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Biomedical subjects

K Lennert

Publications and source records attributed to K Lennert.

At least 91 records · Page 5Linked to original sources

Mast cell sarcoma of the larynx.

A 74 year old woman presented with a primary subglottic tumour. Neither cutaneous mastocytosis (urticaria pigmentosa) nor spread to the bone marrow, liver, or spleen were detected. About two years after initial manifestation of the tumour nodular skin metastases appeared, as well as local recurrence in the larynx. Despite chemotherapy and radiation the disease progressed and was fatal. The terminal phase was characterised by generalisation of the mast cell tumour with diffuse infiltration of bone marrow and, shortly before death, leukaemic transformation. The patient died four years after onset of disease with symptoms of a hemorrhagic diathesis. As far as we know this is the first case of mast cell sarcoma to be reported in man.

Aged↗

[Morphology, immunohistochemistry and genetics of peripheral T cell lymphomas].

T-cell lymphomas are relatively rare in our material; they comprise less than 20% of all non-Hodgkin's lymphomas. A definitive classification of the T-cell lymphomas still does not exist. Nonetheless, it is now possible to distinguish thymic and prethymic, i.e. lymphoblastic lymphomas, from postthymic, i.e. peripheral T-cell lymphomas. Of the peripheral T-cell lymphomas the following are relatively well defined: chronic lymphocytic leukemia of T type (T-CLL) and prolymphocytic leukemia of T type (T-PLL), mycosis fungoides and Sézary's syndrome, lymphoepithelioid lymphoma (Lennert's lymphoma), T-zone lymphoma T-immunoblastic lymphoma, and large cell anaplastic lymphoma (so-called Ki1 lymphoma). Recently, a T-cell lymphoma termed lymphogranulomatosis X (AILD)-type was defined whose chromosomal abnormalities and rearrangement of the beta-chain of the T-cell receptor appear to distinguish it from cases of non-neoplastic lymphogranulomatosis X. Histological and cytochemical criteria enable the identification of many cases of T-cell lymphoma. By contrast, the large number of available monoclonal antibodies can do little more than confirm the T-cell nature and proliferation rate of the tumor cells. DNA rearrangement techniques now make it possible to distinguish between polyclonal and monoclonal T-cell proliferations. Lymphoepithelioid lymphoma, lymphogranulomatosis X and large cell anaplastic lymphoma (Ki1 lymphoma) are treated in detail. The boundary between Hodgkin's disease and peripheral T-cell lymphoma is not as distinct as textbooks would make it appear.

Antibodies, Monoclonal↗

Rearrangement of the beta chain of the T cell antigen receptor and immunoglobulin genes in lymphoproliferative disorders.

55 samples representing Hodgkin's and non-Hodgkin's lymphoma and other hyperplastic lesions of the lymph node were examined for rearrangement of the beta chain of the T cell antigen receptor (TcR) and Ig genes. In non-Hodgkin's lymphoma, rearrangement of TcR beta was found in all 14 T cell lymphomas and in two of the seven B cell lymphomas. Ig gene rearrangement was found in none of the 14 T cell lymphomas and in all seven B cell lymphomas. We also examined DNA from lymph nodes in which the lineage of the malignant cell is not clear. Rearrangement of TcR beta was found in all five lymphoepitheloid cell (Lennert's) lymphomas; four of eight Hodgkin's lymphomas; seven of ten Ki 1+ lymphomas; and all nine cases of angioimmunoblastic lymphoadenopathy (AIL). Ig gene rearrangement was found in none of five lymphoepitheloid cell lymphomas; none of eight Hodgkin's lymphomas; three of ten Ki 1+ lymphomas; and four of nine cases of AIL. These findings indicate that genetic studies of TcR and Ig genes are useful in identifying the presence of a clonal population in a lymph node, in determining the extent of the clonal population, and aid in identifying lineage. Of special interest was the finding that some cases of Hodgkin's lymphoma and AIL contain clonal rearrangement of the TcR genes, which suggests that in those cases the malignant cells may be of T cell origin.

DNA↗

Lymphoepithelioid lymphoma (Lennert's lymphoma) is a monoclonal proliferation of helper/inducer T cells.

Lymphoepithelioid lymphoma (Lennert's lymphoma) was first described as a special variant of Hodgkin's disease. This lesion is characterized by a high percentage of epithelioid and T cells and rarely contains the classical Hodgkin's/Reed-Sternberg cells. Cytogenetic abnormalities indicate that Lennert's lymphoma is of T cell origin. In the present study, immunohistochemical investigation of four cases of Lennert's lymphoma revealed two major cell populations of T cells that predominantly express the helper-inducer phenotype and Ki-M6- and Ki-M8-positive macrophages and epithelioid cells. Double-staining experiments for the detection of cell surface antigens and the proliferation-associated antigen Ki67 showed that only the CD4-positive cells (helper-inducer T cells) were proliferating. Examination of the DNA of these Lennert's lymphoma samples also indicated that monoclonal rearrangement of the T cell receptor beta-chain genes has occurred, whereas the immunoglobulin heavy- and kappa-chain genes remained in germline configuration. Our results strongly suggest that Lennert's lymphoma is a CD4-positive T cell lymphoma.

Antibodies, Monoclonal↗

The structure of the T cell gamma chain gene in lymphoproliferative disorders and lymphoma cell lines.

During the development of B and T cells, a number of genes undergo rearrangement. In this paper we have studied the structure of the T cell gamma-chain gene in primary lymphomas and cell lines derived from patients with lymphoma. Samples derived from patients with angioimmunoblastic lymphadenopathy (AIL), Lennert's lymphoma, and Hodgkin's disease were also examined. TcR gamma was rearranged in all T cell lymphomas and in some B cell lymphomas and B cell lymphoma cell lines. Rearrangement of the gamma-chain gene was also found in AIL, Lennert's lymphoma, and four of eight cases of Hodgkin's disease. These studies indicate that rearrangement of TcR gamma is a useful clonal marker but does not aid in the identification of cell lineage.

Cell Line↗

Rearrangement of the T-cell-receptor beta-chain gene in the diagnosis of lymphoproliferative disorders.

The arrangement of the T-cell-receptor and immunoglobulin genes has been analysed in 77 cases of lymphoproliferative disorder. All 6 T-cell leukaemias and 16 of 19 T-cell lymphomas showed rearrangement of the gene coding for the beta chain of the T-cell receptor, associated in all cases with a germline arrangement of the immunoglobulin genes. All 36 B-cell leukaemias and all 16 B-cell lymphomas showed rearrangement of immunoglobulin genes; the T-cell-receptor gene was in the germline configuration in most of these cases but showed a rearranged pattern in 3 cases (2 chronic lymphatic leukaemias and 1 immunoblastic lymphoma). The combined use of T-cell-receptor and immunoglobulin gene probes promises to be a valuable means of identifying and classifying T-cell neoplasms.

Autoradiography↗

HTLV-positive and -negative T-cell lymphomas. Morphological and immunohistochemical differences between European and HTLV-positive Japanese T-cell lymphomas.

A total of 56 cases of malignant lymphoma presumed to be of peripheral T-cell origin were investigated with regard to histological and immunohistochemical features. The goal of the study was to determine whether virus-associated T-cell lymphomas can be morphologically or immunohistochemically distinguished from presumably virus-negative T-cell lymphomas. The cases came from endemic and non-endemic regions of Japan, the United Kingdom (including 4 Caribbean cases) and the Federal Republic of Germany. Sera of all Japanese and Caribbean patients and 8 German patients were tested for antibodies to adult T-cell leukaemia virus-associated antigen HTLV-A. In all cases sections were examined blind by 5 well-trained histopathologists. In most cases cryostat sections could be prepared from fresh tissue specimens and stained with a large panel of monoclonal antibodies. All HTLV-A-positive cases were morphologically classifiable as the pleomorphic type of T-cell lymphoma. Approximately 70% of the tested cases of pleomorphic T-cell lymphoma, however, showed a positive serum reaction for HTLV-A. All other types of peripheral T-cell lymphoma (T-immunoblastic lymphoma, chronic lymphocytic leukaemia of T type, T-zone lymphoma, "AILD type" and lymphoepithelioid cell lymphoma) were HTLV-A-negative and mostly observed in European patients. Thus virus-associated T-cell lymphomas appear to be invariably of the pleomorphic type; but pleomorphism is not specific to HTLV-A-positive cases. This was also evident from the results of an experiment in which 2 Japanese histopathologists attempted to recognize HTLV-A positivity in a blind study of pleomorphic T-cell lymphomas. A maximum of about 80% of cases were correctly identified, with about 10% false-positive diagnoses (in HTLV-A-negative or presumably negative cases) and 10% false-negative diagnoses. The immunohistochemical analysis revealed not only many common features but also 2 distinct differences between HTLV-A-positive and -negative T-cell lymphomas. All but one of the HTLV-A-positive cases showed reactivity with anti-Tac and all cases in the virus-positive group were negative for TU14. All other cases were Tac-negative and approximately 65% of these cases exhibited reactivity with TU14. Preliminary cytogenetic observations suggest that there are also differences in specific chromosome aberrations.

Antibodies, Monoclonal↗

Histological, immunohistological and autopsy findings in lymphogranulomatosis X (including angio-immunoblastic lymphadenopathy).

172 cases of lymphogranulomatosis X (LgX) were studied by light microscopy. In 53 cases immunohistological techniques for detecting intracytoplasmic immunoglobulins were applied. In the lymph nodes of all cases the nodal architecture was found to be effaced. Active germinal centres were absent, and there was a generalized, markedly increased proliferation of epithelioid venules. A polymorphic infiltrate was present in all cases. It was dominated by immunoblasts in 14%, by plasma cells in 16%, by epithelioid cells in 23% and by lymphocytes in 6% of the cases. In the remaining 41% of the cases no special type of cell predominated (mixed cell type of LgX). The clusters of clear cells present in some cases with immunoblastic predominance did not stain for intracytoplasmic immunoglobulins; in contrast, the basophilic immunoblasts exhibited a polyclonal Ig pattern. In some of the cases with lymphocytic predominance most of the lymphocytes showed abundant cytoplasm with azurophil granules. Transformation into malignant lymphoma was proven at autopsy in 5 of 38 cases (13.2%). Malignant transformation (biopsy and autopsy material) was confirmed in a total of 11 of 172 cases (6.4%) and suspected in an additional 7%. Among the malignant lymphomas were one immunologically proven B-immunoblastic lymphoma, one peripheral T cell lymphoma and 5 cases of Hodgkin's disease. An association between LgX and carcinoma was histologically verified in 7 cases. 26 cases with active germinal centres and 11 cases with only locally pronounced vascularization but with histological and cytological changes that were otherwise similar to LgX were designated as hyperimmune reactions (HR). These cases had a significantly better prognosis. Two cases that presented as HR with active germinal centres later developed into LgX. It is suggested that the disappearance of active germinal centres is important in the pathogenesis of LgX. The possibility that this may correspond morphologically to an alteration of different components of the T-cell system is discussed.

Bone Marrow↗

The blood microvasculature in T-cell lymphomas. A morphological, ultrastructural and immunohistochemical study.

The microvasculature of lymph nodes of 55 cases of T-cell lymphoma was studied by light microscopy, immunohistochemistry and electron microscopy. A modified peroxidase-antiperoxidase (PAP) method was used for staining paraffin sections with lectin I of Ulex europaeus (UEA-I), which is a specific marker for vascular endothelial cells. The T-cell nature of each case was proven by immunohistochemistry, including immunoperoxidase staining of frozen sections with monoclonal T-cell antibodies. The cases were subclassified according to previously established criteria, but with the addition of a separate group showing a high content of clear cells. For the purpose of the present study, the small blood vessels were separated into two main variants, viz.: high endothelial venules (HEV) and all other types of vessels with flat endothelium (SVFE). The development of each of these variants and the extent of lymphocyte migration through the vascular wall were assessed semiquantitatively. The findings suggest that the blood microvasculature, as a whole, is similar in all types of T-cell lymphoma. There were distinct differences, however, in the development of the two main categories of small vessels between the various types. Chronic lymphocytic leukaemia of T-type (T-CLL) and Sézary's syndrome were poor in SVFE and rich in HEV, and there was considerable lymphocyte traffic through the latter. In contrast, T-immunoblastic and especially T-lymphoblastic lymphocyte traffic. The appearance of the microvasculature varied markedly in the various subtypes of "pleomorphic T-cell lymphoma". In the small cell subtype HEV predominated and SVFE represented only a small or moderate fraction of the microvasculature. As the size of the neoplastic lymphoid cells increased towards the medium-sized and large cell subtype, there was a decrease in the number of HEV and an increase in the number of SVFE accompanied by a decrease in lymphocyte migration. In T-cell lymphoma of the clear cell type the microvasculature showed features between those of T-CLL and the small cell subtype of pleomorphic T-cell lymphoma. Electron microscopy confirmed the light microscopic findings and revealed many similarities in vascular changes between "pleomorphic T-cell lymphomas" and lymphogranulomatosis X.

Histocytochemistry↗

Follicular malignant non-Hodgkin's lymphoma with pronounced plasmacytic differentiation: a plasmacytoma-like lymphoma.

A case of follicular centroblastic-centrocytic lymphoma with an unusually pronounced plasmacytic component occurring in the gingiva and cervical lymph nodes of a 74-year-old male patient is described. Immunohistological analysis revealed a monotypic intracytoplasmic immunoglobulin pattern (IgM/lambda). The relation between follicular malignant non-Hodgkin's lymphomas and extramedullary plasmacytome is discussed. In the present case the tumour may represent the development of an autonomous plasma cell clone within a follicular centroblastic-centrocytic lymphoma.

Aged↗

Bone marrow findings in systemic mastocytosis.

The neoplastic proliferation of tissue mast cells constitutes a group of rare diseases that have localized and systemic variants. The cytologic (n = 7) and histologic (n = 38) findings in bone marrow from a total of 45 patients with systemic mastocytosis were evaluated. Three distinct histologic patterns of marrow involvement were distinguished. In 21 cases a patchy or focal infiltration pattern was encountered. Mast cell aggregates were located predominantly in peritrabecular and perivascular areas. The adjacent trabeculae were thickened. A dense network of reticulin fibers and foci of lymphocytes accompanied the mast cell infiltrates. Increased numbers of eosinophils frequently demarcated the mast cell infiltrates from the surrounding tissue. In the noninfiltrated marrow areas hematopoiesis and the distribution of fat cells appeared to be normal. This histologic pattern, designated type 1, was observed exclusively in patients showing primary involvement of the skin, indistinguishable from urticaria pigmentosa. In 14 additional cases peritrabecular and perivascular sheets of mast cells, with concomitant fibrosis and osteosclerosis, were also present. Unlike the findings in type 1, however, the noninfiltrated marrow areas showed marked reductions in fat cell content and markedly increased granulocytopoiesis or increased numbers of blast cells (infiltration pattern type 2). On the basis of the hematologic and clinical findings, chronic myeloid leukemia was diagnosed in six of these cases, myelomonocytic leukemia in three cases, and acute myeloid leukemia in two cases. The bone marrow of three patients was diffusely infiltrated by atypical mast cells, leading to marked hypoplasia of fat cells and blood cell precursors. These histologic features were identified as infiltration pattern type 3. The diagnosis of mast cell leukemia was confirmed in all three cases by the presence of numerous mast cells in the blood. The prognosis for patients with the type 1 marrow infiltration pattern and primary skin involvement was favorable (actuarial survival rate five years after diagnosis, 0.75). This variant was called benign systemic mastocytosis. Primary skin involvement did not occur in the patients with type 2 or 3 infiltration patterns. The prognosis for these patients was poor (actuarial survival five years after diagnosis, 0.17 for type 2 and 0.00 for type 3). These two forms were accordingly designated malignant systemic mastocytosis.

Adult↗

Tissue mast cells in health and disease.

Mast cells (MC) are regular constituents of soft tissue and occur with varying frequency in nearly every organ. They derive from monocytic cells occurring in the adhering mononuclear fraction of the peripheral blood. Their subsequent evolution into mature MCs is primed by a MC generating lymphokine released by sensitized T-cells on restimulation by the antigen. MC granules contain preformed heparin histamine and eosinophil chemotactic factors. Other factors such as leukotriene B4 can be produced by MCs following stimulation. This is the case during the initial phase of nonspecific inflammations, when MCs are stimulated by complement activation. In the immediate type hypersensitivity reaction giving rise to IgE, MC degranulation occurs independent from complement. In IgG and IgM mediated reactions, however, MC involvement is effected by complement consumption and C5 a generation. In delayed type hypersensitivity MCs increase locally. Their functional significance remains obscure. MC neoplasias are rare and generally confined to the dermis. Cutaneous mastocytoses are called benign mastocytoma when localized and urticaria pigmentosa when disseminated. Generalized mastocytosis involves extracutaneous tissue irrespective of skin involvement. Those associated with urticaria pigmentosa-like skin lesions, present at the onset of the disease, have a significantly higher survival rate than those lacking a primary skin involvement. The term urticaria pigmentosa should be reserved for cases of cutaneous mastocytosis without extracutaneous involvement. Cases of mastocytoses lacking primary skin lesions assume a malignant course and are additionally aggravated by high incidence of myeloproliferative disorders and MC leukemia. MC sarcoma is an extremely rare neoplasia of MCs which may also terminate as a MC leukemia.

Bone Marrow↗

Bimodal differentiation prospectives for promyelocytes.

In accordance with the long-range goal to demonstrate the direct derivation of blood monocytes from promyelocytes in human bone marrow, the promyelocytic cell line HL-60 in the present study was differently stimulated with various inducers for the purpose of documenting its capability to evolve into granulocytes or monocytes-macrophages. Each differentiation line was monitored with the use of marker enzymes, antigens, and cell-specific monoclonal antibodies. In addition, studies were done on normal human bone marrow and leukemias. The results provided strong evidence for the close cytogeneic relationship of granulocytes and monocytes and for a common progenitor at the maturation stage of promyelocytes-myelocytes for both cell lineages.

Antibodies, Monoclonal↗

Mycosis fungoides and lymphoplasmacytoid immunocytoma in the same patient. A case report.

The simultaneous occurrence of two different lymphomas in a 57-year-old white woman is reported: mycosis fungoides and a leukemic lymphoplasmacytoid immunocytoma. The first was confirmed by histologic study and electron microscopy, and the latter by histologic study and immunoperoxidase staining. The lymphoid cells in the involved bone marrow and peripheral blood expressed the same surface immunoglobulin as was found in the cytoplasm of the immunocytoma cells, i.e., IgM-lambda. The clonal B-cell expansion was brought into a lasting remission by chlorambucil, but the cutaneous lymphoma proved to be refractory to therapy. The patient died 38 months after diagnosis.

Chlorambucil↗

[5 years' general drug prevention of thromboembolism in general surgery. Comparison of personal experiences with results from the literature].

Despite wide use of physical methods the number of fatal postoperative pulmonary embolisms in surgical patients increased in Kiel until 1976. Because of these results, additional general prophylaxis with 2-3 X 5000 i U of heparin-dihydroergotamine was introduced in 1978. The rate of fatal pulmonary embolism in general surgery proven by autopsy decreased to 0,3% between 1979 and 1983. It should be noted that six of the nine patients who died from pulmonary embolism had also suffered from an infaust disease. This is an excellent result since our study also includes high risk patients after emergency surgery, cases which Kakkar and Gruber did not include in their studies. Due to the extensive analysis of medical records and the pertinent post-mortem reports, the high effectivity of drug induced prophylaxis with 2-3 X 5000 i U of heparin-dihydroergotamine in order to reduce fatal pulmonary embolism in general surgery could be proven.

Adolescent↗

Blood findings in lymphogranulomatosis X.

A quantitative analysis of leukocytes in the peripheral blood of 16 patients with lymphogranulomatosis X revealed the following findings: The number of total leukocytes, monocytes, neutrophils, and eosinophils varied considerably and showed no clear common tendency. Blood basophils were found to be clearly increased with a mean value of 0.17 +/- 0.18 X 10(9)/1 as compared to 55 normal donors (0.04 +/- 0.01 X 10(9)/1). Lymphocyte counts were within the normal range. Lymphopenia was seen in 2 patients. Lymphocytes with azure granules which encompass T-suppressors were found to exceed normal values by a factor of 15. In 14 cases a variable number of hyperbasophil cells were present. Lymphogranulomatosis X seems to present with a characteristic blood picture which might be of diagnostic aid.

Adult↗