Lymphoproliferative Disorders

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Monique C Pfaltz - One of the best experts on this subject based on the ideXlab platform.

  • mum1 expression in cutaneous cd30 Lymphoproliferative Disorders a valuable tool for the distinction between lymphomatoid papulosis and primary cutaneous anaplastic large cell lymphoma
    British Journal of Dermatology, 2008
    Co-Authors: Werner Kempf, Heinz Kutzner, Antonio Cozzio, Christian A Sander, Monique C Pfaltz, Barbara Muller
    Abstract:

    BACKGROUND: Primary cutaneous CD30+ Lymphoproliferative Disorders include lymphomatoid papulosis (LyP) and primary cutaneous CD30+ anaplastic large T-cell lymphoma (ALCL). Because of overlapping histological features, it is impossible to distinguish ALCL from LyP on histological grounds. MUM1 (Multiple Myeloma oncogene 1) is expressed in systemic ALCL and classical Hodgkin lymphoma. MUM1 expression has not been studied in detail in CD30+ Lymphoproliferative Disorders. OBJECTIVES: To examine the expression of MUM1 in CD30+ Lymphoproliferative Disorders and to assess its value as a diagnostic marker. METHODS: Thirty-one formalin-fixed paraffin-embedded specimens of LyP (n = 15), primary cutaneous ALCL (n = 10), secondary cutaneous infiltrates of systemic ALCL (n = 4) and secondary cutaneous Hodgkin lymphoma (n = 2) were analysed by immunohistochemistry with a monoclonal antibody against MUM1. RESULTS: Positive staining for MUM1 was observed in 13 cases of LyP (87%), two cases of primary cutaneous ALCL (20%), four cases of secondary cutaneous ALCL (100%) and two cases of secondary cutaneous Hodgkin lymphoma (100%). In 11 of 13 LyP cases (85%), MUM1 was displayed by the majority, i.e. 50-90%, of the tumour cells. In contrast to LyP and secondary cutaneous ALCL, only two cases of primary cutaneous ALCL (20%) harboured MUM1-positive tumour cells. There was a statistically significant difference in the expression of MUM1 between LyP and primary cutaneous ALCL (P = 0.002) and between primary cutaneous ALCL and secondary cutaneous ALCL (P = 0.015). CONCLUSIONS: MUM1 expression is a valuable tool for the distinction of LyP and ALCL and thus represents a novel adjunctive diagnostic marker in CD30+ Lymphoproliferative Disorders.

Werner Kempf - One of the best experts on this subject based on the ideXlab platform.

  • cutaneous cd30 positive t cell Lymphoproliferative Disorders clinical and histopathologic features differential diagnosis and treatment
    Seminars in Cutaneous Medicine and Surgery, 2018
    Co-Authors: Werner Kempf, Katrin Kerl, Christina Mitteldorf
    Abstract:

    Cutaneous CD30+ T-cell Lymphoproliferative Disorders (CD30+ LPD) are the second most common form of cutaneous T-cell lymphoma. CD30+ LPD include lymphomatoid papulosis, primary cutaneous anaplastic large-cell lymphoma, and borderline lesions. Despite expression of CD30 by the neoplastic cells as the hallmark of these Disorders, they differ in their clinical presentation and histological features as well as the course, the prognosis, and consecutively in the treatment. Diagnosis of CD30+ LPD and distinction from the broad spectrum of differential diagnoses essentially depends on clinicopathologic correlation as well as the results of staging examinations. Although the histological findings indicate a high-grade lymphoma, CD30+ LPD in most cases have a favorable prognosis. Recent advances in targeted therapy have led to new therapeutic approaches to CD30+ LPDs. This review describes the clinicopathologic features of CD30+ LPDs, their differential diagnoses, the treatment, and the role of CD30 as a diagnostic marker and therapeutic target.

  • characterization of the tumor microenvironment in primary cutaneous cd30 positive Lymphoproliferative Disorders a predominance of cd163 positive m2 macrophages
    Journal of Cutaneous Pathology, 2016
    Co-Authors: Aieska De Souza, Marianne Tinguely, Daniel R Burghart, Arbeneshe Berisha, Kirsten D Mertz, Werner Kempf
    Abstract:

    BACKGROUND The tumor microenvironment is essential for tumor survival, growth and progression. There are only a few studies on the tumor microenvironment in cutaneous CD30-positive Lymphoproliferative Disorders. METHODS We assessed the composition of the tumor microenvironment using immunohistochemistry studies in skin biopsies from cases diagnosed with lymphomatoid papulosis (LyP: 18 specimens), primary cutaneous anaplastic large-cell lymphoma (PC-ALCL: 8 specimens), and reactive diseases harboring CD30-positive cells (18 specimens). RESULTS The predominant cells present in LyP and PC-ALCL were CD163+ M2 macrophages (44.7%, 35%), followed by CD8+ tumor infiltrating lymphocytes (11%, 15%), FOXP3+ T-regulatory cells (9%, 4.5%) and programmed cell death 1(PD-1) + lymphocytes (2.2%, 6.8%). In contrast, CD30-positive reactive inflammatory and infectious Disorders were characterized by higher numbers of CD123+ plasmacytoid dendritic cells (6.3%) when compared to LyP (1%), and PC-ALCL (1.1%). CONCLUSIONS Key differences exist between the microenvironment of CD30-positive Lymphoproliferative Disorders and reactive conditions harboring CD30-positive lymphocytes. The high number of tumor associated macrophages, and the close vicinity of these immune cells to the CD30-positive tumor cells might suggest that tumor associated macrophages have direct influence on tumorigenesis in LyP and ALCL. Therefore, modulation of M2 macrophages may represent a new therapeutic strategy in cutaneous CD30-positive Lymphoproliferative Disorders.

  • loss of expression of 5 hydroxymethylcytosine in cd30 positive cutaneous Lymphoproliferative Disorders
    Journal of Cutaneous Pathology, 2014
    Co-Authors: Aieska De Souza, Marianne Tinguely, Daniel R Burghart, Madeleine Pfaltz, Werner Kempf
    Abstract:

    Background The methylation of DNA at position 5 of cytosine, and the subsequent reduction in intracellular 5-hydroxymethylcytosine (5-hmC) levels, is a key epigenetic event in several cancers, including systemic lymphomas. However, no studies have analyzed this epigenetic marker in cutaneous lymphomas. Therefore, we aimed to analyze the expression of 5-hmC in cutaneous CD30-positive Lymphoproliferative Disorders and compare it with a control group composed of reactive infectious and inflammatory Disorders with CD30-positive cells. Methods Retrospective case series study with immunohistochemical analysis using anti-CD30 and anti-5-hmC antibodies in control (n = 19), lymphomatoid papulosis (LyP) (n = 27) and primary cutaneous anaplastic large cell lymphoma (ALCL) (n = 14) specimens. Results Complete loss of 5-hmC nuclear staining by CD30+ cells was observed in 63% of LyP cases, 57% of ALCL cases and 0% of control cases. Conclusions The presence of 5-hmC+ and CD30+ lymphocytes was highly suggestive of a benign process. In contrast, loss of 5-hmC nuclear staining was highly suggestive of a Lymphoproliferative disorder (ALCL or LyP). Under these circumstances, the use of 5-hmC staining can be a useful adjunctive tool for discriminating between neoplastic CD30+ lymphoproliferations and inflammatory/infectious simulators harboring reactive CD30+ cells.

  • cutaneous cd30 positive Lymphoproliferative Disorders
    Surgical Pathology Clinics, 2014
    Co-Authors: Werner Kempf
    Abstract:

    Cutaneous CD30+ Lymphoproliferative Disorders are the second most common types of cutaneous T-cell lymphomas. They represent a well-defined spectrum encompassing lymphomatoid papulosis (LyP), primary cutaneous anaplastic large-cell lymphoma (pcALCL), and borderline lesions. They share the expression of CD30 as a common phenotypic hallmark, but they differ in their clinical presentation, course, and histologic features. New variants have been recently identified, including CD8+ epidermotropic LyP type D, angioinvasive LyP type E, and ALK-positive pcALCL. This review describes clinical, histopathologic, and phenotypic variants; their differential diagnoses (benign and malignant); and the role of CD30 as a diagnostic, prognostic, and therapeutic marker.

  • mum1 expression in cutaneous cd30 Lymphoproliferative Disorders a valuable tool for the distinction between lymphomatoid papulosis and primary cutaneous anaplastic large cell lymphoma
    British Journal of Dermatology, 2008
    Co-Authors: Werner Kempf, Heinz Kutzner, Antonio Cozzio, Christian A Sander, Monique C Pfaltz, Barbara Muller
    Abstract:

    BACKGROUND: Primary cutaneous CD30+ Lymphoproliferative Disorders include lymphomatoid papulosis (LyP) and primary cutaneous CD30+ anaplastic large T-cell lymphoma (ALCL). Because of overlapping histological features, it is impossible to distinguish ALCL from LyP on histological grounds. MUM1 (Multiple Myeloma oncogene 1) is expressed in systemic ALCL and classical Hodgkin lymphoma. MUM1 expression has not been studied in detail in CD30+ Lymphoproliferative Disorders. OBJECTIVES: To examine the expression of MUM1 in CD30+ Lymphoproliferative Disorders and to assess its value as a diagnostic marker. METHODS: Thirty-one formalin-fixed paraffin-embedded specimens of LyP (n = 15), primary cutaneous ALCL (n = 10), secondary cutaneous infiltrates of systemic ALCL (n = 4) and secondary cutaneous Hodgkin lymphoma (n = 2) were analysed by immunohistochemistry with a monoclonal antibody against MUM1. RESULTS: Positive staining for MUM1 was observed in 13 cases of LyP (87%), two cases of primary cutaneous ALCL (20%), four cases of secondary cutaneous ALCL (100%) and two cases of secondary cutaneous Hodgkin lymphoma (100%). In 11 of 13 LyP cases (85%), MUM1 was displayed by the majority, i.e. 50-90%, of the tumour cells. In contrast to LyP and secondary cutaneous ALCL, only two cases of primary cutaneous ALCL (20%) harboured MUM1-positive tumour cells. There was a statistically significant difference in the expression of MUM1 between LyP and primary cutaneous ALCL (P = 0.002) and between primary cutaneous ALCL and secondary cutaneous ALCL (P = 0.015). CONCLUSIONS: MUM1 expression is a valuable tool for the distinction of LyP and ALCL and thus represents a novel adjunctive diagnostic marker in CD30+ Lymphoproliferative Disorders.

A Orfao - One of the best experts on this subject based on the ideXlab platform.

  • aberrant expression of tetraspanin molecules in b cell chronic Lymphoproliferative Disorders and its correlation with normal b cell maturation
    Leukemia, 2005
    Co-Authors: Susana Barrena, Julia Almeida, Monica Yunta, A Lopez, Nuria Fernandezmosteirin, M Giralt, M Romero, Luis Perdiguer, M Delgado, A Orfao
    Abstract:

    Aberrant expression of tetraspanin molecules in B-cell chronic Lymphoproliferative Disorders and its correlation with normal B-cell maturation

  • incidence of phenotypic aberrations in a series of 467 patients with b chronic Lymphoproliferative Disorders basis for the design of specific four color stainings to be used for minimal residual disease investigation
    Leukemia, 2002
    Co-Authors: Menendez Sanchez, Julia Almeida, Belen Vidriales, M C Lopezberges, M A Garciamarcos, M J Moro, A Corrales, M J Calmuntia, J San F Miguel, A Orfao
    Abstract:

    Multiparameter immunophenotypic analysis of neoplastic cells has proven to be of great help for the investigation of minimal residual disease in acute leukemias; however, its utility has not been systematically explored in B cell chronic Lymphoproliferative Disorders. The aim of the present study was to investigate the incidence of phenotypic aberrations in a series of 467 consecutive leukemic B cell chronic Lymphoproliferative Disorders through the comparison of the phenotypic characteristics of tumor vs normal peripheral blood (n = 10) and bone marrow (n = 10) B cells, in order to explore the applicability of this strategy for minimal residual disease monitoring. An additional goal of our study was to evaluate the sensitivity of multiparameter flow cytometry for the detection of minimal residual disease in leukemic B cell chronic Lymphoproliferative Disorders through dilutional experiments (n = 19). From the patients analyzed 382 corresponded to B cell chronic lymphocytic leukemia/small lymphocytic lymphoma (353 typical and 29 atypical); five to prolymphocytic leukemia; 13 to hairy cell leukemias; 12 to lymphoplasmacytic lymphomas; 14 to splenic marginal zone lymphomas; 22 were follicular lymphomas; and 19 mantle cell lymphomas. The following triple stainings were systematically applied to both normal and leukemic samples: FMC7/CD5/CD19, CD22/CD23/CD19, CD103/CD25/CD19, CD10/CD11c/CD19 and sIg/sIg(lambda)/CD19. Overall, 98% of the leukemic B cell chronic Lymphoproliferative Disorders cases displayed aberrant phenotypes at diagnosis with no significant differences being found between cases analyzed in peripheral blood vs bone marrow samples. The most common types of aberrant criteria detected included asynchronous antigen expression (92%) and antigen over-expression (54%); abnormally light scatter characteristics were found in 17% of the cases. Most of the cases studied (90%) displayed four or more phenotypic aberrations. Once patients were divided according to the different diagnostic subgroups, the overall incidence of aberrant phenotypes ranged from 79 to 80% among atypical B cell chronic lymphocytic leukemia/small lymphocytic lymphoma and prolymphocytic leukemia to 97% of follicular lymphoma and 100% of typical B cell chronic lymphocytic leukemia/small lymphocytic lymphoma, hairy cell leukemia, lymphoplasmacytic lymphomas, splenic marginal zone lymphomas and mantle cell lymphomas. Based on the aberrant phenotypes detected unique four-color stainings could be built for the specific identification of aberrant phenotypes. These include CD22/CD23/CD19/CD5 and sIg(kappa)/sIg(lambda)/CD19/CD5 for lymphocytic leukemia/small lymphocytic lymphoma and prolymphocytic leukemia, CD103/CD25 or CD22/CD19/CD11c for hairy cell leukemia, FMC7/CD22/CD19/CD103 and sIg(kappa)/sIg(lambda)/CD22/CD19 for splenic marginal zone lymphomas, CD22/CD23/CD19/CD10 for follicular lymphomas and CD10/CD22/CD19/CD5 for mantle cell lymphomas. Serial dilutional experiments showed that the sensitivity level of immunophenotyping ranges between 10(-4) and 10(-5). In summary, the present study shows that immunophenotypic analysis allows the identification of aberrant phenotypes in 98% of leukemic B cell chronic Lymphoproliferative Disorders and these phenotypes can be used for minimal residual disease monitoring with a sensitivity limit of 10(-4)-10(-5).

Youn H Kim - One of the best experts on this subject based on the ideXlab platform.

  • cd30 cutaneous Lymphoproliferative Disorders the stanford experience in lymphomatoid papulosis and primary cutaneous anaplastic large cell lymphoma
    Journal of The American Academy of Dermatology, 2003
    Co-Authors: Howard L Liu, Richard T Hoppe, Sabine Kohler, Jeff D Harvell, Sunil Reddy, Youn H Kim
    Abstract:

    Abstract Background CD30 + cutaneous Lymphoproliferative Disorders (CLPDs) include lymphomatoid papulosis, borderline cases of CD30 + CLPDs, and primary cutaneous anaplastic large cell lymphoma (PCALCL). Prior studies have shown CD30 + CLPDs have an excellent prognosis. Objective We sought to present the single-center experience of Stanford University, Stanford, Calif, in the management of CD30 + CLPDs. Methods A retrospective cohort analysis of 56 patients with CD30 + CLPDs treated at our institution was performed. Results No patients with lymphomatoid papulosis died of disease, and overall survival was 92% at 5 and 10 years. Disease-specific survivals at 5 and 10 years for PCALCL were 85%. Disease-specific survival at 5 years for localized versus generalized PCALCL was 91% versus 50% ( P = .31). PCALCL was highly responsive to treatment, but the relapse rate was 42%. In all, 3 patients progressed to extracutaneous stage of disease. No clinical or histologic factors analyzed were predictive of worse outcome in lymphomatoid papulosis and PCALCL. Conclusion Similar to prior reports from multicenter European groups, the single-center experience at our institution demonstrates CD30 + CLPDs have an overall excellent prognosis; however, cases of PCALCL with poor outcome do exist.

P Ljungman - One of the best experts on this subject based on the ideXlab platform.

  • management of epstein barr virus infections and post transplant Lymphoproliferative Disorders in patients after allogeneic hematopoietic stem cell transplantation sixth european conference on infections in leukemia ecil 6 guidelines
    Haematologica, 2016
    Co-Authors: Jan Styczynski, W J F M Van Der Velden, Dan Engelhard, R De La Camara, Catherine Cordonnier, P Ljungman
    Abstract:

    Epstein-Barr virus-related post-transplant Lymphoproliferative Disorders are recognized as a significant cause of morbidity and mortality in patients undergoing hematopoietic stem cell transplantation. To better define current understanding of post-transplant Lymphoproliferative Disorders in stem cell transplant patients, and to improve its diagnosis and management, a working group of the Sixth European Conference on Infections in Leukemia 2015 reviewed the literature, graded the available quality of evidence, and developed evidence-based recommendations for diagnosis, prevention, prophylaxis and therapy of post-transplant Lymphoproliferative Disorders exclusively in the stem cell transplant setting. The key elements in diagnosis include non-invasive and invasive methods. The former are based on quantitative viral load measurement and imaging with positron emission tomography; the latter with tissue biopsy for histopathology and detection of Epstein-Barr virus. The diagnosis of post-transplant Lymphoproliferative disorder can be established on a proven or probable level. Therapeutic strategies include prophylaxis, preemptive therapy and targeted therapy. Rituximab, reduction of immunosuppression and Epstein-Barr virus-specific cytotoxic T-cell therapy are recommended as first-line therapy, whilst unselected donor lymphocyte infusions or chemotherapy are options as second-line therapy; other methods including antiviral drugs are discouraged.