Search PubMed⌕ Search

Biomedical subjects

L M Weiss

Publications and source records attributed to L M Weiss.

At least 307 records · Page 17Linked to original sources

Large-cell hematolymphoid neoplasms of uncertain lineage.

In almost every large study attempting to characterize non-Hodgkin's lymphomas, there is a small subset of tumors for which the lineage remains poorly defined. The investigators studied a series of 20 hematolymphoid neoplasms that could not be clearly assigned to the B or T cell lineage by phenotypic criteria. Histologically, 12 cases had an appearance suggesting a histiocytic origin, seven cases resembled a pleomorphic immunoblastic lymphoma, and one had a sarcomatoid appearance. By immunologic studies, a variety of B cell, T cell, and monocyte/macrophage markers were expressed on the neoplasms, often with coexpression of markers for different lineages. Twelve cases expressed the Ki-1 antigen. In immunogenotyping studies of T cell receptor (TCR) and immunoglobulin genes, 13 cases showed clonal rearrangements of the beta or gamma TCR gene; one of these cases also had clonal rearrangements of a light chain immunoglobulin gene. Seven cases showed a germline configuration with all combinations of probes and enzymes used. We conclude that a small subset of hematolymphoid neoplasms shows a pattern of diverse immunologic marker expression that does not appear to reflect normal differentiation. However, a majority of these cases contain clonal TCR gene rearrangements, suggesting a frequent relationship to the T lineage.

Adolescent↗

An immunoperoxidase study of renal cell carcinomas: correlation with nuclear grade, cell type, and histologic pattern.

We applied a panel of antibodies to formalin-fixed, paraffin-embedded sections of 55 renal cell carcinomas using a three-stage immunoperoxidase technique. The antibody panel included two anti-keratins, AE1 and CAM5.2, anti-epithelial membrane antigen (EMA), anti-vimentin, anti-S100 protein, and the anti-leukocyte marker PD7/26. Forty-eight of 55 renal cell carcinomas expressed keratins. CAM5.2 stained 46 tumors (84%) and AE1 stained 37 neoplasms (67%). AE1 reacted with two CAM5.2-negative tumors. EMA was expressed by 35 carcinomas (64%), including three of the CAM5.2-negative neoplasms. Therefore, using all three antibodies, 50 neoplasms (91%) expressed antigens of epithelial differentiation. Anti-EMA and AE1 were complementary to each other; the combination stained 46 of the carcinomas, comparable with CAM5.2 alone. Vimentin was expressed by 26 tumors (47%), and S100 was expressed by one. PD7/26 did not stain any of the cases. Vimentin expression correlated with nuclear grade; low nuclear grade neoplasms infrequently expressed vimentin, while the converse was true for high nuclear grade tumors. Keratin expression was related to tumor cell type and histologic pattern, as fewer neoplasms of clear cell type and with a solid pattern expressed keratins. In contrast, all papillary and eight of nine (89%) spindled carcinomas expressed keratins.

Adult↗

Intermediate lymphocytic lymphoma: an immunophenotypic study with comparison to small lymphocytic lymphoma and diffuse small cleaved cell lymphoma.

Sixteen cases of intermediate lymphocytic lymphoma (ILL), including eight cases with mantle zone architecture, were studied using cryostat sections, a biotin-avidin immunoperoxidase technique, and a large panel of monoclonal antibodies. The neoplastic cells invariably expressed IgM, most B lineage antigens (B1, TO15, Leu-12, 6A4, 41H, BA-1, and LN-2), and Ia. IgD was expressed in 12 cases. Leu-1 and Leu-8 were weakly expressed by the tumor cells in 12 and 11 cases, respectively. The neoplastic cells did not express common acute lymphoblastic leukemia antigen (CALLA) or the T10 antigen in any case. Because ILL is difficult to differentiate from small lymphocytic lymphoma (SLL) and diffuse small cleaved cell lymphoma (DSCCL) on the basis of light microscopic criteria, the immunologic findings of ILL were compared to 31 cases of B cell SLL and 11 cases of B cell DSCCL previously studied in the laboratory to determine if immunologic findings might aid in the distinction. No absolute, and five statistically significant, differences were found; IgD in combination with IgM was seen more commonly in cases of ILL and DSCCL than in SLL (P less than .01), IgG was found more often in SLL than in ILL and DSCCL (P less than .05), Leu-8 was more commonly expressed in ILL and SLL than in DSCCL (P less than .05), T9 expression was less frequent in ILL as compared with SLL (P less than .05) and more proliferating cells were seen in ILL and DSCCL than in SLL (P less than .01). The investigators conclude that these three classes of lymphoma are remarkable much more for their immunologic similarities than for their differences and that immunologic studies are of limited usefulness in differentiating the three neoplasms. Their results also support the concept that these lymphomas are closely related to each other. In particular, DSCCL immunologically appears to be more closely related to SLL and ILL than to follicular small cleaved cell lymphoma.

Adult↗

Western blot analysis of the antibody response of patients with AIDS and toxoplasma encephalitis: antigenic diversity among Toxoplasma strains.

We used immunoblotting to ascertain if toxoplasma encephalitis in disease caused by the human immunodeficiency virus (HIV) could be diagnosed by the appearance of characteristic antibodies recognizing specific Toxoplasma antigens. The profile of antibodies to Toxoplasma was examined in human serum and cerebrospinal fluid from patients with chronic and acute toxoplasmosis with or without HIV infection. Many Toxoplasma antigens were recognized by all sera; the majority were presumably surface proteins, as determined by 125I labeling. All sera recognized antigens at 38, 35, 28, and 26 kilodaltons. No specific antibody or pattern of antibodies distinguished between groups of patients. A 120-kilodalton antigen recognized by sera from Atlanta was not, however, seen in most sera from New York. Study of the recognition of the antigens of different strains of Toxoplasma gondii (RH, C56, T100) by the same human sera demonstrated strain-specific antigenic differences. These strain variations may account for the antibody diversity among the patients studied.

Acquired Immunodeficiency Syndrome↗

Malignant lymphoma presenting as pseudoepitheliomatous hyperplasia. A report of two cases.

The authors report two patients with cutaneous and submucosal non-Hodgkin's lymphoma of probable T-cell phenotype that presented as florid pseudoepitheliomatous hyperplasia. The first patient presented with lesions of the nasopharynx and nose that were originally misdiagnosed as invasive squamous cell carcinoma, causing a delay in appropriate treatment. In the second patient, skin lesions of the thigh and arm closely mimicked squamous cell carcinoma. To prevent misdiagnosis of these lesions, pathologists should adhere to strict morphologic criteria for the diagnosis of squamous cell carcinoma and be aware that malignant lymphoma may be associated with overlying pseudoepitheliomatous hyperplasia. The pathogenesis of pseudoepitheliomatous hyperplasia arising in association with neoplasms is still not clear, but it may be related to the production of cellular growth factors by the inciting tumor.

Carcinoma↗

Applications of antigen receptor gene rearrangements to the diagnosis and characterization of lymphoid neoplasms.

During early stages of lymphocyte development, genes for antigen receptors (immunoglobulin and T-cell receptor proteins) undergo rearrangements of their DNA sequences. The resulting configurations of rearranged DNA are highly variable from cell to cell and serve as genetic markers for individual lymphocytes. These markers can be utilized to detect clonal lymphocytic proliferations, as seen in lymphoid malignancies, and to identify the lineage of lymphoid neoplasms. Chromosomal rearrangements involving recombination between the DNA of antigen receptor genes and other sites in the genome also occur in lymphoid neoplasms, and molecular analysis of such rearrangements is potentially useful in the diagnosis of lymphomas and leukemias.

DNA, Neoplasm↗

Expression of lymphocyte homing receptor antigen in non-Hodgkin's lymphoma.

In man, lymphocyte binding to high endothelial venules (HEVs) involves specific 85-95 kd cell surface glycoprotein(s) recognized by the monoclonal antibodies Hermes-1 and Hermes-3. These putative "homing receptor" molecule(s) are believed to play an important role in the normal regulation of lymphocyte circulation. To investigate the possibility that homing receptors also play a role in the biology of lymphoid malignancies, the authors studied over 300 cases of non-Hodgkin's lymphoma by immunohistologic staining with Hermes-1 and -3, antibodies that define two distinct epitopes on the gp 85-95 putative homing receptor molecules. Furthermore, they directly compared expression of the Hermes-3 antigen with clinical extent of disease in 57 patients with diffuse large cell lymphoma. They found that staining of the various subtypes of lymphoma was heterogeneous, and in general correlated with patterns of expression seen in benign lymphoid populations. Essentially all normal lymphoid populations examined, except germinal center B cells and most cortical thymocytes, bear a high level of homing receptor antigen. Similarly, nearly all peripheral T-cell lymphomas, diffuse small cell lymphomas of B lineage, and plasma cell tumors were positive for homing receptor antigen (95%, 97%, and 100%, respectively). Small noncleaved cell, follicular, and diffuse large cell lymphomas of B lineage, tumors having morphologic or immunologic features resembling germinal center cells, frequently failed to express Hermes-defined epitopes (81%, 41%, 25% Hermes-3-, respectively). Antigen expression in T-lymphoblastic lymphomas strongly correlated with immunophenotypic subtypes: only 8% of CD4+/CD8+ were Hermes-1+ versus 86% of CD4-/CD8- and 43% of CD4+/CD8-. Hermes-3 expression by cases of diffuse, large cell lymphoma which showed generalized lymph node involvement (a pattern strongly suggestive of HEV-mediated spread; 100% Hermes-3+, mean intensity 3.4) was higher than that of cases with localized or multifocal, contiguous involvement (consistent with lymphatic spread; 69% Hermes-3+, mean intensity 2.2), but these differences did not achieve statistical significance. The results indicate that homing receptor antigen expression, although perhaps necessary for wide-spread blood-borne lymphoma dissemination to lymphoid sites, is not in and of itself sufficient to predict such behavior in this subtype of lymphoid malignancy.

Antibodies, Monoclonal↗

Absence of clonal beta and gamma T-cell receptor gene rearrangements in a subset of peripheral T-cell lymphomas.

The authors describe a set of seven peripheral T-cell lymphomas that lack detectable rearrangements of T-cell receptor (TCR) genes. All cases showed antigenic profiles consistent with T-cell lymphoma, including expression of Leu-5 (CD2) antigen. However, few other T-lineage markers were found, and none of the cases tested (6 of 7) bound antibody recognizing the constant region of the beta TCR protein. Each case showed exclusively germline configurations of DNA for the beta TCR genes in Southern blot analyses with the use of several different combinations of restriction enzymes and DNA hybridization probes. One case contained clonal rearrangements of the gamma TCR gene and of the immunoglobulin heavy chain gene. Our results suggest that certain cases of peripheral T-cell lymphoma may lack rearrangements of TCR genes--particularly those cases expressing restricted numbers of T-lineage antigens. In view of these findings, failure to detect rearrangements of TCR genes by Southern blot analyses is not necessarily inconsistent with malignant lymphocytic proliferations in T-lineage neoplasia.

Adult↗

Molecular analysis of the t(14;18) chromosomal translocation in malignant lymphomas.

One of the most common karyotypic abnormalities is the t(14;18) translocation, which is found in many lymphomas that have a characteristic follicular morphology. Recent molecular studies have shown that this chromosomal translocation results in the juxtaposition of the candidate proto-oncogene bcl-2 (B-cell leukemia-lymphoma) on chromosome 18 with the immunoglobulin heavy-chain locus on chromosome 14. However, because performing accurate cytogenetic studies in solid hematolymphoid neoplasms is difficult, knowledge of the prevalence of the t(14;18) translocation and, by association, the extent of bcl-2 involvement in human lymphomas is limited. We used a number of chromosome-18 DNA probes to analyze various subtypes of Hodgkin's and non-Hodgkin's lymphomas and test for structural abnormalities near or within the bcl-2 gene. Molecular features of the t(14;18) translocation were found in virtually all follicular neoplasms and about 28 percent of diffuse large-cell lymphomas. No changes in bcl-2 were found in several other subtypes of Hodgkin's and non-Hodgkin's lymphomas, including those previously suggested to originate from follicular-center cells and those about which cytogenetic data have been difficult to obtain. Our findings suggest a close pathogenetic relation between bcl-2 and a large group of non-Hodgkin's lymphomas, both with and without a follicular morphology. The methods employed in this study may be useful in improving the accuracy of diagnosis and subclassification of malignant lymphomas.

Chromosome Mapping↗

Clinical and pathologic features of follicular large cell (nodular histiocytic) lymphoma.

Clinicopathologic correlations were made in 50 patients with follicular large cell (FLC) lymphoma to better define the influence of a variety of clinical and pathologic features on survival and the potential for continuous freedom from disease. The 5- and 10-year actuarial survivals for the entire group of patients are 77% and 63%, respectively, but disease-free survival is only 46% at 5 years and 22% at 10 years. No significant survival differences were found with various treatment approaches, although a single relapse occurred after 3 years among patients treated with modern combination chemotherapy containing doxorubicin. Median survivals of approximately 10 years despite recurrent disease are characteristic of the majority of follicular lymphomas. Furthermore, the reproducibility of cytologic diagnosis among follicular lymphomas is known to be variable. At this time, it is unclear whether intensive chemotherapy will cure a significant number of FLC patients or novel approaches are necessary as for the other follicular lymphomas.

Actuarial Analysis↗

Monoclonal antibodies reactive in routinely processed tissue sections of malignant lymphoma, with emphasis on T-cell lymphomas.

The immunoreactivity of eight monoclonal antibodies was evaluated on 45 routinely processed lymphomas (22 T-cell lymphomas, 11 B-cell lymphomas, and 12 cases of Hodgkin's disease). Two antibodies reactive with leukocyte common (T200) antigens (PD7/26 and 2B11) stained most of the B- and T-cell lymphomas but did not stain the Reed-Sternberg cells and variants in Hodgkin's disease. Two antibodies known to stain B cells (LN-1 and LN-2) reacted with some of the B-cell lymphomas, but LN-2 also reacted with the neoplastic cells in six of 22 T-cell lymphomas and with the Reed-Sternberg variants in eight of 12 cases of Hodgkin's disease. The granulocyte antibody anti-Leu M1 reacted with most cases of Hodgkin's disease but also reacted with two of 11 B-cell non-Hodgkin's lymphomas. An antibody to epithelial membrane antigen (anti-EMA) stained some cases of T-cell lymphoma, B-cell lymphoma, and Hodgkin's disease. Leu 7 was expressed in one T-cell lymphoma and in one case of Hodgkin's disease. A novel antibody reactive with T cells (L60) stained all cases of T-cell lymphoma but also stained some cases of B-cell lymphoma and one case of Hodgkin's disease. We conclude that none of these antibodies, when used alone on routinely fixed paraffin-embedded material, is completely sensitive and specific for T-cell lymphoma, B-cell lymphoma, or Hodgkin's disease. However, a panel of antibodies is useful in distinguishing Hodgkin's disease from non-Hodgkin's lymphoma and in suggesting the B- or T-cell phenotype of non-Hodgkin's lymphomas.

Antibodies, Monoclonal↗

Proliferative rates of non-Hodgkin's lymphomas as assessed by Ki-67 antibody.

The Ki-67 antibody, a monoclonal antibody that reacts with nuclei in actively proliferating cells, was used in an immunohistochemical study to assess the growth fractions of non-Hodgkin's lymphomas and related disorders. The lowest proliferative indices were found in small lymphocytic lymphoma/chronic lymphocytic leukemia and intermediate lymphocytic/mantle zone lymphoma. An intermediate proliferative index was seen in the follicular lymphomas and diffuse small cleaved cell and diffuse mixed cell lymphomas. A high index was seen in the diffuse large cell lymphoma and lymphoblastic lymphoma. The highest and most consistent proliferative index was seen in small noncleaved cell lymphoma. Cases of reactive follicular hyperplasia had a significantly higher proliferative index than those of follicular lymphoma. We conclude that the Ki-67 antibody has great utility in providing an estimate of the proliferative rate of non-Hodgkin's lymphomas. Prospective studies may show this information to have prognostic value independent of histologic classification.

Antibodies, Monoclonal↗

Quantitation and estimation of lymphocyte subsets in tissue sections. Comparison with flow cytometry.

A quantitation method for lymphocyte subsets in immunoperoxidase-stained frozen tissue sections was compared with flow cytometry in 23 cases of non-Hodgkin's lymphoma. Close correlations were obtained, demonstrating the accuracy of the technic. Weak intensity of fluorescence and fragility of the tumor cells during the fluorescence-activated cell sorter (FACS) analyses were the most likely explanations for a number of the discrepancies observed. The tissue quantitation method was precise, particularly at low values, where it was better than the FACS. A simpler and faster estimation method employing categories within 10 percentage units was also tested in this study; this method correlated as well with the FACS as the quantitation method and gave the best interobserver correlations.

Antigens, Differentiation, T-Lymphocyte↗