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Biomedical subjects

R J Lukes

Publications and source records attributed to R J Lukes.

At least 37 records · Page 2Linked to original sources

Limitations of numerical ratios for defining monoclonality of immunoglobulin light chains in B-cell lymphomas.

Hematopathologists sometimes rely upon the "monoclonality" of immunoglobulin light chains of B-cells as an indicator of malignancy in lymph node biopsies. The validity of using the ratio of kappa to lambda light chains for defining monoclonality has not been statistically established, however. We examined with flow cytometry 57 unequivocal B-cell lymphomas and 49 benign lymphoid hyperplasias. Our purpose was to define and study the optimal numerical criteria for discriminating between B-cell lymphomas and benign hyperplasia on the basis of the kappa:lambda ratio. The data indicate that ratios less than .7 or greater than 5.5 are the optimum for discriminating between lymphoma and benign hyperplasia, but they have a false negative rate of approximately 27% and a 6% false positive rate. The reasons for the relatively low sensitivity are discussed. We conclude that kappa:lambda ratios are a fairly specific but insensitive parameter for distinguishing between B-cell lymphoma and benign lymphoid hyperplasia.

Antibodies, Monoclonal↗

Non-Hodgkin's lymphoma in 90 homosexual men. Relation to generalized lymphadenopathy and the acquired immunodeficiency syndrome.

We describe the histologic and clinical features of non-Hodgkin's lymphoma diagnosed between January 1980 and December 1983 in 90 homosexual men from San Francisco, Los Angeles, Houston, and New York. The median age was 37 years, with an age distribution identical to that for cases of AIDS reported to the Centers for Disease Control. Sixty-two per cent of the patients had high-grade (aggressive) subtypes of lymphoma, 29 per cent had subtypes of intermediate grade, and 7 per cent had low-grade subtypes. Histologic subtypes and malignant cell phenotypes were consistent with a B-cell origin. All but two men had extranodal lymphoma: central-nervous-system, bone-marrow, bowel, and mucocutaneous sites were most commonly involved. Thirty-five of 66 evaluable men (53 per cent) had complete responses to combination chemotherapy or radiotherapy or both, and thus far, 19 (54 per cent) of them have had a relapse. Mortality and morbidity were closely related to prodromal manifestations; death or illness have occurred in 19 (91 per cent) of the 21 men who presented with AIDS, in 26 (79 per cent) of the 33 who presented with generalized lymphadenopathy, and in 5 (42 per cent) of the 12 who had no prodromal manifestations. Mortality rates analyzed according to histologic grade were higher than currently reported rates in other patient populations. Kaposi's sarcoma or severe opportunistic infections characteristic of AIDS developed in 14 of 33 men (42 per cent) who presented with generalized lymphadenopathy and in 3 of 12 (33 per cent) without prodromal manifestations. We conclude that non-Hodgkin's lymphoma in members of an AIDS risk group is a serious manifestation of AIDS and the AIDS-related complex.

Acquired Immunodeficiency Syndrome↗

Mycosis fungoides/Sezary's syndrome progressing to immunoblastic sarcoma. A T-cell lymphoproliferation with both helper and suppressor phenotypes.

Multiparameter studies of an unusual patient exhibiting cutaneous manifestations of both mycosis fungoides and Sezary's syndrome are presented. The neoplastic cells of dermal and nodal infiltrates and peripheral blood expressed both helper and suppressor immunologic phenotypes. Cytofluorographic analysis of cells isolated from lymph node and peripheral blood showed a population of neoplastic cells that were stained with the monoclonal antibodies OKT 3, 4, 8, and 11. Immunoperoxidase staining of frozen sections with monoclonal antibodies Leu 1, 2, and 3 provided a topographical identification of an identically marking population of cells in dermis and lymph node. In light of current models depicting normal T-cell lineage, the authors suggest that the neoplastic population in this patient, expressing both helper and suppressor phenotypes, reflected a phenotypic stage of immunologic maturation (OKT 6-, OKT 10-, OKT 3+, OKT 11+, OKT 4+, OKT 8+) in which the neoplastic cells had not yet segregated into distinctive T-cell subsets. While excess helper activity was suggested by serum hypergammaglobulinemia, in vitro helper and suppressor function was not determined. The range of studies employed illustrates the wide variety of technics required to adequately characterize complex clinico-immunopathologic disorders, as represented by this case, and the wealth of information that can be gleaned.

Antibodies, Monoclonal↗

Development of B-cell lymphoma in homosexual men. Clinical and immunologic findings.

Serious infections, neoplasms, and immunologic abnormalities have been found in homosexual men. We describe the development of malignant lymphoma in six such patients, three of whom had persistent, generalized lymphadenopathy. In biopsies done before the lymphoma developed, the lymphadenopathy was characterized morphologically by a distinctive pattern of B-cell follicular hyperplasia. All lymphomas were of B-lymphocytic origin, including B-cell immunoblastic sarcoma; small noncleaved, Burkitt-like lymphoma; and plasmacytoid lymphocytic lymphoma. Extranodal presentation with B symptoms occurred in five patients. Median age of our patients was 33 years. Three patients had histories of repeated systemic infections. The peripheral blood lymphocyte count was depressed in four, with depression of OKT 4+ (helper phenotype) cell levels and reversal of the T-helper: T-suppressor ratio in all. We conclude that these patients are at risk for the development of abnormalities of the B-lymphocytic system, manifested by abnormal hyper-B-cell response in enlarged reactive lymph nodes and aggressive, extranodal B-cell lymphomas.

Adult↗

Small noncleaved follicular center cell (FCC) lymphoma: Burkitt and non-Burkitt variants in the United States. I. Clinical features.

With the understanding that Burkitt's lymphoma was of follicular center cell (FCC) derivation, Lukes and Collins classified the tumor, descriptively, as small noncleaved FCC lymphoma. Two subtypes were described: Burkitt and non-Burkitt. Attempting to define the clinicopathologic features of the subtypes, we studied 42 patients: 25 Burkitt and 17 non-Burkitt. Histologically, the Burkitt tumor demonstrated remarkable uniformity of nuclear size and contour, whereas the non-Burkitt variant had greater variability. Immunoglobulin monoclonality was demonstrated in 83% of Burkitt and 81% of non-Burkitt cases. Burkitt patients tended to be younger. Gastrointestinal disease was seen in 15 Burkitt and only four non-Burkitt patients (P less than 0.05). Disseminated disease was found in the majority of both variants. Marrow involvement was demonstrated in 4.5% of Burkitt and 37.5% of non-Burkitt patients (P less than 0.05). Median survival of Burkitt patients was 10.5 months versus 7.7 months in the non-Burkitt group. The authors believe that significant biologic differences between the variants have been demonstrated, which may be of potential value to the clinician.

Adolescent↗

T-lymphocyte subsets in lymph nodes from homosexual men.

To evaluate further the immunodeficiency of homosexual men, blood and lymph node specimens were obtained from five homosexual men with lymphadenopathy and from seven homosexual men with Kaposi's sarcoma. Monoclonal antibodies were used to identify T-lymphocyte subsets in blood by cytofluorometry and in frozen sections of nodes by immunoperoxidase techniques. The homosexuals with Kaposi's sarcoma had a T-helper/suppressor ratio in blood of 0.7; the homosexuals with lymphadenopathy had a ratio of 0.6, compared with controls of 2.1. Control lymphoid tissue had a ratio of 3.0 in the interfollicular areas compared with the reactive lymph nodes in the homosexuals with lymphadenopathy, which was 0.7, and nodes from patients with Kaposi's sarcoma, 0.9. The nodes from homosexual men had evident numerous suppressor cells in the follicular center and mantle regions, locations in normal lymphoid tissue where suppressor cells were uncommon.

Flow Cytometry↗

Benign and malignant mast cell proliferations. Diagnosis and separation using a pH-dependent toluidine blue stain in tissue section.

Using a pH-adjusted toluidine blue stain (pH range, 2.5-6.5), we sequentially examined the staining patterns of mast cells in tissue sections taken from patients with localized or reactive mast cell lesions and benign or malignant mastocytosis syndromes. Reactive or benign lesions stained well over the entire range of pHs and were separated from malignant mast cell proliferations which stained poorly and with greatest intensity in the less acidic range (pH greater than 3.5). Patients with disseminated mast cell lesions but without tumor masses or leukemia had a staining pattern between that of benign and malignant lesions. Basophils stained intensely at pH 2.5, and metachromasia rapidly diminished at higher pH. The use of the pH dependent toluidine blue stain may be an adjunct in recognizing patients with mast cell lesions, predicting their prognosis, and distinguishing basophils from mast cells.

Adult↗

An immunohistochemical study of hemoglobin A, hemoglobin F, muramidase, and transferrin in erythroid hyperplasia and neoplasia.

The bone marrow biopsy specimens of 35 patients with benign and malignant erythroid hyperplasias were examined for the presence of hemoglobin A, hemoglobin F, muramidase (lysozyme), and transferrin, using an indirect immunoperoxidase method (PAP) on Zenker's-fixed paraffin-embedded bone marrow biopsy specimens and particles. Five cases of each of the following entities were studied: erythroleukemia and erythremic myelosis, acute granulocytic leukemia with maturation (FAB M2), polycythemia rubra vera, myeloproliferative syndrome in childhood, megaloblastic anemia (B12 and folate deficiency), erythroid hyperplasia (regenerating bone marrow and hemolytic anemia), and Ph' chromosome positive chronic granulocytic leukemia. Hemoglobin A was present in both the early and late erythroid precursors in all conditions. Hemoglobin F was the predominant hemoglobin in early erythroblasts of pernicious anemia and in both early and late erythroid elements in erythroleukemia and erythremic myelosis. Small quantities of hemoglobin F were present in a few isolated clusters in other conditions. Staining for hemoglobin F may be useful in identifying immature erythroid precursors and in distinguishing some cases of dysplastic erythroid hyperplasia from neoplasia. Additionally, these findings suggest that the maturational switch in hemoglobin synthesis operates with distinct pathways under different conditions.

Bone Marrow↗

Reactive lymphoid hyperplasia with single class (monoclonal) surface immunoglobulin.

Lymphoid tissues from 12 patients were diagnosed as reactive lymphoid hyperplasia, but surface immunoglobulin studies revealed monoclonal (single class) immunoglobulin staining patterns. Infectious, autoimmune, and immunodeficient conditions were diagnosed on the basis of histology and clinical features. Such surface immunoglobulin restriction has been used as an indicator of a neoplastic lymphoid proliferation, but the cases of these patients, in whom the histologic diagnosis was benign, emphasize the importance of a multiparameter approach to diagnosis. Although at the time of this report none of the patients still available to follow-up study have developed known lymphoid neoplasms, the possibility that monoclonal SIg patterns are a harbinger of neoplastic disease makes continuing follow-up of such patients important.

Adolescent↗

Immunohistochemical characterization of reactive and neoplastic mast cells.

Mast cells are connective tissue elements likened to unicellular endocrine organs because of the wide diversity of physiologic and pathologic events associated with the secretion of biologically active compounds. Using an immunoperoxidase method (PAP), we studied tissue from patients with benign and malignant systemic mastocytosis and with a variety of reactive conditions. The following immunoreactive antigens were identified in mast cells: a heparinlike compound or compounds (HLC), prostaglandin, serotonin, and fibronectin. HLC is constantly present, staining mast cells in a granular fashion from most lesions. Serotonin and prostaglandin stain in a diffuse cytoplasmic manner in occasional lesions. Fibronectin is found in a surface location in selected cases. We found no clear association between the immunoreactivity of one compound in mast cells and one clinical symptom, e.g., HCL with bleeding, prostaglandin, or serotonin with systemic vasomotor activity or fibronectin with increased tissue fibrosis. However, patients with localized and systemic disease had symptoms that might have been attributed to more than one compound. Only occasional patients with reactive conditions showed such symptoms. The presence of these compounds, either alone or in combination, did not separate benign from malignant conditions. Other cells within selected tissues also stained with the antibodies tested. Despite the lack of exclusivity, these antibodies are useful in identifying mast cells within tissue sections and may have a role in the study of mast cell constituents.

Animals↗

Demonstration of a subpopulation of Ia+ T-helper cells in mycosis fungoides and the Sézary syndrome.

This is a report of the finding of a T-cell subpopulation bearing T-helper cells and Ia antigens in specimens of skin from patients with mycosis fungoides and the Sézary syndrome. Frozen sections of skin tissue from eight patients examined with monoclonal antibodies against mature T-cells, helper T-cells, suppressor T-cells, and Ia antigens exhibited similar staining patterns by a modified immunoperoxidase method. Antibodies against mature T-cells and helper T-cells stained 70-80% of the lymphocytes in the dermis. The antibody defining the phenotype of suppressor T-cells labelled 5-10% of the lymphocytes scattered throughout the lesions. Eighty to 90% of the lymphocytes took the stain for Ia antigen. Anti-thymocyte antibody (OKT6) stained cells in both the epidermis and dermis of the specimens. Of nonmalignant conditions examined, lesions from five cases of lichen planus exhibited a quantitatively different staining pattern than that of mycosis fungoides in that the number of T-helper cells was about equal to the number of T-suppressor cells. The findings reported are evidence for a homogeneous population of T-helper, Ia-positive lymphocytes in the cutaneous lesions of mycosis fungoides and the Sézary syndrome.

Adult↗

Concordance of the Kiel and Lukes-Collins classifications of non-Hodgkin's lymphomas.

The Kiel and Lukes-Collins classifications of non-Hodgkin's lymphomas are the only classifications based on immunological concepts. Their cytological types have been confirmed by numerous immunological studies as B- and T-cell types and have been related to clinico-pathological entities. In this presentation, the cytological types of the two classifications are compared. Eleven of the 13 major types of the Lukes-Collins classification are essentially identical with the Kiel counterparts, though the terminology differs in four of the 11 types. In the two types in which discordance occurs, the relationship between the types of the two classifications are clarified. As a result, the two classifications are placed into effective alignment for understanding and translating terminological differences. Both classifications represent sound bases for morphological diagnoses and also for relating the results of the broad range of current and future immunological studies to morphology.

B-Lymphocytes↗

Immunoblastic sarcoma in patients with systemic lupus erythematosus-like disorders.

Five patients, predominantly older men, had abnormal immune states for prolonged periods of time with manifestations of multisystem involvement, including features of systemic lupus erythematosus, rheumatoid arthritis, and Sjögren's syndrome. In the course of their disease, all had malignant lymphoma (immunoblastic sarcoma) develop. The development of lymphoma was associated with generalized lymphadenopathy in four cases.

Adult↗

Successful therapy of convoluted T-lymphoblastic lymphoma in the adult.

Fifteen adult patients with biopsy-proven convoluted T-lymphoblastic lymphoma were treated with an aggressive regimen, modified from the LSA2-L2 protocol used for childhood lymphoma. The treatment schema consisted of induction phase, including cyclophosphamide, vincristine, prednisone, adriamycin, and 2000 rads to mediastinum, as well as intrathecal methotrexate. Consolidation phase included cytosine arabinoside, 6-thioguanine, L-asparaginase, and CCNU, along with cranial irradiation and further intrathecal methotrexate. Maintenance consisted of cyclical chemotherapy and intrathecal methotrexate, continuing for a total of 3 yr. Median age in the group was 25 yr (range 16-73). There were 8 males and 7 females. At diagnosis, 9 patients had mediastinal involvement, and 9 had bone marrow involvement. Five of these demonstrated malignant cells in the peripheral blood. Complete clinical response was attained in 11 patients. Three patients achieved partial response. Four complete responders have relapsed, 1 in the central nervous system at 6 mo. and 1 in nodal sites at 3 mo, 1 in multiple sites at 24 mo. and 1 in bone marrow at 42 mo while off all chemotherapy for 6 mos. At this time, median survival of all patients is 28.3 mo. and median relapse-free survival is 21 mo. The median survival for complete responders in excess of 71 mo. while the median relapse-free survival for this group is 41 mo.

Adolescent↗

Presentation of malignant lymphoma in the rectum.

Because of their rarity, rectal malignant lymphomas are generally included in the group of large intestine lymphomas. A study of eight cases of rectal lymphomas revealed distinctive clinicopathologic correlations. Using the Lukes-Collins classification of malignant lymphomas, the authors interpreted all the cases as B-cell lymphomas, supported by immunologic studies in four cases. Seven cases were classified diffuse follicular center cell (FCC) lymphomas; four as small cleaved FCC; and three as small noncleaved FCC. One case was interpreted as plasmacytoid lymphocytic lymphoma. Monoclonality was demonstrated by immunoperoxidase staining of cytoplasmic immunoglobulin in three cases and by immunologic surface marker studies in another case . The small noncleaved follicular center cell lymphomas presented as localized tumors (clinical Stage I), so-called primary lymphomas. The small cleaved follicular center cell lymphomas, by contrast, were part of a generalized lymphomatous process in three of the four cass with demonstrated involvement of the gastrointestinal tract elsewhere in two cases.

Aged↗