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Biomedical subjects

M L Geerts

Publications and source records attributed to M L Geerts.

At least 37 records · Page 2Linked to original sources

Keratinocyte induced chemotaxis in the pathogenesis of Paget's disease of the breast.

In Paget's disease of the breast, the epidermis contains large clear neoplastic cells. To explain the pathogenesis of this disease, the immunohistochemical characteristics of these cells were investigated in 25 patients. The cytoplasmic presence of low molecular weight cytokeratin and the absence of high molecular weight cytokeratin in all cases confirmed the glandular origin of the Paget cells. Membrane over-expression of the neu-protein was established in 96% of cases. It was hypothesized that epidermal keratinocytes release a chemotactic factor which attracts neu-over-expressing breast carcinoma cells by chemotaxis into the epidermis. The biological assays showed that normal keratinocytes release one or more chemotactic factor(s) into their conditioned medium, which induced spreading and motility of neu-over-expressing SK-BR-3 human breast cancer cells. The conditioned medium of keratinocytes also attracted the SK-BR-3 cells by chemotaxis in a modified Boyden chamber. Furthermore, MCF-7 human breast cancer cells, which do not over-express the neu-protein, were not attracted by chemotaxis of conditioned medium of human keratinocytes. The involvement of the neu-protein in spreading, motility and chemotaxis is further indicated by the inhibition of these processes by monoclonal antibodies against the extracellular domain of the neu-protein. We conclude, therefore, that the Paget cells spread through the epidermis due to the motility induced by a chemotactic factor, which is released by epidermal keratinocytes and whose influence is mediated by the neu-protein.

Breast Neoplasms↗

Skin involvement in myelogenous leukemia: morphologic and immunophenotypic heterogeneity of skin infiltrates.

A systematic morphological analysis of cutaneous infiltrates in acute myelogenous leukemia and myelodysplastic syndrome revealed that in many cases the infiltrating cells have a different phenotype from those in the bone marrow. This study sought to answer two questions: (a) How wide is the range of cytological features and immunoreactivity of the cutaneous infiltrates and what danger is there of misinterpretation? (b) What are the possible causes of the wide spectrum of differentiation of the cells infiltrating the skin? Skin biopsy specimens from 16 patients with myelogenous leukemia or myelodysplastic syndrome were investigated. The diagnosis was acute myelomonocytic leukemia (M4, according to the French-American-British/FAB system of classification of acute leukemias) in eight cases, acute monocytic leukemia (M5) in four cases, aleukemic leukemia cutis as a recurrence of M2 leukemia after treatment in one case, and myelodysplastic syndrome in three cases, including one case of myelodysplasia with an excess of bone marrow blasts (RAEB-T) and two cases of chronic myelomonocytic leukemia, one of which presented as aleukemic leukemia cutis. Reactivity with the macrophage-associated antibodies anti-CD68, Ki-M1p, and anti-lysozyme was the most consistent. However, the naphthol AS-D chloroacetate esterase reaction and staining with DAKO-M1, Ki-My2p, anti-neutrophil elastase, and anti-CD34 were found to be of little value for identifying the cutaneous infiltrate as myelogenous. Some antibodies (e.g., anti-S100 protein and MB2) even produced staining in a few cases that could have led to a mistaken diagnosis of histiocytic neoplasm or malignant lymphoma.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigen-Presenting Cells↗

Mantle-cell lymphomas of the skin.

The skin lesions of two elderly women lead us to the diagnosis of small cleaved lymphocytic B-cell non-Hodgkin's lymphoma, TNM stage IVb after clinical staging examinations. Relapses occurred within less than 1 year. Morphology, enzymhistochemistry (alkaline phosphatase in the first case), and immunohistochemistry (CD 5 positivity in the second case) in the skin biopsies supported the diagnosis of mantle-cell lymphoma. The histogenesis of the mantle-cell lymphoma is reviewed.

Aged↗

The Bazex-Dupré-Christol syndrome.

BACKGROUND: The Bazex-Dupré-Christol syndrome is characterized by follicular atrophoderma, congenital hypotrichosis, and basal cell neoformations that include basal cell carcinomas and basal cell nevi. OBSERVATIONS: We describe a large family in which 20 persons across four generations present with typical features of the Bazex-Dupré-Christol syndrome. However, the clinical picture in this family differs with regard to gender and age. Male subjects have a uniformly severe disease, whereas female subjects exhibit a range of severity of the syndrome. The most striking difference between male and female subjects is provided by hypotrichosis. In male subjects, hypotrichosis is diffuse and affects all scalp hairs. On the other hand, female subjects do not have hypotrichosis, but normal hairs are intermingled with abnormal hairs. In infancy and childhood, multiple milia are present, whereas in adults only a few milia are observed. CONCLUSIONS: The family pedigree seems to be consistent with an X-linked inheritance, since male-to-male transmission does not occur. Moreover, further evidence of an X-linked dominant mode of inheritance could be derived from the observation of gender differences that can be attributed to the lyonization phenomenon in female subjects. From a clinical and morphologic point of view, the Bazex-Dupré-Christol syndrome seems to be a disorder of the hair follicle.

Adult↗

Diagnostic and prognostic significance of clonal T-cell receptor beta gene rearrangements in lymph nodes of patients with mycosis fungoides.

In this study, 25 involved and uninvolved lymph nodes from 22 patients with mycosis fungoides (MF) and seven dermatopathic lymph nodes from patients with benign skin disorders were studied for the presence of clonal T-cell receptor beta (TCR beta) gene rearrangements by Southern blot analysis. These results were correlated with the histological classification, follow-up data, and survival. The results of the histological classification and Southern blot analysis were concordant in 26 of 32 cases. Clonal TCR beta gene rearrangements were found in all six MF lymph nodes showing (partial) effacement of the normal lymph node architecture, but in none of the eight uninvolved dermatopathic MF lymph nodes and in none of the seven dermatopathic control lymph nodes. In addition, in 5 of 11 dermatopathic MF lymph nodes that were considered to have early involvement by MF at histological examination, clonal TCR beta gene rearrangements were detected. In the group of MF patients with dermatopathic lymphadenopathy, patients with detectable clonal T-cell populations had a significantly shorter survival than patients without such a population (P < 0.01). The results of this study indicate that within the group of dermatopathic MF lymph nodes, prognostically different groups can be distinguished and that TCR beta gene rearrangement analysis may be an important adjunct in the early diagnosis of lymph node involvement by MF.

Clone Cells↗

A translocation (8;14) in a cutaneous large B-cell lymphoma.

A 62-year-old man with a cutaneous large-cell (cleaved, noncleaved) lymphoma had multiple facial lesions and two enlarged cervical lymph nodes. Cytogenetic analysis performed on the involved skin and lymph node revealed the following karyotype: 47,XY,inv dup(1)(q11-->q32),+3,t(8;14)(q24;q32). A t(8;14)(q24;q32) translocation is the chromosome anomaly in 75% of Burkitt's lymphomas. Other types of non-Hodgkin's lymphomas, however, may show the same translocation, especially large-cell lymphomas. Duplication of material belonging to the long arm of chromosome 1 is the most frequent additional aberration to Burkitt's translocations in Burkitt's lymphoma/leukemia. Trisomy 3 may be seen in both B- and T-cell malignancies, as well as in angioimmunoblastic lymphadenopathy. Immunogenotyping of malignant cells from a lymph node showed rearrangement of the immunoglobulin heavy and lambda light chain genes. Epstein-Barr virus (EBV) serology was positive for EBV nuclear antigen and EBV capsular antigen. No integration of EBV DNA in tumor tissue, however, could be detected by polymerase chain reaction. These results may be useful in defining the biologic characteristics of cutaneous B-cell non-Hodgkin's lymphomas.

Antigens, Differentiation↗

Cutaneous immunocytomas: a clinicopathologic study of 26 cases.

The clinical and histological features of 16 patients with a primary cutaneous immunocytoma and 10 patients with a secondary cutaneous immunocytoma are reported. In all cases the diagnosis was based on the presence of monotypic plasma cells or lymphoplasmacytoid cells. Our data show that primary cutaneous immunocytomas are a distinct type of cutaneous lymphoma, characterized by (a) the presence of solitary or localized skin lesions (13 of 16 cases); (b) preferential localization on arms and legs (15 of 16 cases); (c) excellent response to local treatment (15 of 16 cases) and (d) a favourable prognosis. Histologically, these primary cutaneous immunocytomas are characterized by the presence of nodular or diffuse infiltrates with monotypic lymphoplasmacytoid/plasma cells located at the periphery of the infiltrates. Important clinical and histological differences were noted between primary and secondary immunocytomas. In the latter group more widespread skin disease was seen, often in the presence of paraproteins and/or autoimmune diseases. In contrast with the peripheral localization of the monotypic cells in primary cutaneous immunocytomas the monotypic lymphoplasmacytoid/plasma cells in secondary immunocytomas formed diffuse infiltrates or these cells were found dispersed throughout the infiltrate. There were no differences in clinical presentation or course between the different subtypes of cutaneous immunocytomas (lymphoplasmacytic, lymphoplasmacytoid and polymorphic immunocytomas). The differential diagnosis between primary cutaneous immunocytomas and cutaneous plasmacytomas, primary follicular centre cell lymphomas and cutaneous 'pseudolymphomas' is discussed.

Adult↗

Demonstration of clonal immunoglobulin gene rearrangements in cutaneous B-cell lymphomas and pseudo-B-cell lymphomas: differential diagnostic and pathogenetic aspects.

Twenty-five patients with a benign or malignant cutaneous B-cell lymphoproliferative disease, including seven cutaneous pseudo-B-cell lymphomas, eight primary cutaneous B-cell lymphomas (CBCL), and 10 secondary cutaneous B-cell lymphomas, were investigated for the presence of clonal immunoglobulin (Ig) gene rearrangements using Southern blot hybridization analysis. The selection of pseudo-B-cell lymphomas was based on the presence of polyclonal light-chain expression with immunohistochemical analysis. All cases of CBCL demonstrated monotypic light-chain expression or absence of detectable Ig on CD20+ B cells. Clonal rearrangements of one or more Ig genes were demonstrated in four of seven cases of cutaneous pseudo-B-cell lymphomas, six of eight cases of primary CBCL, and in all cases of secondary CBCL. The observation that cutaneous pseudo-B-cell lymphomas as defined by immunohistochemical criteria often contain occult monoclonal B-cell populations implies that differentiating between pseudo-B-cell lymphomas and CBCL is not always possible by means of gene-rearrangement analysis. These findings may support the concept that cutaneous pseudo-B-cell lymphomas and primary CBCL are part of a continuous and progressive spectrum of B-cell lymphoproliferative skin disorders.

Adult↗

[Acute hemorrhagic edema in an infant].

The clinical and histological features of acute haemorrhagic oedema of childhood are discussed with reference to an actual case. Although closely related to Schoenlein-Henoch syndrome, it is considered a distinct entity, on the basis of the typical clinical picture and the excellent prognosis.

Capillaries↗

Lectin binding patterns of human tissue mast cells indicate marked phenotypical diversity.

Glycoconjugate expression by human tissue mast cells (MCs) from various sources (including lymph nodes with signs of chronic non-specific lymphadenitis, skin lesions of urticaria pigmentosa, and bone marrow infiltrates associated with systemic mastocytosis) was studied histochemically with a broad panel of fluorescein-labelled lectins. Of the 19 lectins applied, 11 (sugar specificities: fucose, N-acetylgalactosamine and neuraminic acid) did not stain any MCs, while 8 (sugar specificities: mannose, N-acetylglucosamine, and galactose) were found to bind to MCs. These lectins exhibited different binding patterns in various disease entities. Only a few of these 8 lectins (in particular, phythaemagglutinin-L) produced strong staining of the MCs in most or all of the cases. Some (e. g. phythemagglutinin-E) produced only weak staining, and this in only a few cases. The lectins used, however, did not distinguish between reactive and tumorous MCs. Although lectins are therefore unlikely to be of use in resolving problems of differential diagnosis concerning proliferation of MCs, our investigation has shown that tissue MCs exhibit marked phenotypical diversity with regard to their lectin-binding properties.

Biopsy↗

Use of monoclonal antibody KP1 for identifying normal and neoplastic human mast cells.

The monoclonal antibody KP1 (CD68) was used to stain normal and neoplastic monocytes and macrophages in routinely processed, paraffin wax embedded tissue: mast cells also exhibited strong, consistent cytoplasmic immunoreactivity. Light microscopic findings were corroborated by electron microscopical and immunocytochemical findings. The predominant sites of immunoreactivity were the specific intracytoplasmic granules of the mast cells. All mast cell subtypes--that is, normal and reactive mast cells, such as those in lymph nodes exhibiting chronic non-specific lymphadenitis, and malignant or neoplastic mast cells in various types of mastocytosis--reacted with this antibody. This finding is of diagnostic importance, because mast cell proliferation could be mistaken for histiocyte proliferation. It also supports the hypothesis that mast cells derive from the bone marrow.

Antibodies, Monoclonal↗

Naevus sudoriferus.

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Abdominal Muscles↗