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Biomedical subjects

M L Hansmann

Publications and source records attributed to M L Hansmann.

At least 109 records · Page 6Linked to original sources

Tracing B cell development in human germinal centres by molecular analysis of single cells picked from histological sections.

Germinal centres are areas of intense B lymphocyte proliferation inside primary B cell follicles in spleen and lymph nodes. Rearranged V genes from single human B cells, isolated from histological sections of two such structures by micromanipulation, were amplified and sequenced. Cells from the follicular mantle were clonally diverse and largely expressed germline V genes. Germinal centres were dominated by a few large B cell clones dispersed throughout these structures and exhibiting intraclonal diversity by ongoing somatic hypermutation. Pronounced counterselection of replacement mutations seen in one of the germinal centres may indicate a late phase of the germinal centre reaction. A polyclonal population of activated B cells expressing unmutated antibodies in the dark zone of the other germinal centre may represent the initial founder cells.

Adult↗

Demonstration of light chain mRNA in Hodgkin's disease.

The lineage of Hodgkin and Reed-Sternberg cells is still unclear. Detection of both immunoglobulin light chains in Hodgkin and Reed-Sternberg cells by immunohistochemistry is a well-known phenomenon. However, up to now, in situ hybridization techniques have failed to demonstrate light chain messenger(m) RNA in Hodgkin and Reed-Sternberg cells. In this investigation, we have analysed 26 cases of Hodgkin's disease (nodular lymphocyte predominant Hodgkin's disease, mixed cellularity, and nodular sclerosis type) using digoxigenin-labelled oligonucleotide probes for kappa and lambda light chains by in situ hybridization. In nearly half of the cases of nodular lymphocyte predominant Hodgkin's disease and in one case of mixed cellularity type, mRNA for only one light chain could be clearly demonstrated in the lymphocytic and histiocytic cells, Hodgkin, and Reed-Sternberg cells. These results support the idea that at least some cases of Hodgkin's disease are B-cell neoplasms.

Hodgkin Disease↗

Follicular dendritic cells in extranodal non-Hodgkin lymphomas of MALT and non-MALT type.

Extranodal lymphomas of the thyroid (n = 19), kidney (n = 15) and testis (n = 30) were investigated histologically and immunohistochemically for follicular dendritic cell pattern using the monoclonal antibody Ki-FDClP. This recognizes follicular dendritic cells in paraffin sections. Follicular dendritic cells were most predominant in lymphomas of the thyroid. These thyroid lymphomas showed the morphological features of mucosa-associated lymphoid tissue (MALT) type lymphomas in 18 of 19 cases and were classified as high-grade malignant lymphoma of MALT type with evidence of a low-grade malignant component (n = 18). Ten of these cases contained destroyed reactive follicles of follicular dendritic cells. In 6 of these 10 cases follicular dendritic cells occurred in a pattern of tumour-associated abortive follicle type. The remaining lymphoma of the thyroid was an immunoblastic lymphoma of B-cell type showing no detectable follicular dendritic cells. In extranodal lymphomas of non-MALT type follicular dendritic cells occurred in only two cases where immunocytoma involved the kidney. Malignant lymphomas of the kidney (chronic lymphocytic leukaemia, n = 2; immunocytoma, n = 4; centroblastic lymphoma, n = 9) and of the testis (immunocytoma, n = 2; centroblastic lymphoma, n = 27; immunoblastic lymphoma of B-cell type, n = 1) revealed no characteristics of MALT type lymphoma, cytologically or with respect to follicular dendritic cells. Classical lymphoepithelial lesions formed by centrocyte-like cells, a hallmark of MALT, occurred exclusively in thyroid lymphomas of MALT type. Although occurrence of classical lymphoepithelial lesions formed by centrocyte-like cells was limited to thyroid lymphomas of MALT type, a growth pattern of lymphoid blasts, with formation of lesions mimicking lymphoepithelial lesions superficially, was found in 6 of 27 testicular centroblastic lymphomas. Follicular dendritic cells in non-Hodgkin's lymphomas of MALT type show distinct follicular patterns not found in other extranodal lymphomas such as those found in the kidney and testis.

Dendritic Cells↗

Expression of the proliferating cell nuclear antigen in the different types of Hodgkin's disease.

Thirty-eight cases of Hodgkin's disease (HD, lymphocyte-predominant, n = 10; nodular sclerosis, n = 10; mixed cellularity, n = 10; lymphocyte depletion, n = 8) were investigated with the antibody PC10 directed against the proliferating cell nuclear antigen (PCNA) with B- and T-cell markers using a double-staining technique in paraffin-embedded material. It could be shown that nearly all (95-97%) Hodgkin's and Reed-Sternberg (HRS) cells and their variants were PCNA-positive regardless of the type of HD. There was only a low number of PCNA-positive lymphocytes (2.8-3.4%) in all types mostly consisting of MT1-positive T lymphocytes. In contrast to the other types, lymphocyte-predominant type showed a relatively high percentage (5%) of Leu-7-positive lymphocytes. The high percentage of PCNA-positive HRS cells correlates with their malignant nature, and might be another example of dysregulated expression of PCNA.

Antigens, Differentiation↗

The cytological spectrum of the monocytoid B-cell reaction: recognition of its large cell type.

To analyse the cytological features of benign monocytoid B-cells, we investigated, histologically and immunohistochemically, 78 reactive lymphadenopathies expressing monocytoid B-cell reactions. Within a broad cytological spectrum of reactive monocytoid B-cells, two cytological types can be recognized: 1 the common type composed of medium-sized cells with irregular or bean-shaped nuclei and inconspicuous nucleoli, and 2 the large cell type composed of cells considered to represent large transformed monocytoid B-cells, with less pleomorphic round nuclei with vesicular chromatin and moderately basophilic, prominent nucleoli. In between these variants transitional forms showing evolution to large transformed monocytoid B-cells occurred. While monocytoid B-cell reactions in 70.5% of all cases were composed predominantly of the common type of monocytoid B-cells, in 29.5% of cases the large transformed cells prevailed. The two distinctive cytological types of reactive monocytoid B-cells seem to have their neoplastic counterparts in monocytoid B-cell lymphoma, including its large cell variant.

Antigens, Differentiation, B-Lymphocyte↗

Detection of clonal B cell populations in paraffin-embedded tissues by polymerase chain reaction.

A method was established to detect clonal B cell populations in frozen and paraffin-embedded tissues. The method is based on the polymerase chain reaction amplification of rearranged VH and V kappa genes using V gene family-specific primers. Monoclonal B cell populations could be detected in peripheral blood lymphocyte DNA in all 16 cases of B-CLL and immunocytoma investigated and in 8 of 10 cases of B cell non-Hodgkin's lymphoma using frozen and paraffin sections. The amplification of V kappa rearrangements in addition to the VH amplification is a useful tool to verify the results of the heavy chain rearrangement and to detect proliferation of a B cell clone in cases in which no VH product was obtained. In spite of the degradation of DNA in paraffin-embedded tissues, we were able to find amplified polymerase chain reaction products of about 350 bp length in 8 of 10 cases analyzed. The method presented here may be helpful in routine diagnosis of B cell non-Hodgkin's lymphoma using frozen or paraffin-embedded specimens.

B-Lymphocyte Subsets↗

[Plasma cell and sclerosing osteomyelitis. A follow-up of 21 patients].

Plasma cellular osteomyelitis was seen in the metaphysis while sclerosing osteomyelitis affected the diaphysis of long bones. In only about 20% of both forms local bacteria were noted. The onset of symptoms was inconspicuous and both clinical and radiological signs were nonspecific. Curettment or resection usually cured the disease. In some cases, however, aggressive surgery was necessary. As to surgery and outcome sclerosing osteomyelitis appeared less riskful than plasma cellular osteomyelitis. Both forms apparently represent the same basic pathological condition.

Adolescent↗

Macrophage- and lymphocyte-subtypes in the endometrium during different phases of the ovarian cycle.

The presence of immunocompetetive cells in the endometrium during the proliferative and secretory phase of the ovarian cycle is demonstrated on the light and electron microscopic level using monoclonal antibodies (MoAb). Subtypes of monocytes, macrophages and T-lymphocytes appear during the different phases in variable extent and different localization. Some subpopulations of the monocyte/macrophage system and T-helper lymphocytes increase in number on day 21/22. Our observations indicate that cells with bone marrow origin take part in functional events of the endometrium during the ovarian cycle.

Antibodies, Monoclonal↗

Monocytoid B-cell lymphomas: an assessment of diagnostic criteria and a perspective on histogenesis.

To determine which morphologic criteria are most useful in distinguishing reactive from malignant monocytoid B cells (MBCs), we compared 16 monoclonal cases (11 nodal, five extranodal) of monocytoid B-cell lymphoma (MBCL) with 12 cases of various reactive diseases in which MBCs were polyclonal. The results of our study showed that in MBCL the MBC component was the predominant architectural finding and that there was confluence of MBCs in all but one case. In contrast, the MBC component did not predominate in the reactive group (P less than .000001) and focal confluence was seen in only one case. A cytologic comparison showed that in MBCL areas there were more large transformed (prominent nucleolated) MBCs (P = .003), a higher mitotic rate (P = .03), and more nuclear irregularities (P = .007) than were present in the reactive group. In addition, evolution to an aggressive histologic type was found in four cases of MBCL. Our results also revealed concomitant multiple, monoclonal, morphologically distinct populations in other compartments (follicular center cells in seven, mantle cells in five, small lymphocytes in five, and plasma cells in 11). These unique findings can be reconciled by postulating (1) that the simultaneous presence of these diverse cytologic types represents morphologic expressions of a B cell whose population is in different phases of its cell cycle and/or its evolution or (2) that the histogenesis of MBCL is possibly from a nodal pluripotent B-stem cell that can differentiate directly into these various cytologic types.

Adult↗

Expression of the bcl-2 oncogene product and chromosomal translocation t(14;18) in Hodgkin's disease.

The B-cell lymphoma/leukemia oncogene bcl-2 takes part in crucial regulatory events in B-cell maturation and differentiation. The reciprocal chromosomal translocation t(14;18), leading to overexpression of this oncogene, can be found in the majority of follicular lymphomas and much less frequently in B-cell leukemias and diffuse lymphomas. We have studied the expression of this protein in different subtypes of Hodgkin's disease using monoclonal antibodies directed against a formalin-resistant epitope of the bcl-2 protein and also have investigated these cases by polymerase chain reaction for evidence of the t(14;18) translocation. We were particularly interested to determine whether nodular paragranuloma (lymphocyte-predominant, nodular), which differs from other subtypes of Hodgkin's disease by virtue of the B-cell nature of its malignant cell population, is characterized by expression of the bcl-2 protein. Our data indicate that only a small number of nodular paragranulomas express the bcl-2 protein and that the expression is not specific for this type of Hodgkin's disease. In a smaller number of cases this expression of bcl-2 could be explained by the presence of the translocation t(14;18).

Antibodies, Monoclonal↗

Immunohistochemical monitoring of plasmacytoid cells in lymph node sections of Kikuchi-Fujimoto disease by a new pan-macrophage antibody Ki-M1P.

The new monoclonal antibody Ki-M1P, which detects a formalin-resistant epitope on conventional paraffin sections, was applied in 20 cases of different stages of Kikuchi-Fujimoto disease. This new pan-macrophage immunoreagent detects plasmacytoid T cells, referred to as plasmacytoid cells, and renders a reliable delineation of these cells against other similar cell types, such as blasts of high-grade B- and T-cell lymphoma. Histiocytes as well as macrophages were strongly positive, and plasmacytoid cells showed a somewhat weaker and primarily granular, intracytoplasmic immunoreactivity. Plasmacytoid cells, being a diagnostic feature of the Kikuchi-Fujimoto disease, facilitate a clear distinction of this disease entity from large cell or high-grade lymphomas. These results may represent an additional argument favoring the histiocytic origin of plasmacytoid cells. Additionally, they may point to an immunohistochemical tool that facilitates the differential diagnosis between Kikuchi-Fujimoto disease, especially in early stages of the disease, and malignant lymphoma.

Antibodies, Monoclonal↗

Influence of Epstein-Barr virus genomes on patient survival in Hodgkin's disease.

In previous studies, Epstein-Barr virus was considered a possible etiologic factor in Hodgkin's disease. Two hundred twenty-nine cases of Hodgkin's disease were investigated for the presence of Epstein-Barr virus DNA using the polymerase chain reaction technique on formalin-fixed, paraffin-embedded lymph node tissue to clarify the clinical importance of the incidence of this genome. In 42 cases (18.3%), genomic DNA was not amplifiable. The remaining 187 cases included the following subtypes: lymphocyte-predominant type (n = 13), nodular sclerosis type (n = 98), mixed cellularity type (n = 68), and lymphocyte-depleted type (n = 8). Sixty-six cases (35.2%) were positive for Epstein-Barr virus DNA. In the statistical analysis of available follow-up data from 130 patients, no influence of a positive Epstein-Barr virus DNA finding on length of survival time was revealed. This was true within the cohort of all patients and within the histologically defined subtypes of Hodgkin's disease. In this investigation, detection of Epstein-Barr virus DNA by polymerase chain reaction showed no prognostic relevance for patients with Hodgkin's disease.

Analysis of Variance↗

Oncogenes in Hodgkin's disease.

The following manuscript reviews data presented at the Cologne meeting relating to oncogene expression in Hodgkin's disease. Presented data ranged from investigations of oncogene expression in cell lines, where transcripts of unique size were identified and lineage related expressions of transcription factors described to detailed cytogenetic investigations of fresh Hodgkin's biopsy tissue. Particular attention was centred on discrepancies in the described expression of t(14; 18) and the molecular demonstration of translocated bcl-2 breakpoints in Hodgkin's disease. A large volume of data was presented relating to the relative expression of bcl-2 breakpoints by either genomic hybridization or hybridization following DNA amplification, the expression of the bcl-2 protein or the defined cytogenetic presence of the translocation. Certain other cytogenetic abnormalities of interest in Hodgkin's disease were discussed.

Cell Line↗

Laryngeal paraganglioma and pregnancy.

Paraganglioma is an uncommon tumor of the larynx. We present a 30-year-old woman with a paraganglioma which took a heretofore not described clinical course. The first clinical sign was persistent hoarseness, when she was 26 weeks pregnant. A histological examination of a piece of the reddish, racemose tumor removed during microlaryngoscopy revealed only some slight nonspecific inflammatory changes. The patient remained free of symptoms following this operative procedure until 3 years later when she presented with a recurrence of hoarseness and a laryngeal tumor and was 25 weeks pregnant. Histology showed a laryngeal paraganglioma in the same supraglottic localization as before. Histological studies failed to confirm the obvious suspicion that the episodic growth of the paraganglioma may have been induced by estrogen or gestagen. To date, 6 years after the removal of the tumor, there has been no recurrence.

Adult↗

Organ-limited laryngeal amyloid deposits: clinical, morphological, and immunohistochemical results of five cases.

Five cases of organ-limited laryngeal amyloid deposits with no evidence of systemic disease are reported in detail and classified immunohistochemically. In four of the five cases the amyloid reacted with anti-A lambda antibodies and in one case with anti-A kappa antibodies. Four of our five female patients had already passed the fifth decade of life. One was 11 years old. Hoarseness was the predominant symptom in four cases, in which we found amyloid deposits in the glottic area. Only one patient, with amyloid deposits in the aryepiglottic fold, complained of pain. The therapy of choice of idiopathic, localized, or organ-limited amyloid deposits without underlying disease may be local excision. In one of the cases reported in this paper, a laryngofissure was performed, and in another a partial laser resection was performed. No therapy was performed in three of our five cases. In the larynx, as in many other locations and only if possible, removal at intervals is more feasible than radical resection, because these amyloid tumors grow slowly.

Amyloidosis↗

[Which are the proliferating cells in Hodgkin's disease?].

This investigation characterizes the proliferating cells in Hodgkin's disease. We used the antibody PC 10 which reacts with the proliferating cell nuclear antigen (PCNA) and works on paraffin sections in combination with B- and T-cell markers in a double-staining technique. In all 38 cases of Hodgkin's disease (lymphocyte predominant type n = 10, nodular sclerosis type n = 10, mixed cellularity type n = 10, lymphocyte depletion type n = 8) a high percentage of the Hodgkin and Sternberg-Reed cells (95%-97%) expressed PCNA. There was no statistical significance between the different types. In contrast, only a small amount of the reactive lymphocytes (2.8%-3.4%) demonstrated positivity for PCNA in the four types of Hodgkin's disease. Nearly all of these lymphocytes were T-lymphocytes.

Antigens, CD↗

[Bcl-2 in potentials precursors of nodular paragranuloma and its dedifferentiated variant (large cell B-lymphoma)].

We have investigated seven cases of large cell lymphomas (LCL) developing simultaneously or metachronously to nodular lymphocyte-predominant Hodgkin's disease (nodular paragranuloma, NP) for the presence of EBV and the chromosomal translocation t(14;18) by use of the polymerase chain reaction (PCR). The expression of the bcl-2 oncogene product in these cases and in five cases of progressive transformation of germinal centres as a potential precursor of NP was detected immunohistochemically with the monoclonal antibodies bcl-2-100 and bcl-2-124. All cases investigated were negative for EBV genomic material. The chromosomal translocation t(14;18) was also absent. Expression of the bcl-2 oncogene could be detected only in one case of nodular paragranuloma and in an unrelated case of LCL. Hence, LCL developing out of NP differ from other germinal center derived high-grade lymphomas.

Adult↗