Diabetic kidney disease develops in approximately 40% of patients who are diabetic and is the leading cause of CKD worldwide. Although ESRD may be the most recognizable consequence of diabetic kidney ...disease, the majority of patients actually die from cardiovascular diseases and infections before needing kidney replacement therapy. The natural history of diabetic kidney disease includes glomerular hyperfiltration, progressive albuminuria, declining GFR, and ultimately, ESRD. Metabolic changes associated with diabetes lead to glomerular hypertrophy, glomerulosclerosis, and tubulointerstitial inflammation and fibrosis. Despite current therapies, there is large residual risk of diabetic kidney disease onset and progression. Therefore, widespread innovation is urgently needed to improve health outcomes for patients with diabetic kidney disease. Achieving this goal will require characterization of new biomarkers, designing clinical trials that evaluate clinically pertinent end points, and development of therapeutic agents targeting kidney-specific disease mechanisms (
, glomerular hyperfiltration, inflammation, and fibrosis). Additionally, greater attention to dissemination and implementation of best practices is needed in both clinical and community settings.
Excretion of monoclonal free light chains (MFLC) beyond the renal threshold can cause kidney injury, but evidence for polyclonal free light chains (PFLC)-mediated injury is limited. We aimed to study ...the degree of PFLC deposition in the proximal tubules of chronic kidney disease (CKD) and hypothesized that excess deposition may contribute to tubular injury.
In this retrospective study, immunohistochemical staining to assess the degree of FLC deposition, periodic acid-Schiff staining for the degree of tubular brush border injury and trichrome staining for interstitial fibrosis were evaluated. Normal renal parenchyma from tumor nephrectomy specimens (control group I, n = 39), minimal change disease controls (group II, n = 13), renal biopsies from CKD and proteinuria (polyclonal study group III, n = 33) and monoclonal light chain nephropathy (group IV, n = 37) were studied. The results of the study including serum creatinine were compared between groups.
Both polyclonal and monoclonal groups (groups III and IV) had significantly higher light chain deposition and brush border injury by periodic acid-Schiff scores compared to control groups (groups I and II). When the first three polyclonal groups (groups I-III) were analyzed together, polyclonal light chain deposition was significantly correlated with serum creatinine levels, brush border injury and interstitial fibrosis.
The results of our study suggest that in CKD patients with proteinuria, excess PFLC deposition in the proximal tubules may cause acute tubular injury akin to monoclonal gammopathy and lead to renal chronicity.
A rat model of antineutrophil cytoplasmic antibody (ANCA) associated vasculitides reveals crescentic glomerulonephritis as seen in human renal biopsies and diffuse lung hemorrhage that is not well ...documented in human lung biopsies. A 64-year-old male, with shortness of breath and mild elevation of serum creatinine, was found to have a positive serum test for ANCA, but negative antiglomerular basement membrane antibody. A renal biopsy showed pauci-immune type of crescentic glomerulonephritis and focal arteritis. The prior lung wedge biopsy was retrospectively reviewed to show diffuse hemorrhage and hemosiderosis with focal giant cells. In addition, small arteries revealed subtle neutrophil aggregation, and margination along vascular endothelium, but no definitive vasculitis. The pathology of ANCA associated vasculitides results from activated neutrophils by ANCA and subsequent activation of the alternative complement cascade with endothelial injury, neutrophil aggregation and margination. Our findings, after the correlation between lung biopsy and renal biopsy, imply that the top differential diagnosis in the lung biopsy should be microscopic polyangiitis when diffuse pulmonary hemorrhage and hemosiderosis are present in this ANCA-positive patient.
CD23 and FMC-7 are normal B-cell antigens used during diagnostic immunophenotyping of suspected lymphoproliferative disorders, but the diagnostic usefulness of antigenic expression patterns of ...simultaneous 2-color staining and flow cytometric analysis has not been reported. We evaluated the FMC-7 and CD23 expression pattern in 201 cases of B-cell lymphoma from tissue biopsy specimens by multiparameter flow cytometry. The CD23-/FMC-7+ pattern was the most common pattern in large cell, mantle cell, and marginal zone lymphomas. The CD23 and FMC-7 antigen, along with the CD5 coexpression pattern, permitted accurate classification of all 71 cases of small lymphocytic, mantle cell, and marginal zone types of lymphoma. The widest variation of patterns was with follicular cell lymphoma, although most cases expressed the CD23 +/-/FMC-7+ pattern (+/-, partial or minor subset expression). The CD23 and FMC-7 antigen expression pattern was predictive of subtypes in more than 95% of lymphoma cases and could narrow the differential diagnosis in the remaining cases. We conclude the flow cytometric CD23/FMC-7 expression pattern achieved by dual staining facilitates accurate and reproducible classification of B-cell lymphomas and has diagnostic usefulness.
BK virus infection is a significant threat to renal transplant outcome. Detecting viral infection in renal transplant biopsies using SV40 staining is less than ideal. SV40 antibody reacts with the ...large T-antigen of BK virus only at the early phases of infection and can miss cells in later stages of infection. As p53 is upregulated during both early and late phases of infection, this study set out to determine whether p53 staining could improve detection of BK virus infection in renal transplant patients. The control group consisted of 16 renal allograft biopsies without histologic evidence of BK virus infection, while the BK group consisted of 15 renal allograft biopsies with histologic evidence of BK virus infection. The biopsies from both groups were immunohistochemically stained with both SV40 and p53 antibodies. Dual staining with both markers was also performed to identify their nuclear co-localization. In the BK group, the percent of p53 staining (16.6 ± 4.8 %) was significantly higher than the percent of SV40 staining (5.4 ± 2.7%). BK virus infected cells revealed a unique p53 immunostaining pattern (strong nuclear staining with a central halo). Co-localization of SV40 and p53 was identified in cells that had characteristic nuclear features of BK virus infection by histology. The sensitivity and specificity for using p53 staining to identify BK infected cells was 92% and 86 %, respectively. In conclusion, p53 staining detects a higher percentage of BK virus infected cells than SV40 staining alone. Thus, for diagnosis of BK virus infection in renal allograft biopsies, p53 staining is a sensitive and specific method when used along with SV40 staining.
Background: A minority of patients (30–40%) with advanced non-small cell lung cancer (NSCLC) have objective responses to chemotherapy. Therefore, defining molecular features that determine resistance ...or response to chemotherapy would have important implications in this disease. Several studies have suggested that patients whose tumors have neuroendocrine features may be more responsive to chemotherapy. In addition, increased expression of p53 may play a role in chemotherapy resistance in patients with NSCLC.
Methods: The objective of this study was to analyze retrospectively, the correlation between marker expression and response to chemotherapy and survival using immunohistochemistry for neuroendocrine markers and p53. Ninety patients with unresectable stage III or IV NSCLC, treated with platinum based combination chemotherapy were evaluated. The pathological specimens were obtained prior to chemotherapy.
Results: There was no statistically significant correlation between any individual marker and response to chemotherapy. However, patients with tumors with increased expression of p53 were more likely to have progressive disease following chemotherapy (
P=0.02). Similarly, patients with tumors lacking neuroendocrine expression and with increased expression of p53 were more likely to have progressive disease when compared to patients with tumors with normal p53 expression and neuroendocrine differentiation (
P=0.03). Normal expression of p53 along with the presence of neuroendocrine differentiation was a favorable factor for both survival (
P=0.05) and time to disease progression (
P=0.04) in the multivariate analysis.
Conclusion: The presence of neuroendocrine markers alone was not predictive of response to chemotherapy and did not impact on the survival of this group of patients with advanced stage NSCLC. The normal expression of p53 together with neuroendocrine differentiation seems to impact favorably on overall survival time and time to disease progression without significant improvement in response to chemotherapy.
CD133 has recently been characterized as a progenitor cell marker in the kidney. However, the expression of this marker has not been thoroughly investigated in kidney injury and variants of renal ...tumors for pathology practice. We quantified CD133 expression in kidney biopsies from patients with acute renal failure and compared staining intensity with serum creatinine levels. CD133 expression levels were also evaluated in several subtypes of renal neoplasms. Normal adult renal parenchyma showed CD133 expression in parietal epithelium and in less than 5% of the epithelial cells in proximal and distal nephron tubules. However, CD133 was diffusely upregulated in the injured proximal and distal tubular epithelium and the CD133 expression scores in renal tubules were significantly correlated with serum creatinine levels. Amongst the renal tumors, CD133 was diffusely expressed in clear cell papillary renal cell carcinoma but was only focally present in other types of renal tumors. In summary, CD133 is a useful marker to detect renal tubular injury and to differentiate clear cell papillary renal cell carcinoma from other tumor types.
Benign fetal rhabdomyoma is a tumor of striated muscle origin that rarely is seen in the extremities. Because of the similarities of fetal rhabdomyoma to its malignant counterpart, rhabdomyosarcoma, ...an important distinction is to be made to avoid errors in treatment. The clinical presentation, radiographic, and pathologic features of the first known case of an isolated upper extremity rhabdomyoma are described. The authors discuss, the distinction between this and rhabdomyosarcoma and also describe a unique histologic feature in rhabdomyoma, the presence of psammoma bodies.
Lymphoma presenting as a soft tissue mass is rare and thus may be confused with the more common soft tissue sarcoma. No previous analysis of the clinical and radiologic features of lymphomas ...presenting as soft tissue masses is available because most of the cases reviewed are from the pathology literature. Four patients with diagnoses of extranodal lymphomas of the soft tissues were reviewed retrospectively with respect to their clinical features, primary tumor characteristics, stage, radiographic characteristics, treatment, and followup. Mean age was 72.5 years (range, 52-85 years). The soft tissue mass occurred in the thigh (three cases) and shoulder (one case). The median size of the soft tissue mass was 6.7 cm (range, 2-15 cm) in the largest dimension, as measured on magnetic resonance imaging. These patients each had evidence of lymphadenopathy at the time of diagnosis. Lactate dehydrogenase was increased significantly in two cases and increased slightly in two other cases. One case was Stage II(E) at presentation, one was Stage III(E), and two were Stage IV. All were B cell immunophenotype. All patients died between 2 and 24 months after diagnosis, despite the use of Cytoxan, vincristine, adriamycin, and prednisone chemotherapy in each case. Clinical and radiographic features that favor extranodal soft tissue lymphoma over sarcoma include pain and tenderness, lymphadenopathy (particularly when confluent radiologically), ipsilateral extremity swelling, and elevated lactate dehydrogenase.
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