Dara Wakefield

The central nervous system solitary fibrous tumor: A review of clinical, imaging and pathologic findings among all reported cases from 1996 to 2010

OBJECTIVE Central nervous system (CNS) solitary fibrous tumor (SFT) is a rare lesion first identified as a unique entity in 1996. We describe two cases treated at the University of Florida followed by a review of all reported cases of CNS SFT between 1996 and 2010. METHODS A review of the literature was performed to identify all reported cases of CNS SFT. RESULTS 189 cases (including the two presented herein) were discovered, of which 46 were spinal and 143 were intracranial. Demographic, imaging, and pathologic findings are presented. Roughly 6% of reported lesions are malignant. Subtotal resection (STR) was associated with a 16-fold increased odds of recurrence (OR 15.9, 95% CI 5.5-46.1), although mean follow-up was shorter in those cases of GTR without recurrence. CONCLUSION CNS SFT is a rare lesion. Six percent of lesions are malignant. GTR is superior to STR although the degree of superiority is not clear.

Expression of sodium-dependent dicarboxylate transporter 1 (NaDC1/SLC13A2) in normal and neoplastic human kidney

Regulated dicarboxylate transport is critical for acid-base homeostasis, prevention of calcium nephrolithiasis, regulation of collecting duct sodium chloride transport, and the regulation of blood pressure. Although luminal dicarboxylate reabsorption via NaDC1 (SLC13A2) is believed to be the primary mechanism regulating renal dicarboxylate transport, the specific localization of NaDC1 in the human kidney is currently unknown. This studys purpose was to determine NaDC1s expression in normal and neoplastic human kidneys. Immunoblot analysis demonstrated NaDC1 expression with an apparent molecular weight of ~61 kDa. Immunohistochemistry showed apical NaDC1 immunolabel in the proximal tubule of normal human kidney tissue; well-preserved proximal tubule brush border was clearly labeled. Apical NaDC1 expression was evident throughout the entire proximal tubule, including the initial proximal convoluted tubule, as identified by origination from the glomerular tuft, and extending through the terminal of the proximal tubule, the proximal straight tubule in the outer medulla. We confirmed proximal tubule localization by colocalization with the proximal tubule specific protein, NBCe1. NaDC1 immunolabel was not detected other than in the proximal tubule. In addition, NaDC1 immunolabel was not detected in tumors of presumed proximal tubule origin, clear cell and papillary renal cell carcinoma, or in tumors of nonproximal tubule origin, oncocytoma and chromophobe carcinoma. In summary, 1) in the human kidney, apical NaDC1 immunolabel is present throughout the entire proximal tubule, and is not detectable in other renal cells; and 2) NaDC1 immunolabel is not present in renal tumors. These studies provide important information regarding NaDC1s role in human dicarboxylate metabolism.

Use of C4d as a diagnostic tool to classify membranoproliferative glomerulonephritis

BACKGROUND Membranoproliferative glomerulonephritis (MPGN type I, II and III) was reclassified in 2013 as MPGN and C3 glomerulopathy (C3G) based on the complement system activation mechanism. OBJECTIVES To evaluate whether C4d, a component of the classical pathway, could be a diagnostic tool in differentiating between MPGN and C3G. METHODS We conducted a retrospective study of 15 MPGN type I, II and III and 13 minimal change disease (MCD) patients diagnosed between 2000 and 2012. C4d staining using the peroxidase method was employed. RESULTS Using the 2013 C3G consensus classification, the 15 MPGN types I, II and III biopsies were re-classified as MPGN (8) and C3G (7). Following C4d staining, of the 8 biopsies diagnosed as MPGN, 4 had classical pathway involvement [C1q (+), C3 (+), C4d (+)]; two had lectin pathway involvement [C1q (-), C3 (+), C4d (+)]; and, two were reclassified as C3G because the absence of C4d and C1q suggested the presence of the alternative pathway [C1q (-), C3 (+), C4d (-)]. Three of the seven C3G biopsies presented classical pathway involvement and were reclassified as MPGN. The alternative pathway was present in one of the other 4 biopsies considered to be C3G. Two C3G biopsies involved the lectin pathway and the one case of dense deposit disease had lectin pathway involvement. CONCLUSIONS C4d staining may help to differentiate between MPGN and C3G. In addition, the lectin pathway could play a role in the pathogenesis of these glomerulopathies.

Selective Deletion of Heparan Sulfotransferase Enzyme, Ndst1, in Donor Endothelial and Myeloid Precursor Cells Significantly Decreases Acute Allograft Rejection

Early damage to transplanted organs initiates excess inflammation that can cause ongoing injury, a leading cause for late graft loss. The endothelial glycocalyx modulates immune reactions and chemokine-mediated haptotaxis, potentially driving graft loss. In prior work, conditional deficiency of the glycocalyx-modifying enzyme N-deacetylase-N-sulfotransferase-1 (Ndst1f/f TekCre+) reduced aortic allograft inflammation. Here we investigated modification of heparan sulfate (HS) and chemokine interactions in whole-organ renal allografts. Conditional donor allograft Ndst1 deficiency (Ndst1−/−; C57Bl/6 background) was compared to systemic treatment with M-T7, a broad-spectrum chemokine-glycosaminoglycan (GAG) inhibitor. Early rejection was significantly reduced in Ndst1−/− kidneys engrafted into wildtype BALB/c mice (Ndst1+/+) and comparable to M-T7 treatment in C57Bl/6 allografts (P < 0.0081). M-T7 lost activity in Ndst1−/− allografts, while M-T7 point mutants with modified GAG-chemokine binding displayed a range of anti-rejection activity. CD3+ T cells (P < 0.0001), HS (P < 0.005) and CXC chemokine staining (P < 0.012), gene expression in NFκB and JAK/STAT pathways, and HS and CS disaccharide content were significantly altered with reduced rejection. Transplant of donor allografts with conditional Ndst1 deficiency exhibit significantly reduced acute rejection, comparable to systemic chemokine-GAG inhibition. Modified disaccharides in engrafted organs correlate with reduced rejection. Altered disaccharides in engrafted organs provide markers for rejection with potential to guide new therapeutic approaches in allograft rejection.

MPO-C-ANCA-associated necrotising and crescentic glomerulonephritis:

The patterns of ANCA staining usually relate closely to antibodies against myeloperoxidase and proteinase-3. C-ANCA is mainly antibodies to proteinase-3 and P-ANCA is antibodies to myeloperoxidase. C-ANCA with antibodies to MPO with clinical sequelae is unusual.

A 61-year-old male with generalised lymphadenopathy presenting with shortness of breath and infiltrates on chest radiography

A 61-year-old man presented for evaluation of a 6-week history of dyspnoea on exertion that had worsened over the past week. He denied having any recent illness, fevers, night sweats, nausea, vomiting, cough, chest pain, palpitations, or leg or back pain. He was diagnosed with chronic lymphocytic leukaemia (CLL) 5 years previously and had never been on chemotherapy. Can you diagnose this 61-year-old male with generalised lymphadenopathy, dyspnoea and radiographic infiltrates? http://ow.ly/AXDg306hfqo

Quiz Page October 2015: Acute Kidney Injury in an Intravenous Drug User.

CLINICAL PRESENTATION A 32-year-old man with a history of intravenous drug abuse and hepatitis C virus infection presented with a nonhealing left arm wound 8 weeks after falling on a wooden floor. Physical examination findings were unremarkable except for the left forearm abscess and blood pressure of 149/ 84 mm Hg. Laboratory studies showed serum creatinine (Scr) level of 2.3 mg/dL (corresponding to estimated glomerular filtration rate [eGFR] of 33 mL/min/1.73 m as calculated by the isotopedilution mass spectrometry–traceable 4-variable MDRD [Modification of Diet in Renal Disease] Study equation) and proteinuria with protein excretion of 4.1 g per gram of creatinine. Urine drug screen was positive for opioids, including oxymorphone. The patient also had anemia and thrombocytopenia (hemoglobin, 5.8 g/dL, and platelets, 135,000/mL) with evidence of hemolysis (lactate dehydrogenase, 579 [reference range, 135225] U/L) with undetectable serum haptoglobin (reference range, 30-200 mg/dL) and numerous schistocytes on peripheral-blood smear. Serum complement levels were unremarkable, as were other immunologic study results. ADAMTS13 activity level was .100% (reference range, .60%). A kidney biopsy was performed (Figs 1 and 2).