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Biomedical subjects

S Falk

Publications and source records attributed to S Falk.

At least 73 records · Page 4Linked to original sources

[Malignant lymphoma of the spleen. Histological and immunohistochemical studies of morphology and differential diagnosis].

450 splenectomy specimens showing involvement by all save a few very infrequently occurring types of malignant lymphomas (ML) recognized by the updated Kiel classification of ML were investigated by conventional histologic and immunohistochemical methods. The results confirm and augment the findings of previous studies and facilitate a comparison of infiltration patterns of different ML in the spleen. These studies in conjunction with immunohistochemical detection of neoplastic cells may thus contribute to the diagnosis of minimal, i.e. early, splenic infiltration by ML and to the differential diagnosis of ML with advanced splenic involvement. Initially, most low grade NHL lead to nodular involvement of the splenic white pulp which may evolve into larger tumor nodules and/or diffuse red pulp involvement by invasion of adjacent red pulp structures. As a rule, the infiltrates are angiotropic, i.e. neoplastic cells accumulate in the vicinity of arterial and venous blood vessels both in the white and in the red pulp. Sinus involvement is frequently associated with leukemic generalisation of the neoplasm. High grade NHL are also localized predominantly in the splenic white pulp. However, their intrasplenic spread is characterized by the formation of large nodular and/or diffuse infiltrates which may efface the splenic architecture. Hodgkin lymphomas (HL), in contrast, cause coalescing tumor nodules which show expansive growth rather than progressive infiltration of the splenic parenchyma. These infiltration patterns of ML in the spleen are a constant finding. In conjunction with cytologic features and immunophenotype of the neoplastic cells they thus constitute reliable criteria for the differential diagnosis of ML in the spleen, although their anatomical and functional basis has not yet been fully elucidated. B and T cell lymphomas initially tend to show selective involvement of the original B and T cell areas of the spleen. Most high grade ML exhibit a similar behavior, although the size of the splenic lesions usually does not permit an exact identification of the ML's primary manifestation in the spleen. They thus exhibit a "homing phenomenon" to the two large lymphoid compartments of the spleen which is most conclusively illustrated by the "organoid" ML such as CB-CC or T zone lymphoma. This behavior has been interpreted to reflect the histogenesis of the neoplastic cells of the ML under study. In addition, specialised types of accessory cells such as CD35+ FDC and CD1/S100+ IDRC appear to be essential for the creation of conditions which are suitable for B and T lymphocytes, respectively. Progressive infiltration by neoplastic cells will lead to destruction of the normal microenvironment, i.e. alterations of FDC networks.(ABSTRACT TRUNCATED AT 400 WORDS)

Antigens, CD↗

Littoral cell angioma. A novel splenic vascular lesion demonstrating histiocytic differentiation.

Seventeen cases of a novel type of vascular tumor of the spleen are described. The lesions, whose size ranges from minute foci to large nodules almost completely replacing the splenic tissue, are composed of anastomosing vascular channels resembling splenic sinus and have irregular lumina, often featuring papillary projections and cyst-like spaces; they are lined by tall endothelial cells that slough off into the vascular lumina and show hemophagocytosis. Atypical cells are absent and mitotic activity very low. In contrast to normal sinus endothelia, which express only FVIIIag, neoplastic cells express both endothelial (FVIII-AG, BMA 120) and histiocytic (KP1, lysozyme) antigens; occasionally S-100 protein is also present. The morphologic and immunohistochemical findings in this tumor reflect the dual differentiation potential of the reticuloendothelial cells lining the splenic sinus, justifying the term littoral cell angioma, and recognize a distinct entity that is different from other vascular lesions of the spleen, notably angiosarcoma. This distinction is all the more important because the clinical behaviour of this lesion is apparently benign.

Adolescent↗

Effect of aortic sclerosis on bone mineral measurements by dual-photon absorptiometry.

Measurements of the bone mineral content (BMC) of lumbar spine by dual-photon absorptiometry (DPA) are performed mainly in the anteroposterior (AP) projection. Due to superimposition of the abdominal aorta, the BMC measured for patients with aortic calcification usually is too high. To determine the influence of aortic calcifications, DPA scans were performed in the AP-projection on 100 dissected abdominal aortae with different degrees of atherosclerosis placed on a human lumbar spine cast in lucite. The measured values were compared with those obtained in the same projection without the aortae. The average increase of the BMC values relative to the mean for the vertebrae L2 to L4 for aortae with severe complicated lesions, i.e., those containing larger amounts of calcium, was 0.03 g/cm2, with a maximum deviation of 0.09 g/cm2. Aortae with fatty streaks or fibrous plaques did not cause significant increases of the BMC. The mean deviation for aortae with mild complicated lesions, i.e., those containing smaller amounts of calcium, was within the range of instrument precision.

Absorptiometry, Photon↗

Primary malignant lymphomas of the spleen. A morphologic and immunohistochemical analysis of 17 cases.

Seventeen cases of primary malignant lymphoma of the spleen (PMLS) were identified among 500 splenectomy specimens showing involvement by Hodgkin's disease or non-Hodgkin's lymphoma. All PMLS represented non-Hodgkin's lymphoma and most of them were of B-cell origin. In two cases PMLS were associated with hamartomas of the spleen (splenomas). Histologic and immunohistochemical studies did not reveal any differences between PMLS and disseminated malignant lymphomas with splenic involvement with regard to morphologic features, immunophenotype, host cell infiltrates, or proliferation activity. The reasons for the infrequent occurrence of primary lymphomas in the spleen may not be sought in a special immunophenotype of PMLS, a vigorous host response in the spleen, or in a lower proliferation activity of splenic lymphomas.

Antigen-Presenting Cells↗

Effects of recombinant human interleukin-3 in aplastic anemia.

In a phase I/II study, nine patients with aplastic anemia were treated with recombinant human interleukin-3 (rhIL-3) to assess the toxicity and biologic effects of this multipotential hematopoietic growth factor. Doses ranging from 250 micrograms/m2 to 500 micrograms/m2 were administered as subcutaneous bolus injections daily for 15 days. An increase in platelet counts from 1,000/microL to 31,000/microL was induced by rhIL-3 in one patient, and an increase in reticulocyte counts by more than 10,000/microL in four patients. The blood leukocyte counts temporarily increased in eight patients 1.5- to 3.3-fold (median, 1.8-fold), mainly due to an increase in the number of neutrophils, eosinophils, lymphocytes, and monocytes. In two patients, bone marrow cellularity increased from 7% to 33% and from 10% to 80%, respectively, but without resulting in a substantial improvement of peripheral blood counts. Mild side effects (headache and flushing) were observed in some patients, while low-grade fever occurred in all patients. Transient thrombocytopenia necessitating discontinuation of rhIL-3 treatment occurred in one patient. In conclusion, rhIL-3 can stimulate hematopoiesis in patients with aplastic anemia; however, no lasting effects were obtained.

Adolescent↗

Effects of recombinant human interleukin-3 in patients with myelodysplastic syndromes.

In a phase I-II study, nine patients with myelodysplastic syndromes and concomitant severe transfusion-dependent cytopenias were treated with recombinant human interleukin-3 (rhIL-3) to improve hematopoietic function. Doses of rhIL-3 ranged from 250 micrograms/m2 to 500 micrograms/m2 and were given as daily subcutaneous bolus injections for 15 days. Blood leucocyte counts increased 1.3- to 3.6-fold in all nine patients, including neutrophils, eosinophils, lymphocytes, basophils, and monocytes. The mean absolute neutrophil counts increased from 1,350/microL (range, 150 to 2,420) to 2,660/microL (range, 300 to 9,380) (P less than .05) immediately after the end of rhIL-3 therapy and to a maximum count of 4,096/microL (range, 350 to 10,820) (P less than .01). Platelet responses were seen in two of four profoundly thrombocytopenic patients, resulting in discontinuation of platelet transfusion. The requirements for red blood cell transfusion temporarily improved in one patient. Stimulation of plasma cells was evident by a significant increase in serum IgM and IgA levels. Mild side effects (fever, headache, local erythema, and bone pain) were observed in some patients, while transient thrombocytopenia developed in two patients. Disease progression with an increase in blast cells was seen in one patient. These results suggest that rhIL-3 is effective in stimulating hematopoiesis of all lineages in patients with myelodysplastic syndromes and may produce at least short-term hematologic improvement.

Adult↗

Early immunoscintigraphic localisation of a mediastinal tumour with indium 111-DTPA CEA-specific F(ab')2 monoclonal antibody fragments (BW 431/31) using second tracer isocontour technique.

A female patient with steadily increasing carcinoembryonic antigen (CEA) serum levels of unknown origin was referred for immunoscintigraphy with indium 111-labelled CEA-specific monoclonal antibody. The procedure revealed a tumour, undetectable by conventional diagnostic methods. Anatomical landmarking using the second tracer isocontour technique allowed the distinction between an intra- or extrapulmonary lesion. Two months later, tumour infiltration along the aortic arch was confirmed by a targeted angio-CT scan. Upon surgery, the diagnosis was definitely established histologically (undifferentiated, solid large cell carcinoma, most probably arising from the bronchus), and staining by CEA-specific immunohistochemistry confirmed the presence of the CEA antigen.

Adult↗

The spleen in osteomyelofibrosis. A morphological and immunohistochemical study of 30 cases.

30 spleens from patients with biopsy proven primary osteomyelofibrosis were studied by histological and immunohistochemical methods. The presence of trilinear haematopoiesis along the splenic circulatory pathway supports the theory that the spleen acquires haematopoietic precursor cells by filtration of the peripheral blood. In addition, impairment of intrasplenic circulation with subsequent red pulp congestion, pulp cord fibrosis and haemophagocytosis is of importance for the pathogenesis of both marked splenic haematopoiesis and complications due to hypersplenism.

Aged↗

[Effects on bone marrow during stimulation of hematopoietic stem cells with recombinant human interleukin-3].

Bone marrow aspirates and biopsies of 20 patients with malignant tumors (n = 6), bone marrow failure due to chemotherapy (n = 4), myelodysplastic syndromes (n = 5) and aplastic anemia (n = 5) were analysed before and after treatment with recombinant human interleukin-3. rhIL-3 led to increased overall bone marrow cellularity with trilinear stimulation of hematopoietic cells. In all patients marked eosinophilia and, in some, fibrosis was observed. These results show that rhIL-3 stimulates the proliferation and differentiation of pluripotent hematopoietic progenitor cells and may contribute to the treatment of bone marrow failure.

Anemia, Aplastic↗

[In vitro and in vivo effects of recombinant human interleukin-3 on hematopoietic progenitor cells].

As part of a phase I/II clinical trial with recombinant human Interleukin-3 (rhIL-3), bone marrow and peripheral blood cells from patients treated with rhIL-3 were assessed in vitro for effects on the cycling status and frequencies of erythroid, myelomonocytic and multilineage progenitor cells. Treatment with rhIL-3 induced a pronounced increase in S-phase rate of BFU-E, CFU-GEMM and day 14 CFU-GM. Circulating CFU-GEMM and day 14 CFU-GM were increased on day 7 of therapy whereas circulating BFU-E were reduced in the majority of patients. After i.v. bolus injection of IL-3 an acute effect on the peripheral blood count with neutrophilia and, after an initial nadir, monocytosis was observed. IL-6 serum-levels increased in 5 out of 14 patients after IL-3 administration with concomitant side effects in 2 patients in whom IL-6 levels increased above 75 pg/ml. In the majority of the patients a stimulation of peripheral leukocytes and platelets was observed during the 15 day treatment course. In conclusion rhIL-3 induces a multilineage response in vivo by stimulating proliferation of hemopoietic progenitor cells with a resulting elevation in peripheral blood counts.

Bone Marrow↗

Immunohistochemical assessment of splenic lymphocyte and macrophage subpopulations in patients with gastric cancer.

In order to assess the effects of malignant tumors on the immune system, 25 spleens from patients with gastric carcinoma were studied by in situ immunohistochemical methods for lymphocyte subsets and cells of the mononuclear phagocyte system. Highly significant reductions of CD4+ T cells (P less than 0.001), Ki M2+ and Ki M-3+ MPS cells (P less than 0.02 and P less than 0.05), and a stage-dependent reduction of Ki 67+ B cell proliferation activity (P less than 0.05) were seen in spleens of patients with gastric cancer. These results, which were obtained by morphologic methods in a noninvolved lymphatic organ, reflect the systemic immunosuppressive and immunodepleting effects of malignant tumors that are probably mediated by tumor-associated cytokines.

Adult↗

Morphological and immunohistochemical studies of Hodgkin's disease in the spleen.

Hodgkin's disease in the spleen - with the exception of its B cell variant - behaves quite differently from non Hodgkin's lymphomas with respect to both its spread and microenvironment. Each type of HD appears to create its own microenvironment by the secretion of cytokines responsible for the characteristic cellular composition of the infiltrates and thereby alters the normal immunoarchitecture of the spleen profoundly. While some histological findings seem to imply the presence of a host response against HD especially in the nodular sclerosis subtype, morphological and immunohistochemical evidence in the spleen cannot conclusively substantiate this hypothesis.

Adult↗

Splenic metastasis in an ileal carcinoid tumor.

The case of an ileal carcinoid tumor metastatic to the spleen causing splenomegaly and symptoms that necessitated splenectomy is described. Morphological analysis reveals that viable tumor cells are present along the whole pathway of splenic circulation and, accordingly, may lead to metastatic deposits at different sites within the spleen.

Carcinoid Tumor↗