ISH. Conclusions. cFSGS following KTx presents with higher proteinuria, diminished renal function, more severe vascular disease and higher rate of graft loss compared with the non-collapsing form. There was no evidence for infection by pvB19 or polyomaviruses.

Chronic lymphocytic leukemia (CLL) is the most common leukemia in the Western world and is characterized by a progressive accumulation of functionally incompetent monoclonal lymphocytes. Renal involvement has been described in CLL but is uncommon. Granulomatous interstitial nephritis is a rare but characteristic hallmark of certain diseases such as sarcoidosis and tuberculosis. These epithelial reactions have also been reported with medications, infections, inflammation, Wegener's granulomatosis, and jejunoileal bypass. We present a 74-year-old woman with a stage 0 chronic lymphocytic leukemia who developed acute renal failure following the initiation of alendronate. The renal biopsy revealed an acute granulomatous interstitial nephritis. Infectious and inflammatory etiologies were ruled out. Hemodialysis was required despite discontinuation of all medications. Partial recovery of renal function occurred after 6 weeks of prednisone therapy and cyclophosphamide. This report describes a unique case of acute granulomatous interstitial nephritis and leukemic cell kidney infiltration by CLL.

● Goodpasture’s disease is characterized by crescentic glomerulonephritis and lung hemorrhage in the presence of anti– glomerular basement membrane (anti-GBM) antibodies. This disease usually is mediated by IgG autoantibodies directed against the noncollagenous domain of the 3(IV) collagen chain, the Goodpasture autoantigen. In rare cases, anti-GBM antibodies of IgA or IgM class are involved, but their specificity has not been determined, and their target antigen remains unknown. The authors present the case of a 62-year-old man with anti-GBM disease mediated by a monoclonal IgA- antibody, which progressed to end-stage renal disease despite intensive immunosuppression. The patient underwent living-related kidney transplantation, but lung hemorrhage and crescentic glomerulonephritis recurred, causing the loss of the allograft 2 years later. Indirect immunofluorescence found the presence of circulating IgA antibodies reactive with a basement membrane component, identified by enzyme-linked immunoabsorbent assay and Western blot as the 1/2(IV) collagen chains. Sensitivity to digestion with collagenase indicated that IgA bound to epitopes located in the collagenous domain. This is the first case of recurrent Goodpasture’s disease secondary to an autoreactive IgA antibody. The specificity of an IgA antibody implicated in the pathogenesis of anti-GBM disease has been investigated for the first time, identifying the 1/2(IV) collagen chains as a novel target for nephritogenic antibodies. Am J Kidney Dis 45:397– 406. © 2004 by the National Kidney Foundation, Inc. INDEX WORDS: Goodpasture’s disease; anti– glomerular basement membrane (GBM) disease; paraproteinemia; IgA- antibodies; crescentic glomerulonephritis; pulmonary hemorrhage; kidney transplantation; 1/2 chains of type IV collagen.

Wegener’s granulomatosis (WG) is a systemic disease characterized pathologically by necrotizing granulomatous inflammation of the respiratory tract and generalized vasculitis involving mediumand smallsized vessels. Kidney involvement is usually manifested as a focal segmental necrotizing glomerulonephritis, with crescents [1]. Anti-neutrophil cytoplasm antibody (ANCA) testing has provided a very useful diagnostic aid. The majority of patients with WG have antibodies towards proteinase 3 (PR3-ANCA) (>70%), but antibodies towards myeloperoxidase (MPO-ANCA) is seen in 20% of cases. A few patients (

The purpose of this study was to characterize the histology of antibody-mediated rejection (AMR) in ABO blood-group-incompatible (ABOI) kidney transplants as well as on protocol biopsies performed at the time of stable allograft function. Between 5/99 and 1/02, we performed 32 ABOI kidney transplants (13 A2, 19 non-A2 blood-group living donors). Nineteen biopsies were performed for allograft dysfunction, and 127 protocol biopsies were performed 0, 3, 7, 14, 28 days and 3 and 12 months post transplant. Twenty-five of 32 patients have functioning allografts (mean 585 days post transplant). Nine of 32 (28%) developed clinical AMR. Biopsy revealed glomerular thrombi (78%), mesangiolysis (78%), peritubular capillary C4d staining (56%) and neutrophil infiltration (67%), interstitial hemorrhage and necrosis (56%) and arteriolar thrombi (33%). Subclinical AMR was diagnosed by protocol biopsies in four patients. Findings consisted of glomerular thrombi (100%), mesangiolysis (25%), and C4d staining (100%). In late protocol biopsies performed 214-420 days post transplant, mild mesangiolysis was seen in 2/17 (11.7%), and C4d immunostaining was detected in 3/12 (25%). AMR is characterized by glomerular thrombi, mesangiolysis, peritubular capillary neutrophil infiltration interstitial hemorrhage, necrosis, and C4d deposition. Glomerular thrombi appear early in AMR and may appear prior to graft dysfunction.

Influence of surveillance renal allograft biopsy on diagnosis and prognosis of polyomavirus-associated nephropathy. Background Polyomavirus-associated nephropathy (PVAN) is an increasingly prevalent cause of allograft dysfunction. Methods In 18 histologically proven cases of PVAN managed by reduced immunosuppression, monitoring of serum creatinine, and repeated biopsy, graft outcomes were correlated with clinical and histologic indices. Six months postdiagnosis the status of each graft was classified as poor ( N = 7) or satisfactory ( N = 11). Poor transplant status was defined as graft loss, increased severity of PVAN on repeat biopsy, or serum creatinine>3.0mg/dL. Diagnosis resulted from either surveillance allograft biopsies ( N = 8) or biopsies performed for increased serum creatinine (nonsurveillance, N = 10). Results The surveillance biopsy group was more likely than the nonsurveillance group to have satisfactory graft status at 6months (eight of eight vs. three of ten, P = 0.004) and had significantly lower serum creatinine at diagnosis, 3, and 6months. Histologic scoring for chronic interstitial and tubular injury was lower in diagnostic surveillance biopsies compared to nonsurveillance biopsies ( P = 0.01). Satisfactory transplant status was also associated with reduced or absent virus on repeat biopsy ( P = 0.01). Poor transplant status was associated with a higher frequency of recipient neg /donor pos cytomegalovirus (CMV) serology (71% vs. 9%, P = 0.01). Conclusion Surveillance allograft biopsy provides an important means for earlier detection of PVAN and permits timely alterations to immunosuppression. Early diagnosis is associated with a lesser degree of interstitial fibrosis at diagnosis and lower baseline and subsequent serum creatinine.

Background. Given the scarcity of cadaveric organs, efforts are intensifying to increase the availability of living donors. The current study assessed the feasibility of using ABO-incompatible living-donor kidneys to expand the donor pool. Methods. The authors performed 18 ABO-incompatible living-donor kidney transplants between May 1999 and April 2001. Ten patients received living-donor kidneys from A2 and eight patients received kidneys from non-A2 blood group donors. Immunosuppression consisted of Thymoglobulin antibody induction, tacrolimus, mycophenolate mofetil, and prednisone. Eight non-A2 and two A2 kidney recipients also received a pretransplant conditioning regimen of four plasmapheresis treatments followed by intravenous immunoglobulin and splenectomy at the time of transplantation. Antidonor blood group antibody titer was measured at baseline, pretransplant, at 1- to 3-month and 1-year follow-up, and at the time of diagnosis of antibody-mediated rejection. Results. No hyperacute rejection episodes occurred. One-year graft and patient survival rates in the 18 ABO-incompatible recipients were only slightly lower than those of 81 patients who received ABO-compatible kidney transplants during the same period (89% vs. 96% and 94% vs. 99%, respectively). Glomerular filtration rate and serum creatinine levels did not differ between the groups. Antibody-mediated rejection occurred in 28% of ABO-incompatible recipients, and was reversible with plasmapheresis, intravenous immunoglobulin, and increasing immunosuppression in all patients except one. Conclusions. ABO-incompatible living donor kidney transplants can achieve an acceptable 1-year graft survival rate using an immunosuppressive regimen consisting of Thymoglobulin induction, tacrolimus, mycophenolate mofetil, and prednisone combined with pretransplant plasmapheresis, intravenous immunoglobulin, and splenectomy.

A 27-year-old Caucasian male presented with a one-month history of diarrhoea, severe abdominal cramping, heartburn and weight loss. The symptoms began right after breakfast in the morning and continued with 3–4 watery stools throughout the day, but none during the night. Spicy foods, alcoholic beverages and excessive water intake seemed to exacerbate the pain, but soda seemed to alleviate it. The patient denied use of antibiotics, antispasmodics, or antihypertensive drugs, and drank minimal milk. The patient denied any recent international travel or contact with diapers or ill persons but confirmed that the symptoms started about a week after a river trip. There was no known family history of GI disease. …

We studied 4 new cases of juxtaglomerular cell tumor and compared their morphologic and immunohistochemicalfeatures with 2 renal hemangiopericytomas and 5 cutaneous glomus tumors. The juxtaglomerular tumors were resectedfrom 2 males and 2 females (mean age at diagnosis, 23 years). Three patients manifested with severe hypertension. Tumors ranged from 2.2 to 8.0 cm and were well circumscribed. The tumors consisted of solid sheets and nodules of variably sized tumor cells with round, oval, and spindled nuclei alternating with edematous microcystic foci. Nuclear atypia, present in all tumors, was a prominent feature in 2. Mitotic activity was not identified. All cases showed hemorrhage, numerous mast cells, and thick-walled blood vessels. Unusual features included coagulative tumor necrosis, a hemangiopericytoma-like vascular pattern, and hyalinized stroma. All tumors were immunoreactive for CD34 and actin. Ultrastructural analysis revealed the presence of rhomboid-shaped renin protogranules. Patients were treated by partial or radical nephrectomy and followed up for 14 to 48 months. There were no recurrences or metastases. The characteristic clinical and morphologic features of juxtaglomerular cell tumor permit distinction from renal hemangiopericytoma and other renal tumors.

Metanephric adenoma (MA) is a renal tumor that is generally detected in adults and occasionally in children. These tumors usually behave in a benign fashion. Although the histogenesis of MA is unclear, a morphologic similarity to Wilms' tumor (WT) complex exists. Six cases of MA, five cases of childhood WT (CWT), two cases of adult WT (AWT), and four cases of treated MWT and/or nephrogenic rests (MWT/NR), with paraffin blocks available for use, were retrieved from the surgical pathology files of the Mayo Clinic. Clinical information was extracted from the medical record. Immunoperoxidase stains for WT1, AE1, CK7, CD57, CD56, and desmin were performed on paraffin sections from all cases. All six cases of MA were strongly and diffusely positive with antibodies to WT1 and CD57 and focally positive with antibodies to CK7. Three cases showed focal faint staining in

We present the case of a 17-year-old woman with a history of bipolar disorder, who developed a clinical syndrome manifested by fever, lymphadenopathy, skin rash, diarrhea, and acute renal failure requiring dialysis after the use of lamotrigine. Renal biopsy showed acute interstitial nephritis (AIN) with focal granulomas. Similarly, colonic biopsy specimens showed colitis and ileitis with non-necrotizing epithelioid granulomas. The patient had a complete recovery after withdrawal of the medication and steroid treatment. Although lamotrigine has been previously implicated in the development of anticonvulsant hypersensitivity syndrome, there have been no previous reports of acute granulomatous interstitial nephritis or colitis associated with the use of this drug.

Testicular hemangiomas are benign vascular neoplasms usually occurring in children. Pathologists must be aware of this entity when performing intraoperative frozen sections as, after diagnosis, testicle-sparing surgery is adequate. The authors present a typical case with immunohistochemical studies and a review of the literature.

Background. Primary malignant cervical schwannomas (malignant peripheral nerve sheath tumors) are extremely rare tumors that grossly may resemble many other more common lesions. The diagnosis, management, and follow-up of a malignant cervical schwannoma are presented with a review of the literature. Case. A 51-year-old female presented with a 3-year history of perimenopausal vaginal bleeding. A 3 × 3 cm friable, spongy lesion was noted on the posterior aspect of the cervix. Frozen-section analysis could not rule out a malignant smooth muscle tumor. The patient underwent an exploratory laparotomy, total abdominal hysterectomy, and bilateral salpingo-oophorectomy. Immunohistochemistry and electron microscopy aided in the final diagnosis of a malignant cervical schwannoma. The patient is alive and well 1 year from her definitive surgery. Another patient with the same tumor received the same surgical management. This patient is now 10 years from her surgery and is alive with no evidence of disease. Conclusion. Immunohistochemistry and electron microscopy are useful in the diagnosis of a malignant cervical schwannoma. This case and long-term follow-up from another case provide evidence that simple hysterectomy may be sufficient therapy for this uncommon lesion.

C.V. is a 22-year-old woman, who presented to the emergency room (ER) with shortness of breath, coughing and frank haemoptysis. She had been seen in the ER twice over the previous 3 weeks for similar symptoms, but with only mild blood-tinged sputum. Chest X-ray showed bilateral infiltrates. She was treated with Zithromax and subsequently Biaxin for a presumed pneumonia. There was no history of fevers, chills or weight loss. However, the haemoptysis persisted with increasing shortness of breath, forcing her back to the ER. Her history was significant in that she is a smoker and works as a bartender in a smoky restaurant. Laboratory investigations at admission: haemoglobin 10 gm/dl, platelet count 309 10/ml, sodium 138mEq/l, potassium 3.8mEq/l, serum creatinine 0.7mg/dl, blood urea nitrogen 11mg/dl, total bilirubin 1.5mg/dl, PCO2 34, PO2 48. Urinalysis was unremarkable. Chest X-rays showed worse diffuse alveolar infiltrates compared with the previous X-rays. The clinical diagnosis was that of acute interstitial lung disease with haemoptysis and included a differential diagnosis Wegner’s granulomatosis, lupus, sarcoidosis, pneumonitis, Goodpasture’s disease, etc. Titres for anti-GBM antibodies returned high positive (>32U/ml, normal

Leydig cell tumors of the testis are rare and account for a small proportion of testicular neoplasms. The objective of this study was to identify clinical and morphologic features predictive of metastasis in a large series of Leydig cell tumors, and to determine whether ploidy or proliferative activity were predictive of malignancy. Thirty cases of Leydig cell tumor of the testis (23 tumors that had not metastasized and 7 that had metastasized) were studied. Clinical history and follow-up were collected in all cases. The morphologic features examined included tumor size, mitotic index (mitotic figures/10 high-power fields), necrosis, angiolymphatic invasion, cell type, tumor-testicle interface, presence of extension beyond the testicular parenchyma, and presence of lipochrome and Reinke crystals. Most patients (93%) had a testicular mass. Patients with Leydig cell tumors that metastasized were diagnosed at a mean age of 62 years (range, 39-70 years) compared with 48 years (range, 9-79 years) in patients with nonmetastasizing tumors (p = 0.25). Leydig cell tumors that metastasized were significantly larger than nonmetastasizing tumors (mean, 4.7 versus 2.6 cm, respectively; p = 0.008), and had a significantly higher mitotic index (mean, 13.9 versus 1.9, respectively; p < 0.0001). Metastasizing Leydig cell tumors were significantly associated with atypical mitotic figures (p < 0.0001), nuclear variation (p = 0.0025), necrosis (p < 0.0001), angiolymphatic invasion (p = 0.009), infiltrative margins (p < 0.0001), high grade (p = 0.0004), and invasion into rete testis, epididymis, or tunica (p = 0.001) when compared with nonmetastasizing tumors. There was no significant difference between metastasizing and nonmetastasizing tumors in regard to cell type, lipochrome content, presence of Reinke crystals, or nuclear inclusions. All Leydig cell tumors that metastasized and 7 of 18 (38.9%) nonmetastasizing tumors were DNA aneuploid by static image analysis (p = 0.02). Metastasizing Leydig cell tumors had a significantly higher mean MIB-1 activity of 18.6% (range, 5.8-33.6) compared with 1.2% (range, 0.04-8.2) in nonmetastasizing tumors (p = 0.001). In this study, the presence of cytologic atypia, necrosis, angiolymphatic invasion, increased mitotic activity, atypical mitotic figures, infiltrative margins, extension beyond the testicular parenchyma, DNA aneuploidy, and increased MIB-1 activity were significantly associated with metastatic behavior in Leydig cell tumors.

OBJECTIVE: Late "recurrence" of ovarian cancer may result from either regrowth of dormant tumor cells or from development of a new cancer caused by the phenomenon of field cancerization. Clinically, some recurrent ovarian cancers show the same therapeutic sensitivities to chemotherapy and surgery as did the primary disease, whereas others are refractory to all therapy. We hypothesize that recurrent ovarian cancers are distinguishable on the basis of a molecular genetic fingerprint and that some are actually new primary cancers of the peritoneum rather than recurrent ovarian cancer. STUDY DESIGN: We constructed molecular genetic fingerprints of 13 paired primary and late recurrent ovarian cancers to study their clonal relationships. The tumor pairs were analyzed for p53 mutations and allelotypes, patterns of X-chromosome inactivation, loss of heterozygosity, and microsatellite instability at 12 different loci on 6 different chromosomes. Techniques used included single-strand conformational polymorphism mutation screening and polymerase chain reaction–based sequence analysis of the p53 locus, restriction digestion of the androgen receptor locus to determine X-chromosome inactivation, and polyacrylamide gel electrophoresis of highly polymorphic dinucleotide, trinucleotide, and tetranucleotide repeats. RESULTS: The average age at initial diagnosis for this cohort was 54.7 years (range 45.3 to 65.5). Mean interval to recurrence was 42.7 months (range 28 to 62). Molecular fingerprints were characterized for 4 to 8 informative loci per tumor pair. The fingerprints of 10 (77%) differed significantly, strongly suggesting that a second primary cancer had developed. The remaining 3 tumor pairs demonstrated identical allelotypes consistent with regrowth of dormant tumor cells. CONCLUSION: Our results are consistent with the "field cancerization" hypothesis of ovarian carcinogenesis but could also be explained by a polyclonal tumor origin, which contrasts with the currently accepted monoclonal theory of ovarian carcinogenesis. Late development of a new primary cancer may herald the proband as a member of a familial cancer phenotype. These studies provide a molecular genetic rationale that both explains and prognosticates the clinical course of recurrent ovarian cancer. (Am J Obstet Gynecol 1998;178:641-9.)

A case of Stage IIIC primary ovarian leiomyosarcoma in a premenopausal woman with multiple recurrences alive and well 7 years after diagnosis is presented. In addition to the typical light microscopic, immunohistochemical, and electron microscopic features of ovarian leiomyosarcoma, the tumor was progesterone receptor positive. This is 28th report of primary ovarian leiomyosarcoma and the first report of progesterone receptor in this tumor. This is the longest reported survival in a woman with this disease.

Fifty-seven cases of acute myeloid leukemia (AML), which had been subtyped by French-American-British morphologic and cytochemical criteria as myeloid (M1, M2) or monocytic (M4, M5), were retrieved from the files of the Division of Hematopathology, University of Iowa. Corresponding immunophenotyping data were reviewed with attention to the expression of CD14 (MY4) and CD24 (BA-1). Of 20 cases expressing CD24, 19 were M4 or M5, whereas all 14 cases expressing CD14 were of monocyte lineage. Therefore, CD14 was a highly specific (100%) but only moderately sensitive (58%) marker for distinguishing classes M1 or M2 from M4 or M5. By contrast and unexpectedly, CD24 was nearly as specific (97%), but more sensitive (79%) in marking M4 or M5 cells. This appears to be true even though CD24 is apparently not expressed on normal monocytes. When positive staining for either or both antibodies (CD24 or CD14) was considered indicative of a monocytic leukemia, the sensitivity of immunophenotyping in distinguishing M4/M5 from M1/M2 AML rose to 92%, while maintaining 97% specificity. The authors discuss a recent observation that may help explain the unexpected expression of CD24 in monocytic AML. They conclude that the usefulness of CD24 in identifying monocytic AML may exceed that of CD14, and that the use of CD24 and CD14 in combination improves the ability of flow cytometry to distinguish myeloid from monocytic acute leukemias.

Background. Subclinical rejection, defined as histologic acute rejection in the absence of graft dysfunction, has been suggested as a cause of chronic allograft rejection. In cyclosporine-treated patients, the incidence of subclinical rejection 3 months after transplant is reported to be approximately 30%. The intent of our study was to determine the incidence of subclinical rejection in tacrolimus-treated renal allograft recipients. Methods. We prospectively studied the incidence of subclinical rejection on surveillance biopsies performed 3 months after transplantation in 114 patients transplanted between September 1, 1998 and November 30, 2000. All patients received tacrolimus, mycophenolate mofetil, and prednisone, and 56% received antibody induction. Results. Subclinical rejection was detected in 2.6% of patients (3/114, 95% confidence interval 0.5-7.5%). Borderline changes were detected in 11% (12/114). Subclinical rejections were treated with bolus methylprednisolone. Conclusions. The incidence of subclinical rejection early after kidney transplantation is extremely low in tacrolimus-treated patients in whom early rejections are aggressively treated, suggesting that surveillance biopsies may not be necessary with this regimen.

BACKGROUND.: Anti-human leukocyte antigen antibodies (a-HLA) cause graft injury identified by C4d in peritubular capillaries. We investigated whether a-HLA relate to episodes of C4d negative acute rejection (AR). METHODS.: We analyzed 878 kidney recipients transplanted from January 2000 to December 2006. Pretransplant, 36% of these crossmatch negative recipients had a-HLA measured by solid phase assays. RESULTS.: AR occurred in 154 patients (18%) and 11 of them (9.4%) were C4d+. Forty-six percent of ARs were diagnosed by protocol biopsy. The risk of C4d-AR was increased in patients with a-HLA class I with donor specificity (DSA-I) (hazard ratio=1.519; confidence interval, 1.02-2.26; P=0.039). DSA-II were not associated with an increased risk of C4d-AR. The relationship between DSA-I and C4d-AR was independent of recipient age, BK nephropathy, and HLA mismatches. Compared with DSA-, in DSA+ recipients C4d-AR were most often histologically "borderline." DSA+ was associated with capillaritis in the biopsy (glomerulitis, 6.1% vs. 32%, P=0.003; peritubular capillaritis: 13% vs. 40%, P=0.0009). Compared with no AR, C4d-AR with capillaritis was associated with reduced graft survival (hazard ratio=4.164; confidence interval, 1.763-9.832; P=0.001), independent of other variables. This association was observed even in the cases of borderline AR. CONCLUSIONS.: DSA-I increases the risk of C4d-AR. The presence of DSA-I or II is associated with capillaritis during AR. Capillaritis is associated with reduced graft survival.

Renal dysfunction commonly occurs in multiple myeloma (MM) and is caused by deposition of abnormal light chain within various compartments of the kidney. Renal pathologic findings are diverse and include cast nephropathy (CN), amyloidosis and light-chain deposition disease (LCDD). We report a case of renal failure in a patient with MM caused by concurrent CN, amyloidosis and LCDD which has not been previously described.

The causes of kidney allograft loss remain unclear. Herein we investigated these causes in 1317 conventional kidney recipients. The cause of graft loss was determined by reviewing clinical and histologic information the latter available in 98% of cases. During 50.3 +/- 32.6 months of follow-up, 330 grafts were lost (25.0%), 138 (10.4%) due to death with function, 39 (2.9%) due to primary nonfunction and 153 (11.6%) due to graft failure censored for death. The latter group was subdivided by cause into: glomerular diseases (n = 56, 36.6%); fibrosis/atrophy (n = 47, 30.7%); medical/surgical conditions (n = 25, 16.3%); acute rejection (n = 18, 11.8%); and unclassifiable (n = 7, 4.6%). Glomerular pathologies leading to failure included recurrent disease (n = 23), transplant glomerulopathy (n = 23) and presumed nonrecurrent disease (n = 10). In cases with fibrosis/atrophy a specific cause(s) was identified in 81% and it was rarely attributable to calcineurin inhibitor (CNI) toxicity alone (n = 1, 0.7%). Contrary to current concepts, most cases of kidney graft loss have an identifiable cause that is not idiopathic fibrosis/atrophy or CNI toxicity. Glomerular pathologies cause the largest proportion of graft loss and alloinmunity remains the most common mechanism leading to failure. This study identifies targets for investigation and intervention that may result in improved kidney transplantation outcomes.

To determine the outcome of kidney transplantation in patients with fibrillary glomerulonephritis (FGN), a rare glomerular disease, we followed 12 patients, 5 with FGN and 7 patients with monoclonal gammopathy and fibrillary deposits (MGFD), who underwent 15 kidney transplants since 1988 with a median follow-up of 52 months. Recurrent disease did not arise in any of the patients with FGN but developed in 5 patients with MGFD. Seven allografts failed: 1 in the FGN group and 6 in the MGFD group. Median allograft survival for patients with MGFD was 37 months but had not been reached in FGN patients. One patient with FGN had primary allograft failure secondary to graft thromboembolism. Three patients with MGFD were re-transplanted and one lost the second allograft to recurrent disease, but the other two died from hematological malignancy. Another patient was diagnosed with MPGN type III and did not have detectable fibrillary material 22 months after transplantation. One patient with MGFD had stable allograft function 6 months post-transplant but another, with recurrent disease, underwent peripheral blood stem cell transplantation and regained stable allograft function. Our study shows that kidney transplantation appears safe in patients with FGN with little risk of recurrence. However, patients with MGFD have a significant risk for disease recurrence. Whether the development of hematological malignancies following transplantation in this group is related to their original disease or was coincidental requires further studies.

Membranous nephropathy (MN) is considered the most common cause of nephrotic syndrome in white adults, but recent studies have shown an increasing incidence of focal segmental glomerulosclerosis (FSGS). These studies are difficult to interpret because the majority of cases came from urban tertiary referral centers. For validating these findings in the general population, trends in the incidence of various forms of glomerular disease (glomerulonephritis [GN]) among the residents of Olmsted County, MN were studied. Biopsy data of local patients who had a diagnosis of a nondiabetic glomerular disease from 1974 through 2003 were reviewed. Biopsies were categorized as (1) FSGS, (2) MN, (3) minimal change, (4) lupus nephritis, (5) membranoproliferative GN (MPGN), (6) IgA nephropathy (IgAN), (7) crescentic/necrotizing GN, and (8) other. Time trends in the annual age- and gender-adjusted (2000 US population) incidence rate per 100,000 Olmsted County population were estimated. A total of 195 biopsies were analyzed. Overall, IgAN was present in 22%, FSGS was present in 17%, and MN was present in 10%. Between 1974 to 1983 and 1994 to 2003, the incidence of any type of GN among Olmsted County residents increased more than two-fold (P < 0.001), FSGS by 13-fold (P < 0.001), and IgAN by three-fold (P = 0.002). Increases in MN were nonsignificant (2.5-fold; P = 0.13). Currently (1994 to 2003), the most frequent type of GN is IgAN (25%), followed by FSGS (20%) and MN (11%), with annual incidence rates of 2.1, 1.8, and 1.0 per 100,000/yr, respectively. This study confirms that the incidence of GN is growing overall, particularly for FSGS, which is the leading cause of nephrotic syndrome in white adults.

CASE PRESENTATION A 52-year-old man with a past medical history of asthma, well-controlled diabetes and hypertension was referred to our hospital for acute renal failure. The patient reported a 2-month history of fatigue and arthralgia involving his shoulders, elbows, wrists, metacarpophalangeal joints as well as his knees and ankles. Six weeks before admission, he started naproxen 400 mg twice daily without improvement. Subsequently he was evaluated by a local rheumatologist who suspected rheumatoid arthritis and started him on prednisone 30 mg daily. A month later, his laboratories revealed an elevated serum creatinine (12.3mg/dl, 1087/μmol/l) and potassium (7.9 mEq/l). His serum creatinine was 1.8 mg/dl (159.1 /μmol/l) 6 weeks earlier and 1.3 mg/dl 7 years earlier (Figure 1). The hyperkalemia was treated with intravenous insulin and dextrose, and he was admitted to our hospital for further management. He denied fever, chills, weight loss, shortness of breath, lower extremity edema, and did not have any uremic symptoms (no nausea, vomiting, hiccups, or itching). He had normal urine output and no dysuria or hematuria. He had hypertension that was diagnosed 13 years earlier and based on records it was well controlled (

Mixed epithelial stromal tumor of the kidney (MEST)/adult cystic nephroma (CN) is a lesion characterized by epithelial lined tubular or cystic structures interspersed within a variably prominent, distinctive spindle-cell stroma. Although typically benign, cases with malignant features have been reported. Herein, we report a MEST/CN with malignant stromal features and rhabdoid differentiation arising in the left kidney of an 84-year-old woman. Histologically, the tumor displayed multiple tubules and variably sized cystic structures lined by benign epithelium with an intervening malignant-appearing spindle-cell stroma. The malignant stroma displayed condensation in the regions surrounding the epithelial component consistent with the ovarian-like stroma typically observed in MEST/CN. In addition, the stromal cells displayed extensive rhabdoid differentiation. Immunohistochemical analysis revealed strong expression of cytokeratin 7, CAM 5.2, AE1/AE3, wide-spectrum keratin, and epithelial membrane antigen by the epithelial component. The stromal component displayed strong immunohistochemical expression of WT-1, CD-99, CD-56, INI1, and estrogen receptor; focal actin positivity; and was negative for desmin, myogenin, and progesterone receptor. Analysis by reverse transcriptase polymerase chain reaction failed to identify the SYT-SSX1 or SYT-SSX2 fusion transcripts characteristic of synovial sarcoma. To our knowledge, this represents the first report in the literature of malignant MEST with rhabdoid features and suggests that this entity should be considered in the diagnosis of renal stromal malignancies with prominent rhabdoid features.

Fabry disease is a metabolic disorder caused by the genetic deficiency of alpha-galactosidase A. Deposition of glycosphingolipids in podocytes, endothelial cells, and other cell types leads to formation of myelin-like inclusions, which are the hallmark of the disease. In most untreated males, the disorder progresses to end-stage kidney disease. Fabry disease is rare, and no renal biopsy series focusing on pathologic findings has been published in the past 25 years. We retrieved kidney biopsies diagnosed with Fabry disease from our files, and reviewed clinical data as well as the light and electron microscopy. In total, 11 patients were identified: six male subjects aged 17-43 years and five female subjects aged 30-73 years. On average, male patients presented more than 10 years earlier then female patients. A total of 10 patients had proteinuria, two with the nephrotic syndrome. Four male and three female patients had decreased renal function. Light microscopy showed vacuolization of the podocyte cytoplasm and variable glomerular sclerosis. Older patients and males had more advanced glomerular and interstitial sclerosis, but three of the five female patients also had advanced renal disease. Electron microscopy showed the characteristic myelin-like inclusions most prominently in the podocyte cytoplasm. Seven patients also had podocyte foot process effacement. A second type of deposit, unexpected and conspicuous, was identified in three males, and found to be associated with glomerular basement membrane duplications. These deposits were composed of layered membrane-like material, and therefore morphologically distinct from myelin-like inclusions. They probably represent remnants of damaged endothelial cells.

Anti-glomerular basement membrane (anti-GBM) glomerulonephritis is a rare disease caused by IgG autoantibodies against the glomerular basement membrane. We describe clinical and pathologic findings in a series of renal biopsy specimens from 80 patients. The patients ranged in age from 16 to 87 years. The age distribution was bimodal, with one peak at a young age predominated by males and a second peak in the sixth to eighth decades with females predominating. Most patients (70 [88%]) had severe necrotizing glomerulonephritis with crescents in more that 50% of glomeruli. The fraction of crescentic glomeruli in biopsy specimens correlated well with serum creatinine levels but not with serologic titers for anti-GBM antibodies. Interstitial fibrosis was uncommon and, when present, minimal to mild. Linear IgG deposition defines this entity, but immunofluorescent costaining for other immunoglobulins and complement is found frequently. To our knowledge, this is the largest series of renal biopsy specimens with anti-GBM glomerulonephritis studied to date.

Polyomavirus-associated nephropathy (PVAN) is managed by reduced immunosuppression with or without antiviral therapy. Data from 55 patients with biopsy-proven PVAN were analyzed for adverse outcomes and influence of baseline variables and interventions. During 20 ± 11 months follow-up, the frequencies of graft loss, major and any functional decline were 15%, 24% and 38%, respectively. Repeat biopsies were performed in 45 patients with persistent PVAN in 47%. Low-dose cidofovir, IVIG and cyclosporine conversion were used in 55%, 20% and 55% of patients. No single intervention was associated with improved outcome. Of the variables examined, only degree of interstitial fibrosis at diagnosis was associated with kidney function decline. In contrast, donor source, interstitial fibrosis, proportion of BKV positive tubules and plasma viral load at diagnosis were all associated with failure of histological viral clearance. This retrospective, nonrandomized analysis suggests that: (i) Graft loss within 2 years of PVAN diagnosis is now uncommon, but ongoing functional decline and persistent infection occur frequently. (ii) Low-dose cidofovir, IVIG and conversion to cyclosporine do not abrogate adverse outcomes following diagnosis. (iii) Fibrosis at the time of diagnosis predicts subsequent functional decline. Further elucidation of the natural history of PVAN and its response to individual interventions will require prospective clinical trials.

The recently described mixed epithelial and stromal tumor (MEST) of the kidney and adult cystic nephroma (CN) (multilocular cyst) are rare benign cystic renal neoplasms that are composed of epithelial and stromal elements. Consensus criteria for distinguishing these entities have not been well established. Our objective in this study was to evaluate cases of CN and MEST to define the morphological, immunophenotypic, and clinical features of these two entities. Eleven cases from the files of a single institution diagnosed from 1996 to the present as either CN or MEST were reviewed. Architecturally, all lesions were composed of multiple noncommunicating cysts lined by a single layer of epithelial cells. All cases had areas with increased stromal cellularity and 8 cases had ovarian-like stroma present at least focally within the tumor. No stromal or epithelial cell atypia, blastemal elements, or increased mitotic activity was appreciated. The immunoprofile was also similar in the 7 cases stained and included epithelial reactivity with keratin and CAM 5.2 and stromal reactivity with estrogen receptor, progesterone receptor, smooth muscle actin, WT-1, vimentin, and focal desmin. All cases have acted in a benign fashion with no history of recurrence or metastasis. We propose that CN and MEST of the kidney represent a spectrum of the same entity. If the diagnosis of CN is limited to cases that are comprised entirely of thin fibrous-walled cysts, all 11 of our cases would be classified as MEST.

Background Although most protocols for ABO-incompatible kidney transplantation have employed splenectomy, its utility is unproven. The aim of the current study was to compare the outcomes of ABO-incompatible living donor kidney transplantation with splenectomy versus a protocol involving intensive posttransplant antibody monitoring to maintain low levels of antiblood group antibody. Methods We retrospectively studied all ABO-incompatible living donor kidney transplants at our institution between September 1999 and November 2004 (n=34). Prior to May 2003, all patients were included in a protocol involving pretransplant plasmapheresis and splenectomy at the time of transplant (n=23). After May 2003, splenectomy was not performed and a protocol that involved pretransplant anti-CD20 antibody and a more intensive posttransplant plasmapheresis regiment aimed at maintaining low levels of antiblood group antibody during the first 2 weeks following transplantation was utilized (n=11). Results Patient and graft survival was similar in the two groups. Humoral rejection occurred in 18% nonsplenectomized and 30% of splenectomized patients (P=0.68). Humoral rejection correlated with the baseline antibody titer in both groups. Individuals with elevated baseline antibody titer (> or =1:256) appear to be at high risk for humoral rejection regardless of protocol used. Antiblood group antibody levels 3 and 12 months after transplantation were similar in both groups. Conclusions Splenectomy is not essential for successful ABO-incompatible kidney transplantation, although individuals with high baseline antidonor blood group antibody titers are at high risk for humoral rejection. The use of intensive posttransplant monitoring may help prevent antibody-mediated graft damage.

A distinct entity mimicking immune-complex-mediated glomerulonephritis characterized by a proliferative glomerulonephritis with monoclonal immunoglobulin G (IgG) deposits recently was described. We now report a case of a 35-year-old woman who presented with sudden onset of edema, proteinuria, hematuria, and hypertension. Renal biopsy showed diffuse endocapillary proliferation, mesangial cellularity, and amorphous material in the mesangium. Immunofluorescence examination showed mesangial and capillary wall staining for IgA (2+), C3 (2+), fibrinogen (2+), and lambda (2+). Congo red stain was negative. Electron microscopy showed mesangial and subendothelial deposits with a paracrystalline lattice-like substructure forming parallel linear arrays. Extensive laboratory evaluation showed a small population of monoclonal plasma cells with lambda restriction. The present case suggests that monoclonal IgA deposits also can cause proliferative glomerulonephritis. However, the presence of paracrystalline deposits in association with monoclonal IgA deposits has not been described previously.

Metanephric metaplasia of the parietal epithelium of the Bowman capsule is a rare pathologic finding of unknown pathogenesis that has occurred in patients with widespread malignant neoplasms of various types. We report this finding in a 25-year-old woman with partial expression of the Carney triad who died of a disseminated gastrointestinal stromal tumor, specifically a gastric stromal sarcoma. The metaplasia involved both kidneys diffusely. It originated in the parietal epithelium of the Bowman capsule, extended into the proximal tubules, and focally surrounded the glomeruli in a semicircular manner Immunohistochemical analysis revealed that the cells of metanephric metaplasia expressed the Wilms tumor gene product, bcl-2 protein, and CD57 and cytokeratin 7 and keratin AE1/AE3 focally, but not CD56. This immunophenotype parallels that of metanephric adenoma, Wilms tumor, and nephrogenic rests and overlaps with antigen expression in certain periods of renal development.

Background: Light-chain deposition disease (LCDD) is a monoclonal gammopathy characterized by nonamyloid deposition of light chain in various organs. A small number of kidney transplantations have been performed on LCDD patients in whom end-stage renal disease (ESRD) developed. Methods: The authors retrospectively reviewed the clinical and histologic findings and outcome of 7 patients with LCDD who underwent kidney transplantation at our institution. Results: Renal insufficiency, hypertension, and proteinuria were present in all 7 patients. Proteinuria level was greater than 3.5 g/24 h in 3 patients. Three patients had microscopic hematuria. Monoclonal protein was detected in the serum in 3 patients, urine in 5, and was undetectable in 2. Median age at presentation was 42.7 (range, 33 to 58) years. The most common renal biopsy findings were mesangial expansion, mesangial nodules, tubular basement membrane thickening, and tubular atrophy. Kappa light chain was detected in all 7 renal biopsy results. Five patients were on dialysis before transplantation. LCDD recurred after a median of 33.3 (range, 2 to 45) months in 5 of the 7 patients. One patient remains on dialysis, whereas the other 4 have died. One patient died of progression of multiple myeloma 3 months after kidney transplantation without evidence of recurrence. Only 1 patient remains recurrence free after 13 years with normal renal allograft function. Conclusion: Although long-term benefits are occasionally seen, renal allograft survival is reduced significantly in LCDD patients. Kidney transplantation should not be an option for LCDD patients unless measures have been taken to reduce light chain production.

Most reports on the natural history, manifestations, and treatment of polycystic liver disease are based on the disease as it manifests in patients with autosomal dominant polycystic kidney disease (ADPKD). The purpose of this study was to develop a clinical profile of isolated autosomal dominant polycystic liver disease (ADPLD) using nonaffected family members as controls. The study included 146 probands, known affected relatives, and first-degree relatives of affected individuals. Participants underwent a formalized medical history interview and physical examination, ultrasonographic examination of the liver and kidneys, magnetic resonance angiography of the brain, and echocardiography. Thirty-eight of the 49 individuals diagnosed with polycystic liver disease before participation in the study were or had been symptomatic. Of 97 previously undiagnosed at-risk individuals, 23 were affected, 39 were unaffected, and 35 were indeterminate. Compared with patients with a negative or indeterminate diagnosis, those with polycystic liver disease had slightly higher levels of serum alkaline phosphatase and total bilirubin and lower levels of total cholesterol and triglycerides. Female patients had a significantly higher mean cyst score than male patients. The cysts were found to arise from the dilatation of biliary microhamartomas and from peribiliary glands. Structural mitral leaflet abnormalities were detected more frequently in affected than in indeterminate or nonaffected individuals. A vascular phenotype was detected in 5.6% of the patients with isolated ADPLD diagnosed clinically and/or by linkage analysis but in none of the unaffected patients. In conclusion, isolated ADPLD is underdiagnosed and genetically distinct from polycystic liver disease associated with ADPKD but with similar pathogenesis, manifestations, and management.

OBJECTIVE To describe 6 patients who developed progressive renal failure and renal thrombotic microangiopathy (TM) not accompanied by the characteristic hematologic disturbances of TM syndromes. Patients and Methods Portions of renal biopsy specimens from each patient were examined by light and electron microscopy for histopathologic evidence of TM. Antecedent clinical events, laboratory evidence of hemolysis and thrombocytopenia, and clinical outcome were documented. Medical records were reviewed and clinical data, including laboratory values, treatment, and outcome, were recorded. Results In each case, a slowly progressive uremia evolved after radiation and/or chemotherapy without laboratory evidence of acute hemolysis or thrombocytopenia. Renal biopsy specimens in all cases showed TM and tubulointerstitial scarring, suggesting both acute and chronic renal injury. Two of the 6 patients underwent plasma exchange therapy without improvement of renal function. Three patients treated with angiotensin-converting enzyme inhibitors for coexisting systemic hypertension remained stable or had mild improvement in renal function. Conclusions A small subset of patients treated for malignancy developed slowly evolving uremia associated with renal TM without marked hematologic abnormalities. In the absence of thrombocytopenia and other typical laboratory findings, the diagnosis of renal TM may be overlooked.