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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.

Cytogenetic studies of mesenchymal chondrosarcoma are few and to date, no specific or recurrent aberrations have been found. In this investigation, the cytogenetic and molecular cytogenetic (spectral karyotypic and fluorescence in situ hybridization) findings for two mesenchymal chondrosarcomas, one arising skeletally and the other extraskeletally, are reported. An identical Robertsonian translocation involving chromosomes 13 and 21 [der(13;21)(q10;q10)] was detected in both cases, possibly representing a characteristic rearrangement for this histopathologic entity. Both cases also exhibited loss of all or a portion of chromosomes 8 and 20 and gain of all or a portion of chromosome 12. The observation of similar chromosomal abnormalities in both skeletal and extraskeletal mesenchymal chondrosarcoma supports a genetic as well as histopathologic relationship between these anatomically distinct neoplasms.

Giant cell reparative granuloma (GCRG) is an unusual, benign bone lesion that most commonly affects the maxilla and mandible; skull involvement is rare. The etiology is uncertain but may be related to trauma. GCRG is difficult to distinguish from giant cell tumor of the bone and has a lower recurrence rate. Thirteen reports of temporal bone GCRG in 11 patients have been reported. One report of a petrous GCRG in a 3-year-old girl has been identified. A 38-year-old male presented with a 2-year history of fullness in his left ear, ipsilateral hearing loss, and intermittent cacosmia. Computed tomography and magnetic resonance imaging revealed a large left-sided anterior temporal extradural mass. The patient underwent a left frontotemporal craniotomy and resection of a left temporal fossa tumor that involved the petrous and squamous parts of the temporal bone. The patient's post-operative course was uneventful, except for increased hearing loss secondary to opening of the epitympanum. Follow-up at one month revealed no other problems. Histopathology of the specimen was consistent with a giant cell reparative granuloma.

Ewing's sarcoma, a highly malignant neoplasm, is characterized by an 11;22 translocation [t(11;22) (q24;q12)], resulting in the fusion of genes FLII and EWS. Adamantinoma of extragnathic bones, a low-grade malignant neoplasm with epithelial features, is not typically considered in the differential diagnosis of Ewing's sarcoma. In this study, three osseous Ewing's sarcomas with histological, immunohistochemical, or ultrastructural epithelial features were subjected to reverse transcription-polymerase chain reaction and sequencing studies for the Ewing's sarcoma molecular rearrangement. (Two of the three cases were originally described as adamantinomas or nontypical Ewing's sarcoma before the availability of genetic characterization.) In addition, traditional cytogenetic analysis and a unique combined interphase molecular cytogenetic/ immunocytochemical approach with bicolor 11;22 translocation breakpoint flanking probes (cosmids) and pancytokeratin antibodies were performed on one neoplasm. At(11;22) (q24;q12) was found in one neoplasm and a type II EWS/FLI-1 fusion transcript was detected in all three neoplasms. The combined genetic/immunocytochemical approach revealed the presence of the 11 ;22 translocation in the nuclei of cytokeratin immunoreactive cells. These genotypic and phenotypic findings delineate a novel Ewing's sarcoma histologic variant, "adamantinoma-like Ewing's sarcoma."

Acute interstitial nephritis (AIN) is an important cause of acute kidney injury, especially in hospitalized patients. The cause and outcome of AIN, particularly that due to drugs, is changing with prevalent medication use. The effectiveness of steroids for treatment of AIN is debated.Case series.133 patients with biopsy-proven AIN from 1993 through 2011 at a single center.Recovery of kidney function by 6 months, either complete, partial, or none. Complete recovery was defined as improvement in serum creatinine level to within 25% of baseline (or1.4 mg/dL), and partial recovery, as a ≥ 50% decrease in serum creatinine level from its peak value but not reaching within 25% of its baseline value.Causes of AIN included drugs (70%), autoimmune diseases (20%), and infections (4%). Drug-induced AIN was due to antibiotics in 49%, proton pump inhibitors (PPIs) in 14%, and nonsteroidal anti-inflammatory drugs (NSAIDs) in 11%. Overall, the top 3 drug causes were omeprazole (12%), amoxicillin (8%), and ciprofloxacin (8%). Patients with drug-induced compared to non-drug-induced AIN were older and had higher baseline kidney function, but more severe acute kidney injury. Patients with PPI-induced AIN were older, were less symptomatic, and had longer durations of drug exposure and longer delays in getting kidney biopsy and steroids than for antibiotic-induced or NSAID-induced AIN. At 6 months postbiopsy, 49% of patients with drug-induced AIN treated with steroids achieved complete recovery; 39%, partial recovery; and 12%, no recovery. Correlates of poor recovery included a longer duration of drug exposure (15 vs 30 vs 130 days for complete, partial, and no recovery, respectively; P = 0.04) and longer delay in starting steroid therapy (8 vs 11 vs 35 days, respectively; P = 0.05).Retrospective study, selection bias in patients who had kidney biopsy, single-center experience.The cause of AIN may be shifting; PPIs are emerging as an important contributor to this disease. Delays in discontinuation of the culprit drug and in initiating steroid treatment adversely affect recovery of kidney function.

Thrombotic thrombocytopenic purpura (TTP), hemolytic uremic syndrome (HUS), and scleroderma renal crisis (SRC) all present with features of thrombotic microangiopathy. Distinguishing among these entities is critical, however, as treatments differ and may be mutually exclusive. We describe the case of a 25-year-old woman with an undefined mixed connective tissue disease who presented 6 weeks post-partum with fever, transient aphasia, thrombocytopenia, hemolytic anemia, and acute kidney injury eventually requiring initiation of hemodialysis. Renal biopsy revealed thrombotic microangiopathy. Renal function did not improve despite immediate initiation of plasma exchange, and an angiotensin-converting enzyme (ACE) inhibitor was initiated following discontinuation of plasma exchange. At last follow up, she remained dialysis dependent. Due to the myriad causes of thrombotic microangiopathy and potential for diagnostic uncertainty, the patient’s response to therapy should be closely monitored and used to guide modification of therapy.

Little is known about the rare entities of heavy- and light-chain amyloidosis (AHL) and heavy-chain amyloidosis (AH). Here, we report the renal and hematological characteristics, pathology, and outcome of 16 patients with renal AH/AHL (5 with AH and 11 with AHL) and compare them with 202 patients with renal light-chain amyloidosis (AL) diagnosed during the same time period. All cases were diagnosed by kidney biopsy that showed Congo red–positive deposits. Amyloid typing was done by laser microdissection and mass spectrometry (LMD/MS) on 12 patients or by immunofluorescence on four patients. All patients with renal AH/AHL were Caucasians, with a male/female ratio of 2.2 and a median age at biopsy of 63 years. Compared with patients with renal AL, those with renal AH/AHL had less frequent concurrent cardiac involvement, higher likelihood of having circulating complete monoclonal immunoglobulin, lower sensitivity of fat pad biopsy and bone marrow biopsy for detecting amyloid, higher incidence of hematuria, and better patient survival. The hematological response to chemotherapy was comparable with renal AL. In 42% of patients, AH/AHL could not have been diagnosed without LMD/MS. Thus, renal AH/AHL is an uncommon and underrecognized form of amyloidosis, and its diagnosis is greatly enhanced by the use of LMD/MS for amyloid typing. The accurate histological diagnosis of renal AH/AHL and distinction from AL may have important clinical and prognostic implications.

IgG4-related disease (IgG4-RD) is a systemic immune-mediated disease that typically manifests as fibro-inflammatory masses that can affect nearly any organ system. Renal involvement by IgG4-RD usually takes the form of IgG4-related tubulointerstitial nephritis, but cases of membranous glomerulonephritis (MGN) have also been described. Here we present a series of 9 patients (mean age at diagnosis 58 years) with MGN associated with IgG4-RD. All patients showed MGN on biopsy, presented with proteinuria (mean 8.3 g/day), and most had elevated serum creatinine (mean 2.2 mg/dl). Seven patients had known extrarenal involvement by IgG4-RD, with 5 patients having concurrent IgG4-related tubulointerstitial nephritis. Immunohistochemical analysis for the phospholipase A2 receptor, a marker of primary MGN, was negative in all 8 biopsies so examined. Six of 7 patients with available follow-up (mean 39 months) were treated with immunosuppressive agents; one untreated patient developed end-stage renal disease and underwent transplantation, without recurrence at 12 years after transplant. All 6 treated patients showed decreased proteinuria (mean 1.2 g/day), and most showed decreased serum creatinine (mean 1.4 mg/dl). Thus, MGN should be included in the spectrum of IgG4-RD and should be suspected in proteinuric IgG4-RD patients. Conversely, patients with MGN and an appropriate clinical history should be evaluated for IgG4-RD.

Accurate diagnosis and typing of renal amyloidosis is critical for prognosis, genetic counseling, and treatment. Laser microdissection and mass spectrometry are emerging techniques for the analysis and diagnosis of many renal diseases. Here we present the results of laser microdissection and mass spectrometry performed on 127 cases of renal amyloidosis during 2008–2010. We found the following proteins in the amyloid deposits: immunoglobulin light and heavy chains, secondary reactive serum amyloid A protein, leukocyte cell–derived chemotaxin-2, fibrinogen-α chain, transthyretin, apolipoprotein A-I and A-IV, gelsolin, and β-2 microglobulin. Thus, laser microdissection of affected areas within the kidney followed by mass spectrometry provides a direct test of the composition of the deposit and forms a useful ancillary technique for the accurate diagnosis and typing of renal amyloidosis in a single procedure.

We assessed the earliest manifestations of recurrent membranous glomerulonephritis (MGN) in renal allografts. Clinical, laboratory and pathologic data were reviewed in 21 patients at the initial biopsy within 4 months post-transplant with evidence of MGN and on follow-up biopsies, compared to a biopsy control group of eight transplants without recurrent MGN. The mean time of first biopsy with pathologic changes was 2.7 months. In each earliest biopsy, immunofluorescence (IF) showed granular glomerular basement membrane (GBM) staining for C4d, IgG, kappa and lambda. IF for C3 was negative or showed trace staining in 16/21. On each MGN biopsy positive by IF, 14/19 showed absence of deposits or rare tiny subepithelial deposits by electron microscopy (EM). At the earliest biopsy, the mean proteinuria was 1.1 g/day; 16 patients had1 g/day proteinuria. Follow-up was available in all patients (mean 35 months posttransplant). A total of 13 patients developed1 g/day proteinuria; 12 were treated with: rituximab (n = 8), ACEI and increased prednisone dose (n = 2), ACEI or ARB only (n = 2). All patients showed reduction in proteinuria after treatment. A total of 11/16 patients showed progression of disease by EM on follow-up biopsy. Recognition of early allograft biopsy features aids in diagnosis of recurrent MGN before patients develop significant proteinuria.

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.

Summary Background and objectives To better define the clinical-pathologic spectrum and prognosis of monoclonal immunoglobulin deposition disease (MIDD), this study reports the largest series. Design, setting, participants, & measurements Characteristics of 64 MIDD patients who were seen at Mayo Clinic are provided. Results Of 64 patients with MIDD, 51 had light chain deposition disease, 7 had heavy chain deposition disease, and6hadlightandheavychaindepositiondisease.Themeanageatdiagnosiswas56years,and23patients(36%) were #50 years of age. Clinical evidence of dysproteinemia was present in 62 patients (97%), including multiple myeloma in 38 (59%). M-spike was detected on serum protein electrophoresis in 47 (73%). Serum free light chain ratio was abnormal in all 51 patients tested. Presentation included renal insufficiency, proteinuria, hematuria, and hypertension. Nodular mesangial sclerosis was seen in 39 patients (61%). During a median of 25 months of follow-up(range,1–140)in 56patients,32 (57%) hadstable/improvedrenal function,2(4%)had worsening renal function, and 22 (39%) progressed to ESRD. The mean renal and patient survivals were 64 and 90 months, respectively. The disease recurred in three of four patients who received a kidney transplant. Conclusions Patients with MIDD generally present at a younger age than those with light chain amyloidosis or light chain cast nephropathy. Serum free light chain ratio is abnormal in all MIDD patients, whereas only threequarters have abnormal serum protein electrophoresis. The prognosis for MIDD is improving compared with historical controls, likely reflecting earlier detection and improved therapies. Clin J Am Soc Nephrol 7: 231–239, 2012. doi: 10.2215/CJN.08640811

We report four cases of de novo amyloidosis occurring after 16, 18, 28 and 31 years following kidney transplantation. These patients presented with proteinuria and progressive allograft dysfunction. Kidney biopsy showed AL amyloidosis in all compartments of the allograft kidney. Serum immunofixation studies revealed monoclonal lambda light chains in all four cases. Bone marrow examination showed 10% plasma cells in one case, 5-10% in two cases and less than 5% in one case. Two patients died unexpectedly within 3 months and 1 year of the diagnosis of allograft AL amyloidosis. Of the remaining two, one underwent autologous stem cell transplant that resulted in complete hematologic remission. However, the patient relapsed within 2 years and also developed progressive kidney allograft failure. The patient received a second autologous stem cell transplant with complete hematologic response, followed by a second kidney transplant, which showed no evidence of amyloid at 1-year posttransplant. The remaining case was treated with prednisone and bortezomib, which has stabilized kidney function in the short term. In conclusion, this study shows that AL amyloidosis is an uncommon but important cause of late onset proteinuria in the kidney allograft that results in kidney allograft failure.

The long-term survival of persons with Down syndrome has dramatically increased over the past 50 years. There are no studies addressing the spectrum of glomerular lesions in these patients. We reviewed the clinical-pathologic characteristics of 17 patients with Down syndrome who underwent renal biopsy. The cohort consisted of 12 whites and 5 African Americans with mean age of 29 years (range, 6-45 years). History of hypothyroidism was present in 8 patients. Renal presentations included renal insufficiency (15 patients, mean serum creatinine 3.4 mg/dL), proteinuria (all patients, including 3 with nephrotic syndrome, mean 24-hour urine protein 4.2 g), and hematuria (14 patients, including 4 with gross hematuria). The glomerular diseases found on biopsy were IgA nephropathy (n = 5 patients), focal segmental glomerulosclerosis (n = 4), membranoproliferative glomerulonephritis (n = 2), acute postinfectious glomerulonephritis (n = 2), pauci-immune crescentic glomerulonephritis (n = 2), membranous glomerulonephritis (n = 1), and lupus nephritis (n = 1). Follow-up (mean, 47 months; range, 2-141 months) was available on 16 patients (94%). Two patients (1 with membranous glomerulonephritis and 1 with acute postinfectious glomerulonephritis) had complete remission; 8 patients (4 with IgA nephropathy, 2 with focal segmental glomerulosclerosis, 1 with lupus nephritis, and 1 with acute postinfectious glomerulonephritis) had chronic kidney disease; and 6 patients (2 with pauci-immune crescentic glomerulonephritis, 2 with membranoproliferative glomerulonephritis, 1 with IgA nephropathy, and 1 with focal segmental glomerulosclerosis) progressed to end-stage renal disease, 4 of whom died. In summary, a wide spectrum of glomerular diseases can be seen in patients with Down syndrome, with IgA nephropathy and focal segmental glomerulosclerosis being the most common. Renal biopsy is necessary to determine the type of glomerular lesion and appropriate treatment.

Postinfectious glomerulonephritis (PIGN) is primarily a childhood disease that occurs after an upper respiratory tract infection or impetigo; its occurrence in older patients is not well characterized. Here, we report 109 cases of PIGN in patients ≥65 years old diagnosed by renal biopsy. The male to female ratio was 2.8:1. An immunocompromised background was present in 61%, most commonly diabetes or malignancy. The most common site of infection was skin, followed by pneumonia and urinary tract infection. The most common causative agent was staphylococcus (46%) followed by streptococcus (16%) and unusual gram-negative organisms. Hypocomplementemia was present in 72%. The mean peak serum creatinine was 5.1 mg/dl, and 46% of patients required acute dialysis. The most common light microscopic patterns were diffuse (53%), focal (28%), and mesangial (13%) proliferative glomerulonephritis. IgA-dominant PIGN occurred in 17%. Of the 72 patients with ≥3 months of follow-up (mean, 29 months), 22% achieved complete recovery, 44% had persistent renal dysfunction, and 33% progressed to ESRD. The presence of diabetes, higher creatinine at biopsy, dialysis at presentation, the presence of diabetic glomerulosclerosis, and greater tubular atrophy and interstitial fibrosis predicted ESRD. In summary, the epidemiology of PIGN is shifting as the population ages. Older men and patients with diabetes or malignancy are particularly at risk, and the sites of infection and causative organisms differ from the typical childhood disease. Prognosis for these older patients is poor, with fewer than 25% recovering full renal function.

Background 2,8-dihydroxyadeninuria (DHA) disease (also called 2,8 dihydroxyadeninuria) is a rare autosomal recessive disorder caused by complete adenine phosphoribosyltransferase deficiency and typically manifests as recurrent nephrolithiasis. Only rare cases of DHA nephrolithiasis have been reported from the USA. Herein, we report three American patients who developed DHA crystalline nephropathy leading to end-stage renal disease (ESRD) with recurrence in the allograft. Methods Three cases of DHA crystalline nephropathy were identified from the Renal Pathology Laboratory of Mayo Clinic. Detailed clinical and pathologic descriptions are provided. Results All three patients were Caucasian adults with no history of obstructive nephropathy. Two patients had no history of nephrolithiasis and one had a single episode of stones 36 years prior to presentation. All patients presented with severe renal failure with a mean serum creatinine of 7.5 mg/dl. Renal biopsies revealed numerous tubular and interstitial brown DHA crystals, tubular degenerative changes and moderate to marked tubulointerstitial scarring. Two patients were initially misdiagnosed, one as primary hyperoxaluria and the other as chronic interstitial nephritis. All three patients progressed to ESRD, within 1 month following renal biopsy in two and after 9 months in one. All three patients underwent renal transplantation with early disease recurrence in three allografts in two patients. Conclusions DHA disease is an under-recognized condition that can lead to irreversible renal failure and frequently recurs in the transplant. It should be included in the differential diagnosis of crystalline nephropathy, even in the absence of history of nephrolithiasis.

Increasing numbers of patients receive kidney transplants before initiation of dialysis or shortly thereafter. Some of these patients have significant proteinuria pre-transplant making the interpretation of post-transplant proteinuria problematic. In this study, we evaluated post-transplant proteinuria in 115 patients who had urine protein measured within 3 months of transplant and assessed the association of proteinuria with allograft pathology. Proteinuria declined rapidly from 3650 +/- 3702 mg/day pre-transplant to 550 + 918 at 3 weeks (p0.0001) and continued to decline until 1 year post-transplant (472 +/- 1116, p0.0001 vs. 3 weeks). Proteinuria greater than 3000 mg/day was present in 48 patients (42%) pre-transplant, in 1 patient (1%) at 3 weeks and in 4 patients (4%) at 1 year. Surveillance graft biopsies were done at 1 year in 93% of patients. Proteinuriaor = 1500 mg/day and/or an absolute increase in proteinuria500 mg/day after 3 weeks post-transplant was associated with allograft glomerular pathology. In conclusion, pre-transplant proteinuria, even when high grade, declines rapidly after transplantation. Failure to decline or persistence of proteinuria greater than 1500 mg/day is indicative of allograft pathology.

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.

Carcinoid tumors have been described in almost every organ and may affect virtually every body system. Cardiac involvement manifesting as right-sided valvular disease is characteristic of the carcinoid syndrome; however, direct myocardial involvement is unusual. We present a case of an invasive carcinoid tumor whose primary manifestation was myocardial invasion.

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 variety of tumors may arise in the kidneys, which vary widely in clinical significance. In adults, the most common form of malignant renal tumor is the adenocarcinoma, which arises from tubular epithelium. In part because the kidneys are located in the retroperitoneum, renal cell adenocarcinomas are characterized by a lack of early clinical warning signs; a substantial proportion of patients with renal cancer present with disseminated metastases. At present, surgical removal of renal cell adenocarcinomas is the only effective means of curing the disease, as these tumors are resistant to standard chemotherapy and radiation therapy. A potential role for immunotherapy in treating advanced renal cell cancer is being evaluated. Increased utilization of radiologic imaging techniques has led to the identification of small renal lesions in asymptomatic patients. Early detection of renal tumors has prompted the development of objective criteria for the classification of renal tumors of low and high metastatic potential and the establishment of uniformly accepted pathologic features of prognostic significance. Studies of patients with inherited predisposition to developing renal cell cancer have greatly contributed to our understanding of the pathogenesis of renal cell carcinoma. Inherited mutations in different genes predispose to the development of histologically distinct types of renal cancer. These studies provide support for the inclusion of genetic alterations in the histopathologic classification of renal tumors..

Objectives. To our knowledge, the chronic histopathologic effects of radiofrequency ablation (RFA) of renal parenchyma have not been extensively documented. In this study, we report the light and electron microscopic features of renal RFA in acute and chronic porcine models. Methods. Eleven animals underwent renal RFA of the lower pole kidney bilaterally. RFA was performed laparoscopically in 6 acute animals and percutaneously in 5 chronic animals. Acute animals were killed immediately following surgery. One chronic animal each was killed on postoperative day 3, 7, 14, 30, and 90. Histopathologic evaluation of all renal tissue specimens was carried out with light and electron microscopy. Results. Acutely, the renal radiolesion appeared as a yellowish white, well-circumscribed, necrotic area on gross examination, with evidence of extensive coagulative necrosis and marked inflammation on microscopic examination. From day 1 through 90, light and electron microscopy revealed evidence of progressive, irreversible cell death and necrosis with diminishing inflammatory response in the glomeruli, tubules, and renal interstitium. RFA lesions underwent gradual spontaneous resorption of the necrotic area with ultimate autoamputation. Conclusions. RFA results in necrosis of the ablated renal parenchyma.

Background. We present a case report of thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS) developing in a kidney/pancreas transplant recipient after the initiation of treatment with clopidogrel for symptomatic coronary artery disease. Methods. A 35-year-old male kidney/pancreas recipient developed unstable angina 5 years after transplantation. The patient was treated with clopidogrel as adjunct therapy. A TTP/HUS condition developed, was diagnosed early, and successfully reversed with the implementation of plasmapheresis and cessation of clopidogrel and cyclosporine A. Results. The patient continues taking cyclosporine A with good renal function 6 months after the incident, and successfully underwent coronary artery by-pass grafting 3 months after the event. Discussion. This case demonstrates that early identification and treatment can reverse the TTP/HUS process associated with thienopyridine-derived agents. We strongly recommend that drugs of the thienopyridine class be used cautiously in transplant recipients, especially those taking calcineurin-inhibitors.

Objectives. The chronic effects of renal radiofrequency ablation are unknown. Herein, we investigate the anatomic and physiologic sequelae of laparoscopic and percutaneous renal radiofrequency ablation in acute and chronic porcine models. Methods. Our study comprised two phases—an acute phase and a chronic phase. In the acute phase, bilateral laparoscopic renal radiofrequency ablation was performed in 6 animals (12 renal units), which were euthanized immediately after surgery. In the chronic study, bilateral percutaneous renal radiofrequency ablation was performed in 5 animals (10 renal units). One animal each was euthanized at postoperative day 3, 7, 14, 30, and 90. Results. Ultrasound-monitored laparoscopic (n = 12) and percutaneous (n = 10) radiofrequency ablations of the lower pole of the kidney were technically successful in each instance. No intraoperative complications occurred. In the survival experiments, the radiolesions showed gradual spontaneous resorption and ultimate renal autoamputation, while maintaining pelvocalyceal integrity as confirmed by ex vivo retrograde ureteropyelogram. Serum creatinine and hematocrit remained stable in all survival animals. Postoperative complication occurred in 1 chronic animal with nonobstructive small bowel dilation at autopsy. Conclusions. Laparoscopic and percutaneous renal radiofrequency ablation are technically feasible. The anatomic and physiologic sequelae of renal radiosurgery are favorable. Improved techniques of real-time monitoring of the evolving renal radiolesion are necessary.

Cytogenetic studies of epithelioid sarcoma, a rare malignant soft tissue neoplasm of adolescents and young adults, are few. A characteristic anomaly has not yet been identified for this sarcoma. In this study, cytogenetic studies of a primary epithelioid sarcoma of a 15-year-old male revealed the following abnormalities: t(6;8)(p25;q11.2) and add(7)(p15).

Pulmonary chondrosarcoma is a rarely encountered primary tumor of the lung. We present a case with computed tomography and magnetic resonance imaging features mimicking a bronchogenic cyst.

Abstract 3992 Little is known about the rare entities of heavy and light chain amyloidosis (AHL) and heavy chain amyloidosis (AH). In this study, we report the renal and hematologic characteristics, pathology, and outcome of 17 patients with renal AH/AHL including 5 with AH (4 IgG and 1 IgA) and 12 with AHL (7 IgGλ, 3 IgAκ, 1 IgAλ, and 1 IgMλ), and compare them with 202 patients with renal AL amyloidosis (AL) diagnosed during the same time period. All cases were diagnosed by kidney biopsy that showed Congo red-positive deposits. Amyloid typing was done by laser microdissection and mass spectrometry (LMD/MS) (12 patients) or by immunofluorescence (5 patients). All patients with renal AH/AHL were Caucasians, with a M:F ratio of 2.4 and a median age at biopsy of 63 years. Compared with patients with renal AL, those with renal AH/AHL had less frequent concurrent cardiac involvement, higher likelihood of having circulating complete monoclonal Ig, lower sensitivity of fat pad biopsy and bone marrow biopsy for detecting amyloid, higher incidence of hematuria, and better patient survival. The hematologic and renal responses to chemotherapy were comparable to renal AL. In 42% of patients, AH/AHL could not have been diagnosed without LMD/MS. In conclusion, renal AH/AHL is an uncommon but under-recognized form of amyloidosis, and its diagnosis is greatly enhanced by the use of LMD/MS for amyloid typing. The accurate histological diagnosis of renal AH/AHL and distinction from AL may have important clinical and prognostic implications. Table 1. Demographics and hematologic characteristics AH/AHL AL p value No. of patients 17 202 Gender: Male/female 12/5 (71%/29%) 126/76 (62%/38%) 0.61 Age, median (range) 63 (50–77) 62 (36–86) 0.73 Additional organ involvement 8 (47%) 126 (62%) 0.3 Cardiac involvement 3 (18%) 100 (50%) 0.01* % of plasma cells in bone marrow, median (IQR) 8 (5–15) 6 (5–10) 0.82 ≥30 plasma cells 4 (24%) 11/198 (6%) 0.02* Positive SPEP/SIF for paraprotein 15 (88%) 158/200 (79%) 0.53 Presence of whole monoclonal protein on SPEP 14 (82%) 108/200 (54%) 0.04* Positive UPEP/UIF for paraprotein 13/16 (81%) 158/189 (84%) 0.73 Presence of whole monoclonal protein on UPEP 10/16 (63%) 61/189 (32%) 0.03* Abnormal serum FLC ratio (1.65) 9/12 (75%) 150/188 (80%) 0.71 Markedly abnormal FLC ratio (< 0.125 or > 8) 5/12 (42%) 100/188 (53%) 0.55 Positive bone marrow for amyloid 6/16 (38%) 135/183 (74%) 0.004* Positive fat pad biopsy for amyloid 2/14 (14%) 105/145 (72%) Table 2. Renal characteristics at kidney biopsy AH/AHL AL p value No. of patients 17 202 24h urine protein in g, median (IQR) 5.1 (3.2–9.0) 6.0 (3.2–10.0) 0.9 Full nephrotic syndrome 9/16 (56%) 132/197 (67%) 0.42 Serum albumin in g/dl, median (IQR) 2.7 (2.2–3.3) 2.5 (1.9–2.9) 0.29 % albuminuria on UPEP, median (IQR) 68 (61–72) 70 (60–76) 0.47 Serum creatinine in mg/dl, median (IQR) 1.4 (1.1–2.1) 1.2 (0.9–1.8) 0.25 Serum creatinine >1.2 mg/dl 10/16 (63%) 92/201 (46%) 0.3 eGFR, median (IQR) 47 (27–67) 58 (36–75) 0.29 Decreased eGFR 10/16 (63%) 103/201 (51%) 0.44 Microscopic hematuria 9/16 (56%) 44/169 (26%) 0.02* IQR, interquartile range. Disclosures: No relevant conflicts of interest to declare.

Myeloproliferative neoplasms are clonal hematopoietic stem cell disorders that can produce an undefined glomerulopathy. To better characterize the glomerular disease associated with myeloproliferative neoplasms, we evaluated features of 11 patients with myeloproliferative neoplasm-related glomerulopathy that included 8 patients with primary myelofibrosis, and 1 each with chronic myelogenous leukemia, polycythemia vera, and essential thrombocythemia. Indications for biopsy were nephrotic-range proteinuria (nephrotic syndrome in four) and chronic renal insufficiency. The mean time from diagnosis of the neoplasms to biopsy was 7.2 years. Histologically, mesangial sclerosis and hypercellularity were seen in all 11 cases, segmental sclerosis in 8, features of chronic thrombotic microangiopathy in 9, and intracapillary hematopoietic cells in 4. On follow-up, seven patients had persistent renal dysfunction and four progressed to end-stage renal disease (ESRD). Thus, glomerulopathy appears to be a late complication of myeloproliferative neoplasms, particularly primary myelofibrosis, with guarded prognosis. Greater awareness of this entity and larger studies are needed to define possible therapies.