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Biomedical subjects

K Lennert

Publications and source records attributed to K Lennert.

At least 73 records · Page 4Linked to original sources

Rearrangement of T-cell delta locus in lymphoproliferative disorders.

Studies of lymphoproliferative disorders using immunoglobulin and T-cell receptor genes have contributed to our understanding of clonality and lineages of these disorders. In this study, we examined the rearrangement of the recently discovered T-cell delta chain genes in a variety of lymphoproliferative diseases. We show here that six of 14 T-cell lymphomas and five of 23 B-cell lymphomas or B-cell leukemia cell lines have rearranged the delta loci, while two of two hyperimmune reactions retain germline configuration within these genes. Seven of ten cases of AILD were rearranged, and Lennert's lymphoma, which has been previously described as a T-cell malignancy, also contains rearrangements in the delta chain genes (three of five). Large cell anaplastic lymphomas positive for the activation antigen CD 30 also contain rearrangement in about one-half (five of 11) of the tumors examined. Two of seven of the Hodgkin's lymphomas studied contained a rearrangement for this gene. This study indicates that this newly identified T-cell delta gene is useful in evaluating clonality but is not lineage specific. However, with only one exception (in 28 rearrangements), this gene rearranges in tumors with gamma and beta chain gene rearrangements, indicating that when used in conjunction with the other TcR genes, delta rearrangement may also be useful in evaluating lineages.

B-Lymphocytes↗

Clonal rearrangements of T-cell receptor and immunoglobulin genes and immunophenotypic antigen expression in different subclasses of Hodgkin's disease.

Twenty-two cases of Hodgkin's disease (HD), representing the 4 different subclasses, were studied by immunophenotypic and immunogenotypic analysis. Quantitative immunophenotypic analysis of HD infiltrates showed a predominance of CD3-positive T cells in all subtypes except the lymphocytic depletion (HDLD) subtype. Only 5 samples of HD [2 of lymphocytic predominance (HDLP), 2 of mixed cellularity (HDMC), and one of nodular sclerosis type (HDNS)] were found to have both their Ig and T-cell antigen receptor (TcR) genes in the germ-line configuration. The remaining patients with HDLP (3 cases), HDNS (5 cases), and HDMC (4 cases), all exhibited rearrangements of either TcR gamma or TCR gamma and TcR beta genes, while all 5 cases of HDLD had either TCR gamma or immunoglobulin heavy-chain gene rearrangement. These results substantiate the view that Hodgkin's lymphomas contain clonal lymphocyte populations and that different rearrangement patterns may be associated with different subclasses of HD.

Antigens, Differentiation, T-Lymphocyte↗

Chromosomal abnormalities in lymphogranulomatosis X (LgrX)/angioimmunoblastic lymphadenopathy (AILD).

Histologically, lymphogranulomatosis X (LgrX) is a Morbus Hodgkin-like disease which until now has been considered as an abnormal immune reaction or a prelymphoma. Chromosome analyses showed that LgrX and angioimmunoblastic lymphadenopathy AILD) are characterized by chromosomal aberrations. Chromosome analyses of 18 cases of LgrX with sequential banding techniques showed abnormalities in 13 out of 18 cases. They were monoclonal in 7 cases. The most frequent abnormalities were trisomies of chromosomes Nos 3 and 5 and duplication of the X-chromosome. The abnormal karyotypes always appeared with normal mitosis in single or clonal cells. They were found in unstimulated and in PHA-stimulated cultures from lymph node and peripheral blood. Thus, it can be concluded that at least some cases of LgrX are monoclonal cell proliferations. An attempt is made to define the role of chromosomal abnormalities in the development of malignant lymphomas.

Aged↗

Immunocytology of plasmacytoid T cells: marker analysis indicates a unique phenotype of this enigmatic cell.

Clusters of plasmacytoid T cells (PTC) were detected in axillary lymph nodes draining an invasive ductal breast cancer in a 64-year-old woman. Immunocytology of PTC revealed a remarkable antigenic profile. Analysis with a broad spectrum of monoclonal antibodies demonstrated that PTC bear the CD4 surface antigen (Leu-3a+ and OKT4+), the transferrin receptor (OKT9+), and components of the HLA class-II antigens (TU35+, TU39+, Leu-10+). Surprisingly, PTC were stained by two monoclonal antibodies recognizing monocytes and macrophages (Ki-M6 and Ki-M7). Finally, Leu-8, which detects most mature T lymphocytes, also identified the PTC, and all pan T-cell markers (Leu-1, UCHT 1, and Lyt 3) were constantly negative. The cytogenesis and the functional properties of PTC remain a matter of discussion.

Antibodies, Monoclonal↗

New aggressive variant of suppressor/cytotoxic T-CLL.

Three cases of CD8+ CLL are reported. The patients are young (28, 18, 27 years old). The leukemia cells are predominantly small lymphocytes with irregular nuclei bearing notches and lobations. Cytoplasmic azurophilic granules are absent. Cytochemistry shows periodic acid-Schiff granular, alpha-naphthylacetate esterase focal, and acid phosphatase focal/granular positivities. Immunophenotypically cells are CD2+, CD3+, and CD8+ and lack CD4 as well as B-cell and NK cell antigens. All patients died within 20, 16, and 9 months, respectively. The clinicopathologic features of these cases differ clearly from those of the CD8+ CLL with azurophilic granules. These three cases represent a morphologically distinctive and more aggressive variant of CD8+ CLL.

Adolescent↗

Skin tumor of T accessory cells (interdigitating reticulum cells) with high content of T lymphocytes.

A case of T-accessory cell tumor of the skin in a 67-year-old man is reported. The limbs, shoulders, and face were affected, but no visceral involvement is evident 6 years after onset. Tumor cells are nonphagocytic mononuclear cells with folded irregular nuclei. Immunologically, cells were positive for S100 protein, HLA-DR, Ki-M1, Leu 3a (CD4), Leu 6 (CD1); that is, they are identical to the phenotype of Langerhans or interdigitating reticulum cells (IDCs). Birbeck granules were absent. The clinical course appears to be less aggressive than that of the reported IDC sarcomas in other anatomical sites. The similarity of our case to some cases of so-called "non-X histiocytosis" of the skin is discussed. It is suspected that the "non-X histiocytosis of the skin" reported in the literature might have included T-accessory cell tumors, especially those of IDC origin. More immunological studies on the histiocytic disorders of the skin are necessary to clarify their cytogenesis.

Aged↗

Histopathology and immunohistochemistry of peripheral T cell lymphomas: a proposal for their classification.

Based on the results of histological and immunohistochemical observations of a large number of peripheral T cell lymphomas from China, England, Germany and Japan, histological and cytological morphology were correlated with immunophenotype, aetiological association with HTLV-1, and clinical behaviour to produce a working classification of the T cell lymphomas. This classification, based mainly on cytological criteria, divides the peripheral T cell lymphomas into tumours of low grade and high grade malignancy. Adult T cell lymphoma/leukaemia (ATLL) is caused by HTLV-1 and belongs chiefly to the high grade category. Some tumours are characterised by an admixture of other cells (epithelioid cells, follicular dendritic cells, etc) and structures (high endothelial venules, follicles), which may indicate the secretion of lymphokines by the tumour cells. Clear cells seem to be specific for T cell lymphomas and may occur in various types of peripheral T cell lymphoma.

Adult↗

[Multicenter study of the treatment of highly malignant non-Hodgkin's lymphomas with polychemotherapy (CHOPV) and irradiation].

In a multicenter study 46 untreated patients with highly-malignant non-Hodgkin's lymphomas stage II-IV received 6 courses of the following drug combination: cyclophosphamide 750 mg/m2 i.v. day 1, adriamycin 50 mg/m2 i.v. day 1, vincristine 2 mg i.v. day 1, prednisolone 100 mg p.o. days 1-5, and etoposide 100 mg/m2 i.v. days 3-5. Between courses 4 and 5 an involved field irradiation with a total dose of 25 Gy was employed. The overall response rate was 91%, with 38 patients achieving a complete remission (82%), 4 patients achieving a partial remission (9%), and 4 patients showing no response (9%). During a median follow-up period of 34 months 16 out of 38 patients relapsed, 4 of them achieving a second complete remission with the same drug regimen. A maintained complete remission up to 52 months was seen in 51% of all patients initially achieving CR. The overall survival curve shows a plateau at 60% at 30 months, while disease-free survival shows a plateau at 51% at 36 months. Mean side effects of this drug regimen were alopecia (89%), nausea/vomiting (76%), and leukopenia (61%). No therapy-related deaths were reported. The results of this study demonstrate that this treatment produces high complete remission rates and that the majority of these patients achieves long-term disease-free survival.

Adolescent↗

[The relations between Hodgkin's and non-Hodgkin's lymphoma].

Contrary to the generally accepted dogma that Hodgkin's and non-Hodgkin's lymphomas represent two clearly distinct tumor entities, studies with morphologic and immunological methods revealed many overlappings. Thus Sternberg-Reed cells are not specific to Hodgkin's lymphoma. In addition, the reactivity of the monoclonal antibody Kil, which was developed from Hodgkin cell lines, is by no means restricted to Hodgkin and Sternberg-Reed cells. Moreover, some high grade malignant variants of Hodgkin's lymphoma are morphologically identical to high grade malignant non-Hodgkin's lymphomas. Although the borders between Hodgkin's and non-Hodgkin's lymphoma are often poorly defined, clinical and therapeutic considerations demand that a distinction be attempted whenever possible. It is likely that molecular-genetic methods will enable us to recognize whether and where clear-cut borders exist.

Hodgkin Disease↗

Cytogenetic findings in nodular paragranuloma (Hodgkin's disease with lymphocytic predominance; nodular) and in progressively transformed germinal centers.

Cytogenetic studies were performed in a case of progressively transformed germinal centers (PTGC), and in a case of nodular paragranuloma (NP; Hodgkin's disease with lymphocytic predominance, nodular type). No cytogenetic abnormalities were detected in PTGC. Chromosomal aberrations (hyperdiploidy, 6q-, +21, and several unidentified markers) were found in NP. The results support the proposal that PTGC are reactive in nature and NP is a neoplasm. Chromosomal analysis could provide practical diagnostic aids in the differential diagnosis of PTGC and NP.

Adult↗

Germinal center derived malignant lymphoma in cystadenolymphoma.

Two cases of malignant non-Hodgkin's lymphoma arising in an Albrecht-Arzt-tumour are reported. In the first case a centroblastic-centrocytic lymphoma in a palatinal cystadenolymphoma of a 64-year-old female is described. In the other case a centroblastic lymphoma developed in an Albrecht-Arzt-tumor of the submandibular region in an 82-year-old man. The occurrence of a high-grade malignant lymphoma in cystadenolymphoma has not been reported in the literature so far.

Adenolymphoma↗

Immunoelectron microscopic localization of immunoglobulin in B-cell lymphomas.

Subcellular localization of immunoglobulin (Ig) by immunoelectron microscopy was performed on 20 B-cell lymphomas of low- and high-grade malignancy. The efficiency in demonstrating Ig by pre-embedding technique depends on the antibodies used. F(ab')2 fragments of antibodies were more sensitive than both intact polyclonal and monoclonal antibodies in detecting cytoplasmic Ig. With immunoelectron microscopy Ig could be demonstrated in all cell types of B-CLL and LP-immunocytoma, even in some of the small lymphocytes in B-CLL. Thus, the presence of intracytoplasmic Ig has no diagnostic relevance in differentiating B-CLL from LP-immunocytoma. However, the amount of Ig in the tumor cells of LP-immunocytoma seemed to be greater than in B-CLL. Centrocytic lymphoma and centroblastic/centrocytic lymphoma could be differentiated by their different localization of Ig. In centrocytic lymphoma Ig was localized mainly on the surface membrane, whereas in centroblastic/centrocytic lymphoma moderate amounts of Ig could be detected in the rough endoplasmic reticulum and perinuclear space of the centroblasts and in roughly one third of the centrocytes. In malignant lymphomas of high-grade malignancy (ML centroblastic, ML immunoblastic, and ML lymphoblastic) Ig was localized mainly in the rough endoplasmic reticulum and sometimes in the perinuclear space.

B-Lymphocytes↗

Cytogenetic and immunohistochemical analysis of lymphoepithelioid cell lymphoma (Lennert's lymphoma): further substantiation of its T-cell nature.

In 1968 a special variant of Hodgkin's disease, epithelioid cellular lymphogranulomatosis--later on termed lymphoepithelioid cell lymphoma/Lennert's lymphoma--was defined. There are increasing indicators that Lennert's lymphoma is of T-cell origin. Seven cases of Lennert's lymphoma are studied with cytogenetic as well as immunohistochemical techniques. Six of them have cytogenetic abnormal clones always including aberrations of chromosome No. 3 (+3, break in q22, dup q22----q24). In all cases band 3q22 is either broken or duplicated. Immunohistochemically it is clearly demonstrated that the proliferating cells are of T-cell nature (Ki67+, Leu4+, Leu1+). Under consideration in the literature it can be stated in conclusion that (1) lymphoepithelioid cell lymphoma (Lennert's lymphoma) with aberrations has to be designated as malignant lymphoma, (2) immunohistochemical double labeling proved the T-cell nature of this lymphoma, (3) there are remarkable similarities between the chromosomal patterns of lymphoepithelioid cell lymphoma, lymphogranulomatosis X/angioimmunoblastic lymphadenopathy and probably Hodgkin's disease: many normal mitoses and abnormalities of chromosome No. 3, especially trisomy. It is discussed that abnormalities of chromosome No. 3 involving band q22 are an indicator of a common genetic background of these lymphomas.

Adult↗

Immunophenotyping of T-lymphoblastic lymphoma/leukemia: correlation with normal T-cell maturation.

Twenty-nine cases of T-lymphoblastic lymphoma/leukemia were classified with conventional morphologic methods and the aid of monoclonal antibodies. All cases were investigated with a sensitive immunohistochemical method, using a panel of 22 monoclonal antibodies. In addition, normal thymus glands in the 22nd and 36th weeks of gestation were studied. Eight different groups of T-lymphoblastic lymphomas/leukemias could be distinguished, each of which showed a characteristic marker constellation. The results indicate that a complete detection of all thymic and prethymic lymphomas and leukemias is possible. By comparison with the phenotypic pattern of normal peripheral T-lymphocytes and their thymic precursors, the groups could be arranged in a sequence that resembles normal T-cell maturation, monoclonal antibodies.

Adolescent↗

Amyloid deposits in lymph nodes: a morphologic and immunohistochemical study.

In a series of approximately 80,000 lymph nodes, amyloid deposition was found in 18; 12 of those nodes were selected, on the basis of availability of specimens, for investigation by immunohistochemical typing to identify the protein of origin and by correlation with morphologic criteria and clinical information. Four patterns of amyloid deposition were identified: lymph node vessel involvement, follicular deposition, diffuse deposition, and a combination of follicular and diffuse deposition. All cases were classified immunohistochemically with the amyloid type-specific antisera anti-AA, anti-A lambda, anti-A kappa, anti-ASc1, and anti-AF. Immunoglobulin-derived protein (AL) in lymph nodes was found in every case of isolated amyloidosis, lymphoplasmacytic/lymphoplasmacytoid immunocytoma, plasmacytoma, and idiopathic amyloidosis. Among the cases of AL amyloidosis were nine of A lambda and one of the A kappa type. AA protein was present in two cases of reactive systemic amyloidosis. There was no useful morphologic correlation with the immunohistochemically identified amyloid types.

Aged↗

Reed-Sternberg and Hodgkin cells in lymphocyte-predominant Hodgkin's disease of nodular subtype contain J chain.

To throw light on the question of whether B-cell-derived forms of Hodgkin's disease exist, more than 100 cases of Hodgkin's disease (including all four major histologic categories) were investigated for the presence of J chain and were also immunostained for epithelial membrane antigen and the granulocyte-associated antigen X hapten. Reed-Sternberg and Hodgkin cells (RS & H) expressed J chain in 22 cases, 8 of which also expressed epithelial membrane antigen (EMA). X hapten was found in 62 cases, but all of these were J chain negative. J chain-positive RS & H cells were restricted to cases of lymphocyte-predominant disease, while X hapten-positive tumor cells were found frequently in nodular sclerosis, mixed cellularity, and lymphocyte-depletion Hodgkin's disease, but only occasionally in cases of lymphocyte-predominant disease. These findings indicate that nodular lymphocyte-predominant Hodgkin's disease differs from the other subtypes of Hodgkin's disease and that the neoplastic cells are of B-lymphoid origin.

Fluorescent Antibody Technique↗

T-cell origin of Lennert's lymphoma.

The arrangement of the T-cell receptor and immunoglobulin genes has been analysed in five cases of Lennert's lymphoma. All cases showed rearrangement of the gene coding for the beta chain of the T-cell receptor and a germline configuration of the immunoglobulin genes. This provides strong evidence that Lennert's lymphoma is a T-cell lymphoma.

Antibodies, Monoclonal↗