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Biomedical subjects

K Lennert

Publications and source records attributed to K Lennert.

At least 19 recordsLinked to original sources

Treatment of angioimmunoblastic lymphadenopathy (AILD)-type T-cell lymphoma using prednisone with or without the COPBLAM/IMVP-16 regimen. A multicenter study. Kiel Lymphoma Study Group.

OBJECTIVE: To describe the clinical course of patients with angioimmunoblastic lymphadenopathy (AILD)-type lymphoma with a sequential treatment with prednisone and COPBLAM/IMVP-16. DESIGN: A multicenter, prospective, nonrandomized trial. SETTING: University medical centers and community hospitals. PATIENTS: Sixty-seven patients were registered, 28 were excluded, and 39 patients were evaluable for response (median age, 59 years; range, 25 to 82 years) (stages I and II, 10%; stages III and IV, 90%; B symptoms, 74%). MEASUREMENTS: Response, survival, and relapse. INTERVENTION: Patients initially received prednisone and no further treatment if a complete remission was achieved. Relapsing or refractory patients were treated with COPBLAM/IMVP-16. Patients with life-threatening tumor progression or extension received COPBLAM/IMVP-16 initially. Treatments were chosen in accordance with tumor extension and response to prednisone. Treatment modalities were not compared. RESULTS: Twenty-eight patients received primary prednisone, 18 received secondary prednisone, and 11 received primary chemotherapy. The complete response rates (with 95% CIs) were 29% (CI, 12% to 46%), 56% (CI, 33% to 79%), and 64% (CI, 36% to 92%), respectively. The median observation time of surviving patients was 28 months (range, 7 to 53). The median overall survival time was 15 months. The probabilities (with 95% CIs) of overall survival, event-free survival, and relapse at 36 months were 40.5% (CI, 24% to 56%), 32.3% (CI, 17% to 47%), and 34.6% (CI, 14% to 56%), respectively. At the time of evaluation, 22 of 39 patients had died, 7 of noninfectious complications and 14 of infections. CONCLUSIONS: Prednisone with or without COPBLAM/IMVP-16 treatment in AILD-type lymphoma leads to complete remissions in about half of the patients and in long-term, disease-free survival for one third.

Adult

Lectin-binding profile of plasmacytoid monocytes.

The lectin-binding profile of plasmacytoid monocytes, also known as plasmacytoid T cells, was studied in 18 axillary lymph nodes draining invasive breast carcinomas. The plasmacytoid monocytes bound fluorescein-conjugated lectins from Canavalia ensiformis (Con A), Phaseolus vulgaris (PHA-L), Arachis hypogaea (PNA), Ricinus communis (RCA I and II), and Triticum vulgaris (WGA), but no reaction was found with those from Dolichos biflorus (DBA) and Ulex europaeus (UEA I). Fluorescence was bright and the reactivity was distributed in a granular pattern in the cytoplasm of plasmacytoid monocytes, a staining pattern similar to that of monocytes and macrophages. B and T lymphocytes usually exhibited weak staining with the same lectins, and this was limited to the cell membrane. Plasmacytoid monocytes were originally thought to be closely related to the T-cell system. The results of recent immunocytologic studies and the lectin-binding profile of plasmacytoid monocytes observed in this study, however, suggest that these cells are related to the mononuclear phagocytic system.

Biomarkers

Lymph node findings in generalized mastocytosis.

Lymph nodes from 21 cases of generalized mastocytosis were studied histologically to confirm or exclude mast cell infiltration, and to investigate their micro-architecture. Mast cell infiltrates were detected in 17 (80%) of the lymph nodes and were found mainly in the medullary cords and sinuses. Diffuse infiltration was seen in 14 cases and focal infiltration in three cases. The following pathological findings were frequently observed: germinal centre hyperplasia (n = 14), which is probably a nonspecific finding; and hyperplasia of small blood vessels, which sometimes resembled high endothelial venules (14), eosinophilia (8), plasmacytosis (7) and collagen fibrosis (6), all of which may well be related to the effects of mediators released by mast cells. Infiltrates of acute or chronic myeloid leukaemia were seen in six lymph nodes. Division of the cases into two prognostically different groups, i.e. systemic mastocytosis, in which the skin lesions of urticaria pigmentosa are present and the prognosis is favourable, and malignant mastocytosis, in which there is no cutaneous involvement and the prognosis is poor, revealed that all six lymph nodes exhibiting leukaemic infiltrates came from the malignant mastocytosis group; eosinophilia, plasmacytosis and fibrosis were seen significantly more often in malignant than in systemic mastocytosis, but blood vessel hyperplasia and germinal centre hyperplasia were encountered with the same high frequency in both groups; and mast cell atypia tended to be more pronounced in malignant mastocytosis; this diagnosis could therefore easily be missed without naphthol AS-D chloroacetate esterase staining.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans

[Non-Hodgkin's lymphomas: principles and application of the Kiel classification].

In the Kiel classification malignant non-Hodgkin's lymphomas (NHL) are defined essentially according to their constituent cells, based on their morphologically and immunologically defined normal equivalents. For pragmatic reasons they are also divided into low and high grade malignant lymphomas. The most important condition for applying the classification is technical excellence, especially in embedding. The usual criteria of malignancy are only partially applicable to the division into reactive and malignant lymph node diseases. There are borderline cases between nonneoplastic and neoplastic lymph node diseases that cannot presently be distinguished with certainty with any method--including immunohistochemistry and molecular and classical genetics. Thus the gold standard of lymphoma diagnostics remains the subtle morphological investigation. In doubtful cases there should be close feedback between pathologists and clinicians.

Humans

Primary B-cell gastric lymphoma: a clinicopathological study of 145 patients.

Resection specimens from 145 patients with primary B-cell gastric lymphoma at stage IE (n = 88) and at stage IIE (n = 57) were investigated. Histologically, low-grade malignant B-cell lymphomas arising from the mucosa-associated lymphoid tissue, including immunocytoma (n = 71), could be distinguished from high-grade malignant B-cell lymphomas with (n = 25) and without (n = 49) evidence of a low-grade component. The very rare low-grade B-cell lymphomas of centroblastic-centrocytic, centrocytic, and plasmacytic type were not considered. All patients had undergone primary gastric resection, and 65 received additional chemotherapy (n = 33), radiotherapy (n = 22), or both (n = 10). Actuarial overall survival rates calculated by the Kaplan-Meier life-table method were 76% after 5 years and 58% after 10 years. According to the Mantel test and a multivariate analysis using the Cox regression method, patients at stage IE had a significantly better survival probability than those at stage IIE (P less than 0.0001); 5-year survival rates were 87% and 61%, respectively. The survival probability for low-grade malignant lymphomas was significantly better than for tumors with secondary high-grade transformation (P less than 0.05) or for primary high-grade lymphomas (P less than 0.0001), whereas the two high-grade groups were not significantly different. Five-year survival rates were 91% for low-grade, 73% for secondary high-grade, and 56% for primary high-grade malignant lymphomas. Retrospectively, no significantly different survival rates were found between patients who had undergone gastric resection alone and patients who had received additional treatment. However, survival analyses showed that classification and grading according to the histopathological concept of mucosa-associated lymphoid tissue-derived gastric lymphomas into low-grade B-cell lymphomas of mucosa-associated lymphoid tissue type and high-grade B-cell lymphomas with or without evidence of a low-grade component has great prognostic relevance.

Actuarial Analysis

Follicular dendritic cells in Hodgkin's disease.

The distribution of follicular dendritic cells (FDCs) was studied in 66 lymph nodes affected by Hodgkin's disease (HD) from as many patients with the use of the monoclonal antibody Ki-FDC1P, which stains FDCs in paraffin sections. Two distinct FDC patterns were distinguishable in the neoplastic areas: pattern A, showing FDC networks occupied by nongerminal center cells, often expanded and disrupted; and pattern B, with FDCs rare or lacking. Pattern A, with follicle-occupying cells represented by epithelioid and lymphocytic and histiocytic (L and H) cells, was found in about 90% of the cases of nodular lymphocyte predominance type and in about half of the cases of nodular sclerosis type, with the follicle-occupying cells being lacunar cells. In the group of mixed cellularity type, approximately one-fifth of the cases exhibited pattern A and in these cases the follicle-occupying cells were Sternberg-Reed, Hodgkin's, and epithelioid cells. The presence of follicular structures, although abnormal, is a more common occurrence in HD than is appreciable with the use of conventional histologic methods.

Antibodies, Monoclonal

Monocytoid B-cell lymphoma: morphological variants and relationship to low-grade B-cell lymphoma of the mucosa-associated lymphoid tissue.

Twenty-eight cases of monocytoid B-cell lymphoma of lymph nodes and 16 lymph node metastases of primary gastric lymphomas, mostly low-grade B-cell lymphomas of mucosa-associated lymphoid tissue (MALT) type were investigated morphologically and immunohistochemically. Both groups showed the same morphological and immunohistochemical features: diagnostically important sites of infiltration were the sinuses and the marginal zones. The tumour cells were either medium-sized or small. The cytoplasm stained grey with Giemsa and was sometimes rather pale. In imprints the grey colour of the cytoplasm was a characteristic feature. The medium-sized cell type was more frequent; in one third of the cases it was combined with a prominent lymphoplasmacytic component from the same clone, and it resembled the monocytoid B-cells of the sinuses. The small cell type was less common, was not combined with a lymphoplasmacytic component and more closely resembled marginal zone cells. The difference was underlined by the negative reaction with the monoclonal antibody Ki-B3 in the small cell type, which, conversely, was positive in the medium-sized cell type and in the monocytoid B-cell reaction of the sinuses. Both of these cell types, however, showed a granular reaction with the new monoclonal antibody Ki-Mlp. The morphological and immunohistochemical parallels are arguments in favour of the assumption that monocytoid B-cell lymphoma is the nodal equivalent of low-grade B-cell lymphoma of MALT type. This is further supported by the fact that in nine of our 28 cases of monocytoid B-cell lymphoma, lymphomas were found simultaneously or subsequently in organs of the MALT. Monocytoid B-cell lymphoma must be differentiated from an infiltration that occurs in the form of clusters of monocytoid B-cells in other low-grade B-cell lymphomas, especially in immunocytoma with a high content of epithelioid cells.

Adult

Recombinant human interferon-alpha in the treatment of angioimmunoblastic lymphadenopathy: results in 12 patients.

Peripheral T-cell lymphomas of the angioimmunoblastic lymphadenopathy (AILD) type roughly correspond to lymphogranulomatosis X (LgX). They are currently treated with prednisone, either as a single treatment or with combination chemotherapy. However, both approaches are associated with high risks in this usually elderly patient population (median age 64 years). While looking for therapeutic alternatives to avoid these problems, the efficacy of low dose recombinant interferon-alpha 2a was examined. Patients received 3 x 10(6) IU daily as a subcutaneous (s.c.) injection. Those who achieved a complete remission continued with a maintenance treatment of 3 x 10(6) IU s.c. three times per week. A total of 14 patients received interferon. Twelve were evaluable for response. Six received interferon as primary and six as secondary treatment after the failure of previous treatment with prednisone or chemotherapy. Complete remissions were achieved in four, partial remissions in another four of 12 patients, whereas in the remaining four patients no change or progressive disease was observed. The median remission duration was 3.5 months; the longest durations of complete remissions were 6+ and 7 months. It is concluded that low dose interferon-alpha is an effective and well tolerated drug in T-cell lymphomas of the AILD (LgX) type. It is useful for salvage treatment in patients with contraindications or refractory to combination chemotherapy. It may be useful in adjuvant or maintenance treatment.

Aged

Stepwise development of chromosomal abnormalities in angioimmunoblastic lymphadenopathy.

Cytogenetic studies of lymphoproliferative diseases, such as angioimmunoblastic lymphadenopathy (AILD), may provide a clue to the understanding of tumor development. Angioimmunoblastic lymphadenopathy may evolve from a nonmalignant lymphoproliferation into a peripheral T-cell lymphoma or even into a high-grade B-cell lymphoma and thus offers the chance to observe cytogenetic changes during lymphoma development. We report the cytogenetic findings in 24 cases of AILD. They are discussed together with 18 previously published cases from the same series. A striking feature was that unrelated chromosome abnormalities, both clonal and nonclonal, were frequently observed. Eighteen of 25 cases with aberrant clones show trisomy 3 (a characteristic chromosome abnormality in peripheral T-cell lymphoma), trisomy 5, or both. This finding provides cytogenetic evidence that these cases are definitely peripheral T-cell lymphomas. From the results of the 42 cases, hypotheses of stepwise evolution of the chromosome abnormalities in AILD are deduced: the first step is the appearance of chromosome abnormalities in different cells because of a genetic instability. At this time, clonal proliferation of T cells was already demonstrated by the rearrangement of T-cell receptor genes. As a second step, chromosomally aberrant clones become established. A cytogenetically detectable monoclonal proliferation represents the third step.

Aged

B-cell lymphoma of the mucosa-associated lymphatic tissue (MALT) presenting with bone marrow and peripheral blood involvement.

A 46-year-old female patient was diagnosed as having a low-grade malignant B-cell lymphoma of the gastric MALT, stage IV, with bone marrow involvement and a leukaemic blood picture. Different from the infiltrate in the gastric mucosa, which consisted mainly of centrocyte-like cells, the leukaemic cells presented with a blood-picture resembling infectious mononucleosis but showing a predominance of plasma cells. Despite these cytological differences, a common clonal origin for both cellular compartments was demonstrated immunophenotypically and genotypically. Low-grade B-cell lymphomas of the MALT may thus initially present with stage IV disease and a leukaemic blood picture.

B-Lymphocytes

Proliferation of marginal zone cells mimicking malignant lymphoma.

An enlarged axillary lymph node from a 58-year-old woman showed a proliferation of marginal zone cells in nodules or large band-forming aggregates within the cortex. The marginal zone cells also infiltrated the adjacent fatty tissue. They showed polytypic surface immunoglobulins (IgM++, IgG+, kappa+, lambda+). Their immunophenotype (IgD-, CD23-, KiB3-) differed from that of the small lymphocytes of the mantle zone. They were also positive for alkaline phosphatase. The lesion is reactive and must be differentiated from low-grade malignant lymphomas, especially centrocytic lymphoma.

Antigens, CD

Lymphoplasmacytic/lymphoplasmacytoid immunocytoma with a high content of epithelioid cells. Histologic and immunohistochemical findings.

Fifty-four lymph node biopsy specimens from 36 patients with lymphoplasmacytic/lymphoplasmacytoid immunocytoma with a high content of epithelioid cells (LPICep) were studied by light microscopy using conventional histologic and immunohistochemical techniques. Three other patients with extranodal involvement only were also included in the study. Of a total of 39 patients, 31 had the polymorphic subtype, six the lymphoplasmacytoid subtype, and two the lymphoplasmacytic subtype. Cellular composition and histologic structure are described in detail as a basis for discriminating LPICep from similar lymphomas with a high content of epithelioid cells, especially from lymphoepithelioid cell lymphoma (Lennert's lymphoma), angioimmunoblastic peripheral T-cell lymphoma with a high content of epithelioid cells, and Hodgkin's disease, mixed cellularity type with a high content of epithelioid cells. In 10 patients (26%) LPICep developed into a high-grade malignant lymphoma of B-immunoblastic type. Forty-seven biopsy specimens were studied with the peroxidase-antiperoxidase method to detect intracytoplasmic immunoglobulin. Plasma cells and plasma cell precursors revealed a monotypic immunoglobulin pattern in all specimens. In 25 biopsy specimens in which giant cells resembling Sternberg-Reed and Hodgkin's cells were found, these cells were CD15 negative. A comparison of the main clinical and laboratory data in these four lymphomas with a high content of epithelioid cells revealed both similarities and differences.

B-Lymphocytes

Primary lymphomas of the lung: morphological, immunohistochemical and clinical features.

Sixty-two cases of primary malignant lymphoma of the lung were investigated. Fifty-eight lymphomas were of B- and two of T-cell type. Two cases of high-grade lymphoma could not be further classified. The largest group (43 cases) consisted of low-grade B-cell lymphoma of the bronchus-associated lymphoid tissue. These showed features similar to low-grade B-cell lymphomas of the mucosa-associated lymphoid tissue of the stomach. The low-grade lymphomas showed a peak occurrence in the sixth decade, the high-grade lymphomas in the seventh decade. Males predominated slightly. Three-quarters of the patients with low-grade B-cell lymphoma of the bronchus-associated lymphoid tissue showed solitary or multiple sharply defined nodules of the lung. The prognosis of the B-cell-derived lung lymphomas without constitutional symptoms was relatively favourable, regardless of whether they were of low- or high-grade malignancy, whereas patients with constitutional symptoms and the two patients with T-cell lymphomas showed a bad prognosis. However, recurrences and metastases in the lung, stomach, lymph nodes and salivary glands were seen in about 46% of the cases of low-grade B-cell lymphoma of the bronchus-associated lymphoid tissue.

Age Factors

Monocytoid B cell lymphoma: clinical and prognostic features of 21 patients.

Twenty one patients between 34 and 83 years of age with monocytoid B cell lymphoma (MBCL) of the lymph node were studied. The histological picture characteristically showed broad strands of medium sized cells with irregularly shaped nuclei and a fairly broad rim of slightly basophilic cytoplasm. One case developed into a centroblastic polymorphic lymphoma. Bone marrow infiltration was documented in three cases and leukaemic conversion in one case of MBCL. Seven patients had enlarged spleens. Eight patients were in stage I, five in stage II/IIE, two in stage IIIs and six in stage IV at the time of diagnosis. Of 18 patients subsequently followed up, eight were in complete remission, two in partial remission, and three were undergoing treatment at completion of the study; five patients had died. Relapse occurred in nine patients and was a common feature of MBCL. The prognosis of MBCL was comparable with that of other low grade malignant lymphomas. Fourteen patients presented with primary nodal lymphoma. In seven patients with nodal MBCL, however, a concomitant low grade B cell lymphoma of the mucosa-associated lymphoid tissue (MALT) was also found in the stomach (n = 4), nasopharynx (n = 1), salivary glands (n = 1) and thyroid gland (n = 1). Two of these cases developed into high grade lymphoma. These extra-nodal manifestations were found simultaneously with MBCL in five patients. In another two patients, however, these symptoms occurred in a later phase of the disease. It is emphasised that adequate staging procedures must be carried out in any case of nodal MBCL to exclude underlying low grade B cell lymphoma of the MALT.

Adult