lewis-x-antigen and Lymphoma--Non-Hodgkin

Resting human NK cells require a two-stage activation process that we have previously described as "priming" and "triggering." NK-sensitive tumor cells provide both priming and triggering signals. NK-resistant tumors evade lysis, mostly by failure to prime; however, we recently reported a tumor cell line (CTV-1) that primes resting NK cells but fails to trigger lysis. In this article, we report two additional leukemia cell lines that prime NK cells but are resistant to lysis. Tumor-mediated NK priming is via CD2 binding to a ligand within CD15 on the tumor cell. NK-resistant RAJI cells became susceptible to NK lysis following transfection and expression of CD15. Blockade of CD15 on K562 cells or on CD15(+) RAJI cells significantly inhibited lysis, as did blockade of CD2 on resting NK cells. NK priming via CD2 induced CD16 shedding, releasing CD3ζ to the CD2, leading to its phosphorylation and the subsequent phosphorylation of linker for activation of T cells and STAT-5 and synthesis of IFN-γ. Blockade of C-type lectin receptors significantly suppressed the tumor-mediated priming of NK cells, whereas blockade of Ig-superfamily-like receptors had no effect at the NK-priming stage. Tumor priming of resting NK cells was irrespective of HLA expression, and blockade of HLA-killer Ig-like receptor interactions did not influence the incidence or degree of priming. However, CD15-CD2 interactions were critical for NK priming and were required, even in the absence of HLA-mediated NK inhibition. Tumor-mediated priming led to a sustained primed state, and the activated NK cells retained the ability to lyse NK-resistant tumors, even after cryopreservation.

Topics: CD2 Antigens; Cell Differentiation; Cell Line, Tumor; Cell Lineage; Coculture Techniques; Cytotoxicity, Immunologic; Disease Resistance; Fucosyltransferases; Humans; Killer Cells, Natural; Leukemia, Monocytic, Acute; Leukemia, Myelomonocytic, Acute; Lewis X Antigen; Ligands; Lymphocyte Activation; Lymphoma, Non-Hodgkin; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Protein Binding; Receptors, KIR; Resting Phase, Cell Cycle; Signal Transduction

CD15 is a useful immunohistochemical marker to identify Reed-Sternberg cells in classical Hodgkin's lymphoma (HL) and to distinguish it from HD-like neoplasms, but data from the literature concerning its expression in HL are quite variable. Using immunohistochemistry we compared the reactivity of three different anti-CD15 clones (MMA, C3D1 and BY87) and found that anti-CD15 MMA clone is a superior reagent in identifying atypical cells, detecting more numerous cells in 28.2%, and being the only positive marker in 12.8% of cases. We conclude that it is advisable to include this reagent in diagnostic immunohistochemical panels.

Topics: Animals; Antibodies, Monoclonal; Antigen-Antibody Reactions; Antigens, Neoplasm; Diagnosis, Differential; Hodgkin Disease; Humans; Immunoglobulin M; Lewis X Antigen; Lymphoma, Non-Hodgkin; Lymphoma, T-Cell, Peripheral; Mice; Reed-Sternberg Cells; Sensitivity and Specificity

Inflammatory malignant fibrous histiocytoma (IMFH), consisting of large, atypical histiocyte-like cells set amidst an inflammatory backdrop of eosinophils, neutrophils, lymphocytes, and xanthoma cells, can be difficult to distinguish from Hodgkin's disease and non-Hodgkin's lymphoma, particularly of the Ki-1 anaplastic large-cell type in small biopsy specimens. This problem is becoming more prevalent with the use of needle biopsies guided by computed tomography for definitive diagnosis. For this reason, we studied the expression of a battery of leukocyte markers in IMFH to evaluate whether they could serve as an independently reliable means of distinguishing amongst the three neoplasms. Eight examples of histologically typical IMFH were stained with a number of leukocyte markers that included CD30 (BerH2), CD15 (leuM1), CD45/ CD45RB (2B11,PD7/26/16), CD43 (leu 22), CD45RO (A6), CD20 (L26), and CD68 (KPI). The large anaplastic tumor cells within IMFH consistently lacked CD30, CD15, CD45/CD45RB, CD43, CD45RO, and CD20. In one case, the anaplastic cells expressed CD68. Benign histiocytes within IMFH expressed CD68 and displayed variable expression of CD15, CD45/CD45RB, and CD43. The reactive lymphocytes consisted mostly of scattered small T cells with a few B cells, mainly within lymphoid aggregates. We conclude that the immunophenotypic profile of the anaplastic cells in IMFH (lack of CD15, CD30, CD43, CD45/CD45RB, CD45RO, CD20) differs from most cases of Hodgkin's disease (ICD30+, CD15+/-) and from Ki-1 anaplastic large cell lymphoma (CD30+, CD45/CD45RB+/-, CD43+/-, CD45RO+/-, CD20-/+). Immunohistochemistry is an important diagnostic adjunct, provided care is taken to exclude benign histiocytes and inflammatory cells from consideration.

Topics: Adult; Aged; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Biomarkers; Diagnosis, Differential; Female; Histiocytoma, Benign Fibrous; Hodgkin Disease; Humans; Immunohistochemistry; Lewis X Antigen; Lymphoma, Non-Hodgkin; Male; Middle Aged; Retrospective Studies

We compared the clinical and pathological features of 10 HIV+ CD30+ anaplastic large cell lymphoma (ALCL) patients with 28 HIV+ CD30- non-Hodgkin's lymphoma (NHL) patients. The incidence of ALCL among 38 HIV+ systemic NHL patients was 26%. Clinical features were similar in all the HIV-related NHL cases, but ALCL patients seemed to differ from HIV+ CD30- systemic NHL only in the greater frequency of lung tumours (40% v 21%) without concomitant mediastinal mass, bone marrow (75% v 18%) and gastroenteric involvement (40% v 25%). Among the HIV+ ALCL patients, histologic subtypes did not differ in frequency from ALCL in the general population. The B phenotype was predominant (50%) as in other HIV-related NHL. EBV genoma, studied in all HIV+ ALCL patients, was present in 3/10 by in situ hybridization (ISH) and in 5/10 cases using PCR. The clinical course of lymphomas was similar in CD30 positive and negative NHL patients. Overall survival also was short in our series, particularly in HIV+ ALCL (84 v 188 d), probably because of profound immunodepression of the ALCL patients. Our findings suggest that severe immunodepression due to HIV infection determines-more than any other factor-the clinical features of HIV+ ALCL, making them very similar to those of other high-grade systemic HIV+ NHL.

Topics: Adult; Antigens, CD20; Female; Humans; Immunophenotyping; Ki-1 Antigen; Leukocyte Common Antigens; Lewis X Antigen; Lymphoma, AIDS-Related; Lymphoma, Large-Cell, Anaplastic; Lymphoma, Non-Hodgkin; Male; Middle Aged; Survival Rate

The clinical histopathological and immunophenotypic features in 5 patients with Ki-1 positive non-Hodgkin's lymphoma (NHL) were studied. When first seen, 4 patients presented enlargement of superficial lymph nodes, with skin lesions in 2 patients. Two patients in stage IV with fever, hepato-splenomegaly and bone marrow invasion, died. Histologically, the tumor cells showed diffused or patchy hyperplasia. The cells were relatively large in size, rich in bosophilic or slightly eosinophilic cytoplasm with irregularly-shaped nuclei, prominent nucleoli, and distinct anaplasia and pleomorphism. Some of the cells looked very much like the Reed-Sternberg cells. Multinucleated giant cells were seen. Immunophenotypically, all the cells were CD30 (Ki-1) and CD25 (IL-2 receptor) positive but CD15 (Leu M1) negative. Thus, the 5 patient T Ki-1 positive NHL were all of T cell type.

Topics: Adolescent; Aged; Diagnosis, Differential; Hodgkin Disease; Humans; Immunophenotyping; Ki-1 Antigen; Lewis X Antigen; Lymphoma, Non-Hodgkin; Lymphoma, T-Cell; Male; Middle Aged; Receptors, Interleukin-2

Both immunophenotypic overlaps between Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL), and evolution of one into the other have been reported. However, the underlying assumption that the antigenic expression of Reed-Sternberg (RS) cells is consistent in the same patient has not been evaluated. Such an evaluation was undertaken by immunophenotyping paraffin-embedded lymphoid tissue biopsies with HD from 56 patients in whom multiple specimens were obtained, either simultaneously from different sites or at different times. The panel of antibodies we used included: CD3 polyclonal antiserum, DAKO-M1 (CD15), L26 (CD20), BerH2 (CD30), MT1 (CD43), DAKO-LCA (CD45RB), UCHL1 (CD45R0), LN2 (CD74), and DAKO-EMA. The phenotype of RS cells was identical in simultaneous biopsies in only 11 of 39 patients (28%) and remained constant in consecutive biopsies in only 4 of 21 patients (19%). Major differences (relative to cell lineage specific antigens) were observed in 10 of 39 patients with simultaneous biopsies and in 10 of 21 patients over time; they mainly involved expression of T-cell antigens. Minor differences (relative to any other antigen) were observed in 22 of 39 patients with simultaneous biopsies and in 15 of 21 patients over time; these mainly involved CD15 or CD74. This striking variability of the immunophenotype of RS cells in the same patient may be due to aberrant marker expression, as a result of the neoplastic state, and/or to modulation of antigenic expression in relation to the host environment. This inconsistency suggests caution when interpreting the relationship between HD and NHL by paraffin immunophenotyping alone.

Topics: Antibodies; Antigens, CD; Antigens, Differentiation, B-Lymphocyte; Biomarkers; Biopsy; Histocompatibility Antigens Class II; Histological Techniques; Hodgkin Disease; Humans; Immunophenotyping; Lewis X Antigen; Lymphoid Tissue; Lymphoma, Non-Hodgkin; Paraffin; Reed-Sternberg Cells

Immunohistochemistry is a valuable adjunct to the identification of Hodgkin's disease (HD) Reed-Sternberg (RS) cells, and in the differential diagnosis between HD, non-Hodgkin's lymphomas, and nonlymphoid neoplasms containing RS-like cells. The characteristic phenotype of RS cells in different subtypes of HD is described, with an emphasis on routine immunohistochemical stains. Some of the conflicting literature on this subject is reviewed to highlight pitfalls and controversies in the field.

Topics: Antigens, CD; Antigens, Neoplasm; Diagnosis, Differential; Hodgkin Disease; Humans; Immunohistochemistry; Ki-1 Antigen; Leukocyte Common Antigens; Lewis X Antigen; Lymphoma, Non-Hodgkin; Reed-Sternberg Cells

Composite lymphomas have rarely been reported in Hodgkin's disease (HD), except in the lymphocyte predominance sub-type, and immunohistochemical investigations have been performed in only few cases. We describe the histological and immunophenotypical findings in a case of composite nodular sclerosing HD and high-grade, large cell non-Hodgkin's lymphoma (NHL). In our case HD and NHL cells displayed striking morphological and immunophenotypical divergence, suggesting a lack of correlation between the two neoplasms.

Topics: Adult; Antigens, CD; Antigens, CD20; Antigens, Differentiation, B-Lymphocyte; Antineoplastic Agents; beta-D-Galactoside alpha 2-6-Sialyltransferase; Histocompatibility Antigens Class II; HLA-DR Antigens; Hodgkin Disease; Humans; Lewis X Antigen; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Male; Membrane Glycoproteins; Mucin-1; Neoplasms, Multiple Primary; Phenotype; Sialyltransferases

The gene encoding p53 phosphoprotein, originally believed to be an oncogene, recently has been proposed as a candidate antioncogene (tumor-suppressor gene). Abnormalities of the p53 gene expression have been demonstrated in different human malignancies including carcinomas and sarcomas, but little information concerning p53 immunoreactivity in human lymphomas is so far available. In this study immunohistochemical staining for p53-protein was performed on frozen- and paraffin-embedded samples from patients with Hodgkin's (HD) and non-Hodgkin's lymphomas (NHL). No p53 immunoreactivity could be demonstrated in any cell type in nonneoplastic lymphoid samples, including germinal center cells in reactive lymph nodes and cortical thymocytes. On the other hand, a significant proportion of p53+ neoplastic cells was observed in 23 of 31 cases of HD and 17 of 68 cases of NHL. All positive lymphoma cases were diagnosed as high-grade or CD30+ anaplastic NHL. The demonstration of abnormal expression of p53 protein in these diseases can contribute to addressing unresolved issues regarding the origin and pathogenesis of HD and CD30+ anaplastic lymphomas.

Topics: Antibodies, Monoclonal; Antigens, CD; Antigens, Neoplasm; Gene Expression Regulation, Neoplastic; Genes, p53; Hodgkin Disease; Humans; Ki-1 Antigen; Lewis X Antigen; Lymph Nodes; Lymphoma, Non-Hodgkin; Neoplasm Proteins; Thymus Gland; Tumor Suppressor Protein p53

Using a monoclonal antibody specific to the Lewis X antigen (anti-Lex), the authors studied 103 cases of Hodgkin's disease (HD) in comparison with 57 cases of non-Hodgkin's lymphoma (NHL); three cases of granulocytic sarcoma (GS); two cases of malignant histiocytosis (MH); one case of monoblastic leukemia (ML); one case of interdigitating reticulum cell sarcoma (IRCS); six cases of histiocytosis X (HX); one case of reticulohistiocytoma (RH); 44 various reactive conditions of the lymph node (LN). Reed-Sternberg and related (R-S) cells stained selectively in 80 of 92 cases of HD (87.0%), excluding 11 cases of lymphocyte predominance type. The stain was better in B-5-fixed specimens than in formalin-fixed specimens, showing a dense deposit of reaction products at a paranuclear site and on the cell surface. The staining results were compared with those of Leu-M1 and found to be superior both qualitatively and quantitatively (detection rate of R-S cells: 87.0% versus 68.5% of Leu-M1). Granulocytes, rare epithelioid histiocytes, and some endothelial and/or erythrocytes also stained with anti-Lex. The stain had positive results in three cases of GS showing a diffuse cytoplasmic staining pattern. Of NHL, two of 29 peripheral T-cell lymphomas stained to show rare paranuclear deposits without cell surface staining. The stain had negative results in MH, ML, IRCS, HX, and RH. Of 45 reactive LN, minute subcapsular collections of Lewis X+, altered-appearing Langerhans'-like cells, were observed in all ten LN from human immunodeficiency virus (HIV)-associated persistent generalized lymphadenopathy (PGL). The stain had negative results in all other various reactive conditions of LN. In conclusion, Lewis X staining is useful as a marker for R-S cells in paraffin sections with staining results superior to those of Leu-M1. Lewis X staining also detects subcapsular clustering of altered-appearing Langerhans'-like cells in PGL, which has not been described previously and warrants additional study.

Topics: Acquired Immunodeficiency Syndrome; Antibodies, Monoclonal; Antigens, Differentiation, Myelomonocytic; Biomarkers, Tumor; Diagnosis, Differential; Histiocytic Sarcoma; Histiocytosis, Langerhans-Cell; Hodgkin Disease; Humans; Leukemia, Myeloid; Lewis X Antigen; Lymph Nodes; Lymphoma, Non-Hodgkin; Male; Middle Aged; Staining and Labeling

Monoclonal antibody to LeuM1, a granulocyte-related differentiation antigen, represents a highly effective reagent for detection of diagnostic "Reed-Sternberg" cells and variants in paraffin-embedded tissues of Hodgkin's disease. The "Reed Sternberg" cell in all the cases of Hodgkin's disease except lymphocyte predominance variety revealed positive intracytoplasmic/paranuclear granular staining with LeuM1 marker. The R-S cells in lymphocyte predominance variety contain probably sialylated LeuM1 antigen. All the cases of non-Hodgkin's lymphoma and reactive lymphadenitis showed no staining with LeuM1 monoclonal antibody. Therefore this antibody represents a potentially helpful diagnostic discriminant in the assessment of Hodgkin's disease and its distinction from non-Hodgkin's lymphomas and morphologically similar reactive lymphoid lesions.

Topics: Antibodies, Monoclonal; Antibodies, Neoplasm; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Biomarkers, Tumor; Child; Diagnosis, Differential; Hodgkin Disease; Humans; Lewis X Antigen; Lymphoma, Non-Hodgkin; Male

A case of chemotherapy-resistant non-Hodgkin's lymphoma simultaneously expressing T cell (CD7)-, B cell (CD19)- and myeloid (CD13, CD33)-associated surface antigens is presented. Cytochemical analysis revealed that the lymphoma cells were positive for terminal deoxynucleotidyl transferase, but negative for myeloperoxidase and esterase. Rearrangements of both the T cell receptor beta chain and gamma chain genes were observed, but the immunoglobulin genes showed a germ line configuration. The rearrangement was not detected within the breakpoint cluster region on chromosome 22. These findings are considered to represent aberrant expressions of the B cell- and myeloid-associated antigens in early-stage T cell lineage lymphoma cells.

Topics: Adult; Antigens, Neoplasm; Antigens, Surface; Bone Marrow; Chromosomes, Human, Pair 22; DNA Probes; Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor; Genotype; Histocytochemistry; Humans; Lewis X Antigen; Lymphoma, Non-Hodgkin; Male; Phenotype

Hodgkin's disease (HD) is sometimes difficult to distinguish from non-Hodgkin's lymphomas, and a reliable marker for Reed-Sternberg and related (R-S) cells in paraffin sections would be useful. Ninety-one cases of HD with PNA, anti-Leu M1, and LN-2, and 90 cases with Ber-H2 were studied. The staining results were evaluated independently. R-S cells stained positively with one or more of the reagents in all cases. PNA staining was positive in 78 cases (85.7%); Leu M1, 63 (69.2%); LN-2, 71 (78.0%); and Ber-H2, 80 cases (88.9%). Positively stained cells were readily recognized in 71 cases (91.0%) of PNA+, 51 (80.9%) of Leu M1+, and 51 (71.8%) of LN-2+ and 71 (88.7%) of Ber-H2+ cases; the cells were found only after careful search in the remaining cases. Sixteen cases of peripheral T-cell lymphoma (large cell type, ten; mixed, five; unclassifiable, one) were also stained. Tumor cells did not stain with PNA or anti-Leu M1 in any of the 16 cases but did stain positively with LN-2 in four and with Ber-H2 in five. Thus, the detection rate of R-S cells was the highest with Ber-H2, closely followed by PNA. PNA, however, stained the largest number of R-S cells per case, and the results were least affected by the type of fixative employed. Staining of peripheral T-cell lymphoma appeared to be nil or extremely rare with PNA and Leu M1, whereas it was not uncommon with Ber-H2 and LN-2. In conclusion, to facilitate the detection of R-S cells in paraffin sections, the application of a panel of three markers, PNA, Leu M1, and Ber-H2, appears to be necessary at this point in time.

Topics: Antigens, Differentiation; Antigens, Differentiation, B-Lymphocyte; Antigens, Differentiation, Myelomonocytic; Antigens, Neoplasm; Cytological Techniques; Diagnosis, Differential; Histiocytes; Histocompatibility Antigens Class II; Hodgkin Disease; Humans; Ki-1 Antigen; Lectins; Lewis X Antigen; Lymphoma, Non-Hodgkin; Paraffin; Peanut Agglutinin