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CD20
Terms modified by CD20 Selected AbstractsModulation of antigen expression in B-cell precursor acute lymphoblastic leukemia during induction therapy is partly transient: Evidence for a drug-induced regulatory phenomenon.CYTOMETRY, Issue 3 2010Results of the AIEOP-BFM-ALL-FLOW-MRD-Study Group Abstract Background: Changes of antigen expression on residual blast cells of acute lymphoblastic leukemia (ALL) occur during induction treatment. Many markers used for phenotyping and minimal residual disease (MRD) monitoring are affected. Glucocorticoid (GC)-induced expression modulation has been causally suspected, however, subclone selection may also cause the phenomenon. Methods: We investigated this by following the phenotypic evolution of leukemic cells with flow cytometry from diagnosis to four time points during and after GC containing chemotherapy in the 20 (of 360 consecutive) B-cell precursor patients with ALL who had persistent MRD throughout. Results: The early expression changes of CD10 and CD34 were reversible after stop of GC containing chemotherapy. Modulation of CD20 and CD45 occurred mostly during the GC phase, whereas CD11a also changed later on. Blast cells at diagnosis falling into gates designed according to "shifted" phenotypes from follow-up did not form clusters and were frequently less numerous than later on. Conclusions: Our data support the idea that drug-induced modulation rather than selection causes the phenomenon. The good message for MRD assessment is that modulation is transient in at least two (CD10 and CD34) of the five prominent antigens investigated and reverts to initial aberrant patterns after stop of GC therapy, whereas CD20 expression gains new aberrations exploitable for MRD detection. © 2010 Clinical Cytometry Society [source] Flow cytometric evaluation of CD38 expression assists in distinguishing follicular hyperplasia from follicular lymphoma,CYTOMETRY, Issue 5 2009Kristin Mantei Abstract The distinction of follicular lymphoma (FL) from reactive follicular hyperplasia (FH) can be a diagnostic challenge in flow cytometry. In this study, the median fluorescent intensity (MFI) of CD38 as assessed by flow cytometry on B and T cell subpopulations in 102 lymph nodes specimens with histopathologically confirmed FL was compared with 55 cases of FH. The MFI of CD38 was highly significantly reduced in the neoplastic B cells in FL when compared with the reactive germinal center B cells in FH (P < 1.0E-16). The MFI of CD38 did not differ between the non-neoplastic B-cells in FL and nongerminal center B-cells in FH (P = 0.14) or between T-cells and non-neoplastic B-cells in FL (P = 0.63). A marginal increase in the MFI of CD38 was seen for T cells in FL compared with FH (P = 0.04). An increased difference in the MFI of CD38 was identified for T-cells compared with nongerminal center B-cells in FH (P = 0.005). No difference in CD38 expression was seen between Grades 1, 2, or 3 FL. The study also confirmed increased expression of CD10 (P < 1.0E-9), decreased CD19 (P < 1.0E-22), and CD20 (P < 1.0E-16) in FL in comparison with FH, as has been previously reported. This study identified decreased CD38 as a common finding in FL in comparison with FH and provides an additional tool to help differentiate FL from FH by flow cytometry. © 2009 Clinical Cytometry Society [source] Performance of calibration standards for antigen quantitation with flow cytometry in chronic lymphocytic leukemiaCYTOMETRY, Issue 6 2007Eva D. Rossmann Abstract Background: The fluorescence intensities of CD3, CD4 on T cells and CD20, CD22 molecules on B cells were quantitatively measured on lymphocytes from chronic lymphocytic leukemia (CLL) patients and healthy donors. Methods: The performance of three different types of microbeads was compared, i.e. Quantum molecules of equivalent soluble fluorochrome (Q-MESF), Quantum simply cellular (QSC), and QuantiBRITEÔ (QB). As all PE-conjugates had a F/P ratio of 1:1, the MESF units represented also the antibody binding capacity (ABC). Results: The ABCs of CD4 and CD20 antigens estimated with QSC (ABCQSC) were higher than those assigned with QB (ABCQB) with an average difference 49%. Higher numbers of antigenic sites were obtained with Q-MESF than with QSC for CD20 antigen. On the contrary, CD4 antigenic sites numbers estimated with QSC were higher than those estimated with Q-MESF. ABC values estimated with Quantum MESF PE (ABCQ-MESF) were ,15% higher than ABCQSC, whereas ABCQ-MESF was ,49% higher than ABCQB. Statistically significant correlations were found between the values obtained using various standards. The present study is the first to report down-regulation of CD3 antigen on T cells from patients with CLL. Conclusions: This study emphasizes the relevance of quantitative measurement of fluorescence intensity by flow cytometry as a standardized approach to measure and interpret the expression of some CLL markers and reduce variability of results obtained at different sites in multi-center clinical studies. © 2007 Clinical Cytometry Society [source] Unsupervised immunophenotypic profiling of chronic lymphocytic leukemiaCYTOMETRY, Issue 3 2006Luzette K. Habib Abstract Background Proteomics and functional genomics have revolutionized approaches to disease classification. Like proteomics, flow cytometry (FCM) assesses concurrent expression of many proteins, with the advantage of using intact cells that may be differentially selected during analysis. However, FCM has generally been used for incremental marker validation or construction of predictive models based on known patterns, rather than as a tool for unsupervised class discovery. We undertook a retrospective analysis of clinical FCM data to assess the feasibility of a cell-based proteomic approach to FCM by unsupervised cluster analysis. Methods Multicolor FCM data on peripheral blood (PB) and bone marrow (BM) lymphocytes from 140 consecutive patients with B-cell chronic lymphoproliferative disorders (LPDs), including 81 chronic lymphocytic leukemia (CLLs), were studied. Expression was normalized for CD19 totals, and recorded for 10 additional B-cell markers. Data were subjected to hierarchical cluster analysis using complete linkage by Pearson's correlation. Analysis of CLL in PB samples (n = 63) discovered three major clusters. One cluster (14 patients) was skewed toward "atypical" CLL and was characterized by high CD20, CD22, FMC7, and light chain, and low CD23. The remaining two clusters consisted almost entirely (48/49) of cases recorded as typical BCLL. The smaller "typical" BCLL cluster differed from the larger cluster by high CD38 (P = 0.001), low CD20 (P = 0.001), and low CD23 (P = 0.016). These two typical BCLL clusters showed a trend toward a difference in survival (P = 0.1090). Statistically significant cluster stability was demonstrated by expanding the dataset to include BM samples, and by using a method of random sampling with replacement. Conclusions This study supports the concept that unsupervised immunophenotypic profiling of FCM data can yield reproducible subtypes of lymphoma/chronic leukemia. Expanded studies are warranted in the use of FCM as an unsupervised class discovery tool, akin to other proteomic methods, rather than as a validation tool. © 2006 International Society for Analytical Cytology [source] Pulmonary non-Hodgkin's lymphoma (NHL) of diffuse large B-cell type with simultaneous humeral involvement in a young lady: An uncommon presentation with cytologic implicationsDIAGNOSTIC CYTOPATHOLOGY, Issue 3 2010C.T., Irene Ruben B.Sc. Abstract A bronchogenic carcinoma, almost invariably, presents as a lung mass. Primary pulmonary lymphomas are rare. We report an unusual case of a pulmonary non-Hodgkin's lymphoma (NHL) with simultaneous involvement of the right humerus in a 37 year old lady. Bronchial lavage smears showed atypical cells with irregular nuclear membranes raising a suspicion of a hematolymphoid tumor, over a small cell carcinoma that was the closest differential diagnosis. Biopsy from the lung mass and from the lesion in the humerus showed an identical malignant round cell tumor with prominent apoptosis. On immunohistochemistry (IHC), tumor cells were diffusely positive for leukocyte common antigen (LCA), CD20 and MIB1 (70%), while negative for cytokeratin (CK), epithelial membrane antigen (EMA) synaptophysin, chromogranin, neuron specific enolase (NSE), CD3, and CD10. Diagnosis of a pulmonary NHL of diffuse large B-cell type with involvement of the humerus was formed. The case is presented to create an index of suspicion for the possibility of a NHL on respiratory samples, while dealing with small round cells with irregular nuclear membranes. IHC is necessary to confirm he diagnosis. A simultaneous association in the humerus in our case makes it unusual. Diagn. Cytopathol. 2010. © 2009 Wiley-Liss, Inc. [source] The clinical and epidemiological burden of chronic lymphocytic leukaemiaEUROPEAN JOURNAL OF CANCER CARE, Issue 3 2004A. REDAELLI phd director of global outcomes research-oncology The purpose of this literature review was to identify and summarize published studies describing the epidemiology and management of chronic lymphocytic leukaemia (CLL). Chronic lymphocytic leukaemia represents 22,30% of all leukaemia cases with a worldwide incidence projected to be between <,1 and 5.5 per 100 000 people. Australia, the USA, Ireland and Italy have the highest CLL incidence rates. Chronic lymphocytic leukaemia presents in adults, at higher rates in males than in females and in whites than in blacks. Median age at diagnosis is 64,70 years. Five-year survival rate in the USA is 83% for those <,65 years old and 68% for those 65 + years old. Hereditary and genetic links have been noted. Persons with close relatives who have CLL have an increased risk of developing it themselves. No single environmental risk factor has been found to be predictive for CLL. Patients are usually diagnosed at routine health care visits because of elevated lymphocyte counts. The most common presenting symptom of CLL is lymphadenopathy, while difficulty exercising and fatigue are common complaints. Most patients do not receive treatment after initial diagnosis unless presenting with clear pathologic conditions. Pharmacological therapy may consist of monotherapy or combination therapy involving glucocorticoids, alkylating agents, and purine analogs. Fludarabine may be the most effective single drug treatment currently available. Combination therapy protocols have not been shown to be more effective than fludarabine alone. As no cure is yet available, a strong unmet medical need exists for innovative new therapies. Experimental treatments under development include allogeneic stem cell transplant, mini-allogeneic transplants, and monoclonal antibodies (e.g. alemtuzumab against CD52; rituximab against CD20). [source] Successful treatment of a patient with lymphocyte-predominant Hodgkin's lymphoma with yttrium-90-ibritumomab tiuxetanEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 4 2008Niklas Zojer Abstract Lymphocyte-predominant Hodgkin's lymphoma (LPHL) is known to be radiosensitive, and radiotherapy often forms part of the treatment of patients with stage III or IV LPHL. In addition, as LPHL is thought to arise from a germinal centre B-cell, and LPHL cells express the B-cell marker CD20 there is a rationale for using anti-CD20 therapies for the treatment of LPHL. We report a 42-yr-old man with stage III B LPLH who underwent successful treatment of LPHL with 90Y-ibritumomab tiuxetan. To our knowledge, this is the first report on the use of an anti-CD20 radiolabeled antibody for the treatment of LPHL. [source] Application of combined immunofluorescence and fluorescence in situ hybridization on paraffin-embedded sections to characterize T-cell lymphoma with EBV-infected B-cell blastsGENES, CHROMOSOMES AND CANCER, Issue 4 2004Genevieve K. Temple Combined immunofluorescence (IF) and fluorescence in situ hybridization (FISH) on formalin-fixed, paraffin-embedded tissue sections were used to examine lymph node tissue from two patients diagnosed with T-cell lymphoma with Epstein,Barr virus (EBV),infected B-cell blasts. The majority of cells within the samples comprised T-cells staining positively for CD3. In addition, both patients had a population of large pleiomorphic cells that were positive for the B-cell marker CD20 and for EBV LMP-1. Standard PCR clonality testing of the nodes revealed both immunoglobulin heavy chain (IGH) and T-cell receptor (TCR) clonal rearrangements in one patient, although in the other case monoclonality was demonstrated only for TCRG. Cytogenetics of cultured lymphocytes from nodal tissue revealed two apparently unrelated abnormal clones in both patients. Combined IF and FISH revealed that these phenomena reflected two abnormal populations of B- and T-cells rather than reactive B-cell hyperplasia or biphenotypic evolution from a common ancestral lymphoma. True B-cell malignancy probably emerged within a preexisting but unrelated T-cell lymphoma. This is the first study to relate the phenotype of the abnormal cells in such cases to specific clonal populations of cells, and it demonstrates a method that may easily be introduced into a diagnostic cytogenetics laboratory with access to standard pathology laboratory resources. © 2004 Wiley-Liss, Inc. [source] Severe alterations of endothelial and glial cells in the blood-brain barrier of dystrophic mdx miceGLIA, Issue 3 2003Beatrice Nico Abstract In this study, we investigated the involvement of the blood-brain barrier (BBB) in the brain of the dystrophin-deficient mdx mouse, an experimental model of Duchenne muscular dystrophy (DMD). To this purpose, we used two tight junction markers, the Zonula occludens (ZO-1) and claudin-1 proteins, and a glial marker, the aquaporin-4 (AQP4) protein, whose expression is correlated with BBB differentiation and integrity. Results showed that most of the brain microvessels in mdx mice were lined by altered endothelial cells that showed open tight junctions and were surrounded by swollen glial processes. Moreover, 18% of the perivascular glial endfeet contained electron-dense cellular debris and were enveloped by degenerating microvessels. Western blot showed a 60% reduction in the ZO-1 protein content in mdx mice and a similar reduction in AQP4 content compared with the control brain. ZO-1 immunocytochemistry and claudin-1 immunofluorescence in mdx mice revealed a diffuse staining of microvessels as compared with the control ones, which displayed a banded staining pattern. ZO-1 immunogold electron microscopy showed unlabeled tight junctions and the presence of gold particles scattered in the endothelial cytoplasm in the mdx mice, whereas ZO-1 gold particles were exclusively located at the endothelial tight junctions in the controls. Dual immunofluorescence staining of ,-actin and ZO-1 revealed colocalization of these proteins. As in ZO-1 staining, the pattern of immunolabeling with anti,,-actin antibody was diffuse in the mdx vessels and pointed or banded in the controls. ,-actin immunogold electron microscopy showed gold particles in the cytoplasms of endothelial cells and pericytes in the mdx mice, whereas ,-actin gold particles were revealed on the endothelial tight junctions and the cytoskeletal microfilaments of pericytes in the controls. Perivascular glial processes of the mdx mice appeared faintly stained by anti-AQP4 antibody, while in the controls a strong AQP4 labeling of glial processes was detected at light and electron microscope level. The vascular permeability of the mdx brain microvessels was investigated by means of the horseradish peroxidase (HRP). After HRP injection, extensive perivascular areas of marker escape were observed in mdx mice, whereas HRP was exclusively intravascularly localized in the controls. Inflammatory cells, CD4-, CD8-, CD20-, and CD68-positive cells, were not revealed in the perivascular stroma of the mdx brain. These findings indicate that dystrophin deficiency in the mdx brain leads to severe injury of the endothelial and glial cells with disturbance in ,-actin cytoskeleton, ZO-1, claudin-1, and AQP4 assembly, as well as BBB breakdown. The BBB alterations suggest that changes in vascular permeability are involved in the pathogenesis of the neurological dysfunction associated with DMD. GLIA 42:235,251, 2003. © 2003 Wiley-Liss, Inc. [source] Primary non-Hodgkin lymphoma of the humerus following traumatic injury: case reportHEMATOLOGICAL ONCOLOGY, Issue 3 2003V. Stemberga Abstract A case of primary non-Hodgkin lymphoma of the right humerus which occurred in a 21-year-old male patient after an impact to the right shoulder in a car accident in July 1983 is described. Seventeen years after the injury, due to a civil lawsuit, the biopsy material was revised. Immunohistochemical analysis showed CD20 and CD79a positivity on large pleomorphic cells, while small reactive lymphocytes were CD3, Bcl-2 and CD20 positive. Molecular analysis carried out with PCR revealed a monoclonal B-lymphocyte population. The diagnosis of diffuse large peripheral B cell lymphoma of the bone was confirmed. The present case concurs with the literature on primary bone lymphoma, in which the diagnostic problem, trauma-related presentation and an excellent prognosis of malignant tumour are emphasized. Copyright © 2003 John Wiley & Sons, Ltd. [source] Characteristic appearances of the bone marrow in T-cell large granular lymphocyte leukaemiaHISTOPATHOLOGY, Issue 5 2007N Osuji Aims:, To augment the limited literature on bone marrow (BM) appearances in T-cell large granular lymphocyte (LGL) leukaemia and to identify a histological signature to aid in diagnosis of this condition. Methods and results:, A descriptive analysis of the histology of the BM in T-cell LGL leukaemia was performed (n = 38). Antibodies against CD3, CD4, CD5, CD8, CD16, CD56, CD57 and CD20 or CD79a were employed. Antibodies against CD68 (macrophages) and CD34 (sinusoids) were also included. BM was normocellular or hypercellular in the majority of cases, with interstitial lymphoid infiltration in 97%. Lymphoid nodules were present in 55% and intrasinusoidal permeation in 58%. Apoptotic figures and haemosiderin deposition were common. All cases showed trilinear haematopoiesis with normal or increased megakaryopoiesis and erythropoiesis, but normal/reduced myelopoiesis. Reticulin was increased (Grade II,III). Immunohistochemistry revealed interstitial infiltration in all cases and helped to identify lymphoid nodules in two-thirds of cases. Preferential localization of CD8+ T lymphocytes to the interstitium and CD4+ T lymphocytes to the periphery of CD20+ B-cell nodules was seen in almost 90% of cases. Conclusions:, Nodules with non-clonal B-cell centres surrounded by CD4+ cells, with interstitial CD8+ cells, are a characteristic finding in T-cell LGL leukaemia and may represent a histological signature for this condition. [source] CD20-mediated apoptosis: signalling through lipid raftsIMMUNOLOGY, Issue 2 2002Julie P. Deans Summary CD20 is an effective target for therapeutic B-cell depletion with monoclonal antibodies. One proposed mechanism of action is direct cytotoxicity mediated via tyrosine kinase-dependent signalling pathways activated upon CD20 cross-linking. The association of CD20 with membrane microdomains known as lipid rafts, enriched in src-family tyrosine kinases and other signalling effectors, suggests an indirect mechanism of anti-CD20-induced apoptosis in which activation of src-family kinases occurs as a consequence of lipid raft clustering. [source] Inflammatory infiltrate of chronic periradicular lesions: an immunohistochemical studyINTERNATIONAL ENDODONTIC JOURNAL, Issue 7 2003S. Liapatas Abstract Aim, To determine the cellular profile of human chronic periradicular lesions using immunohistochemical methods in order to study the differences in the cell infiltrate of periradicular granulomas and cysts. Methodology, The study population consisted of 45 individuals without any systemic disease. Biopsies were obtained during periradicular surgery. Paraffin-embedded sections were stained by the avidin,biotin complex method (ABC), whilst cryostat tissue sections were stained using the alkaline phosphatase antialkaline phosphatase assay (APAAP). These methods are highly valid and sensitive using a panel of specific monoclonal antibodies: CD4, CD8, CD3, CD10, HLADR, CD20, CD45RO, CD68 and CD57. The 45 specimens were characterized by the use of both techniques. Results, The 45 specimens were histologically diagnosed as: 25 periradicular granulomas, 17 periradicular cysts and 3 scar tissues. No statistically significant differences were detected in the inflammatory infiltrate between periradicular granulomas and cysts. Observation of the sections showed that the majority of inflammatory cells consisted of T and B lymphocytes and macrophages. T and B lymphocytes were equally distributed in 60% of the cases. The T4/T8 ratio ranged approximately from 1 to 3 and greater, being consistent with inflammation of periradicular tissues. The final differentiation of B lymphocytes to plasma cells was also detected, whilst natural killer (NK) cells were found in only 10 cases (22%). Moreover, antigen presenting cells and T suppressor/cytotoxic cells were found to be associated with both pre-existing and newly formed epithelium. Conclusions, Periradicular granulomas and cysts represent two different stages in the development of chronic periradicular pathosis as a normal result of the process of immune reactions that cannot be inhibited. [source] The preparation of periapical lesions for flow cytometryINTERNATIONAL ENDODONTIC JOURNAL, Issue 2 2000K. Fernando Aim To devise an optimal protocol and to analyse the leucocyte composition of periapical (PA) lesions by flow cytometry. Methodology PA lesions were mechanically agitated, with and without proteolysis. This was with either 0.2% collagenase alone, or in combination with 0.02% DNA-ase in serial incubations until all tissue was digested. The efficacy of each method was assessed by counting total cell yield and cell viability. Phenotype stability was gauged by the percentage of peripheral blood leucocytes (PBL) which expressed CD45RB, CD3, CD20, CD4 and CD8 before and after mechanical and collagenase treatment. Results Disaggregation of PA lesions was superior if collagenase was present, but cell clumping was problematic unless the DNA-ase was also added, and serial digestion with this combination produced optimal cell yield and viability. Nevertheless, the total number of cells released rarely exceeded 105, though viability was in excess of 80%. Mechanical agitation and proteolysis adversely affected PBL phenotypes, but collagenase digestion limited to 10 min caused least damage. Flow cytometric analysis of disaggregated PA lesions failed to identify more than 7.9% (mean, range 6,10%) CD45RB + cells. Conclusions Because of the necessity for single cell suspensions, flow cytometry is not easily applied to the analysis of leucocytes in PA lesions, and further refinements in tissue disaggregation and cell preparation are required. [source] Erythema multiforme-like lesions associated with lesional infiltration of tumor cells occurring with adult T-cell lymphoma/leukemiaINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 4 2008Tomoyuki Ohtani MD A 66-year-old Japanese woman visited our hospital with a complaint of multiple papules on her trunk and extremities. She had a past medical history of appendicitis and blood transfusion 40 years earlier. For the last 10 years, she had noticed multiple, gradually enlarging papulonodular lesions with surrounding erythema on her trunk and extremities. ,Physical examination revealed multiple, violaceous papules or nodules, less than 10 mm in diameter, with surrounding erythema on her trunk and extremities (Fig. 1). The results of routine laboratory examinations, including blood count, liver function, renal function, serum calcium, and lactate dehydrogenase, were within the normal range. The peripheral blood picture showed a small population of atypical lymphocytes below 1% of the total white blood cells. Human T-cell lymphotropic virus type I (HTLV-I) serology was positive. A microscopic examination of a biopsy specimen from a nodule on the abdomen demonstrated diffuse infiltration of large pleomorphic T cells in the upper and middle dermis, although highly atypical lymphocytes, so-called flower cells, could not be recognized. Infiltrating lymphocytes were positive for CD2, CD3, CD4, CD5, CD7, and CD45, but negative for CD8 and CD20, immunohistologically. Bone marrow biopsy also demonstrated the infiltration of lymphocytes expressing CD2, CD3, CD4, CD5, and CD7, but not CD25. Southern blot analysis of the infiltrating cells in the skin revealed an integration of HTLV-I proviral DNA in T cells. Clonal T-cell receptor , gene rearrangement was detected in skin and bone marrow biopsies. No abnormal mass or bone defect was detected by chest or abdominal computed tomographic scanning, systemic gallium-67 citrate scintigraphy, or chest radiography. On the basis of these data, the patient was diagnosed with smouldering-type adult T-cell lymphoma/leukemia. Figure 1. Clinical features of adult T-cell lymphoma/leukemia (ATL) skin lesions. Crusted, target-like, dark-red plaques on the lower legs ,The patient was started on topical steroid and electron beam radiation therapy (27 Gy/14 days). Five days after the start of irradiation, she noticed multiple patches of edematous erythema appearing on the trunk and extremities (Fig. 2). As it was initially suspected that these newly emerging erythema multiforme or toxic eruptions were caused by irradiation, therapy was interrupted. Anti-herpes simplex virus antibody was not checked because no typical herpes simplex lesions were noticed. The patient was not taking any systemic drugs. A skin biopsy was taken from a representative lesion on the chest. The pathologic specimen showed epidermotropism, liquefaction degeneration in the basal layer, marked edema, and dense infiltration of mononuclear cells in the upper dermis. Infiltrating cells possessed abundant cytoplasm and large pleomorphic nuclei with distinct nucleoli (Fig. 3). These findings were consistent with the histopathologic findings of erythema multiforme, except for the atypical lymphoid cell infiltration. Immunohistochemical staining demonstrated that the phenotype of the skin-infiltrating cells was identical to that of the atypical cells in the initial lesions. As the eruptions did not disappear in spite of the interruption of radiation, total skin irradiation was restarted. After completion of therapy, both the erythema multiforme-like lesions and the initial adult T-cell lymphoma/leukemia nodules on the trunk and extremities had resolved, leaving brown pigmentation. The patient has been free of any recurrence of skin lesions or systemic symptoms for 6 years after the completion of total skin irradiation. Figure 2. Appearance of erythema multiforme (EM)-like lesions. Edematous red plaques involving the breast Figure 3. Microscopic examination of a biopsy specimen from (EM)-like lesions on the chest (hematoxylin and eosin staining). (a) Epidermotropism, liquefaction degeneration in the basal layer, and dense infiltration of mononuclear cells and severe edema in the upper dermis (×100). (b) High-power magnification revealed that the dermal infiltration included atypical lymphoid cells with abundant cytoplasm, convoluted large nuclei, and distinct nucleoli (×400) [source] Extramedullary granulocytic sarcoma of the skin, mediastinum, and pericardiumINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 3 2008Mohammad Diab MD A 27-year-old man, with a past history of developmental delay, presented on 18 November 2005 for the evaluation of an acute onset of multiple red,violaceous nodules on the head, neck, and trunk of 5 days' duration. The patient had no associated fever, chills, weight loss, night sweats, chest pain, dyspnea, lymphadenopathy, or organomegaly. He had no previous history of malignancies. A biopsy indicated a diagnosis of leukemia cutis (Fig. 1). His initial complete blood count (CBC) was within normal limits. The 2-week follow-up revealed enlargement of the previous lesions and the development of new lesions (Fig. 2). By the third week, the patient had developed dyspnea, but with normal breath sounds and oxygen saturation. Chest computed tomography demonstrated a mediastinal mass measuring 16 × 5.2 cm and pericardial thickening (Fig. 3). The diagnosis of granulocytic sarcoma of the skin lesion and mediastinal mass was established on the basis of immunohistochemical stains, with positivity to CD43 and Leder's preparation and negativity to CD3, CD4, CD5, CD8, CD10, CD20, CD23, CD30, CD34, CD56, bcl-1, terminal deoxynucleotidyl transferase (TdT), and granzyme. The bone marrow was negative for malignant cells. CBC and chemistry panel were all normal. Nevertheless, the patient experienced increased dyspnea and developed a pericardial effusion which required a pericardial window. Cytology of the pericardial fluid was consistent with granulocytic sarcoma. Once the diagnosis of granulocytic sarcoma was established, the patient started a regimen of cytarabine, daunorubicin, and etoposide. Despite this, the skin lesions and mediastinal mass showed minimal response. Repeat computed tomography showed a mediastinal mass measuring 14.5 × 4.4 cm. The patient's respiratory status required intubation and, 2 weeks later, his family requested that he be withdrawn from life support. Figure 1. Immature myelocytic infiltrate in the dermis (hematoxylin and eosin, ×4) Figure 2. Clinical image of granulocytic sarcoma Figure 3. Computed tomography of the chest illustrating mediastinal pericardial involvement [source] Extranodal NK/T-cell lymphoma, nasal type, presenting after 5 years of remissionINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 3 2008Tomonobu Ito MD A 76-year-old woman with multiple edematous erythemas, erosions, and ulcers on the breast and abdomen was admitted to our hospital in June 2005. She had developed granulomatous bleeding lesions in the right nostril 6 years prior to her visit to our dermatology unit. She had been observed at the otorhinolaryngology department of our hospital, and a biopsy was taken from the nasal lesion. Computerized tomography and gallium scintigraphy (67Ga single-photon emission computed tomography) did not reveal any lesions corresponding to the diagnosis of malignant lymphoma. The histologic examination of the nasal specimen rendered a diagnosis of natural killer (NK)/T-cell lymphoma, nasal. Because imaging analysis indicated a small-sized tumor without metastases, oral prednisolone at 20 mg/day was administered for 1 month. The tumor decreased in size and disappeared after 19 months of low-dose steroid therapy. ,Five years after the initial treatment, the patient developed a fever of 38 °C with infiltrated erythemas and erosions on her breast. Erysipelas was initially suspected, but the antimicrobial agent did not show any effect and the multiple infiltrated erythemas and ulcers spread throughout her chest and abdomen (Fig. 1). The lymph nodes were not palpable. The right nasal cavity showed no granulomatous lesions or other signs of abnormality. The peripheral white blood cell count (3000/µL), red blood cell count (3.54 × 106/µL), and platelet count (112 × 103/µL) were reduced. Atypical lymphocytes were not observed. The serum lactic dehydrogenase (LDH; 1770 U/L; normal, 224,454 U/L), aspartate aminotransferase (AST; 140 U/L; normal, 10,30 U/L), and alanine aminotransferase (ALT; 57 U/L; normal, 3,29 U/L) levels were elevated. The soluble interleukin-2 (IL-2) receptor level was high (25,300 U/mL; normal, 167,497 U/mL). Epstein,Barr virus (EBV) serologic examination showed the immunoglobulin G (IgG) viral capsid antigen (VCA) at 1 : 320 and the EBV nuclear antigen (EBNA) at 1 : 40. IgM VCA and EBV early antigen-diffuse restricted antibody (EA) IgA and IgG were not detectable. Histologic findings from the left chest skin showed a distribution of atypical lymphocytes from the upper dermis to the subcutaneous tissue, and many foamy cells which had phagocytosed the hemocytes (Fig. 2a,b). Immunohistochemical analysis showed that the atypical lymphocytes were sCD3,, CD4,, CD8,, CD20,, CD56+, granzyme B+, and T-cell intracellular antigen (TIA-1) positive. Furthermore, EBV-encoded small RNAs (EBER), detected by in situ hybridization, exhibited a strong signal. The nasal lesions biopsied 6 years previously showed an identical staining pattern with the skin lesions immunohistochemically. Analysis of the T-cell receptor-, (TCR-,), TCR-,, and TCR-, gene did not reveal any clonal rearrangements, but the EBV gene was detected from the skin specimens by Southern blotting. Our patient's condition was diagnosed as a case of extranodal NK/T-cell lymphoma, nasal type, but the patient had concomitantly developed hemophagocytic syndrome (HPS). She was treated with a combination of steroid pulse therapy and chemotherapy (pirarubicin hydrochloride 30 mg/m2, cyclophosphamide 500 mg/m2, vincristine 1 mg/m2, prednisolone 30 mg/m2, etoposide 80 mg/m2). After the first session of chemotherapy, the lesions on the chest and abdomen diminished, but, 2 weeks later, the skin lesions recurred, and disseminated intravascular coagulation (DIC) induced by HPS supervened. The patient died as a result of multiple organ failure induced by HPS. Figure 1. Multiple infiltrated erythemas, erosions, and ulcers on the breast and abdomen Figure 2. Histologic findings of a skin biopsy specimen from the left chest (hematoxylin and eosin staining). (a) Dense infiltration of atypical lymphocytes from the upper dermis to the subcutaneous tissue (×40). (b) Many foamy cells had phagocytosed the hemocytes (×400) [source] Large B-cell lymphoma of the legINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 10 2001Elsa Vasquez-del-Mercado MD A 74-year-old Mexican man presented with an 18-month history of multiple, violaceous, coalescing, firm, tender nodules with an ulcer in the anterior aspect of the right leg (Fig. 1) and slightly infiltrated, ill-defined erythematous plaques affecting the left leg and both forearms. He had not received any treatment for his condition. Past medical history was relevant for noninsulin-dependent diabetes mellitus and hypertension without formal treatment and a history of heavy alcohol intake in his youth. A biopsy specimen of both plaque-type lesions of the forearm and tumorous lesions of the leg showed a diffuse, nonepidermotropic mononuclear infiltrate throughout the dermis and extending to the subcutis. The infiltrate was composed of pleomorphic, atypical, large mononuclear cells (Fig. 2). Immunostaining with CD20 was positive for the atypical cells while CD3 was positive for normal appearing lymphocytes, characterized as reactive T cells. Additional laboratory and image studies ruled out extracutaneous involvement. The diagnosis of primary cutaneous large B cell lymphoma of the leg (LBCLL) was made. The patient was initiated on radiotherapy localized to the right leg with a very good initial response, nevertheless resolution was not achieved and the plaques in the rest of the limbs remained unchanged. Thus, the patient started chemotherapy with CHOP (Cyclophosphamide, Vincristine, Doxorubicin, Prednisone). He has currently finished his fourth cycle with this chemotherapy regimen. The tumorous lesions involuted leaving only residual hyperpigmentation (Fig. 3) and the plaques in the rest of the limbs disappeared, the area of the ulcer diminished considerably. There is still no evidence of extracutaneous involvement. Figure 1. Nodules and ulcer in the anterior aspect of the right leg Figure 2. Atypical lymphocytes, with large, pleomorphic nuclei and multiple nucleoles. Positivity for CD20 antigen was demonstrated by immunohistochemical analysis (hematoxylin and eosin; X 600) Figure 3. Residual hyperpigmentation and granulation tissue after chemotherapy [source] A clonal cutaneous CD30+ lymphoproliferative eruption in a patient with evidence of past exposure to hepatitis EINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 7 2000Freddye M. Lemons-Estes CDR, MC USN The patient was a 52-year-old white man who had worked in remote areas of the world during the past 2 years, including an extended period in rural areas of Central Africa and in Central and South America. He had no acute illnesses during the 2-year period except for rare, mild, upper respiratory tract infections. For approximately 1 year, however, he had developed recurrent, papular-vesicular, slightly painful lesions on the fingers and palms, that spontaneously healed over weeks to months ( Fig. 1). The patient had no other concurrent illnesses and no abnormal laboratory findings, except for positive enzyme-linked immunoabsorbent assay (ELISA) for immunoglobulin G (IgG) antibodies for hepatitis E virus (HEV) using a recombinant expressed HEV antigen (Genelabs Technologies, Inc., San Antonio). Prolonged treatment with minocycline did not appear to moderate the lesions. At approximately 2.5 years after the development of his first cutaneous lesion, however, the patient reported that he had had no new lesions for over 3 months. Figure 1. Vesicular ,lesion on the finger which regressed over a period of weeks A biopsy specimen showed an intraepidermal vesicle with prominent epidermal necrosis and reticular degeneration ( Fig. 2). Within the epidermis, there was a dense infiltrate of lymphoid cells. The majority of these cells were pleomorphic with prominent nucleoli and frequent mitotic figures ( Fig. 3). Sheets of atypical cells were found in the subjacent dermis. The infiltrate extended down into the reticular dermis. With extension into the dermis, the infiltrate became more polymorphous with more small lymphoid cells, large numbers of eosinophils, and some plasma cells located more deeply. Figure 2. Intraepidermal ,blister showing reticular degeneration and marked epidermotrophism of large atypical cells with extension into the dermis with a mixed infiltrate containing eosinophils and plasma cells (30×) Figure 3. Intraepidermal ,infiltrate of large atypical cells with extension into the dermis with a mixed infiltrate containing eosinophils and plasma cells (400×) Immunohistochemical stains for CD3 (DAKO), CD4 (Becton Dickinson), CD8 (Becton Dickinson), CD15 (LeuM1, Becton Dickinson), CD20 (L-26, DAKO), CD30 (Ber-H2, DAKO), CD45RO (UCHL1, DAKO), S-100 protein (DAKO), T-cell intracellular antigen (TIA) (Coulter), epithelial membrane antigen (EMA) (DAKO), KP-1 (CD68, DAKO), MAC-387 (DAKO), Epstein,Barr virus (EBV) latent membrane antigen-1 (LMP-1, DAKO), and EBV-encoded nuclear antigen 2 (EBNA2, DAKO) were performed on formalin-fixed tissue using the ABC method with DABA as the chromagen. CD3 showed diffuse membrane staining of the large atypical lymphoid cells, as well as the majority of the small lymphoid cells ( Fig. 4). CD4 showed positive membrane staining of the large atypical lymphoid cells and the majority of the small lymphoid cells. CD8 showed only scattered light membrane staining of small lymphoid cells. CD15 was negative, and CD20 showed foci of groups of small lymphoid cells mainly within the reticular dermis. CD30 showed positive membrane and paranuclear staining of the large atypical cells, most abundant within the epidermis and papillary dermis ( Fig. 5). CD45RO showed positive membrane staining of the large atypical cells and the majority of the small lymphoid cells. S-100 protein showed increased dendritic cells within the surrounding viable epidermis and the subjacent papillary dermis ( Fig. 6). TIA showed granular staining in the large atypical lymphoid cells and only rare staining in small lymphoid cells ( Fig. 7). EMA staining was essentially negative. KP-1 showed only scattered positive cells mainly in the lower papillary and the reticular dermis. MAC-387 showed membrane staining in the viable epidermis ( Fig. 8). LMP-1 and EBNA2 for EBV were negative within the lymphoid cells as well as within the overlying epidermis. Figure 4. Immunohistochemical ,staining for CD3 showing diffuse staining of lymphoid cells within the epidermis and dermis (150×) Figure 5. Immunohistochemical ,staining for CD30 showing membrane and paranuclear staining of large atypical lymphoid cells within the epidermis and papillary dermis (a, 150× b, 400×) Figure 6. Immunohistochemical ,staining for S-100 protein within the epidermis and in the papillary dermis (a, 150× b, 300×) Figure 7. Immunohistochemical ,granular staining of large atypical lymphoid cells for TIA (200×) Figure 8. Immunohistochemical ,staining for MAC-387 showing epidermal staining (100×) Gene rearrangement studies showed a ,-T-cell receptor gene rearrangement. The monoclonal band was detected with VJ1, VJ2, and D1J2 primer sets. The T-cell receptor , rearrangement assay has a sensitivity of 61% and a specificity of 94% for the detection of a monoclonal rearrangement in T-cell lymphomas for which amplifiable DNA can be recovered. Electron microscopy was performed on formalin-fixed material, positive-fixed with 2.5% phosphate-buffered glutaraldehyde and further with 1% osmium tetroxide by standard techniques. Intracellular, 50,60-nm, cytoplasmic, spherical, viral-like particles were identified ( Fig. 9). Figure 9. Electron ,microscopy showing 50,60-nm diameter, intracellular, viral-like particles (arrows) (70,000×) [source] Unusual presentation of large B cell lymphoma: a case report and review of literatureINTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 5 2006L. AIRAGHI Summary Diffuse large B cell lymphoma (DLBCL) is the largest subtype of non-Hodgkin's lymphomas (NHLs) and is characterized by relatively frequent extranodal presentation. In these cases, the most common extranodal localizations are stomach, CNS, bone, testis and liver. Simultaneous detection of multiple extranodal involvement at presentation is quite uncommon, with the majority of these cases characterized by gastric or intestinal disease localization. Retrospective analysis concerning multifocal extranodal NHLs never pointed out disease features such as those described here. We report a patient with an unusual presentation of DLBCL, characterized by adrenal and renal involvement, associated with symptoms and signs of the cold agglutinin disease and a hypercoagulable state. Subsequently, computed tomography (CT) and fluorodeoxyglucose-positron emission tomography (FDG-PET) scanning disclosed a rapidly extensive spread to nodes and bones. Cytofluorimetric analysis of a renal specimen showed medium-to-large lympho-monocytoid elements positive for CD20 with monoclonal expression of immunoglobulin kappa light chain. Histopathological examination confirmed a renal CD20 positive DLBCL localization. [source] The immunological basis of B-cell therapy in systemic lupus erythematosusINTERNATIONAL JOURNAL OF RHEUMATIC DISEASES, Issue 1 2010Mo Yin MOK Abstract Loss of B-cell tolerance is a hallmark feature of the pathogenesis in systemic lupus erythematosus (SLE), an autoimmune disease that is characterized by hypergammaglobulinemia and autoantibody production. These autoantibodies lead to formation of immune-complex deposition in internal organs causing inflammation and damage. Autoreactive B-cells are believed to be central in the pathophysiology of SLE. Other than its role in the production of antibodies that mediate humoral immune response, B-cells also function as antigen-presenting cells and are capable of activating T-cells. Activated B-cells may also produce pro-inflammatory cytokines that aggravate local inflammation. Abnormal B-cell homeostasis has been described in SLE patients. This may occur as a result of intrinsic B-cell defect or from aberrant regulation by maturation and survival signals. B-cell-based therapy is the current mainstream of research and development of novel therapies in SLE patients with severe and refractory disease. Potential cellular and molecular targets for B-cell therapies include cell surface molecules such as CD20 (rituximab) and CD22 (epratuzumab); co-stimulatory molecules involved in B-cell,T-cell interaction such as CTLA4 and B7 molecules (abatacept); maturation and growth factors such as B-cell activating factor and a proliferation-inducing ligand (belimumab, briobacept, atacicept) and B-cell tolerogen (abetimus). This article provides an overview on normal B-cell physiology and abnormal B-cell biology in SLE that form the immunological basis of B-cell-targeted therapy in the treatment of these patients with refractory diseases. [source] Lymphomatoid papulosis with CD1a+ dendritic cell hyperplasia, mimicking Langerhans cell histiocytosisJOURNAL OF CUTANEOUS PATHOLOGY, Issue 7 2007Chris H. Jokinen Although CD1a+ dendritic cells (DC) in cutaneous T-cell lymphomas (CTCL) have been well documented, the presence of large numbers of DC within lymphoid infiltrates can pose a diagnostic difficulty. We present a case of a 70-year-old man with a 3-year history of recurrent red papules and plaques on the extremities and trunk that was referred to our institution, with the diagnosis of Langerhans cell histiocytosis. Skin biopsies showed a wedge-shaped cellular infiltrate in the superficial and deep dermis consisting of two cell populations. Most prominent were clusters of epithelioid cells with grooved nuclei and abundant eosinophilic cytoplasm, which stained with antibodies to CD1a and S-100. A second, less prominent population of atypical lymphocytes, some with enlarged, hyperchromatic and convoluted nuclei, were intermixed. The latter were positive for CD30, CD3 and CD5 and negative for CD20, CD34, CD68, ALK-1 and TdT. T-cell receptor gene rearrangement studies confirmed a clonal T-cell population, which with the clinical history was consistent with the diagnosis of lymphomatoid papulosis. While previous studies have shown an increased density of dermal DC in CTCL, we believe that this represents the first report of an unusually florid DC proliferation mimicking Langerhans cell histiocytosis and masking a lymphoproliferative disorder. [source] Combined histology and molecular biology for diagnosis of early stage gastric MALT lymphomaJOURNAL OF DIGESTIVE DISEASES, Issue 1 2006Zhi Hui YI OBJECTIVE: To establish a sequential diagnostic procedure of gastric mucosa-associated lymphoid tissue (MALT) lymphoma and provide evidence for selected optimal cases to be treated in the early stage. METHODS: Thirty-one cases of gastric lymphoid hyperplasia (GLH) were selected and multiple investigations including histology, protein level, DNA and chromosome levels, combined with clinical follow-up were performed. Histological grade was according to Isaacson's criteria of GLH; CD20, UCHL-1 (CD45RO), anti-kappa (,), anti-lambda (,) and Ki-67 were used for immunohistochemical staining; semi-nested polymerase chain reaction (PCR) was used to detect IgH gene rearrangement and reverse-transcription PCR (RT-PCR) was used to detect API2-MALT1 fusion of the chromosome translocation t(11;18)(q21;q21). Twenty-nine cases underwent eradication therapy for Helicobacter pylori. Changes in histological grade, endoscopic appearance, expression of Ki-67 and IgH gene rearrangement were compared after eradication treatment. RESULTS: Of the 31 cases of GLH with predominant chronic gastritis and gastric ulcer most were histological grade 2 and 3. Only one case had , light chain restriction and 10 cases had monoclonal IgH gene rearrangement. Expression of Ki-67 and monoclonal IgH gene rearrangement were significantly increased with increased lymphoid hyperplasia (P < 0.05). Two cases had API2-MALT1 fusion. Helicobacter pylori was eradicated in 25 cases and another course of treatment had to be given in 4 cases. All cases were followed up for 1.5,37 months. Of the 27 successful eradication cases, 18 showed complete regression both histologically and endoscopically, 4 had partial regression and 7 were unchanged. CONCLUSIONS: A sequential diagnostic procedure based on histology, expression of Ki-67 combined with clonality of IgH rearrangement and API2-MALT1 fusion helps to diagnosis of early stage gastric MALT lymphoma and choose the best treatment strategy. [source] Alopecia areata in a rhesus monkey (Macaca mulatta)JOURNAL OF MEDICAL PRIMATOLOGY, Issue 3 2007B. Beardi Abstract Background, A 14-year-old female rhesus monkey (Macaca mulatta) of Chinese origin has been suffering from alopecia universalis since childhood. Methods, Recently, the health status of the animal was recorded comprehensively by detailed clinical examination including hematology and serology supplemented by histological and immunohistochemical investigations of skin biopsies and molecular biological techniques to clarify the causes of the persistent hair loss. Results and conclusions, The hairless gene (hr) nonsense mutation was ruled out by polymerase chain reaction and by sequencing of the corresponding gene. Histological examinations revealed a prominent chronic lymphocytic perifolliculitis and folliculitis affecting anagen stage hair follicles as well as miniaturized hair follicles. Immunohistochemistry using the antibodies CD3, CD20 and CD4 confirmed the diagnosis of a T-cell-mediated autoimmune disease resembling alopecia areata universalis in humans. [source] Plasmablastic lymphomas with light chain restriction , plasmablastic extramedullary plasmacytomas?JOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 5 2010Sonja C. Boy J Oral Pathol Med (2010) 39: 435,439 Background:, It is diagnostically difficult to differentiate plasmablastic lymphomas (PBLs) from plasma cell neoplasms with plasmablastic differentiation. Plasmablastic lymphomas are currently classified as ,PBL of the oral mucosa' and ,PBL with plasmacytic differentiation'. Methods:, Forty-five cases of PBL were retrieved from the Departments of Oral Pathology of the Universities of Pretoria and Limpopo, South Africa. Clinical features and HIV status were recorded and each case was classified as ,PBL of the oral mucosa type' or as ,PBL with plasmacytic differentiation'. Immunohistochemistry included: CD45, CD3, CD20, CD79a, CD38, CD138, MUM1, Ki-67 and kappa and lambda light chains. Positivity was recorded based on the percentage of positive staining cells as focal (5,20%); intermediate (20,70%) or diffuse (>70%). In situ hybridization was performed for Epstein,Barr virus (EBV) and HHV-8. Results were recorded as positive or negative. Results:, All cases showed some degree of plasmacytic differentiation. All were negative for CD20 with reactive T cells detected with CD3. Diffuse and strong positive staining was found with Ki-67 and MUM1, but variable immunoreactivity was found with CD79a, CD45, CD38 and CD138. Twenty cases (47%) showed light chain restriction. Epstein,Barr virus was detected in 44/45 cases and HHV-8 in none. Conclusions:, The morphological classification of PBLs is not valid as all cases showed some degree of plasmacytic differentiation. We propose that PBLs with light chain restriction be reclassified as ,plasmablastic extramedullary plasmacytomas' and managed accordingly. The rest represents true PBLs. The true nature of these neoplasms as an entity should be further investigated with molecular and genetic studies. [source] Spontaneous regression of malignant lymphoma of the breastPATHOLOGY INTERNATIONAL, Issue 7 2004Kuniko Iihara A complete spontaneous regression of diffuse large B cell lymphoma involving the right breast, confirmed by aspiration cytology, is reported. The patient visited a hospital due to the rapid growth of a tumor in the right breast. Five years previously she underwent a craniotomy for a brain tumor, diagnosed as B-cell malignant lymphoma, and received several courses of irradiation to the brain. Analysis of the breast tumor cells obtained by aspiration revealed lymphoma cells morphologically, which were similar to the tumor cells in the brain expressing CD20. While waiting for further examination, the tumor regressed rapidly and was not palpable after 20 days. An excisional biopsy of the breast exhibited no definite malignant lymphoma cells among a diffuse population of CD45RO and CD8-positive small lymphocytes. Nucleotide sequencing of HCDR3s of the brain tumor and breast tumor cells showed a completely matched sequence, revealing the breast mass to be a metastatic lesion from the tumor of the brain. Although there was no tumorous lesion, the patient received additional chemotherapy and has shown no sign of recurrence in the breast for 7 years. We were able to confirm that the breast lymphoma shown in the aspiration cytology was a metastatic one, which was not proven histologically prior to chemotherapy, and regard the present case as a malignant lymphoma of the breast showing spontaneous regression. The present case shows a rare occurrence of spontaneous regression of diffuse large B cell malignant lymphoma after aspiration and suggests that CD8-positive T cells might be related to the regression. [source] Lymphoid hyperplasia of the large intestine: A case report with immunohistochemical and gene analysisPATHOLOGY INTERNATIONAL, Issue 9 2000Sakae Nagaoka A case of lymphoid hyperplasia arising in the large intestine of a 54-year-old woman is described. Barium enema X-ray and colonoscopic examination revealed multiple small polyps in the right side of the colon. Pathological findings from forceps biopsy revealed similar features to a mucosa-associated lymphoid tissue (MALT) lymphoma. A right hemicolectomy with mesenteric lymph node dissection was carried out. Histological sectioning demonstrated hypertrophic lymphoid follicles with well-formed germinal centers. Occasionally, lymphocytes infiltrated the crypts, in a way similar to that found in lymphoepithelial lesions, which was suggestive of a MALT lymphoma diagnosis. Cryptitis was also observed in the lamina propria. Immunohistochemically, proliferating lymphocytes were positive for CD20 (L26) and negative for CD45RO (UCHL-1). Analyses of immunoglobulin gene (IgHJH) rearrangement could not detect any monoclonality in these cells. These findings suggested that the present case should be categorized as lymphoid hyperplasia rather than lymphoma. [source] CD19 negative precursor B acute lymphoblastic leukemia presenting with hypercalcemiaPEDIATRIC BLOOD & CANCER, Issue 1 2004Iyad Sultan MD Abstract A 9-month-old infant presented with hypercalcemia and lytic bone lesions. Suspicion for malignancy led to a bone marrow examination, which showed replacement of the marrow by a small round blue cell infiltrate. Flow cytometric analysis of these cells showed an unusual immunophenotype in that these cells were dim CD45, HLA-DR, and CD10 positive, but CD19, CD20, CD79a, and CD34 negative. Southern blotting showed clonal rearrangement of immunoglobulin heavy chain (IgH) which confirmed a diagnosis of precursor B acute lymphoblastic leukemia (ALL). He received supportive treatment with hydration and pamidronate, but had recurrent episodes of hypercalcemia. Once the correct diagnosis of ALL was established, the patient was treated with an infantile ALL chemotherapeutic regimen and the hypercalcemia resolved. This case highlights the usefulness of immunoglobulin gene rearrangement studies in atypical cases of ALL. © 2004 Wiley-Liss, Inc. [source] Generalized Erythrodermic Pemphigus Foliaceus in a Child and Its Successful Response to Rituximab TreatmentPEDIATRIC DERMATOLOGY, Issue 2 2007Elizabeth Alvarez Connelly M.D. The nonendemic or sporadic form of this entity is rare in children and typically presents with a milder, more localized rash that usually follows a benign course of short duration. We describe an affected patient atypical in both her young age and the severity of skin findings. Our patient presented with a full body exfoliative erythroderma at 21 months of age. After an extensive work-up to determine the etiology of her exfoliative erythroderma, direct and indirect immunofluorescence studies confirmed the diagnosis of pemphigus foliaceus. Rituximab therapy was initiated based on the patient's refractory disease course to multiple immunosuppressive agents. Rituximab is a therapeutic monoclonal antibody targeting CD20, an integral membrane protein highly expressed on the surface of pre-B lymphocytes and activated mature B lymphocytes. The patient's skin exhibited marked clinical improvement after the start of rituximab infusions over 12 weeks. Her initial desmoglein 1 antibody level was greater than 1:1280, which decreased to 1:16 after seven rituximab treatments. She has had no skin flares since initiating treatment with rituximab therapy. Based on this clinical and serologic response, the use of rituximab may be helpful in the treatment of pediatric pemphigus foliaceus refractory to mainstays of therapy. [source] Increased Ig-null B lymphocytes in the peripheral blood of pediatric solid organ transplant recipients with elevated Epstein-Barr viral loadsPEDIATRIC TRANSPLANTATION, Issue 3 2009Elizabeth Schauer Abstract:, In this study, the characteristics of Ig-null B cells in high viral load carriers were examined by four-color flow cytometry. The frequency of Ig-null B cells in patients with high, low or undetectable virus loads was found that while patients with a high load had more Ig-null cells, these cells were also present in the low and undetectable load groups. As Ig-null cells from patients with no viral load were EBV-negative, EBV infection was not absolutely required for the generation or survival of Ig-null cells. Ig-null cells were CD19+, sIg - , CD5,, CD10,, CD27,, CD23,, CD38,, and CD69, with variable surface expression of CD20 and CD40. Ig-null cells did not have a proliferating cell phenotype (Ki67 - ) and a high proportion were HLA class I - and class II - . Virus copy number in CD19+ Ig-null cell populations may be much higher than in CD19+ Ig+ cell populations. EBV infected Ig-null cells were common in blood specimens from pediatric solid organ transplant recipients and infected Ig-null cells may pose potential problems for immunotherapies that target infected B cells directly. [source] | ||||||||||||||||||||||||||||||||||