Biomedical subjects

T M Grogan

Publications and source records attributed to T M Grogan.

At least 109 records · Page 6Linked to original sources

PubMed1988

Clonal ambiguity of human immunodeficiency virus-associated lymphomas. Similarity to posttransplant lymphomas.

Initial biopsy specimens from two patients with lymphadenopathy and human immunodeficiency virus antibody-positive serum presented considerable difficulty in making specific histologic and immunologic diagnoses, although subsequent biopsy specimens revealed clear progression to acquired immunodeficiency syndrome (AIDS)-associated lymphomas. The initial biopsy specimens revealed multifocal clusters of large blastic lymphoid cells, with some clusters showing a monoclonal lambda light chain predominance, whereas other clusters showed a kappa predominance, indicating considerable phenotypic ambiguity suggestive of polyclonality. This initial clonal ambiguity was followed within two to three months by overt histologic, phenotypic, and clinical malignant transformation to a diffuse high-grade monoclonal B-cell lymphoma. These data have significant implications for the clonality and pathogenesis of AIDS-associated lymphoproliferative disorders. AIDS-related lymphomas may evolve from an initial multiclonal B-cell expansion similar to that described in other severely immunosuppressed patients (eg, with posttransplantation lymphoma).

AIDS-Related Complex↗

PubMed1988

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↗

PubMed1988

The prognostic significance of the immunotype in diffuse large-cell lymphoma: a comparative study of the T-cell and B-cell phenotype.

The clinical significance of immunophenotyping of the non-Hodgkin's lymphomas is controversial. Therefore, we conducted the present study of 103 consecutively accrued diffuse large-cell lymphoma (DLCL) patients to define, independently of histologic subtypes, the prognostic importance of phenotyping. We used an extensive panel of monoclonal antibodies to T- and B-cell antigens to assign all patients immunologically into the T-cell (20 patients) or B-cell group (83 patients). The only significant differences in pretreatment clinical variables between the two patient groups were the higher frequency of bulky disease (greater than 10 cm) in B-cell patients (P = .008) and more frequent skin involvement in the T-cell group (P less than or equal to .001). Multiagent doxorubicin-containing chemotherapy regimens were employed as initial therapy in over 83% of the patients in each group. Our study revealed that disease-free survival (DFS) was significantly shorter in the T-cell patients than in the B-cell DLCL patients (median DFS, 10.8 months for T-cell and 42.7 months for B-cell; P = .01, log rank). No patient with T-cell DLCL remained disease free for longer than 2 years, whereas 55% of the B-cell group were disease free at 2 years. Univariate and multivariate analyses of all major prognostic factors of DFS suggest that the T-cell phenotype indicates an incurable subset of DLCL patients. Although the B-cell group had a twofold advantage in median survival (35 months v 18 months), actuarial overall survival was not significantly different between the two patient groups (P = .23). Our results indicate the need for new approaches in the search for a curative treatment for T-cell DLCL.

Adolescent↗

PubMed1988

Nuclear contour irregularity correlates with Leu-9-, Leu-8- cells in benign lymphoid infiltrates of skin. An ultrastructural morphometric and quantitative immunophenotypic analysis suggesting the normal T-cell counterpart to the malignant mycosis fungoides/Sézary cell.

The purpose of the present study was to determine if a nonmalignant skin-associated T-cell might exhibit nuclear irregularity and represent the normal counterpart to the malignant Sézary T-cell found in mycosis fungoides (MF) and the Sézary syndrome (SS). Punch skin biopsies from ten benign lymphoid infiltrates of skin were subjected to ultrastructural morphometric analysis and quantitative immunohistochemistry (on serial frozen sections) using a battery of monoclonal antibodies. Form factor (FF) (4 pi A/p2) was used to assess nuclear contour irregularity. The lymphoid infiltrates were morphometrically heterogeneous (range of FF values: 0.482-0.704). Immunophenotypically, there was marked variation in host response to the variety of antigens presented. Linear regression analysis was used to determine if nuclear contour irregularity showed any statistical relationship to immunophenotypically defined lymphocyte subpopulations. It was determined that nuclear contour irregularity (mean FF values) did not correlate with the presence of any surface antigen tested. This included the antigens Leu-2a, Leu-3a + b, Leu-4, Leu-6, Leu-7, Leu-8, Leu-9, Leu-14, and Ia. There was, however, significant correlation of increased nuclear contour irregularity with the presence of Leu-9- and Leu-8- cells (r = 0.7 and 0.6, respectively), lymphocyte subsets reportedly deficient in MF and the SS. This finding leads to the speculation that the Leu-9-, Leu-8- reactive T-cell with an irregular nucleus might represent the normal counterpart to the malignant clonally expanded T-cell found in MF and the SS. It was also determined that helper to suppressor ratios varied 68-fold from 0.2 to 13.5 among these ten benign lymphoid infiltrates of skin. This finding underscores the futility of using helper to suppressor ratios as a diagnostic tool in defining T-cell malignancies.

Adult↗

PubMed1988

Burkitt's-like lymphoma of T-cell type.

Over an 8-yr period, we studied 29 cases of Burkitt's/Burkitt's-like lymphoma and unexpectedly found 2 Burkitt's-like cases of the T-cell type. One case presented as diffuse adenopathy in a 35-yr-old male. A second case presented as a jaw mass in a 2-yr-old girl with Down's syndrome. Histologically, each case demonstrated usual Burkitt's-like morphology (intermediate-size cells with high nuclear/cytoplasmic ratio, 1 to 3 prominent nucleoli, high mitotic rate, basophilic cytoplasm, and cytoplasmic vacuolation). Ultrastructural morphometric data corroborated the Burkitt's-like nature of these neoplasms. Immunologically, the neoplasms were of "novel" T-cell phenotype, as seen in peripheral T-cell lymphoma (PTL). The cases showed variable expression of activation antigens (e.g., Ia) and weak to moderate expression of proliferation antigens as measured by Ki-67. This modest proliferative activity (less than 25% Ki-67 expression) contrasts with Burkitt's-like lymphomas of the B-cell type which usually show greater than 80% Ki-67 expression. The jaw tumor also demonstrated positivity for human progenitor cell antigen (HPCA) as commonly found in leukemia. Both cases mimic granulocytic sarcoma by virtue of their eosinophilic/myelocytic recruitment--a phenomenon previously reported in association with PTL. The patients have survived 62 wk and 20 wk, respectively, surpassing the survival rates seen in our concurrent B-cell Burkitt's-like lymphomas (12 wk). Burkitt's-like lymphoma of the T-cell type appears to be a distinctive immunological subset of potential clinical and prognostic relevance.

Adult↗

PubMed1988

Independent prognostic significance of a nuclear proliferation antigen in diffuse large cell lymphomas as determined by the monoclonal antibody Ki-67.

To assess the prognostic significance of the growth fraction in diffuse large cell lymphoma (DLCL), we studied 105 DLCL patients with the monoclonal antibody Ki-67 applied to frozen tissue sections. Ki-67 detects a nuclear antigen associated with cell proliferation not found in resting cells. Ki-67 findings and other clinical prognostic factors were correlated with outcome using univariate and multivariate analyses in the proportional hazards model. High proliferative activity, defined as nuclear Ki-67 expression in greater than 60% of malignant cells (Ki-67 greater than 60), was found to be a strong predictor of poor survival among these patients (P = .003, log-rank). The 19 patients with Ki-67 greater than 60% had a median survival of 8 months compared with a median survival of 39 months for the 86 patients with Ki-67 less than or equal to 60%. Examination of pretreatment clinical variables indicated the patient groups were similar with regard to age, sex, stage, B symptoms, tumor bulk, and lactate dehydrogenase (LDH). Both patient groups received comparable curative intent therapy and showed comparable complete response rate precluding treatment differences as modifying outcome. Multivariate analysis indicated Ki-67 is an independent predictor of survival (multivariate P = .006). Further statistical analysis using only B-cell DLCL patients treated with CHOP (63 patients) indicated that Ki-67 greater than 60 retained strong prediction of poor outcome (P = .002, log-rank) among this homogeneous group. We conclude that high proliferative activity (Ki-67 greater than 60) is an independent factor allowing laboratory prediction of probable poor outcome of DLCL.

Adolescent↗

PubMed1987

Lethal midline granuloma with a novel T-cell phenotype as found in peripheral T-cell lymphoma.

Lethal midline granuloma (LMG), initially a clinical description, includes an uncommon group of disorders characterized by a relentless, destructive process involving the upper respiratory structures. Its etiology and pathogenesis are uncertain, probably varied, and the distinction between inflammatory and malignant processes is difficult despite extensive clinical and histopathologic evaluation. The need for new techniques for rapid diagnosis has important therapeutic implications. Using an extensive panel of T- and B-cell monoclonal antibodies the authors describe a patient with clinically and pathologically typical LMG demonstrating an "activated" T-cell phenotype with a "novel" pattern characteristic of peripheral T-cell lymphoma, strongly implying that some cases of LMG are more closely related to neoplastic T-cell lymphoproliferative disorders than to inflammatory conditions. Further studies using these immunotyping techniques may help clarify the pathogenesis of LMG, and may uncover specific diagnostic and prognostic phenotypic patterns.

Adult↗

PubMed1987

Post-transplantation T cell lymphoblastic lymphoma.

Immunosuppressed renal transplant recipients are at increased risk for large cell lymphoma of B cell phenotype. This report describes a case of post-transplantation lymphoma presenting with a mediastinal mass causing superior vena cava syndrome, tracheal obstruction, and pleural effusion. Cytospin preparations of pleural fluid documented high-grade lymphoblastic lymphoma morphology and immature T cell (cortical thymocyte) phenotype: Leu 1-6-positive, Leu 9-positive, Tdt-positive, B-negative, Calla-positive. The occurrence of post-transplantation lymphoma of T cell lineage is inconsistent with the postulated Epstein-Barr virus origin and raises important questions regarding the development of lymphoproliferative disorders in immunosuppressed organ transplant recipients.

Adult↗

PubMed1987

Quinidine-induced reactive lymphadenopathy.

This report describes a patient who presented with extensive inguinal lymphadenopathy while taking quinidine for the treatment of arrhythmias. An excisional lymph node biopsy specimen demonstrated atypical, reactive, follicular hyperplasia. Immunologic assessment utilizing 20 monoclonal antibodies indicated a reactive process with follicles shown to be polyclonal B cell. The patient's adenopathy resolved within one month of discontinuation of quinidine and he remains well 15 months later. The histologic and immunologic findings as well as the clinical response are typical for a drug-induced reactive lymphadenopathy.

Biopsy↗

PubMed1987

Recombinant interferon-gamma stimulates the production of human tumor necrosis factor in vitro.

Human peripheral blood monocytes in culture secrete tumor necrosis factor (TNF), which can be detected with a sensitive enzyme-linked immunosorbent assay system. When recombinant human interferon-gamma (rIFN-gamma) is added to cultured cells, TNF production is increased. rIFN-gamma is also able to sustain the elevated production level of TNF over a 4-day period. Recombinant interferon-alpha (rIFN-alpha) was unable to stimulate increased TNF production. Unstimulated mononuclear phagocytes and rIFN-alpha-treated cells decreased secretion of TNF over a 4-day interval. The stimulatory effect of rIFN-gamma was dose dependent and required both new RNA and protein synthesis and was independent of endotoxin in the tissue culture medium.

Adult↗

PubMed1987

A double-blind comparative immunotypic study between two institutions phenotyping non-Hodgkin's lymphomas.

To establish the feasibility of immunotyping specimens transported over great distance, the University of Arizona and the Cleveland Clinic exchanged 39 lymphoma cases (26 B-cell, 13 T-cell cases) via air express for phenotyping. They were exchanged with the use of glass slides with adherent snap-frozen sections. The method involved immunohistochemistry using a common battery of 20 antibodies directed at B- and T-cell antigens. Using similar, but not identical, methods and reagents, cases were assayed before and after transport. Results were generated as paired determinations in a double-blind fashion (1,338 total determinations, 669 paired determinations/669 antigens). Using "pretransport" values as the baseline, there was subsequent agreement with baseline in 624 of 669 antigenic determinations (93.3%) and disagreement in 45 (6.7%). Interinstitutional agreement was 94% for T-antigens (Leu-1-7,9) and 93% for B-antigens (K, lambda; IgM, G, A, D; B1, B2, B4, L14; J5, common acute lymphocyte leukemia antigen [CALLA]; Ia). In spite of 6.7% disagreement, there was agreement of overall phenotypic profile (e.g., B vs. T and subset stage) in all 39 cases. This is because discrepancies were isolated and the battery offset undue reliance on a single antigen. The disagreements relate mainly to certain B-antigens: CALLA/J5 (eight disagreements) and B1 and B2 (six and five disagreements, respectively). T-antigen disagreements were more sporadic (e.g., Leu-5 [three disagreements]). These discrepancies may relate to antigen loss with transport, variable antigen density or antibody avidity, methodologic differences, quality of reagents, or differences of phenotype interpretation. A further exchange of the 45 disagreement slides indicated that difference of observer interpretation was a minor factor (3 of 45). In conclusion, the authors' study demonstrates a high degree of immunotype reproducibility (approximately 93%), suggesting promise for institutions doing collaborative lymphoma studies.

Antibodies, Monoclonal↗

PubMed1987

Delineation of a novel pre-B cell component in plasma cell myeloma: immunochemical, immunophenotypic, genotypic, cytologic, cell culture, and kinetic features.

A novel pre-B cell component in direct and cultured myeloma bone marrow material has been delineated by using immunochemistry and flow cytometry techniques. Our phenotypic studies suggest a novel hybrid expression of pre-B and plasma cell antigens with coexpression of cytoplasmic mu, common acute lymphoblastic leukemia antigen, terminal deoxynucleotidyl transferase, and plasma cell antigens (PCA-1 and PC-1). This suggests that myeloma pre-B-like cells are aberrant malignant cells and not normal pre-B lymphocytic counterparts. With the advantage of a pure and stable source of these cells from M3 culture to allow molecular characterization, we performed one- and two-dimensional gel electrophoresis and Western blotting. We found that the cytoplasmic mu in myeloma pre-B-like cells has a molecular weight of 74,000 daltons and an isoelectric point of 6.3 and that it is strikingly homogeneous and discrete in size and charge compared with standard secretory mu, which suggests an aberrant, mutant, or monoclonal form of mu. Monoclonality was further evidenced by heavy- and light-chain immunoglobulin gene rearrangements demonstrated with JH and C kappa probes. We also established that this novel myeloma pre-B component is a major proliferative element as determined by double-labeling experiments with phenotype coupled to labeling/proliferative indexes. Our stimulatory studies indicate some capacity of these cells to mature on exposure to phorbol esters. These myeloma pre-B cells may represent the stem cell or self-renewal component in myeloma. Our establishment of these cells in long-term culture offers a considerable asset in studying the immature cells, which may be critical to the immortalization of myeloma.

B-Lymphocytes↗

PubMed1987

Chronic myelomonocytic leukemia terminating as malignant histiocytosis.

A patient with a 3.5 year history of chronic myelomonocytic leukemia who transformed to malignant histiocytosis is reported. The terminal event was characterized by fever, hepatosplenomegaly, thrombocytopenia, and a leukemic blood picture. The pathogenesis of this terminal transformation and proposed future studies are discussed.

Aged↗

PubMed1987

An ultrastructural morphometric and immunophenotypic evaluation of Burkitt's and Burkitt's-like lymphomas.

Six cases of Burkitt's lymphoma (BL) and 12 cases of Burkitt's-like lymphoma (BLL) were classified by using strict histologic and cytologic criteria. These cases were processed for electron microscopy and analyzed by using computerized image analysis techniques. Form factor (4 pi A/P2) was used to measure nuclear contour irregularity. The mean of the standard deviation (SD) of nuclear area and form factor was used to assess pleomorphism. Overall, there were 8 similarities and 10 statistically significant dissimilarities out of 18 parameters analyzed. The similarities (p greater than 0.05) between the BL and BLL groups included the means of form factor, nuclear area/cytoplasmic area, SD of nuclear area/cytoplasmic area, number of nuclear pockets/100 nuclei, percentage of cells with nuclear pockets, number of lipid droplets/micron 2 of cytoplasm, percentage of cells with lipid droplets and number of mitochondria/micron 2 of cytoplasm. The dissimilarities (p less than 0.05) included the means of nuclear perimeter, SD of nuclear perimeter, nuclear area, SD of nuclear area, cellular area, SD of cellular area, cytoplasmic area, SD of cytoplasmic area, SD of form factor, and nucleolar frequency. Multiparameter analysis clearly separated these 18 patients into two distinct groups and confirms that the subtleties used in the histologic classification of these lymphoma subtypes are meaningful. Sixteen cases of BL and BLL were snap-frozen in isopentane and analyzed by using 16 lymphoid surface markers. All of the immunoglobulin-positive BL were of the mu isotype, whereas the BLL cases were divided between mu (6 cases) and gamma expression (4 cases). All 4 of the BL evaluated manifested CALLA expression, whereas 3 of the 11 BLL evaluated coexpressed CALLA. One BL case was of a pre-pre-B phenotype and one BLL case was of pre-B phenotype. The BL and BLL were compared to 49 cases of SIg (+) large cell lymphomas. The high incidence of coexpression of lambda, CALLA, and Ki-67 in BL and BLL separates these lymphomas, as a group, from the large cell lymphomas. We have also determined from this study that the separation of patients into distinct BL and BLL subtypes is clinically relevant. The BL group were all children (median of 6.5 years) compared with the BLL group who were all adults (median of 63 years). The complete remission rate was higher in the BL (67%) than in the BLL group (25%).4off

Adult↗

PubMed1987

Cutaneous myiasis. Immunohistologic and ultrastructural morphometric features of a human botfly lesion.

This study documents the immunohistologic and ultrastructural morphometric features of a case of cutaneous myiasis due to Dermatobia hominis. The mixed host inflammatory response surrounding the larvae included lymphoblasts, eosinophils, activated fibroblasts, mature histiocytes, mast cells, plasma cells, and Langerhans cells, indicating a complex interactive immunologic response to the botfly parasite. Immunotyping revealed that the dominant dermal cells were activated (Ia+) T-helper cells. Although the strikingly elevated T-helper/T-suppressor cell ratio might suggest a monoclonal infiltrate, a mixture of Leu 8+ and Leu 8- T-cells indicates both immunoregulatory subsets of T-helper cells as found in a reactive process. Furthermore, our ultrastructural histogram found the lymphoid nuclear shapes were oval with few nuclear invaginations as found in inflammatory infiltrates. As indicated by electron microscopy, there were abundant activated fibroblasts elaborating collagen which may relate to larval containment.

Central America↗

PubMed1986

Mantle zone lymphoma with central nervous system involvement.

A 68-year-old man with a 7-year history of lymphocytosis and lymphadenopathy is described. Accelerated disease, indicated by bilateral optic nerve and cerebrospinal fluid involvement, prompted thorough histologic and immunologic assessment. Although initially believed to have chronic lymphocytic leukemia (CLL), results showed mantle zone lymphoma (MZL) with central nervous system (CNS) involvement. The authors believe that this represents the first case of MZL with CNS involvement.

Aged↗

PubMed1986

Terminal lymphoblastic transformation in polycythemia vera.

A patient with polycythemia vera and lymphoblastic transformation is discussed. Phenotypic characterization revealed that the predominant leukemic cells were classic "null" lymphoid cells with a minority component of pre-B cells. This case provides evidence that the stem cell disorder in polycythemia vera may involve the lymphocyte early in development.

Aged↗

PubMed1986

Immunophenotypes in "well-differentiated" lymphoproliferative disorders, with emphasis on small lymphocytic lymphoma.

The histologic, immunophenotypic, and clinical findings in 24 cases of "well-differentiated" lymphoproliferative disorders are presented, with an emphasis on small lymphocytic lymphoma (SLL; well-differentiated lymphocytic lymphoma, WDLL). SLL was diagnosed in 18 patients, Waldenström's macroglobulinemia in one, mantle zone lymphoma (MZL) in four, and intermediate differentiated lymphocytic lymphoma (IDL) in one. Immunophenotypic analysis revealed one SLL to be of T-cell derivation, while a monoclonal B-cell phenotype was found in the remaining 23 patients; 20 of these neoplasms co-expressed the pan-T-cell antigen Leu-1. This included three of the four patients with MZL and the patient with IDL. All SLLs with pseudofollicular growth centers stained for transferrin receptor. Additionally, a survey of 248 non-Hodgkin's lymphomas of all types revealed four of 70 patients with B-cell large cell lymphoma (LCL; diffuse histiocytic lymphoma, DHL) that also co-expressed the same Leu-1 antigen. Immunoperoxidase study of both frozen tissue sections and cytocentrifuge preparations eliminated the limitations of faint antigen expression and/or interstitial immunoglobulin staining. In addition to detailing the immunophenotype of SLL, the immunologic kinship of MZL/IDL to SLL and the uncommon co-expression of Leu-1 in B-cell LCLs are demonstrated.

Aged↗