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

Epstein-Barr virus (EBV)-positive T non-Hodgkin lymphomas (T-NHLs) have been described, but it is at present unknown how EBV infects T lymphocytes. It has been postulated that cytotoxic T cells (CTLs) or natural killer (NK) cells can be infected by EBV during the killing of an EBV-infected target cell. The objective of this study was therefore to determine whether the neoplastic cells in EBV-positive T-NHLs (n=221) of various locations have a cytotoxic phenotype. To identify EBV-harbouring cells, combinations were used of EBV-encoded RNA (EBER) in situ hybridization (RISH) and immunohistochemistry for T- and B-cell markers and the cytotoxic proteins TIA-1 and granzyme B. EBV was detected in the neoplastic cells of all nasal T-NHLs (n=9), 5/34 gastrointestinal (GI) T-NHLs, and 2/6 lung T-NHLs, but not in primary cutaneous T-NHLs (n=103). Moreover, EBV was found in the neoplastic cells of 2/48 nodal anaplastic large cell lymphomas (ALCLs), but not in neoplastic T cells of other nodal T-NHLs. However, 5/17 nodal peripheral T-NHLs not otherwise specified (PTCLs NOS) and 1/4 T-prolymphocytic leukaemias did contain EBV-positive non-T cells. Double staining revealed that in EBV-positive extranodal T-NHLs (n=16), the EBER-positive cells had a cytotoxic phenotype (TIA-1- and/or granzyme B-positive). In nodal non-ALCL T-NHLs, the EBER-positive cells were not positive for TIA-1 or granzyme B, nor did they express CD3, CD21 or HECA452. Instead, most of these cells expressed the B-cell marker CD20. These PTCLs NOS with EBER-positive cells showed features of AILD-like T-NHL. It is concluded that neoplastic cells of EBV-positive extranodal T-NHLs always have a cytotoxic phenotype, supporting the view that EBV can infect CTLs. In nodal non-ALCL T-NHL, EBV is only found in T-NHL with AILD-like features and is present in B cells, where it may contribute to the outgrowth of a malignant B-cell clone.
 ...
PMID:Epstein-Barr virus is present in neoplastic cytotoxic T cells in extranodal, and predominantly in B cells in nodal T non-Hodgkin lymphomas. 1091 15

Non-Hodgkin s lymphomas (NHLs) constitute a heterogeneous group of lymphoid neoplasms and a majority of them in India are of B-cell phenotype. Varying numbers of T lymphocytes and natural killer (NK) cells are consistently present within the lymph nodes (LNs). The role of these reactive cells is becoming understood. TIA-1 is a cytotoxic granule associated RNA binding protein, the expression of which is restricted to cytotoxic T lymphocytes (CTLs) and NK cells. Snap frozen lymph node biopsies obtained from 41 B-cell NHLs were localized for intra-tumoral TIA-1 + cytolytic cells by immunohistochemistry. Distribution of T cell subsets and NK cells were also quantified. Cells expressing TIA-1 antigen was observed in all the cases, seen as a strong granular cytoplasmic signal. Results indicate significantly higher number of TIA-1 cytolytic cells outside (periphery of the follicle and interfollicular areas) than within the neoplastic follicle in follicular lymphomas (p<0.001). In small lymphocytic lymphomas, cytolytic cells were mainly seen as uniformly scattered single cells, distributed throughout the tumor environment. In mantle cell and diffuse large B-cell lymphomas these were most often seen as small clusters and less frequently as singly scattered cells. Higher numbers of CD4 + than the CD8 + T cells were observed in most cases. Contrary to the follicles in follicular hyperplasia, CD57 + NK cells were predominantly observed outside the neoplastic follicle in follicular lymphomas (FLs). These results outline specific interactions between the potential anti-tumoral cytolytic and the malignant cells of B-cell NHLs.
 ...
PMID:Intra-tumoral cytolytic cells: pattern of distribution in B-cell non Hodgkin s lymphoma. 1093 86

Non-Hodgkin lymphomas (NHL) can involve the gynecologic tract, most often as a manifestation of systemic involvement, and most cases reported have been of B-cell lineage. We describe 2 women with natural killer (NK)-cell lymphoma involving the gynecologic tract that initially presented with vaginal bleeding. In case 1, the patient had a stage IE nasal-type NK-cell lymphoma involving the cervix. The tumor was composed of medium-sized, irregular lymphoid cells with angioinvasion and necrosis. In case 2, the patient had a stage IV blastoid NK-cell lymphoma/leukemia infiltrating all organs in a hysterectomy and bilateral salpingo-oophorectomy specimen. Subsequent biopsy specimens revealed that the bone marrow and lymph nodes were also involved. The neoplasm was composed of small to medium lymphoid cells with fine nuclear chromatin. Case 1 was assessed immunohistochemically and the neoplastic cells were positive for CD3, CD56, and TIA-1. Case 2 was analyzed using both immunohistochemical and flow cytometry methods. The neoplastic cells were positive for cytoplasmic CD3, CD4, CD7, CD43, CD45, and CD56 and were negative for surface CD3. Both cases were negative for Epstein-Barr virus (EBV) ribonucleic acid (RNA) and molecular studies showed no evidence of T-cell receptor gamma chain gene rearrangements. The immunophenotype and absence of T-cell receptor gene rearrangements support NK-cell origin. We report these cases to illustrate that NK-cell lymphomas can involve, and rarely arise in, the gynecologic tract.
 ...
PMID:Natural killer-cell lymphoma involving the gynecologic tract. 1103 85

We studied 10 cases of Lennert's lymphoma (lymphoepithelioid lymphoma) to evaluate the cellular origin of the neoplastic cells. There were six men and four women, aged 38 to 75 years (median, 56 yrs; mean, 59 yrs). The lymphoma cells tended to remain confined to lymph nodes, and extranodal involvement was rare. The mean overall survival was 42.2 months, which is relatively good compared with other peripheral T-cell lymphomas. Morphologically, the lymph node was occupied by small to large clusters of epithelioid cells interspersed with medium to large atypical lymphoid cells. In seven cases, large atypical lymphoid cells resembling Hodgkin's or Reed-Sternberg cells were observed. The phenotypes of these neoplastic cells were CD3+ CD4- CD8+ in five cases, CD3+ CD4+ CD8- in four cases, and CD3+ CD4- CD8- in one case. TIA-1 was positive by immunohistochemical staining in seven cases, whereas four cases were positive for granzyme B. Clonal rearrangement of the T-cell receptor gene was confirmed in all cases by either Southern blot hybridization or a polymerase chain reaction-based denature gradient gel electrophoresis method. Epstein-Barr virus was negative by in situ hybridization in all but one case. Lennert's lymphoma was formerly known as a CD4+ helper T-cell neoplasm. Our results suggest that, at least in some cases, the neoplastic cells are of cytotoxic T-cell origin.
 ...
PMID:Lennert's lymphoma: a variant of cytotoxic T-cell lymphoma? 1111 83

RCAS1 (receptor-binding cancer antigen expressed on SiSo cells) is present in neoplastic cells, induces apoptosis of natural killer (NK)/T cells and plays a role in immune evasion. Fas ligand (FasL) is considered to have similar roles. The Epstein-Barr virus (EBV)-encoded latent membrane protein is expressed by malignant Hodgkin and Reed-Sternberg (H&RS) cells of EBV-associated Hodgkin's disease (HD) and considered to be a target of cytotoxic T lymphocytes (CTLs). However, CTL response is inadequate in HD. To determine whether RCAS1 and FasL are expressed in EBV-associated HD and participate in immune evasion, tissues of 20 EBV(-) and 15 EBV(+) HD cases were immunohistochemically stained for RCAS1, FasL and HLA classes I and II, whose deficiencies could explain CTL escape. Lymphocytes surrounding H&RS cells tended to be CD4(+) cells and rarely CD8(+), TIA-1(+) (cytotoxic marker) or NK cells. HLA class I and/or II were expressed in all EBV(+) HD cases, and RCAS1-expressing H&RS cells were found in 14/15 (93%) EBV(+) HD cases but only 8/20 (40%) EBV(-) HD cases (p < 0.05). FasL was detected in 9/15 (60%) and 7/20 (35%) EBV(+) and EBV(-) HD cases, respectively. ssDNA-positive (apoptotic) lymphocytes, surrounding H&RS cells, were rarely seen but were present in RCAS1(+) cases (20/22 cases, 91%) rather than negative cases (0/13 cases, 0%) (p < 0.005). Our findings suggest that EBV(+) H&RS cells might evade the host immune response by expressing RCAS1 rather than FasL.
 ...
PMID:Expression of human tumor-associated antigen RCAS1 in Reed-Sternberg cells in association with Epstein-Barr virus infection: a potential mechanism of immune evasion. 1139 27

Acute viral lymphadenitis, especially infectious mononucleosis (IM), often shows the presence of Reed-Sternberg-like cells, resulting in confusion with Hodgkin's disease. However, acute viral lymphadenitis requiring differential diagnosis from non-Hodgkin's lymphoma is not widely recognized. We describe the clinicopathological and immunohistochemical features of lymph node lesions from nine such patients which pose serious problems of differential diagnosis from low-grade peripheral T-cell lymphoma. There were three males and six females with ages ranging from 21 to 44 years (median 25 years). All patients had "B" symptoms and multicentric lymphadenopathy. The clinical course was also self-limiting. Each lymph node specimen showed an obvious expansion of an interfollicular area by pleomorphic and polymorphous infiltration with an increased number of arborizing postcapillary venules. The infiltrate was composed of variable numbers of small and medium-sized lymphocytes, immunoblasts, plasma cells in various stage of maturation and occasional granulocytes. The small lymphocytes usually had regular round nuclei, whereas the medium-sized lymphocytes occasionally showed nuclear pleomorphism. Hyperreactivity of B-lymphocytes, including hyperplastic germinal centers and/or foci of monocytoid B-cells, was seen in parts of the lesion. The majority of the interfollicular T-lymphocytes, including T-immunoblasts, expressed CD8 antigen. Various numbers of TIA-1-positive small and medium-sized T-cells were observed in the paracortical area. Despite these findings, the overall histological picture of this series posed serious difficulties when differentially diagnosing this condition from low-grade peripheral T-cell lymphomas such as angioimmunoblastic T-cell (AILD) and T-zone types, indicating that viral lymphadenitis occasionally presents with histological features of AILD and T-zone lymphomas. To avoid overdiagnosis and overtreatment, we emphasize the need to pay careful attention to the clinical and laboratory findings as well as the morphological features.
 ...
PMID:Acute viral lymphadenitis mimicking low-grade peripheral T-cell lymphoma. A clinicopathological study of nine cases. 1150 73

Eosinophils frequently infiltrate tissues involved by Hodgkin's disease (HD), and blood eosinophilia is frequently observed. However, the clinical significance and the mechanisms underlying eosinophilia need further elucidation. In this study the grade of eosinophilic infiltration (EoI) was evaluated in biopsies from 259 HD-patients. In a selected group (n=32), the numbers of Hodgkin-Reed-Sternberg (HRS)-cells were counted, and the phenotype of small lymphocytes, the expression of cytotoxic lymphocyte-associated proteins, CD3-zeta-chain, HLA-DR, proliferation markers, latent membrane protein 1 (LMP-1) and blood lymphocyte function were evaluated. Samples from 88 HD patients (34%) showed high EoI. Significantly higher EoI was seen in nodular sclerosis 2 (NS2; p<0.001), bulky disease (p<0.05) and in patients <50 years (p<0.05). Patients with high EoI did not differ from the remainder with regard to distribution of sex, stage, B-symptoms, blood lymphocyte function and outcome. HRS-cells were significantly more frequent in NS HD as compared to mixed cellularity (MC) (p<0.001) irrespective of EoI. LMP-1-expression, proliferative fraction and phenotypes of small lymphocytes did not differ between the cases with low and high EoI, respectively. MC HD samples had significantly higher numbers of small cells positive for CD8 (p<0.01), T-cell intracellular antigen-1 (p<0.01) and Granzyme B (p<0.05) than NS. LMP-1-positive cases had significantly higher frequency of CD8-positive cells than LMP-1-negative. In conclusion, high EoI remains a feature of certain clinical subgroups of HD. However, there was no association between the degree of EoI and numbers of HRS-cells, phenotypes of small lymphocytes, EBV status and clinical outcome. Determination of EoI is of limited diagnostic and prognostic clinical value in HD. However, the differences in small cell distribution of CD8, TIA-1, GrB and CD57 between the histopathological groups and between LMP-1-expressing/non-expressing cases may contribute to our understanding of the biology of the disease.
 ...
PMID:Tissue eosinophilia in relation to immunopathological and clinical characteristics in Hodgkin's disease. 1169 23

Due to their minority among the non-Hodgkin lymphomas, classification of extranodal T-cell lymphomas, including those of the natural killer (NK) cell type, has long been controversial and unclear, and the clinical outcome is not well clarified. Recently, new well-defined disease entities have been described based on tumor cell biology combined with anatomical site, clinical features, Epstein-Barr virus (EBV) status, and cell lineage as determined by immunophenotype and genotype. Cytological features are usually not specific, and there are no morphologic correlates with the classification of extranodal T/NK-cell lymphomas. From a human T-cell lymphotropic virus type 1 (HTLV-1) endemic area in Japan, we report here the analysis of 144 cases of extranodal T-cell lymphoma, from which fresh tissues were available. As the clinicopathological features were known, we simply reclassified the cases according to cell lineage and anatomical site. The extranodal T-cell lymphomas were classified into three types on the basis of cell lineage: (1) natural killer cell (NK) type [sCD3-, CD56+, T-cell receptor gene (TCR) germline], (2) cytotoxic T lymphocyte (CTL) type [sCD3+, TIA-1+, TCR rearranged, CD8+/-, CD4-/+], and (3) non-NK/CTL type [sCD3+, TIA-1-, TCR rearranged, CD4+/-, CD8-/+]. In addition to cell lineage, the anatomical site and clinical features were added for subclassification. NK type tumors (35 cases) included the lymphoblastic type, nasal/nasal-type NK lymphoma, and NK leukemia. The CTL type (46 cases) included anaplastic large cell lymphoma (ALCL), cutaneous type, intestinal, gamma delta T-cell type, and an unspecified type. The non-NK/CTL type (63 cases) included adult T-cell leukemia/lymphoma (ATLL), mycosis fungoides (MF), and an unspecified type. With the exception of ATLL and MF, most extranodal T-cell lymphomas had a cytotoxic phenotype of NK type or CTL type and were often associated with EBV infection. MF and the unspecified type within the non-NK/CTL tumors, with the exception of ATLL, had a favorable prognosis. However, NK and CTL types, with the exception of ALCL, were associated with a poor prognosis. Our results indicate that anatomical site and cell lineage are useful predictors of clinical outcomes of extranodal T-cell lymphomas.
 ...
PMID:Classification of cell lineage and anatomical site, and prognosis of extranodal T-cell lymphoma -- natural killer cell, cytotoxic T lymphocyte, and non-NK/CTL types. 1195 25

Large cell lymphomas and Hodgkin disease may develop during the course of chronic lymphocytic leukemia (CLL). In some cases the transformed cells are Epstein-Barr virus (EBV)-positive and not clonally related to the CLL cells. In other cases the transformed cells have the same clonal rearrangements as the CLL cells. Here we describe a composite lymphoma in a patient with CLL that exhibits a combination of CLL/small lymphocytic lymphoma, large cell lymphoma with anaplastic morphology, and Hodgkin lymphoma (HL). Although the large cell lymphoma cells are CD45R0 and TIA-1-positive, suggesting a T- or 0-cell anaplastic large cell lymphoma (ALCL), the genetic analysis demonstrates immunoglobulin heavy chain (IgH) gene rearrangements for both alleles, carrying the same somatic mutations as observed in the CLL component. The Reed-Sternberg (R-S) cells in the Hodgkin component also strongly express TIA-1 but differ from the anaplastic large cells by the expression of CD15 and TARC and the presence of a prominent lymphocytic infiltrate. The ALCL and HL components both are EBV negative. Analysis of the IgH gene rearrangements in micromanipulated R-S cells revealed identical Ig gene rearrangements carrying the same somatic mutations as the CLL and the large cell components. The findings indicate transformation of the CLL cells into a large cell lymphoma with anaplastic morphology and a Hodgkin component.
 ...
PMID:Clonal relation in a case of CLL, ALCL, and Hodgkin composite lymphoma. 1214 27

Anaplastic large cell lymphomas (ALCLs) represent a heterogeneous group of malignant lymphoproliferative diseases. Most of the cases are of T-cell line with a loss of cell surface receptors but with a production of cytotoxic cytoplasmatic granules--immunohistochemically (IHC) positive perforin, granzyme B, and TIA-1. The diagnostics of ALCL is based on morphological findings and results of IHC, which further stratify ALCLs to basic immunophenotypes according to ALK (anaplastic lymphoma kinase) protein expression--ALCL CD30+ ALK+ and ALCL CD30+ ALK+. The morphological investigations are supplemented by karyotyping and/or by a demonstration of breakpoint at 2p23 harboring ALK gene (FISH), and by molecular detection of chimeric genes characteristic of ALK+ lymphomas (NPM-ALK, ATIC-ALK, TPM3-ALK, TFG-ALK, and some even rarer rearrangements). Molecular diagnostics is important in monitoring minimal residual disease. As some of the characteristic molecular changes were demonstrated in healthy individuals and in Hodgkin's disease by quantitative PCR, the validation of these findings demands further studies. ALK protein positive ALCLs affect patients in age categories up to the third decade, whereas ALK protein negative cases occur in older patients with an average age of 60 years. Both subgroups of lymphomas are aggressive but ALK+ lymphomas react well to systemic treatment, and have a more favorable prognosis. Primary skin ALCLs belong to a group of T-cell lymphoproliferative diseases of the skin and have, in the majority of cases, a favorable course without generalization.
 ...
PMID:[Anaplastic large-cell lymphoma: review]. 1463 6


<< Previous 1 2 3 4 Next >>