The Experts below are selected from a list of 246 Experts worldwide ranked by ideXlab platform

Alexa J. Siddon - One of the best experts on this subject based on the ideXlab platform.

  • The utility and limitations of B- and T-Cell Gene Rearrangement studies in evaluating lymphoproliferative disorders.
    Pathology, 2020
    Co-Authors: Hadrian Mendoza, Christopher A. Tormey, Henry M. Rinder, John G. Howe, Alexa J. Siddon
    Abstract:

    Summary A hallmark of lymphoid malignancies is the presence of a monoclonal lymphocyte population. Monoclonality of B- and T-Cell populations can be established through immunoglobulin (IG) or T-Cell receptor (TCR) Gene Rearrangement analysis, respectively. The biological rationale of IG and TCR Gene Rearrangement analysis is that due to the extensive combinatorial repertoire made possible by V(D)J recombination in lymphocytes, it is unlikely that any substantive lymphocyte population would share the same IG or TCR Gene Rearrangement pattern unless there is an underlying neoplastic or reactive origin. Modern IG and TCR Gene Rearrangement analysis is typically performed by polymerase chain reaction (PCR) using commercially available primer sets followed by gel capillary electrophoresis. This process is highly sensitive in the detection of nearly all lymphoid malignancies. Several pitfalls and limitations, both biological and technical, apply to IG/TCR Gene Rearrangement analysis, but these can be minimised with high quality controls, performance of assays in duplicate, and adherence to strict criteria for interpreting and reporting results. Next Generation sequencing (NGS) will likely replace PCR based methods of IG/TCR Gene Rearrangement analysis but is not yet widespread due to the absence of standardised protocols and multicentre validation.

  • Evaluation of Positive B- and T-Cell Gene Rearrangement Studies in Patients With Negative Morphology, Flow Cytometry, and Immunohistochemistry.
    Archives of pathology & laboratory medicine, 2020
    Co-Authors: Hadrian Mendoza, Christopher A. Tormey, Alexa J. Siddon
    Abstract:

    Context.— The significance of positive immunoglobulin (IG) or T-Cell receptor (TCR) Gene Rearrangement studies in the context of otherwise normal ancillary findings is unknown. Objective.— To examine long-term hematologic outcomes of individuals with positive Gene Rearrangement studies with otherwise unremarkable blood or bone marrow studies in parallel. Design.— Data from patients who underwent IG or TCR Gene Rearrangement testing at the authors' affiliated Veterans Affairs Hospital January 1, 2013 to July 6, 2018 were extracted from medical records. Date of testing, specimen source, and morphologic, flow cytometric, immunohistochemical, and cytoGenetic characterization of the tissue source were recorded. Gene Rearrangement results were categorized as test positive/phenotype positive (T+/P+), test positive/phenotype negative (T+/P-), test negative/phenotype negative (T-/P-), or test negative/phenotype positive (T-/P+) based on comparison to other studies and/or final diagnosis. Patient records were reviewed for subsequent diagnosis of hematologic malignancy for patients with positive Gene Rearrangements but no other evidence for a disease process. Results.— A total of 136 patients with 203 Gene Rearrangement studies were analyzed. For TCR studies, there were 2 T+/P- and 1 T-/P+ results in 47 peripheral blood assays, as well as 7 T+/P- and 1 T-/P+ results in 54 bone marrow assays. Regarding IG studies, 3 T+/P- and 12 T-/P+ results in 99 bone marrow studies were identified. None of the 12 patients with T+/P- TCR or IG Gene Rearrangement studies later developed a lymphoproliferative disorder. Conclusions.— Positive IG/TCR Gene Rearrangement studies in the context of otherwise negative bone marrow or peripheral blood findings are not predictive of lymphoproliferative disorders.

  • Clinical Utility of B- and T-Cell Gene Rearrangement Studies in Blood and Bone Marrow Samples
    Blood, 2019
    Co-Authors: Hadrian Mendoza, Christopher A. Tormey, Alexa J. Siddon
    Abstract:

    In the evaluation of bone marrow (BM) and peripheral blood (PB) for hematologic malignancy, positive immunoglobulin heavy chain (IG) or T-Cell receptor (TCR) Gene Rearrangement results may be detected despite unrevealing results from morphologic, flow cytometric, immunohistochemical (IHC), and/or cytoGenetic studies. The significance of positive Rearrangement studies in the context of otherwise normal ancillary findings is unknown, and as such, we hypothesized that Gene Rearrangement studies may be predictive of an emerging B- or T-Cell clone in the absence of other abnormal laboratory tests. Data from all patients who underwent IG or TCR Gene Rearrangement testing at the authors' affiliated VA Hospital between January 1, 2013 and July 6, 2018 were extracted from the electronic medical record. Date of testing; specimen source; and morphologic, flow cytometric, IHC, and cytoGenetic characterization of the tissue source were recorded from pathology reports. Gene Rearrangement results were categorized as true positive, false positive, false negative, or true negative. Lastly, patient records were reviewed for subsequent diagnosis of hematologic malignancy in patients with positive Gene Rearrangement results with negative ancillary testing. A total of 136 patients, who had 203 Gene Rearrangement studies (50 PB and 153 BM), were analyzed. In TCR studies, there were 2 false positives and 1 false negative in 47 PB assays, as well as 7 false positives and 1 false negative in 54 BM assays. Regarding IG studies, 3 false positives and 12 false negatives in 99 BM studies were identified. Sensitivity and specificity, respectively, were calculated for PB TCR studies (94% and 93%), BM IG studies (71% and 95%), and BM TCR studies (92% and 83%). Analysis of PB IG Gene Rearrangement studies was not performed due to the small number of tests (3; all true negative). None of the 12 patients with false positive IG/TCR Gene Rearrangement studies later developed a lymphoproliferative disorder, although two patients were later diagnosed with acute myeloid leukemia. Of the 14 false negatives, 10 (71%) were related to a diagnosis of plasma cell neoplasms. Results from the present study suggest that positive IG/TCR Gene Rearrangement studies are not predictive of lymphoproliferative disorders in the context of otherwise negative BM or PB findings. As such, when faced with equivocal pathology reports, clinicians can be practically advised that isolated positive IG/TCR Gene Rearrangement results may not indicate the need for closer surveillance. Disclosures No relevant conflicts of interest to declare.

Maria Grazia Narducci - One of the best experts on this subject based on the ideXlab platform.

  • Single TCR-Vβ2 evaluation discloses the circulating T cell clone in Sezary syndrome: one family fits all!
    Archives of Dermatological Research, 2015
    Co-Authors: Enrico Scala, Debora Pomponi, Nicoletta Russo, Giandomenico Russo, Damiano Abeni, Maria Grazia Narducci
    Abstract:

    Sézary Syndrome (SS/L-CTCL) is a rare but aggressive variant of cutaneous T cell lymphoma (CTCL), characterized by erythroderma, lymphadenopathy, and the presence of a circulating memory CD4^+ T cell malignant clone with a skin homing behavior, lacking CD26 and CD49d and over-expressing CD60. The availability of a panel of monoclonal antibodies recognizing distinct TCR-Vβ families, allows to typify the clone by flow cytometry in about 70 % of cases. The TCR-Vβ repertoire of 533 individuals, comprising 308 patients affected by CTCL, 50 healthy donors, and subjects affected by various non-neoplastic dermatological affections was evaluated by flow cytometry. Statistical analyses were performed using the SPSS statistical software package for Microsoft Windows (SPSS, version 21, Chicago, IL). TCR-Vβ2 levels below 5.4 % or above 39.5 %, within total CD4^+ T cells, showed the best balance between sensitivity (98.1 %) and specificity (96 %) to identify the presence of a clone in the peripheral blood of patients affected by SS. Based on this observation, a “two-step” procedure in the detection of the malignant T cell clone in CTCLs is herein suggested. TCR-Vβ2 assessment in all cases (first step). In the case of TCR-Vβ2 levels above 39.5 %, the presence of a clonal expansion of this family is suggested, deserving further confirmation by means of T cell Gene Rearrangement evaluation. In patients having a TCR-Vβ2 reactivity below 5.4 % (second step), the entire TCR-Vβ repertoire should be evaluated to typify the expanded clone. In conclusion, the single TCR-Vβ2 expression check, instead of the entire repertoire assessment, represents an easy and cost-effective method for the recognition of CTCL aggressive leukemic variant.

  • Single TCR-Vβ2 evaluation discloses the circulating T cell clone in Sezary syndrome: one family fits all!
    Archives of dermatological research, 2015
    Co-Authors: Enrico Scala, Debora Pomponi, Nicoletta Russo, Giandomenico Russo, Damiano Abeni, Maria Grazia Narducci
    Abstract:

    Sezary Syndrome (SS/L-CTCL) is a rare but aggressive variant of cutaneous T cell lymphoma (CTCL), characterized by erythroderma, lymphadenopathy, and the presence of a circulating memory CD4+ T cell malignant clone with a skin homing behavior, lacking CD26 and CD49d and over-expressing CD60. The availability of a panel of monoclonal antibodies recognizing distinct TCR-Vβ families, allows to typify the clone by flow cytometry in about 70 % of cases. The TCR-Vβ repertoire of 533 individuals, comprising 308 patients affected by CTCL, 50 healthy donors, and subjects affected by various non-neoplastic dermatological affections was evaluated by flow cytometry. Statistical analyses were performed using the SPSS statistical software package for Microsoft Windows (SPSS, version 21, Chicago, IL). TCR-Vβ2 levels below 5.4 % or above 39.5 %, within total CD4+ T cells, showed the best balance between sensitivity (98.1 %) and specificity (96 %) to identify the presence of a clone in the peripheral blood of patients affected by SS. Based on this observation, a “two-step” procedure in the detection of the malignant T cell clone in CTCLs is herein suggested. TCR-Vβ2 assessment in all cases (first step). In the case of TCR-Vβ2 levels above 39.5 %, the presence of a clonal expansion of this family is suggested, deserving further confirmation by means of T cell Gene Rearrangement evaluation. In patients having a TCR-Vβ2 reactivity below 5.4 % (second step), the entire TCR-Vβ repertoire should be evaluated to typify the expanded clone. In conclusion, the single TCR-Vβ2 expression check, instead of the entire repertoire assessment, represents an easy and cost-effective method for the recognition of CTCL aggressive leukemic variant.

Hadrian Mendoza - One of the best experts on this subject based on the ideXlab platform.

  • The utility and limitations of B- and T-Cell Gene Rearrangement studies in evaluating lymphoproliferative disorders.
    Pathology, 2020
    Co-Authors: Hadrian Mendoza, Christopher A. Tormey, Henry M. Rinder, John G. Howe, Alexa J. Siddon
    Abstract:

    Summary A hallmark of lymphoid malignancies is the presence of a monoclonal lymphocyte population. Monoclonality of B- and T-Cell populations can be established through immunoglobulin (IG) or T-Cell receptor (TCR) Gene Rearrangement analysis, respectively. The biological rationale of IG and TCR Gene Rearrangement analysis is that due to the extensive combinatorial repertoire made possible by V(D)J recombination in lymphocytes, it is unlikely that any substantive lymphocyte population would share the same IG or TCR Gene Rearrangement pattern unless there is an underlying neoplastic or reactive origin. Modern IG and TCR Gene Rearrangement analysis is typically performed by polymerase chain reaction (PCR) using commercially available primer sets followed by gel capillary electrophoresis. This process is highly sensitive in the detection of nearly all lymphoid malignancies. Several pitfalls and limitations, both biological and technical, apply to IG/TCR Gene Rearrangement analysis, but these can be minimised with high quality controls, performance of assays in duplicate, and adherence to strict criteria for interpreting and reporting results. Next Generation sequencing (NGS) will likely replace PCR based methods of IG/TCR Gene Rearrangement analysis but is not yet widespread due to the absence of standardised protocols and multicentre validation.

  • Evaluation of Positive B- and T-Cell Gene Rearrangement Studies in Patients With Negative Morphology, Flow Cytometry, and Immunohistochemistry.
    Archives of pathology & laboratory medicine, 2020
    Co-Authors: Hadrian Mendoza, Christopher A. Tormey, Alexa J. Siddon
    Abstract:

    Context.— The significance of positive immunoglobulin (IG) or T-Cell receptor (TCR) Gene Rearrangement studies in the context of otherwise normal ancillary findings is unknown. Objective.— To examine long-term hematologic outcomes of individuals with positive Gene Rearrangement studies with otherwise unremarkable blood or bone marrow studies in parallel. Design.— Data from patients who underwent IG or TCR Gene Rearrangement testing at the authors' affiliated Veterans Affairs Hospital January 1, 2013 to July 6, 2018 were extracted from medical records. Date of testing, specimen source, and morphologic, flow cytometric, immunohistochemical, and cytoGenetic characterization of the tissue source were recorded. Gene Rearrangement results were categorized as test positive/phenotype positive (T+/P+), test positive/phenotype negative (T+/P-), test negative/phenotype negative (T-/P-), or test negative/phenotype positive (T-/P+) based on comparison to other studies and/or final diagnosis. Patient records were reviewed for subsequent diagnosis of hematologic malignancy for patients with positive Gene Rearrangements but no other evidence for a disease process. Results.— A total of 136 patients with 203 Gene Rearrangement studies were analyzed. For TCR studies, there were 2 T+/P- and 1 T-/P+ results in 47 peripheral blood assays, as well as 7 T+/P- and 1 T-/P+ results in 54 bone marrow assays. Regarding IG studies, 3 T+/P- and 12 T-/P+ results in 99 bone marrow studies were identified. None of the 12 patients with T+/P- TCR or IG Gene Rearrangement studies later developed a lymphoproliferative disorder. Conclusions.— Positive IG/TCR Gene Rearrangement studies in the context of otherwise negative bone marrow or peripheral blood findings are not predictive of lymphoproliferative disorders.

  • Clinical Utility of B- and T-Cell Gene Rearrangement Studies in Blood and Bone Marrow Samples
    Blood, 2019
    Co-Authors: Hadrian Mendoza, Christopher A. Tormey, Alexa J. Siddon
    Abstract:

    In the evaluation of bone marrow (BM) and peripheral blood (PB) for hematologic malignancy, positive immunoglobulin heavy chain (IG) or T-Cell receptor (TCR) Gene Rearrangement results may be detected despite unrevealing results from morphologic, flow cytometric, immunohistochemical (IHC), and/or cytoGenetic studies. The significance of positive Rearrangement studies in the context of otherwise normal ancillary findings is unknown, and as such, we hypothesized that Gene Rearrangement studies may be predictive of an emerging B- or T-Cell clone in the absence of other abnormal laboratory tests. Data from all patients who underwent IG or TCR Gene Rearrangement testing at the authors' affiliated VA Hospital between January 1, 2013 and July 6, 2018 were extracted from the electronic medical record. Date of testing; specimen source; and morphologic, flow cytometric, IHC, and cytoGenetic characterization of the tissue source were recorded from pathology reports. Gene Rearrangement results were categorized as true positive, false positive, false negative, or true negative. Lastly, patient records were reviewed for subsequent diagnosis of hematologic malignancy in patients with positive Gene Rearrangement results with negative ancillary testing. A total of 136 patients, who had 203 Gene Rearrangement studies (50 PB and 153 BM), were analyzed. In TCR studies, there were 2 false positives and 1 false negative in 47 PB assays, as well as 7 false positives and 1 false negative in 54 BM assays. Regarding IG studies, 3 false positives and 12 false negatives in 99 BM studies were identified. Sensitivity and specificity, respectively, were calculated for PB TCR studies (94% and 93%), BM IG studies (71% and 95%), and BM TCR studies (92% and 83%). Analysis of PB IG Gene Rearrangement studies was not performed due to the small number of tests (3; all true negative). None of the 12 patients with false positive IG/TCR Gene Rearrangement studies later developed a lymphoproliferative disorder, although two patients were later diagnosed with acute myeloid leukemia. Of the 14 false negatives, 10 (71%) were related to a diagnosis of plasma cell neoplasms. Results from the present study suggest that positive IG/TCR Gene Rearrangement studies are not predictive of lymphoproliferative disorders in the context of otherwise negative BM or PB findings. As such, when faced with equivocal pathology reports, clinicians can be practically advised that isolated positive IG/TCR Gene Rearrangement results may not indicate the need for closer surveillance. Disclosures No relevant conflicts of interest to declare.

Enrico Scala - One of the best experts on this subject based on the ideXlab platform.

  • Single TCR-Vβ2 evaluation discloses the circulating T cell clone in Sezary syndrome: one family fits all!
    Archives of Dermatological Research, 2015
    Co-Authors: Enrico Scala, Debora Pomponi, Nicoletta Russo, Giandomenico Russo, Damiano Abeni, Maria Grazia Narducci
    Abstract:

    Sézary Syndrome (SS/L-CTCL) is a rare but aggressive variant of cutaneous T cell lymphoma (CTCL), characterized by erythroderma, lymphadenopathy, and the presence of a circulating memory CD4^+ T cell malignant clone with a skin homing behavior, lacking CD26 and CD49d and over-expressing CD60. The availability of a panel of monoclonal antibodies recognizing distinct TCR-Vβ families, allows to typify the clone by flow cytometry in about 70 % of cases. The TCR-Vβ repertoire of 533 individuals, comprising 308 patients affected by CTCL, 50 healthy donors, and subjects affected by various non-neoplastic dermatological affections was evaluated by flow cytometry. Statistical analyses were performed using the SPSS statistical software package for Microsoft Windows (SPSS, version 21, Chicago, IL). TCR-Vβ2 levels below 5.4 % or above 39.5 %, within total CD4^+ T cells, showed the best balance between sensitivity (98.1 %) and specificity (96 %) to identify the presence of a clone in the peripheral blood of patients affected by SS. Based on this observation, a “two-step” procedure in the detection of the malignant T cell clone in CTCLs is herein suggested. TCR-Vβ2 assessment in all cases (first step). In the case of TCR-Vβ2 levels above 39.5 %, the presence of a clonal expansion of this family is suggested, deserving further confirmation by means of T cell Gene Rearrangement evaluation. In patients having a TCR-Vβ2 reactivity below 5.4 % (second step), the entire TCR-Vβ repertoire should be evaluated to typify the expanded clone. In conclusion, the single TCR-Vβ2 expression check, instead of the entire repertoire assessment, represents an easy and cost-effective method for the recognition of CTCL aggressive leukemic variant.

  • Single TCR-Vβ2 evaluation discloses the circulating T cell clone in Sezary syndrome: one family fits all!
    Archives of dermatological research, 2015
    Co-Authors: Enrico Scala, Debora Pomponi, Nicoletta Russo, Giandomenico Russo, Damiano Abeni, Maria Grazia Narducci
    Abstract:

    Sezary Syndrome (SS/L-CTCL) is a rare but aggressive variant of cutaneous T cell lymphoma (CTCL), characterized by erythroderma, lymphadenopathy, and the presence of a circulating memory CD4+ T cell malignant clone with a skin homing behavior, lacking CD26 and CD49d and over-expressing CD60. The availability of a panel of monoclonal antibodies recognizing distinct TCR-Vβ families, allows to typify the clone by flow cytometry in about 70 % of cases. The TCR-Vβ repertoire of 533 individuals, comprising 308 patients affected by CTCL, 50 healthy donors, and subjects affected by various non-neoplastic dermatological affections was evaluated by flow cytometry. Statistical analyses were performed using the SPSS statistical software package for Microsoft Windows (SPSS, version 21, Chicago, IL). TCR-Vβ2 levels below 5.4 % or above 39.5 %, within total CD4+ T cells, showed the best balance between sensitivity (98.1 %) and specificity (96 %) to identify the presence of a clone in the peripheral blood of patients affected by SS. Based on this observation, a “two-step” procedure in the detection of the malignant T cell clone in CTCLs is herein suggested. TCR-Vβ2 assessment in all cases (first step). In the case of TCR-Vβ2 levels above 39.5 %, the presence of a clonal expansion of this family is suggested, deserving further confirmation by means of T cell Gene Rearrangement evaluation. In patients having a TCR-Vβ2 reactivity below 5.4 % (second step), the entire TCR-Vβ repertoire should be evaluated to typify the expanded clone. In conclusion, the single TCR-Vβ2 expression check, instead of the entire repertoire assessment, represents an easy and cost-effective method for the recognition of CTCL aggressive leukemic variant.

D V Belsito - One of the best experts on this subject based on the ideXlab platform.

  • Carbamazepine-induced pseudolymphoma with CD-30 positive cells.
    Journal of the American Academy of Dermatology, 1998
    Co-Authors: D L Nathan, D V Belsito
    Abstract:

    A 44-year-old woman known to be allergic to phenytoin was treated with carbamazepine for 1 month and developed fever, lymphadenopathy, pneumonitis, hepatitis, and a morbilliform eruption. A skin biopsy specimen showed atypical lymphocytes in the dermis that were CD-3+, CD-30+, and L26-. T-Cell Gene Rearrangement studies were negative. A diagnosis of anticonvulsant hypersensitivity syndrome with histologic features of a pseudolymphoma was made and her illness quickly improved after carbamazepine was discontinued. This case was typical of the anticonvulsant hypersensitivity syndrome and demonstrated cross-reactivity among the aromatic anticonvulsants. However, to our knowledge, this represents the first report of a carbamazepine-induced hypersensitivity with histologic features of a cutaneous pseudolymphoma, including CD-30+ cells.

  • Carbamazepine-induced pseudolymphoma with CD-30 positive cells ☆ ☆☆ ★
    Journal of the American Academy of Dermatology, 1998
    Co-Authors: D L Nathan, D V Belsito
    Abstract:

    Abstract A 44-year-old woman known to be allergic to phenytoin was treated with carbamazepine for 1 month and developed fever, lymphadenopathy, pneumonitis, hepatitis, and a morbilliform eruption. A skin biopsy specimen showed atypical lymphocytes in the dermis that were CD-3 + , CD-30 + , and L26-. T-Cell Gene Rearrangement studies were negative. A diagnosis of anticonvulsant hypersensitivity syndrome with histologic features of a pseudolymphoma was made and her illness quickly improved after carbamazepine was discontinued. This case was typical of the anticonvulsant hypersensitivity syndrome and demonstrated cross-reactivity among the aromatic anticonvulsants. However, to our knowledge, this represents the first report of a carbamazepine-induced hypersensitivity with histologic features of a cutaneous pseudolymphoma, including CD-30 + cells. (J Am Acad Dermatol 1998;38:806-9.)