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H Rappaport

Publications and source records attributed to H Rappaport.

At least 37 records · Page 2Linked to original sources

Imprint cytology of non-Hodgkin's lymphomas based on a study of 212 immunologically characterized cases: correlation of touch imprints with tissue sections.

The classification of non-Hodgkin's lymphomas (NHLs) has been traditionally based on analysis of histologic sections and has been supplemented more recently by immunologic marker studies. It was the purpose of the present study to illustrate, side-by-side, sections and Romanowsky-stained imprints from the same surgical specimen from practically all categories of immunophenotyped NHLs, including rare and atypical variants that were difficult to classify from the histologic sections alone. Our results indicate that imprint cytology may reveal nuclear and cytoplasmic details not discernible in even the best tissue sections and that it may be selectively helpful in contributing to the classification of NHLs. Our results also show that the relative value of imprint cytology in the classification of malignant lymphomas varies greatly among categories. Specifically, we have found that imprints assist in three ways: the recognition of plasmacytoid features in small cell lymphocytic lymphomas, the recognition of plasmacytoid immunoblastic lymphoma, and the differentiation between NHLs which may be difficult to distinguish histologically. These include (1) small lymphocytic lymphoma versus lymphocytic lymphoma of intermediate differentiation, (2) true histiocytic malignancies versus large cell malignant lymphomas with abundant cytoplasm and/or phagocytosis, (3) anaplastic myeloma versus plasmacytoid immunoblastic lymphoma, (4) large noncleaved versus plasmacytoid immunoblastic lymphoma, (5) lymphoblastic lymphoma versus diffuse small cleaved cell lymphoma, and (6) lymphoblastic lymphoma versus small noncleaved cell lymphoma. Lymph node imprints are easy to prepare and readily interpretable by those experienced in the study of abnormal blood and bone marrow films. Their value as an ancillary methodology aimed at optimal accuracy in the classification of NHLs should be recognized.

Humans↗

Cytogenetic studies of Hodgkin's disease. Analysis of involved lymph nodes from 12 patients.

Cytogenetic studies were performed on 12 involved lymph nodes from Hodgkin's disease patients utilizing conditioned medium from 12-O-tetradecanoylphorbol-13-acetate-staphylococcus enterotoxin A induced mononuclear cells. The majority of cells analyzed had a normal karyotype. An unusually high rate of nonclonal karyotypic abnormalities was noted in most cultures. Clonal abnormalities involving chromosomes 3 and 21 were noted in two patients. Cytogenetic analysis of cultures stimulated with conditioned medium or specific growth factors may lead to a better understanding of the genetic mechanisms involved in Hodgkin's disease.

Adult↗

Relationship between eosinophil density and T-cell activation markers in lymph nodes of patients with Hodgkin's disease.

Hodgkin's disease (HD) is characterized morphologically by a variable infiltration of tissues by eosinophilic granulocytes. The lesions also contain numerous T cells, predominantly of the CD4+ immunophenotype. To investigate whether the presence or absence of tissue eosinophilia is related to the immunophenotype of the T cells, we studied 43 cases of HD (28 nodular sclerosing, ten mixed cellularity, and five unclassifiable) for the relative numbers of lymphocytes positive for CD2, CD3, CD4, CD5, CD8, CD25, CD38, T9, TQ1, HLA-DR, and beta F1, and for the number of eosinophils in tissue sections. By univariate and multivariate analysis, we determined that there was an inverse relationship between the number of eosinophils and the presence of TQ1+ (P less than .0005) and CD25+ (P less than .0005) lymphocytes. In addition, we observed that TQ1 stained the Reed-Sternberg cells in these lesions. We also determined that the T cells expressed HLA-DR more frequently in the nodular sclerosis subtype than in other subtypes of HD (P less than or equal to .0001). We therefore conclude that the degree of tissue eosinophilia in the lymph nodes of patients with HD may be explained, at least in part, by the immunophenotype of the T cells present in the affected lymph nodes.

Antibodies, Monoclonal↗

Monocytoid B-cell lymphoma: its evolution and relationship to other low-grade B-cell neoplasms.

Monocytoid B-cell lymphoma (MBCL) is a newly recognized B-cell neoplasm of uncertain histogenesis. The cytologic features of the neoplastic monocytoid B lymphocytes are virtually identical to those of hairy cell leukemia (HCL). As with HCL, progression of MBCL to a higher histologic grade is very unusual. However, whereas circulating leukemic cells are a characteristic feature of HCL, peripheral blood involvement has not been reported in MBCL. We recently studied a patient with MBCL of the spleen and axillary lymph nodes who developed peripheral blood involvement by MBCL cells. Unlike the cells of HCL, the circulating MBCL cells exhibited strong acid phosphatase activity that was tartrate sensitive. The leukemic cells had the antigenic phenotype IgM lambda, CD20+, CD11c+, CD5-, CD25(TAC)-, and PCA-1-. Immunogenetic studies of both lymph node and peripheral blood cells revealed identical immunoglobulin heavy-chain gene rearrangements. When compared with a series of HCL, the immunophenotype was similar except for the absence of PCA-1 and TAC. Progression of the MBCL to a large cell lymphoma, also expressing IgM lambda, was documented in an abdominal lymph node of this patient. Therefore, although rare, peripheral blood involvement by lymphoma cells may occur during the course of MBCL and should be distinguished from HCL with cytochemical and immunophenotypic studies. In addition, comparison of the clinical, pathologic, and immunologic features of MBCL with those of other low-grade B-cell neoplasms suggests that a close lineage relationship exists between MBCL and HCL.

Adult↗

T-cell-rich lymphoproliferative disorders. Morphologic and immunologic differential diagnoses.

To differentiate peripheral T-cell lymphomas (PTCL), the authors evaluated the results of T11 monoclonal antibody studies on consecutive cell suspensions prepared from 509 lymph nodes from various lymphoproliferative disorders (LPD). They used T11 (CD2) positivity to identify those LPD in which the content of T cells was high. There were 266 (52%) cell suspensions which contained more than 50% T11-positive cells. More than 75% of the following non-Hodgkin's lymphomas had over 50% T11-positive cells: diffuse mixed cell (DM), diffuse atypical poorly differentiated lymphocytic and lymphoblastic lymphomas; mycosis fungoides; and true histiocytic lymphoma. Eleven cell suspensions had more than 90% T11-positive cells; four were involved by B-cell lymphomas. The cell suspensions prepared from nine of 14 diffuse large cell lymphomas of the T-cell type had more than 50% T11-positive cells. Of these, three of five cases of the polymorphous subtype had fewer than 50% T11 cells, but six of seven lymph nodes of the clear-cell type had more than 50% T11-positive cells. Each of seven DM samples of the T-cell type contained over 50% T11 cells; none had a polymorphous appearance. In the 112 cases of reactive LPD studied, more than 75% of cases of necrotizing lymphadenitis, dermatopathic lymphadenitis, angioimmunoblastic lymphadenopathy, and those with lymph nodes with no specific reactive pattern had more than 50% T11-positive cells. The authors' findings indicate that T11 positivity is a reliable T-cell marker in reactive and neoplastic LPD except for those cases of PTCL with a polymorphous appearance; these tend to lose T11-expression. A multi-parameter diagnostic approach is required in the following LPD: (1) PTCL which are T11-negative; (2) PTCL of small lymphocytic type having an unremarkable T-cell phenotype; (3) SIg-negative B-cell lymphomas which are rich in nonneoplastic T cells; (4) non-Hodgkin's lymphomas with minimal disease which are rich in reactive T cells; and (5) polymorphous large cell proliferations.

Antigens, Differentiation, T-Lymphocyte↗

Antigenic phenotype of Langerhans cell histiocytosis: an immunohistochemical study demonstrating the value of LN-2, LN-3, and vimentin.

In order to determine the antigenic phenotype of the proliferating cells in Langerhans cell histiocytosis (LCH), we studied 15 such examples by using formalin- and B5-fixed, paraffin-embedded tissues. We used a panel of antibodies that are known to react with lymphocyte- and histiocyte-associated antigens. These included LN-1, LN-2, and LN-3 monoclonal antibodies (MoAbs), MoAbs to leukocyte common antigen (LCA), Leu-M1 antigen, vimentin, and epithelial membrane antigen (EMA), as well as polyclonal antibodies to lysozyme and S100 protein. The antigens encountered most frequently in LCH cells were S100 protein (93% of cases), vimentin (86%), and those detected by LN-2 (80%) and LN-3 (82%). Lysozyme was detected focally in two cases and diffusely in one case. The LCH cells were negative for LN-1, LCA, Leu-M1, and EMA. There was only one specimen in which S100 protein was not demonstrated; in this case, LN-3, vimentin, and T6 on frozen section were positive. The phenotype of LCH cells is similar to that of Langerhans' cells and interdigitating histiocytes. Our results demonstrate the value of using a panel of antibodies, including anti-vimentin MoAb, LN-2, and LN-3 for the immunophenotypic diagnosis of LCH in addition to an antibody to S100 protein.

Antibodies, Monoclonal↗

Immunoarchitecture of the "pseudofollicles" of well-differentiated (small) lymphocytic lymphoma: a comparison with true follicles.

Some human malignant lymphomas of the B-cell type have morphologic and immunologic similarities to follicles seen in nonneoplastic reactive lymph nodes. In contrast, a peculiar, vaguely nodular pattern of growth called "pseudonodules" or "pseudofollicular proliferation centers," which is morphologically distinguishable from "true" follicles, is seen in malignant lymphoma, well-differentiated (small) lymphocytic type (WDL). To characterize the cellular components of "pseudofollicles," we undertook a detailed, comparative immunohistologic study of the architectural relationship and distribution of T cells, B cells, and follicular dendritic reticulum cells (DRCs) in reactive follicles, neoplastic follicles, and pseudofollicles. We report several observations on the presence of DRCs and T-cell subset topography in pseudofollicles. Immunohistologic staining for the C3d complement receptor on DRCs revealed that DRC networks associated with "true" follicles were present in all cases of reactive follicular hyperplasia (RFH) and malignant lymphoma, nodular, poorly differentiated lymphocytic type (PDL) studied. Surprisingly, DRC networks were also identified in 8 of 23 cases of WDL. Although the size distribution of DRC network diameters was nearly identical in RFH and PDL, the sizes were markedly diminished in WDL. Immunohistologic staining for Leu 3+ and Leu 2+ T-cell subsets confirmed cellular arrangements in RFH and PDL reported by others. In only 2 of 23 cases of WDL could T cells localized to "pseudofollicles" in frozen tissue sections be identified in a nonrandom arrangement.

Adolescent↗

Differential expression of adenosine deaminase isozymes in acute leukemia.

Total adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP) activities were measured in cell samples from 13 cases of de novo acute leukemia and from three cases of chronic myeloid leukemia in blast crisis (CMLBC). These cases could be separated into lymphoid and nonlymphoid types on the basis of enzyme activity, with two misclassifications. However, PNP activity added little or no discriminatory information. Analysis for expression of the various molecular weight (mol wt) ADA isozymes, ADA1 (40 Kd) and ADA2 (110 Kd), revealed that ADA2 was expressed exclusively in nonlymphoid cells whereas ADA1 was found in both lymphoid and nonlymphoid cell types. Identification of ADA2 divided these leukemia cases into lymphoid and nonlymphoid types with no misclassifications (P = .0002; Fisher's exact test). Acute nonlymphoblastic leukemia (ANLL) with a monocytic component tended to have a greater percentage of ADA2 than ANLL without a monocytic component. These studies suggest that ADA2 may be a novel biochemical marker for an immature nonlymphoid cell.

Adenosine Deaminase↗

Antigenically defined subgroups of lymphoblastic lymphoma. Relationship to clinical presentation and biologic behavior.

A large panel of monoclonal antibodies and polyclonal antisera were used to ascertain the immunophenotypic characteristics of 36 lymphoblastic lymphomas (LBL). Results showed that this group of lymphomas have significant immunologic heterogeneity. Of the 36 cases, 33 were positive for T-cell antigens; among these, 22 cases were classified as T-cell LBL (TLBL, Group 1) based on their expression of T-cell-restricted and T-cell-associated antigens, and five expressed the common acute lymphoblastic leukemia antigen in addition to T-cell-associated antigens (Group 2). Six cases showed strong reactivity with anti-Leu-11 antibody, which defines a specific subtype of lymphocytes considered to have a natural killer (NK) function (Group 3). Two additional cases had a "pre-B" cell phenotype (Group 4), as determined by reactivity with BA-1 and BA-2 monoclonal antibodies, which react with immature and pre-B-lymphocytes. The neoplastic cells in the remaining case showed monoclonal surface membrane immunoglobulin of the IgMD heavy chain and kappa light chain type (Group 5). Despite immunophenotypic heterogeneity, the morphologic features were essentially similar in all cases. When the clinical features for each immunologic group were compared, however, two statistically significant findings resulted: (1) the frequency of mediastinal masses was highest in TLBL (Group 1, P less than 0.01), and (2) the male-female ratio was significantly lower in patients with LBL expressing NK-associated antigens (Group 3) than in the other groups of patients (P less than 0.01). Our data indicate that LBL can be divided into several immunologic subtypes; larger, prospective clinicopathologic studies are required to determine the clinical significance of the immunophenotypic classifications of LBL.

Adolescent↗

Lymphoblastic lymphoma expressing natural killer cell-associated antigens: a clinicopathologic study of six cases.

We describe six patients with lymphoblastic lymphoma (LBL) whose neoplastic lymphoid cells expressed surface antigens associated with natural killer (NK) cells. The six cases were selected from a series of 38 specimens diagnosed as LBL based on morphologic criteria and further subclassified by the use of an extensive panel of monoclonal and polyclonal antibodies. Although the morphologic features in all six cases were similar to those previously reported for LBL, their expression of NK-associated antigens was unique. All cases were positive with anti-Leu 11b, an antibody which appears to define a specific subtype of lymphocytes considered to have NK function; and all cases expressed T11, a T-cell-restricted antigen. The most commonly encountered immunophenotype of our cases of LBL was: Leu 11b+, T11+, Leu7+, TdT+, Leu 3a+, Ia+, pre-B-, and B-. As compared with more classical LBL of T-cell type, LBL of NK-cell type in our series occurred primarily in females and non-whites. Whereas treatment of classical LBL by multi-agent chemotherapy may lead to long-term survival, only two of our six patients were long-term survivors. The data derived from this study raise the possibility that LBL with the antigenic phenotype of NK cells may represent a biologic subtype of LBL.

Adolescent↗

Concurrent presence of two clonal populations in small lymphocytic lymphoma of the lung.

In a patient with small lymphocytic proliferation (SLP) involving the right middle and right lower lobes of the lung, immunophenotypic studies showed that the neoplastic lymphoid cells in the right middle lobe expressed kappa light chains, whereas those in the right lower lobe expressed lambda light chains on their surface. Gene rearrangement studies with Southern-blot hybridization confirmed the disparate surface immunoglobulin expression, and showed that the SLPs in the two lobes were derived from separate clones. The findings indicate that even morphologically identical lymphomas in the same organ may be immunophenotypically and genotypically heterogeneous. Our findings demonstrate that immunologic and DNA gene rearrangement analyses may complement each other in the study of lymphomas. This case is unique in that it is the first reported case of the concurrent presence of two immunologically distinct clonal populations in an extranodal site.

B-Lymphocytes↗

Monoclonal small (well-differentiated) lymphocytic proliferations of the gastrointestinal tract resembling lymphoid hyperplasia: a neoplasm of uncertain malignant potential.

Three histologically benign-appearing or diagnostically equivocal small lymphocytic proliferations of the gastrointestinal tract were examined by fresh-frozen section immunohistologic techniques. In one case, a dense infiltrate in the small intestine, consisting of small lymphocytes with round nuclei, was limited almost entirely to the mucosa. In another case, a localized colonic polyp was formed by mucosal and submucosal lobules of benign-appearing lymphoid aggregates with centrally located germinal centers. The third case, a penetrating gastric ulcer, was surrounded by histologically hyperplastic lymphoid tissue which included germinal centers. The small lymphocytes in all three cases were strongly positive for B-cell-associated antigens (B1, B2, BA-1), and all exhibited monoclonal light-chain restriction. Even though treatment consisted only of surgical resection of the lesions, no patient has had progressive disease during follow-up periods ranging from 24 to more than 50 months. We believe that the infiltrates in these cases are analogous to the morphologically benign monoclonal small lymphocytic proliferations common to the lung and orbit and that they have an uncertain, but probably low, malignant potential.

Adult↗

Recognition of hairy cell leukemia in a spleen of normal weight. The contribution of immunohistologic studies.

A 68-year-old man with known hairy cell leukemia (HCL) underwent splenectomy; the spleen weighed only 140 g. Microscopic examination of the spleen revealed no clear diagnostic evidence of HCL, but there was an unusual and suspicious subendothelial lymphoid infiltration of the trabecular veins. Cell suspension studies also were not diagnostic because a monoclonal B-cell population could not be defined. Alternatively, when we focused on the subendothelial infiltrate in the frozen sections prepared for immunohistochemical studies, the findings indicated that the subendothelial cells were monoclonal B-cells (IgG, kappa). Staining with monoclonal antibodies disclosed the phenotype Tac+, Leu-14+, Leu-M5+, B2-, BA-1-, and BA-2-, a phenotype characteristic of HCL. In this case, an unusual but nondiagnostic morphologic finding provided guidance for the correlative immunophenotypic analysis of the same site in frozen sections and thereby allowed a definitive diagnosis.

Aged↗

Distinction between undifferentiated (small noncleaved) and lymphoblastic lymphoma. An immunohistologic study on paraffin-embedded, fixed tissue sections.

The morphologic differentiation between malignant lymphoma of the small noncleaved cell (SNC) type and lymphoblastic lymphoma (LBL) is at times difficult, particularly when fresh tissue is not available for immunologic studies. We have examined the reactivities of a panel of monoclonal and polyclonal antibodies, including LN-1, LN-2, and antibodies to immunoglobulin light chains, leukocyte common antigen (LCA), Leu-M1, vimentin, S-100 protein, lysozyme, and alpha-1-antitrypsin, in paraffin-embedded, B5- and formalin-fixed tissue involved by SNC or LBL. The immunophenotypes in all of the cases included in this study had been characterized previously in fresh-frozen sections or cell suspensions. Among 21 samples of B5-fixed SNC, LN-1 was reactive in 17 and LN-2 in 18 cases. Among 13 B5-fixed LBL, LN-1 was reactive in two cases and LN-2 was reactive in two cases. Each of 20 B5-fixed samples of SNC was reactive with at least one of the antibodies, whereas 10 of the 13 B5-fixed samples of LBL were negative for both antibodies. Lesser reactivity was evident in formalin-fixed tissues, with only nine of 27 SNC specimens positive for LN-1 and 16 of 27 positive for LN-2. Most or all of the SNC and LBL samples were negative for immunoglobulin light chains, Leu-M1, vimentin, S-100 protein, lysozyme, and alpha-1-antitrypsin. The majority of both SNC and LBL were positive for LCA. We conclude that LN-1, preferably in combination with LN-2, can be used for distinguishing between SNC and LBL in paraffin-embedded, B5-fixed tissue when fresh tissue is not available.

Adolescent↗

Leu-9 (CD 7) positivity in acute leukemias: a marker of T-cell lineage?

Monoclonal antibody Leu-9 (CD 7) has been reported to be a sensitive and specific marker for T-cell lineage in leukemic processes, since it is positive in patients whose leukemic cells fail to express other T-cell antigens. To test whether Leu-9 is indeed specific for T-cell leukemias, we examined in detail 10 cases of acute leukemia in which reactions were positive for Leu-9 and negative for other T-cell-associated markers including T-11, Leu-1, T-3, and E-rosettes. Morphologically and cytochemically, 2 of these 10 leukemias were classified as lymphoblastic, 4 as myeloblastic, 2 as monoblastic, 1 as megakaryoblastic, and 1 as undifferentiated. The case of acute megakaryoblastic leukemia is the first reported case to be Leu-9 positive. None of the 10 were TdT positive. Of six cases (two monoblastic, one lymphoblastic, one myeloblastic, one megakaryoblastic, and one undifferentiated) in which we evaluated for DNA gene rearrangements, only one, a peroxidase-positive leukemia, showed a novel band on study of the T-cell-receptor beta-chain gene. We therefore conclude that Leu-9 is not a specific marker to T-cell lineage and that, in the absence of other supporting data, Leu-9 positivity should not be used as the sole basis of classifying an acute leukemia as being T-cell derived.

Acute Disease↗

Distribution of lymphocytes with interleukin-2 receptors (TAC antigens) in reactive lymphoproliferative processes, Hodgkin's disease, and non-Hodgkin's lymphomas. An immunohistologic study of 300 cases.

The authors investigated the distribution of interleukin-2 receptors (TAC antigen) in the lymph nodes of 300 patients with lymphoproliferative disorders. They used fresh-frozen sections to evaluate a possible correlation between the immunophenotype of specific lymphoid disorders and the presence or absence of TAC expression and to determine whether the TAC positivity of lymphoid cells contributes to the characterization of lymphoproliferative processes. All of the cases had previously been studied with a large screening panel of monoclonal antibodies and polyclonal antisera. Among 85 patients with a variety of benign reactive processes, the lymph nodes from 47 contained TAC-bearing lymphocytes in various patterns of distribution. Of 41 patients with Hodgkin's disease, 37 had TAC-bearing lymphocytes. Of 26 B-cell, well-differentiated lymphocytic lymphomas (WDL), 14 were diffusely TAC-positive and one had TAC-bearing cells in random distribution. Six cases of intermediate lymphocytic lymphoma were also studied, and three showed randomly distributed TAC-bearing lymphocytes. Of 19 patients with follicular or follicular and diffuse, poorly differentiated lymphocytic (PDL) lymphoma, 14 were TAC-positive. All 3 diffuse PDL lymphomas studied were TAC-negative. Among 23 cases of B-cell and 5 cases of T-cell mixed cell lymphoma, 15 and three, respectively, had TAC-positive lymphocytes. Of 39 large cell lymphomas (B-cell, 33; T-cell, 6), 14 were TAC-positive. All 13 cases of hairy cell leukemia were diffusely positive. Of 23 T-lymphoblastic lymphomas, only 1 showed positive TAC reactivity, which was focal. Of 5 cases of cutaneous T-cell lymphoma, 2 had TAC-bearing lymphocytes. Our study indicates that the TAC antigen is not lineage-specific, and that it may be expressed by lymphoid cells regardless of their phenotype.

B-Lymphocytes↗

Rearrangement of kappa-chain and T-cell receptor beta-chain genes in malignant lymphomas of "T-cell" phenotype.

Detection of immunoglobulin gene rearrangements by molecular hybridization is considered to be a highly sensitive approach to the evaluation of clonality of B-cell-derived neoplasms. Like monoclonal surface immunoglobulin in B cells, which serves as a reliable immunophenotypic marker for clonality, rearrangement of the genes encoding immunoglobulin light chains has been accepted as a reliable genotypic marker for the presence of a clonal expansion of B lymphocytes. The authors now report 3 cases of non-Hodgkin's lymphoma that were immunologically classified as having a T-cell phenotype and in which, in addition to rearrangements of the T-cell receptor beta-chain gene, a rearrangement of an immunoglobulin light-chain gene was clearly identified by Southern blot hybridization. The results demonstrate that the data obtained by molecular hybridization should be interpreted with caution when the immunogenetic findings do not correlate with immunophenotypic expression, and that the results of molecular genetics studies should be interpreted in conjunction with morphologic and immunologic findings.

Aged↗