ABSTRACT
CCR5 KO kidney transplant (KTx) recipients are extraordinarily high alloantibody producers and develop pathology that mimics human antibody-mediated rejection (AMR). C57BL/6 and CCR5 KO mice (H-2b ) were transplanted with A/J kidneys (H-2a ); select cohorts received adoptive cell therapy (ACT) with alloprimed CXCR5+ CD8+ T cells (or control cells) on day 5 after KTx. ACT efficacy was evaluated by measuring posttransplant alloantibody, pathology, and allograft survival. Recipients were assessed for the quantity of CXCR5+ CD8+ T cells and CD8-mediated cytotoxicity to alloprimed IgG+ B cells. Alloantibody titer in CCR5 KO recipients was four-fold higher than in C57BL/6 recipients. The proportion of alloprimed CXCR5+ CD8+ T cells 7 days after KTx in peripheral blood, lymph node, and spleen was substantially lower in CCR5 KO compared to C57BL/6 recipients. In vivo cytotoxicity towards alloprimed IgG+ B cells was also reduced six-fold in CCR5 KO recipients. ACT with alloprimed CXCR5+ CD8+ T cells (but not alloprimed CXCR5- CD8+ or third-party primed CXCR5+ CD8+ T cells) substantially reduced alloantibody titer, ameliorated AMR pathology, and prolonged allograft survival. These results indicate that a deficiency in quantity and function of alloprimed CXCR5+ CD8+ T cells contributes to high alloantibody and AMR in CCR5 KO recipient mice, which can be rescued with ACT.
Subject(s)
Kidney Transplantation , Animals , CD8-Positive T-Lymphocytes , Graft Rejection/pathology , Immunoglobulin G , Isoantibodies , Mice , Mice, Inbred C57BL , Mice, KnockoutABSTRACT
BACKGROUND: Hypertension is a leading cause of chronic kidney disease worldwide. Early studies demonstrated the short-term effects of hypertension on kidney function and morphology in ablative nephropathy. The aim of this study was to investigate the long-term consequences of hypertension in 5/6 nephrectomy (5/6NE) model. METHODS: Reduction of the kidney mass by 5/6NE was created in spontaneous hypertensive rats (SHR) and genetically similar normotensive Wistar Kyoto (WKY) rats. Blood pressure, serum creatinine (SCr), hematuria, and proteinuria were monitored weekly for 23 weeks. Kidney morphology was assessed at the end of the study. Sham-operated rats from both strains were used as controls. RESULTS: Rats with 5/6NE had increased SCr, blood pressure, hematuria, and proteinuria in both SHR and WKY. Even though the SCr levels and blood pressure were greater in 5/6NE SHR as compared with 5/6NE WKY rats, absolute changes from sham-operated rats were not statistically significant between these 2 groups. 5/6NE SHR had earlier onset and higher proteinuria than 5/6NE WKY rats. Hematuria was similar in 5/6NE SHR and 5/6NE WKY rats. However, 5/6NE SHR had enlarged glomeruli, increased interstitial fibrosis, and prominent intimal thickening in the small arteries/arterioles as compared with 5/6NE WKY rats. CONCLUSIONS: The long-term severity of kidney injury correlated with higher blood pressure. Reduction of the kidney mass increases SCr, hematuria, proteinuria, and blood pressure in both normotensive and hypertensive rats. Histological assessment provides better information about underlying chronic kidney injury than actual changes in SCr and urinalysis.
Subject(s)
Hematuria , Hypertension , Kidney , Animals , Rats , bcl-Associated Death Protein/pharmacology , Blood Pressure , Creatinine , Hematuria/pathology , Hypertension/pathology , Kidney/physiopathology , Proteinuria/etiology , Rats, Inbred SHR , Rats, Inbred WKYABSTRACT
Waldenström's macroglobulinemia is a rare hematology malignancy which often presents with "B symptoms," anemia, and thrombocytopenia. A 46-year-old woman presented with 2 months of abdominal distension accompanied by an unintentional 20-lb weight loss. Her abdominal CT scan demonstrated diffuse carcinomatosis with bilateral ovarian lesions and screening labs revealed a markedly elevated CA-125, suggesting a diagnosis of ovarian cancer. Upon admission for workup, patient was found to have a significant protein gap, later attributed to a markedly elevated IgM. Omental and bone marrow biopsy confirmed the diagnosis of Waldenström's macroglobulinemia, with elevation in CA-125 thought to be secondary to peritoneal irritation. This patient has since been successfully treated with six cycles of bendamusine and rituximab with no evidence of disease on staging scans and normalization of both CA-125 and IgM. To our knowledge, this is the first documented case of Waldenström's macroglobulinemia presenting with symptoms classically associated with ovarian cancer and demonstrates the importance of maintaining a broad differential when evaluating patients with abdominal carcinomatosis.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Ascites , CA-125 Antigen/metabolism , Peritoneal Neoplasms , Waldenstrom Macroglobulinemia , Ascites/diagnosis , Ascites/drug therapy , Ascites/metabolism , Ascites/pathology , Bendamustine Hydrochloride/administration & dosage , Female , Humans , Middle Aged , Ovarian Neoplasms/diagnosis , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/metabolism , Ovarian Neoplasms/pathology , Peritoneal Neoplasms/diagnosis , Peritoneal Neoplasms/drug therapy , Peritoneal Neoplasms/metabolism , Peritoneal Neoplasms/pathology , Rituximab/administration & dosage , Waldenstrom Macroglobulinemia/diagnosis , Waldenstrom Macroglobulinemia/drug therapy , Waldenstrom Macroglobulinemia/metabolism , Waldenstrom Macroglobulinemia/pathologyABSTRACT
RATIONALE & OBJECTIVE: In 2009, the first case of acute kidney injury and occlusive red blood cell (RBC) tubular casts associated with a high international normalized ratio in a patient receiving warfarin was identified. This entity, named warfarin-related nephropathy, was later renamed anticoagulant-related nephropathy (ARN) after similar cases with other anticoagulants were described. We provide our 10-year experience with ARN based on a single-center kidney biopsy laboratory. STUDY DESIGN: The kidney pathology database at the Ohio State University Wexner Medical Center (OSUWMC) was searched for native kidney biopsy cases consistent with ARN. Clinical data were obtained from patient medical records. SETTING & PARTICIPANTS: Native kidney biopsies evaluated between January 1, 2009, and December 31, 2017 at OSUWMC. RESULTS: Among 8,636 native kidney biopsies reviewed at the OSUWMC, there were 41 (0.5%) patients for whom deterioration in kidney function could not be explained by kidney biopsy findings alone if anticoagulation was not considered. There were 63% men and 95% were white; average age was 62 ± 14 years. Most were on warfarin therapy (N = 28), although cases were also attributed to direct-acting anticoagulants (N = 2), antiplatelet medications (N = 1), heparin or enoxaparin (N = 4), and disseminated intravascular coagulopathy (N = 6). Morphologically, there was acute tubular necrosis and RBC casts. The majority of biopsies had an underlying glomerular disease and many patients had positive serologic test results. In all these cases, the severity of kidney failure, RBC tubular casts, and hematuria were disproportionate to glomerular morphologic changes. LIMITATIONS: Selection bias in the decision to perform a kidney biopsy. CONCLUSIONS: ARN is an uncommon diagnosis in kidney pathology practice, but it should be considered when the number of RBC tubular casts is disproportionate to the severity of glomerular changes in a kidney biopsy in patients either receiving anticoagulation therapy or who presented with acute coagulopathy. Our data suggest that anticoagulation aggravates underlying glomerular diseases rather than directly affecting the glomerular filtration barrier.
ABSTRACT
BACKGROUND: Erdheim Chester disease (ECD) is a rare, non-Langerhans cell histiocytosis characterized by widespread tissue infiltration by CD68-positive, CD1a-negative foamy histiocytes. ECD can be difficult to identify, and diagnosis relies on the presence of histiocytes with certain histologic and immunophenotypic features in an appropriate clinical and radiologic setting. Clinical signs and symptoms are variable depending on which organ systems are involved. Most patients have at least skeletal involvement with bone pain as well as fatigue. Other common manifestations include diabetes insipidus, cardiac, periaortic, or retro-orbital infiltration/fibrosis, kidney impairment, xanthelasmas, among others. CASE PRESENTATION: Herein, we describe a case of BRAF-mutation positive ECD in a patient with Burkitt lymphoma, and we review recent literature. CONCLUSION: Underlying BRAF and other MAPK pathway mutations are identified in approximately 50% of cases of ECD, which aids in diagnosis as well as enables novel targeted treatments. ECD patients have an increased risk of myeloid neoplasms; however, unlike other histiocytoses, an association with lymphoproliferative disorders has not been recognized.
Subject(s)
Burkitt Lymphoma/therapy , Erdheim-Chester Disease/genetics , Mutation , Proto-Oncogene Proteins B-raf/genetics , Biopsy , Burkitt Lymphoma/complications , Burkitt Lymphoma/diagnosis , DNA Mutational Analysis , Erdheim-Chester Disease/complications , Erdheim-Chester Disease/diagnosis , Genetic Markers , Genetic Predisposition to Disease , Humans , Immunohistochemistry , Male , Middle Aged , Phenotype , Predictive Value of TestsABSTRACT
Lynch syndrome (LS) is the most common form of hereditary colon cancer. Germline mutations in the mismatch-repair (MMR) genes MLH1, MSH2 (EPCAM), MSH6, and PMS2, followed by a second hit to the remaining allele, lead to cancer development. Universal tumor screening for LS is routinely performed on colon cancer, and screening has identified patients with unexplained MMR deficiency that lack MLH1 methylation and a germline mutation. Tumor sequencing has since identified double somatic (DS) mutations in the MMR gene corresponding with the absent protein in 69% of these patients. We assessed whether histomorphology could distinguish patients with DS mutations from those with LS. Colorectal cancer patients with DS mutations were identified from population-based cohorts from Iceland (2000-2009); Columbus, Ohio (1999-2005); and the state of Ohio (2013-2016). Next-generation sequencing was performed on tumors with unexplained MMR deficiency. Patients with LS from Ohio cohorts were the comparison group. The histologic features associated with MMR deficiency (tumor-infiltrating lymphocytes, Crohn-like reaction, histologic subtype, necrosis) were evaluated. We identified 43 tumors with DS mutations and 48 from patients with LS. There was no significant difference in histologic features between tumors in LS patients and tumors with DS mutations. Because histology of tumors with DS mutations is indistinguishable from those caused by LS, tumor sequencing for evaluation of DS mutations should be considered to help clarify sporadic versus hereditary causes of unexplained MMR deficiency.
Subject(s)
Colonic Neoplasms/pathology , Colorectal Neoplasms, Hereditary Nonpolyposis/pathology , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , DNA Mismatch Repair/genetics , Adenocarcinoma/genetics , Adenocarcinoma/pathology , Colonic Neoplasms/genetics , Colorectal Neoplasms, Hereditary Nonpolyposis/genetics , Early Detection of Cancer/methods , Female , Humans , Male , Mutation/geneticsABSTRACT
BACKGROUND: Small glomerular IgA deposits have been reported in patients with liver cirrhosis, mainly as an incidental finding in autopsy studies. We recently encountered nine cirrhotic patients who presented with acute proliferative glomerulonephritis with unusually large, exuberant glomerular immune complex deposits, in the absence of systemic lupus erythematosus (SLE) or monoclonal gammopathy-related kidney disease. Deposits were typically IgA dominant/codominant. Our aim was to further elucidate the etiology, diagnostic pitfalls, and clinical outcomes. METHODS: We present clinical features and kidney biopsy findings of nine cirrhotic patients with an unusual acute immune complex glomerulonephritis. We also identified native kidney biopsies from all patients with liver cirrhosis at our institution over a 13-year period (January 2004 to December 2016) to evaluate presence of glomerular IgA deposits in them (n = 118). RESULTS: Six of nine cirrhotic patients with the large immune deposits had a recent/concurrent acute bacterial infection, prompting a diagnosis of infection-associated glomerulonephritis and treatment with antibiotics. In the remaining three patients, no infection was identified and corticosteroids were initiated. Three of nine patients recovered kidney function (one recovered kidney function after liver transplant); three patients developed chronic kidney disease but remained off dialysis; two patients became dialysis-dependent and one patient developed sepsis and expired shortly after biopsy. Within the total cohort of 118 patients with cirrhosis, 67 others also showed IgA deposits, albeit small; and 42 patients had no IgA deposits. CONCLUSIONS: These cases provide support to the theory that liver dysfunction may compromise clearance of circulating immune complexes, enabling deposition in the kidney. At least in a subset of cirrhotic patients, a superimposed bacterial infection may serve as a "second-hit" and lead to acute glomerulonephritis with exuberant immune complex deposits. Therefore, a trial of antibiotics is recommended and caution is advised before immunosuppressive treatment is offered. Unfortunately, most of these patients have advanced liver failure; therefore both diagnosis and management remain a challenge.
Subject(s)
Glomerulonephritis, IGA/complications , Kidney/pathology , Liver Cirrhosis/complications , Adult , Aged , Biopsy , Female , Glomerulonephritis, IGA/pathology , Glomerulonephritis, IGA/therapy , Humans , Kidney Function Tests , Liver Cirrhosis/pathology , Male , Middle Aged , Renal Dialysis , Treatment OutcomeABSTRACT
Anticoagulant-related nephropathy (ARN) was initially described in patients on warfarin (as warfarin-related nephropathy) and recently in those using dabigatran. Herein, we report clinical history and kidney biopsy findings in a patient on apixaban (Eliquis). Initiation of treatment with apixaban resulted in aggravation of preexisting mild acute kidney injury (AKI). A few days after apixaban therapy, the patient became oligoanuric, and kidney biopsy showed severe acute tubular necrosis with numerous occlusive red blood cell casts. Only one out of 68 glomeruli with open capillary loops had small segmental cellular crescent. Therefore, there was major discrepancy between the degree of glomerular injury and the glomerular hematuria. Considering that the onset of this AKI was associated with apixaban treatment initiation, we propose that this patient had ARN associated with factor Xa inhibitor (apixaban), which has not previously been described. Monitoring of kidney function is recommended after initiation of anticoagulant therapy.
ABSTRACT
Recent advances in the treatment of neuroendocrine tumors (NET), including the combination regimen of capecitabine and temozolomide (CAPTEM), have mostly focused on grade 1 and 2 pancreatic neuroendocrine tumors (pNET). We undertook a retrospective review of 38 patients with advanced NET treated with CAPTEM, including patients with non-pancreatic tumors as well as grade 2 and 3 tumors. O6-methylguanine DNA methyltransferase (MGMT) expression was assessed as a predictive biomarker. We found that CAPTEM demonstrated activity in patients with all grades and in pNET and non-pNET. Median progression free survival (mPFS) was 13.0 months (95% CI: 5.6-17.0) and median overall survival (mOS) 29.3 months (95% CI 17.7 - 45.3). Among evaluable patients, there were 11 (38%) partial responses, 15 (52%) stable disease, and 3 (10%) progressive disease for a disease control rate of 90%. A higher rate of partial responses occurred in patients whose tumors had low levels of MGMT expression (63%) compared to intermediate-high (17%) (p=0.19). Our results show that CAPTEM therapy is active in patients with NET including in previously treated patients and in those with poorly-differentiated histology. We observed a trend towards increased response rate, median PFS, and median OS in patients whose tumors had low MGMT protein expression.
ABSTRACT
Background and Purpose. Anticoagulant therapy is broadly used to prevent thromboembolic events. Intracranial hemorrhages are serious complications of anticoagulation, especially with warfarin. Direct oral anticoagulants reduce but do not eliminate the risk of intracranial hemorrhages. The aim of this study is to determine the degree of intracranial hemorrhage after application of anticoagulants without additional triggers. Methods. Rats were treated with different anticoagulant classes (vitamin K antagonists, heparin, direct thrombin inhibitor, and factor Xa inhibitor). Brain hemorrhages were assessed by the free hemoglobin concentration in the brain parenchyma. Results. Vitamin K antagonists (warfarin and brodifacoum) significantly increased free hemoglobin in the brain. Among direct oral anticoagulants, thrombin inhibitor dabigatran also significantly increased free hemoglobin in the brain, whereas treatment with factor Xa inhibitor rivaroxaban did not have significant effect on the free hemoglobin concentration. Conclusions. Our data indicates that the severity of brain hemorrhages depends on the anticoagulant class and it is more pronounced with vitamin K antagonists.
ABSTRACT
BACKGROUND: Histiocytic sarcoma is a rare histiocytic neoplasm of unknown etiology that constitutes less than 1% of hematologic malignancies. A few cases of histiocytic sarcoma harboring the BRAF V600E mutation have been reported, but this finding has not been confirmed in all studies. CASE PRESENTATION: We report the case of a 63-year-old white woman with a history of splenic marginal zone lymphoma who presented with 2 weeks of right-sided neck swelling. Positron emission tomography revealed an intensely hypermetabolic and destructive soft tissue mass in her right skull base. A bone marrow biopsy was performed, which revealed an infiltrate of malignant cells characterized as large pleomorphic cells with frequent folded/irregular nuclei, variably prominent nucleoli, fine chromatin, and abundant amounts of eosinophilic cytoplasm. The malignant cells were positive for CD163, CD68 (granular), lysozyme (granular), CD4, and CD45 (partial). Based on the biopsy findings, she was diagnosed as having histiocytic sarcoma. The malignant cells tested positive for the BRAFV600E protein using immunohistochemistry. Before treatment of her histiocytic sarcoma could be initiated, she developed disseminated intravascular coagulation and acute hypoxemic respiratory failure secondary to non-cardiogenic pulmonary edema. She decided to pursue comfort care and died in our hospital 2 weeks following admission. CONCLUSIONS: Our case illustrates the aggressive nature of histiocytic sarcoma, and provides rare evidence that histiocytic sarcoma associated with indolent lymphomas may harbor the BRAF V600E mutation. Further research is needed to clarify the role of targeted therapies such as vemurafenib in the treatment of patients with this disorder.
Subject(s)
Histiocytic Sarcoma/diagnosis , Lymphoma, B-Cell, Marginal Zone/diagnosis , Proto-Oncogene Proteins B-raf/metabolism , Skull Base Neoplasms/diagnosis , Splenic Neoplasms/diagnosis , Biomarkers, Tumor/metabolism , Fatal Outcome , Female , Histiocytic Sarcoma/pathology , Histiocytic Sarcoma/therapy , Humans , Lymphoma, B-Cell, Marginal Zone/pathology , Lymphoma, B-Cell, Marginal Zone/therapy , Middle Aged , Patient Comfort , Proto-Oncogene Mas , Skull Base Neoplasms/pathology , Skull Base Neoplasms/therapy , Splenic Neoplasms/pathology , Splenic Neoplasms/therapyABSTRACT
BACKGROUND AND OBJECTIVES: Staphylococcus infection-associated GN (SAGN) is a well recognized disease entity, particularly because of the frequent IgA-dominant glomerular immunoglobulin staining on kidney biopsy. Biopsy features can resemble two other disease entities - primary IgA nephropathy and Henoch-Schönlein purpura nephritis - posing a diagnostic pitfall. This is clinically relevant because of the crucial difference in the therapeutic approach. The diagnosis of SAGN is further complicated by the variability in the degree of glomerular IgA (and C3) staining, the extent of electron dense immune-type deposits, and positive ANCA serology in some patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We performed a thorough histopathologic review of our single-center cohort of 78 culture-proven SAGN biopsies to assess the spectrum of IgA staining, prevalence of ANCA serology, prevalence of subepithelial "humps," and other histologic features to distinguish from primary IgA nephropathy. RESULTS: Among the 78 SAGN biopsies, IgA staining was trace in 25%, mild in 19%, moderate in 44%, and strong in 12% of the cases. C3 was frequently moderate-to-strong but was trace in 14% of the biopsies. Concomitantly trace IgA, IgG, and C3 (pauci-immune pattern) was seen in 13%. Crescents were present in 35% of the SAGN biopsies. Out of 41 patients tested for ANCA, nine (22%) were positive, including patients with endocarditis and other infections. Subepithelial humps were identified in only 31% of the SAGN biopsies. CONCLUSIONS: SAGN biopsies show marked variability in IgA immunofluorescence staining and low frequency of subepithelial humps compared with poststreptococcal GN. Occasional ANCA positivity is present in cases of SAGN, even in infections other than endocarditis. Therefore, biopsy diagnosis can be difficult particularly when clinical symptoms of infection are subtle. Both the pathologist and the nephrologist should be aware of these diagnostic pitfalls.
Subject(s)
Glomerulonephritis, IGA/diagnosis , Glomerulonephritis/diagnosis , Glomerulonephritis/metabolism , Immunoglobulin A/metabolism , Kidney/metabolism , Kidney/pathology , Adult , Aged , Aged, 80 and over , Antibodies, Antineutrophil Cytoplasmic/blood , Biopsy , Complement C3/metabolism , Diagnosis, Differential , Female , Fluorescent Antibody Technique , Glomerulonephritis/microbiology , Humans , Immunoglobulin G/metabolism , Male , Middle Aged , Staphylococcal Infections/complications , Young AdultABSTRACT
Gray zone lymphoma (GZL) is described as sharing features with classical Hodgkin lymphoma (cHL) and diffuse large B-cell lymphoma (DLBCL). However, there remains complexity in establishing diagnosis, delineating prognosis, and determining optimum therapy. Sixty-eight cases diagnosed as GZL across 15 North American academic centers were evaluated by central pathology review to achieve consensus. Of these, only 26 (38%) were confirmed as GZL. Morphology was critical to GZL consensus diagnosis (eg, tumor cell richness); immunohistochemistry showed universal B-cell derivation, frequent CD30 expression, and rare Epstein-Barr virus (EBV) positivity (CD20+, 83%; PAX5+, 100%; BCL6+, 20%; MUM1+, 100%; CD30+, 92%; EBV+, 4%). Forty-two cases were reclassified: nodular sclerosis (NS) cHL, n = 27 (including n = 10 NS grade 2); lymphocyte predominant HL, n = 4; DLBCL, n = 4; EBV+ DLBCL, n = 3; primary mediastinal large BCL n = 2; lymphocyte-rich cHL and BCL-not otherwise specified, n = 1 each. GZL consensus-confirmed vs reclassified cases, respectively, more often had mediastinal disease (69% vs 41%; P = .038) and less likely more than 1 extranodal site (0% vs 25%; P = .019). With a 44-month median follow-up, 3-year progression-free survival (PFS) and overall survival for patients with confirmed GZL were 39% and 95%, respectively, vs 58% and 85%, respectively, for reclassified cases (P = .19 and P = .15, respectively). Interestingly, NS grade 2 reclassified patients had similar PFS as GZL consensus-confirmed cases. For prognostication of GZL cases, hypoalbuminemia was a negative factor (3-year PFS, 12% vs 64%; P = .01), whereas frontline cyclophosphamide, doxorubicin, vincristine, and prednisone ± rituximab (CHOP±R) was associated with improved 3-year PFS (70% vs 20%; P = .03); both factors remained significant on multivariate analysis. Altogether, accurate diagnosis of GZL remains challenging, and improved therapeutic strategies are needed.
ABSTRACT
INTRODUCTION: Outcomes in advanced stage (AS) cutaneous T-cell lymphomas (CTCL) are poor but with great variability. Epstein-Barr virus (EBV) is associated with a subset of non-Hodgkin lymphomas. Frequency of plasma EBV-DNA (pEBVd) detection, concordance with EBV RNA (EBER) in tumor tissue, codetection of plasma cytomegalovirus DNA (pCMVd), and prognostic effect in AS CTCL are unknown. PATIENTS AND METHODS: Patients (n = 46; 2006-2013) with AS CTCL (≥IIB) were retrospectively studied. pEBVd and pCMVd were longitudinally measured using quantitative real-time polymerase chain reaction. EBER in situ hybridization (ISH) was performed on tumor samples. Survival from time of diagnosis (ToD) and time of progression to AS was assessed. RESULTS: Plasma EBV-DNA and pCMVd were detected in 37% (17 of 46) and 17% (8 of 46) of AS CTCL patients, respectively. pCMVd detection was significantly more frequent in pEBVd-positive (pEBVd(+)) than pEBVd(-) patients (35% vs. 7%; P = .038). Tumor tissue for EBER-ISH was available in 14 of 17 pEBVd(+) and 22 of 29 pEBVd(-) patients; 12 of 14 (85.7%) pEBVd(+) patients were EBER(+) versus 0 of 22 pEBVd(-) patients. Frequency of large cell transformation (LCT) tended to be greater in pEBVd(+) patients, but was not significant (10 of 14 pEBVd(+) vs. 10 of 23 pEBVd(-); P = .17). No notable differences in rates of increased levels of serum lactate dehydrogenase (LDH) were observed (17 of 17 pEBVd(+) vs. 27 of 29 pEBVd(-)). pEBVd detection was associated with significantly worse survival from ToD (P = .021) and time of progression to AS (P = .0098). CONCLUSION: Detection of cell-free plasma EBV-DNA was highly concordant with the presence of EBERs in tumor tissue, predicted survival independent of LDH and LCT, and should be further studied as a biomarker in AS CTCL.
Subject(s)
Epstein-Barr Virus Infections/virology , Herpesvirus 4, Human/genetics , Lymphoma, T-Cell, Cutaneous/diagnosis , Lymphoma, T-Cell, Cutaneous/mortality , Viral Load , Adult , Aged , Aged, 80 and over , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Biomarkers , Biopsy , DNA, Viral , Epstein-Barr Virus Infections/complications , Female , Follow-Up Studies , Humans , Lymphoma, T-Cell, Cutaneous/etiology , Lymphoma, T-Cell, Cutaneous/therapy , Male , Middle Aged , Neoplasm Staging , Prognosis , Retrospective Studies , Skin/pathology , Survival Analysis , Treatment OutcomeSubject(s)
Asthma/etiology , Castleman Disease/complications , Facial Pain/etiology , Oral Ulcer/etiology , Pemphigus/etiology , Anti-Asthmatic Agents/therapeutic use , Anti-Bacterial Agents/therapeutic use , Asthma/diagnosis , Asthma/drug therapy , Asthma/immunology , Biopsy , Castleman Disease/diagnosis , Castleman Disease/drug therapy , Castleman Disease/immunology , Diagnosis, Differential , Facial Pain/diagnosis , Facial Pain/drug therapy , Facial Pain/immunology , Fluorescent Antibody Technique , Humans , Immunosuppressive Agents/therapeutic use , Male , Middle Aged , Oral Ulcer/diagnosis , Oral Ulcer/drug therapy , Oral Ulcer/immunology , Pemphigus/diagnosis , Pemphigus/drug therapy , Pemphigus/immunology , Predictive Value of Tests , Treatment OutcomeABSTRACT
Immunofluorescence staining plays a vital role in nephropathology, but the panel of antibodies used has not changed for decades. Further classification of immunoglobulin (Ig)G-containing immune-type deposits with IgG subclass staining (IgG1, IgG2, IgG3, and IgG4) has been shown to be of diagnostic utility in glomerular diseases, but their value in the evaluation of renal biopsies has not been addressed systematically in large renal biopsy material. Between January 2007 and June 2014, using direct immunofluorescence, we stained every renal biopsy for the IgG subclasses if there was moderate to prominent glomerular IgG staining and/or IgG-predominant or IgG-codominant glomerular staining. The total number of biopsies stained was 1084, which included 367 cases of membranous glomerulonephritis, 307 cases of lupus nephritis, 74 cases of fibrillary glomerulonephritis, 53 cases of proliferative glomerulonephritis with monoclonal IgG deposits, and 25 cases of antiglomerular basement membrane disease, among others. We found that monoclonality of IgG deposits cannot always be reliably determined on the basis of kappa and lambda light chain staining alone, particularly if concomitant (frequently nonspecific) IgM staining is present. In IgG heavy and heavy and light chain deposition disease (3 cases), subclass staining is very helpful, and in proliferative glomerulonephritis with monoclonal IgG deposits subclass staining is necessary. IgG subclass staining is useful in differentiating primary from secondary membranous glomerulonephritis. In proliferative glomerulonephritis with polyclonal IgG deposition, IgG1 dominance/codominance with concomitant IgG3 and IgG2 but weak or absent IgG4 staining favors an underlying autoimmune disease. IgG subclass staining is a very useful diagnostic method in a selected cohort of renal biopsies, particularly in biopsies with glomerulonephritis with monoclonal IgG deposits.
Subject(s)
Antibodies, Monoclonal/analysis , Fluorescent Antibody Technique , Glomerulonephritis/immunology , Immunoglobulin G/analysis , Kidney/immunology , Antibodies, Monoclonal/classification , Biomarkers/analysis , Biopsy , Diagnosis, Differential , Glomerulonephritis/classification , Glomerulonephritis/pathology , Humans , Immunoglobulin G/classification , Kidney/pathology , Predictive Value of Tests , Risk FactorsABSTRACT
Hepatitis C virus infection is associated with several glomerular diseases, most commonly cryoglobulinemic glomerulonephritis, which is typically secondary to type II mixed cryoglobulinemia. We present a patient with hepatitis C virus infection and cryoglobulinemic glomerulonephritis secondary to type I (monoclonal) cryoglobulinemia that is likely related to a concurrent hepatitis C virus infection-associated lymphoproliferative disorder. We list the differential diagnosis of cryoglobulinemic glomerulonephritis. Additionally, the case draws attention to the possibility that, rarely, even clinically undetectable "occult" B-cell lymphoproliferative disorders may result in significant kidney disease.