Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019829 (Hodgkin's disease)
 30,247 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Immunostaining for cyclin D1 is essential for reliable diagnosis of mantle cell lymphoma (MCL). However, a small number of cyclin D1-positive lymphomas other than MCL have been encountered. Our goal was to investigate the morphological spectrum of MCL as a disease entity, based on cyclin D1 overexpression. We reviewed 181 biopsy specimens obtained from 168 cases of cyclin D1-positive MCL. Typical findings were the presence of nodular (53.9% of cases) or diffuse (46.1%) histological patterns, containing mantle zone patterns (16.8%), naked germinal centers (33.5%) and perivascular hyaline deposition (83.2%). Unusual findings of residual germinal centers with a mantle cuff (four cases) and follicular colonization (two cases) were seen. High magnification showed a monotonous proliferation of tumor cells with cytological diversity including small (3.0%), intermediate (43.1%), medium (34.1%), medium-large (13.2%) and large (6.6%) cells. Pleomorphic and blastic/blastoid variants were encountered in 9.6 and 7.2% of cases, respectively. Three cases had foci of cells of considerable size, with a moderately abundant pale cytoplasm resembling marginal zone B cells. Two cases showed an admixture of cells which appeared transformed and mimicked the histology of chronic lymphocytic leukemia/small lymphocytic leukemia. In one, neoplastic mantle zones were surrounded by sheets of mature plasma cells, resembling the plasma cell type of Castleman's disease. An admixture of areas characteristic of MCL and of other larger cells, indicating histological progression or a composite lymphoma, were observed in seven cases. In high-grade lesions of five cases, nuclear staining of cyclin D1 was rarely detected. In our experience, cyclin D1 expression was also found in nine lymphomas other than MCL (five plasma cell myelomas, three Hodgkin's disease and one anaplastic large cell lymphoma). The application of cyclin D1 staining prompted us to recognize the broad morphological spectrum of MCL. MCL can be diagnosed with the application of cyclin D1 immunostaining, if careful attention is given to architectural and cytological features.
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PMID:Morphological spectrum of cyclin D1-positive mantle cell lymphoma: study of 168 cases. 1188 27

A 73-year-old man noticed a subcutaneous tumor on the left upper palpebra from April 1998, but did not seek therapy for it. Facial subcutaneous tumors appeared from November 1999, and multiple tumors appeared on the skin of the chest and both upper arms from January 2000. Tumor biopsy revealed that these tumors were non-Hodgkin lymphoma showing CD19 (+), CD20 (+), CD5 (+), CD10 (-), smIgM (+), sm lambda (+) and cyclin D1 (+). The karyotype was t(11;14) (q13;q32), but bcl-1 gene rearrangement was not detected. On the basis of these data, primary mantle cell lymphoma (MCL) of the subcutis was diagnosed. The patient underwent eight courses of THP-COP therapy, and complete remission was achieved. Primary subcutaneous B-cell lymphoma, especially MCL, is rare. MCL is aggressive and difficult to cure; the median survival of patients is 3 to 5 years, and the 5-year survival is 30%. However, the present patient showed a good response to chemotherapy, and complete remission has continued for 17 months since the MCL was first diagnosed.
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PMID:[Primary subcutaneous mantle cell lymphoma treated successfully with THP-COP therapy]. 1209 92

Knowledge of the role of cell-cycle regulators in the pathogenesis of acquired immune deficiency syndrome-related non-Hodgkin's lymphomas (AIDS-NHLs) is scarce. Here we analyzed 86 systemic AIDS-NHLs and 20 AIDS-primary central nervous system lymphomas for expression of p27(Kip1), a negative regulator of cell-cycle progression belonging to the Kip family of cyclin-dependent kinase inhibitors. In parallel, we investigated the relationship between p27(Kip1), the lymphoma proliferation index, Epstein-Barr virus status, expression of cellular cyclin D3 and cyclin D1, and B-cell differentiation stage. We report that AIDS-immunoblastic lymphomas (AIDS-IBLs), either systemic or primarily localized to the central nervous system, consistently express p27(Kip1) protein (19 of 24 and 10 of 14, respectively) despite the high proliferative rate of the lymphoma clone, suggesting a failure of p27(Kip1) to inhibit the cell cycle in AIDS-IBL. Conversely, the remaining systemic AIDS-NHLs and AIDS-primary central nervous system lymphomas preferentially fail to express p27(Kip1). Expression of p27(Kip1) in Epstein-Barr virus-positive AIDS-NHLs generally associates with latent membrane protein 1 (LMP1) expression and is related to a late stage of B-cell differentiation, characterized by the BCL-6-/MUM1+/syn-1+/- phenotypic profile, whereas it seems to be unrelated to the expression of cellular cyclins. In B cells in vitro, induction of LMP-1 expression under the control of inducible promoters up-regulates expression of p27(Kip1), thus providing a putative mechanistic explanation for the association between LMP1 and p27(Kip1) observed in vivo. Overall, these data show that AIDS-IBL pathogenesis is characterized by loss of the inverse relationship between p27(Kip1) positivity and tumor growth fraction that is otherwise generally observed in normal lymphoid tissues and in most other types of NHLs.
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PMID:Expression of cyclin-dependent kinase inhibitor p27(Kip1) in AIDS-related diffuse large-cell lymphomas is associated with Epstein-Barr virus-encoded latent membrane protein 1. 1210 1

Mantle cell lymphoma (MCL) is a distinct type of B cell malignancy and accounts for approximately 5-10% of non-Hodgkin's lymphomas (NHL). The characteristic cytogenetic aberration in MCL is the translocation (11;14)(q13;q32) present in virtually all cases. This rearrangement at the BCL1 locus at 11q13 dysregulates the gene CCND1 following juxtaposition with immunoglobulin heavy chain (IGH) transcriptional enhancers at 14q32 and leading to overexpression of its protein product, cyclin D1, which plays a key role in the control of the cell cycle. Eight continuous cell lines (plus several sister cell lines) have been hitherto established from lymph nodes or peripheral blood of patients with MCL (n=5) or with a lymphoma which would nowadays be classified as MCL (n=3). Six of these cell lines carry the specific t(11;14) translocation and a seventh cell line while being negative for t(11;14) shows a rearranged BCL1 locus and cyclin D1 overexpression. Each of these MCL cell lines is unique with regard to its immunophenotypical, additional cytogenetic and functional features. In light of the relatively low frequency of this lymphoma and the poor results of current treatment strategies, the availability of various types of MCL-derived cell lines for immunologic, cytogenetic, molecular and functional studies is expected to illuminate the biology of this disease, which in turn will be hopefully translated into new and better therapies.
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PMID:Malignant hematopoietic cell lines: in vitro models for the study of mantle cell lymphoma. 1212 50

Recent classifications of non-Hodgkin's lymphomas (NHL) have strictly individualized mantle cell lymphoma (MCL) on the basis of a combination of morphologic, immunophenotypic, and cytogenetic criteria. This clinicopathological entity now appears to be a biological and therapeutic model for the understanding and treatment of hematologic malignancies. The lymphomogenesis of MCL could be explained by a series of genetic abnormalities which occur at different steps of the disease: (1) mutation and/or loss of the ATM gene in centrocytic cells of the follicle mantle of lymph nodes, leading to the loss of ATM function, particularly involved during the V(D)J recombination process; (2) a t(11;14)(q13;q32) translocation which induces a constitutive Bcl-1/PRAD1/CCND1 expression, responsible for cell cycle activation of centrocytic cells characteristic of typical MCL; and (3) secondary additional chromosomal aberrations, such as a p53 mutation, observed in blastic transformation of MCL. Despite the evaluation of a number of treatment modalities, the optimal management of MCL has not yet been defined: (1) conventional and intensified chemotherapy and monoclonal anti-CD20 antibody therapy appear to be effective for the improvement of response rates and event-free or overall survivals; (2) combinations of different treatment modalities must be tested to modify the natural dismal outcome of the disease; and (3) innovative approaches should be developed. From this point of view, all these considerations offer a fine opportunity for extensive medical reflection.
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PMID:Mantle cell lymphoma: a biological and therapeutic paradigm. 1215 64

The expressions of p42/44 mitogen-activated protein kinase(p42/p44MAPK) and cyclin D1 protein were detected by SP immunohistochemical technique in 40 cases of Hodgkin's disease(HD) and 13 cases of reactive hyperplasia(RH). The results showed that p42/p44MAPK and cyclin D1 protein were both overexpressed in RS/H cells of HD(positive rates were 72.5% and 70% respectively), and their positive rates were positively correlated(P < 0.01). The data suggest that MAPK cascades signal transduction may play an important role in genesis of HD. MAPK may induce overexpression of cyclin D1 protein and result in persistent proliferation and progression of RS/H cells.
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PMID:[The expression of p42/p44MAPK and cyclin D1 protein and their relationship in Hodgkin's disease]. 1221 52

Non-random chromosomal translocations are specifically involved in the pathogenesis of many non-Hodgkin's lymphomas and have clinical implications as diagnostic and/or prognostic markers. Their detection is often impaired by technical problems, including the distribution of the breakpoints over large genomic areas. This study reports a fluorescence in situ hybridization (FISH) method which allows the detection of specific chromosomal breakpoints in tissue sections from routinely fixed, paraffin-embedded samples. Hybridization was performed after demasking the DNA. Previously validated locus-specific probes (cosmids, PACs) flanking the BCL1, BCL2 regions and similar new probes for the MYC breakpoint region were used. The cases studied were five mantle cell lymphomas (MCL) and five follicular lymphomas (FL), selected on the basis of a previously proved t(11;14) and t(14;18) and five randomly chosen Burkitt's lymphomas (BL), as well as 21 negative control samples. In all samples, hybridization signals of sufficient intensity were obtained. Three different algorithms were used to score the hybridization signals in tissue sections, two of them taking into account the nuclei and their signal distribution indicative of chromosomal break, and one only considering the colocalization or segregation of the signals. In control tissues, these algorithms resulted in cut-off levels of 9.1%, 1.3%, or 10.0%. In the 15 lymphoma samples the percentages of abnormal cells/signals ranged from 28% to 80%, 13% to 49%, and 40% to 70%, respectively. The results indicate that small locus-specific probes can be used in FISH for regular detection of translocation breakpoints on routine paraffin tissue sections.
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PMID:Detection of three common translocation breakpoints in non-Hodgkin's lymphomas by fluorescence in situ hybridization on routine paraffin-embedded tissue sections. 1223 75

The immunohistochemical analysis of lymphoid neoplasms has led to refined classification schemes based on the profile of antigen expression and correlation with morphological, cytogenetic, molecular, and clinical features. Tissue microarrays (TMAs) are a powerful tool to rapidly characterize the phenotypic profile of a large number of samples. We show that this technique can be readily applied to the study of lymphoma by examining the expression profile of a series of 193 B-cell non-Hodgkin's lymphomas (NHLs) and 29 Hodgkin's lymphomas (HLs) using immunohistochemistry and in situ hybridization (ISH). The NHL cases were studied for the expression of commonly used markers-including CD3, CD5, CD10, CD20, CD23, CD30, CD43, Bcl-2, and cyclin D1 by immunohistochemical staining of TMAs-and these results were compared with whole sections (WS) of the same cases. We found a high degree of correlation between the results achieved with TMAs or WS (86% to 100% of cases). P53 and MIB-1 staining were studied, and the results were similar to that reported in the literature. HL cases were stained for CD20, CD30, CD15 (LeuM1), and latent membrane protein 1 expression, and ISH was performed using probes for EBER-1 and-2 transcripts. The results from HL cases on TMA sections matched exactly with those of WS. We correlated cytogenetic results with immunohistochemical stains and morphology in cases of mantle cell lymphoma [t(11;14)(q13;q32)] and follicular lymphoma [t(14;18)(q32;q24)]. This extensive expression profile of B-cell NHLs and HL tissues discloses the ability of TMAs to rapidly screen a large series of cases and represents the first report of method validation for this technique in the study of lymphoma.
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PMID:Application of tissue microarray technology to the study of non-Hodgkin's and Hodgkin's lymphoma. 1239 66

The incidence of B-cell non-Hodgkin lymphomas (B-NHL) at nodal and extranodal sites is fairly different. Follicular lymphomas (FL) occur predominantly at nodal sites and rarely in the gastrointestinal tract, while marginal zone lymphomas (MZL) of the mucosa-associated lymphatic tissue (MALT) type predominate in the digestive organs and especially in the stomach. We report a 72-year-old female patient admitted for gastroscopy because of epigastric pain. The antral biopsies showed dense lymphocytic infiltrates, partially forming follicles with widened marginal zones and monocytoid cells. Multiple lymphoepithelial lesions (LEL) were also observed. A MZL of the MALT type was suspected morphologically. Immunohistochemical analysis revealed the lymphatic infiltrates to be CD20, bcl-2, bcl-6 and CD10 positive, and negative for CD43, CD5 and cyclin D1. PCR-based analysis showed a JH/bcl-2 rearrangement, corresponding to the translocation t(14;18). An extranodal FL mimicking MZL was diagnosed. The present case is remarkable, as it demonstrates that the detection of LEL and monocytoid B-cells, although suggestive for MZL, is not entirely specific and can also be observed in FL. Pathologists should be aware of this diagnostic pitfall in classifying gastric B-NHL. In equivocal cases, a careful morphological examination, supported by specific immunohistochemical and molecular findings, should lead to the correct diagnosis.
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PMID:Primary gastric follicular lymphoma with parafollicular monocytoid B-cells and lymphoepithelial lesions, mimicking extranodal marginal zone lymphoma of MALT. 1246 20

Intrasinusoidal infiltration of bone marrow (BM) may accompany several malignant lymphoproliferative disorders. In small B-cell lymphomas, this pattern is considered specific for splenic marginal zone lymphoma (SMZL) when exclusive or prominent, although it may occur in other subtypes of non-Hodgkin's lymphomas (NHLs) as a minor feature. Here we report 2 cases of mantle cell lymphoma (MCL) with a prominent intrasinusoidal BM infiltration pattern. Both patients presented with massive splenomegaly and peripheral blood involvement characterized by markedly atypical lymphocytes, but no lymphadenopathy. The cytological features and the phenotype of the lymphoma cells were diagnostic of MCL. The malignant B cells showed coexpression of B-cell markers (CD20+ and CD79a+), CD5 antigen, and cyclin D1 by immunohistochemistry. We discuss the specificity of an intrasinusoidal growth pattern in the bone marrow, emphasizing the importance of using a broader immunohistochemical panel in the differential diagnosis of intrasinusoidal BM infiltration by NHL.
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PMID:Prominent intrasinusoidal infiltration of the bone marrow by mantle cell lymphoma. 1450 40


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