Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report here a series of 16 highly malignant diffuse large B-cell lymphomas of the oral cavity with unique immunohistologic features. Fifteen of these developed in human immunodeficiency virus-positive patients. All cases displayed morphologic features of diffuse large-cell lymphomas but strikingly differed from them in that they showed a minimal or absent expression of the leukocyte common antigen as well as of the B-cell antigen CD20. Instead, the tumor cells showed a constant reaction with the plasma cell characteristic antibody VS38c and a frequent reaction with the CD79a antibody. This, in conjunction with a variable expression of cytoplasmic Ig and a monoclonal rearrangement of the Ig heavy chain gene in all of the three tested cases confirmed the B-cell nature, the clonal origin, and the plasmacellular differentiation of these neoplasms. The majority of these tumors were negative for the BCL-6 protein, with the remaining cases showing only a partial and weak expression of this antigen. An association with the Epstein-Barr virus (EBV) was found in 9 of 15 tested cases showing abundant EBV-encoded nuclear RNA transcripts in the absence of EBNA-2. Five of the EBV-positive cases variably expressed LMP-1. We propose to name these tumors plasmablastic lymphomas, in accordance with their morphologic and immunohistologic features. Knowledge of this lymphoma entity is important to avoid confusion with nonlymphoid malignancies due to the lack of commonly used lymphoid markers.
 ...
PMID:Plasmablastic lymphomas of the oral cavity: a new entity associated with the human immunodeficiency virus infection. 902 65

The incidence of non-Hodgkin's lymphoma is greatly increased in human immunodeficiency virus (HIV)-infected individuals. Most are clinically aggressive B-cell lymphomas exhibiting Burkitt-type, immunoblastic or large-cell morphology. Approximately 80% arise systemically (nodal or extranodal), and the remaining 20% arise in the central nervous system. A small proportion are body cavity-based (primary effusion) lymphomas associated with Kaposi's sarcoma-associated herpesvirus (KSHV) infection. Possible factors contributing to lymphoma development include HIV-induced immunosuppression, chronic antigenic stimulation, and cytokine overproduction. These phenomena are associated with the development of oligoclonal B-cell expansions. The appearance of malignant lymphoma is characterized by the presence of a monoclonal B-cell population displaying a variety of genetic lesions including Epstein-Barr virus (EBV) infections, c-myc gene rearrangement, bcl-6 gene rearrangement, ras gene mutations, and p53 gene mutations/deletions. The number and type of genetic lesions varies according to anatomic site of origin and histopathology. In the case of Burkitt-type lymphoma, virtually 100% exhibit c-myc gene rearrangement, two thirds display p53 gene mutations, one third contain EBV, and none exhibit bcl-6 gene rearrangements. In contrast, in the case of immunoblastic lymphoma, virtually 100% contain EBV, 25% display c-myc gene rearrangements, 20% display bcl-6 gene rearrangements, and few exhibit p53 gene mutations. These findings suggest that more than one pathogenetic mechanism is operational in the development and progression of acquired immunodeficiency syndrome (AIDS)-related lymphoma. Further work is necessary to develop a thorough understanding of the origin and pathogenesis of malignant lymphoma in the setting of HIV infection. AIDS-related lymphoma remains an important biologic model for investigating the development and progression of high-grade non-Hodgkin lymphomas as well as malignant lymphomas that develop in immune-deficient hosts.
 ...
PMID:Molecular pathology of acquired immunodeficiency syndrome-related non-Hodgkin's lymphoma. 904 11

We examined 81 cases of primary gastrointestinal lymphomas in Korea, including 64 gastric lymphomas and 17 intestinal lymphomas, for EBV expression by EBER-1 in situ hybridization (ISH) and EBNA-1 PCR. In EBER-1 positive cases, we performed immunohistochemistry for latent membrane protein-1 (LMP-1) and EBV diffuse early antigen (EA(D)) to compare EBV latent gene expression and lytic process. EBER-1 was detected in 15 of 81 cases of lymphomas. EBER-1 expression showed three different patterns on tumour cells; diffuse 4/81 (5%), localized 4/81 (8%), and a few scattered pattern 7/81 (9%). We regarded diffuse pattern and localized pattern as EBER-1 positive group (8/81: 10%). Diffuse pattern of EBER-1 was shown in all three T-cell lymphomas and one B-cell lymphoma. A localized pattern was seen all in B-cell lymphomas. The EBER-1 expression was 11% in the stomach (7/64) and 6% in the intestine (1/17). Five of the eight EBER-1 positive gastric lymphomas were histologically diffuse large B-cell lymphomas, and the other three were peripheral T-cell lymphoma, unspecified, one angiocentric lymphoma, and one intestinal T-cell lymphoma by REAL classification. Eight MALT type gastric B-cell lymphomas showed no EBV association. EBV nuclear antigen (EBNA-1) was detected in 15 of 45 resected cases (33%) by PCR. EBER-1 positive cases were all EBNA-1 positive. Twelve EBNA-positive/EBER-negative cases consisted of seven cases showing a few scattered EBER-1 positive lymphocytes. LMP-1 and diffuse early antigen (EA(D)) was detected in five and three cases, respectively. Although follow-up information in our series was incomplete, it seemed that there was no significant difference in their staging or prognosis between EBER-positive cases and EBER-negative group. It is concluded that EBV is associated with some lymphomas among Koreans without overt pre-existing immunodeficiency, especially in T-cell lymphomas.
 ...
PMID:Epstein-Barr virus-associated primary gastrointestinal lymphoma in non-immunocompromised patients in Korea. 908 52

To elucidate age-related differences in non-Hodgkin's lymphoma (NHL), the authors evaluated 950 consecutive, human immunodeficiency virus-negative patients (age range, 15 to 96 years) observed between July 1988 and June 1995 in the same Italian cancer institute. Patients were grouped into six age groups and cross-tabulated by Working Formulation (WF) categories and other newly recognized entities according to the Revised European American Lymphoma (REAL) classification, cell immunophenotype, and nodal or extranodal location. There was a tendency of the low-grade category to increase with increasing age (16.8% in the age group 15 to 34 years to 32.4% in the age group 65 to 74 years), although a subsequent decline was seen at age 75 years or older (23.2%). Also the intermediate-grade category was more frequent in the elderly (46.6% and 49.4% at 65 to 74 years and at 75 years or older, respectively). High-grade category showed compared with low and intermediate grade ones, a significant downward trend with age (X2 for trend = 25.31; P < .001), interrupted in only the oldest age group. The relative excess of low-grade NHL in patients older than 55 years. of age was accounted for by the high proportion of small lymphocytic lymphomas, which, however, somewhat declined at age 75 years or older. Conversely, the relative excess of high-grade NHL below age 35 years chiefly derived from the high percentage (28.4%) of CD30-positive anaplastic large cell lymphomas. B- and T-cell lymphomas accounted for 85.9% and 9.0% of all cases, respectively. B- and T- and non-B, non-T-cell and histiocytic NHL accounted for the remaining 5.1%. A highly significant trend of increase in the proportion of B-cell lymphomas with age increase was noted (X2 for trend = 21.90; P < .001); chiefly attributable to the excess of T-cell (15.1%) and undetermined phenotype (18.6%) in patients younger than 35 years of age. Extranodal location was not significantly related to age groups. Thus, the present study showed some interesting differences in NHL morphology and cell phenotype according to age, avoiding, at the same time, the arbitrariness of patients' dichotomization into elderly and nonelderly.
 ...
PMID:Pathological and immunophenotypic features of adult non-Hodgkin's lymphomas by age group. 915 6

SIV infection of macaques is a well-established animal model for studying the pathogenesis of HIV infection in humans. During the course of SIV infection, up to 40% of cynomolgus macaques (Macaca fascicularis) develop SIV-associated non-Hodgkin's lymphomas. In the present study, we characterized malignant lymphomas of SIV(mac) 251/32H-infected rhesus macaques (Macaca mulatto) of our cohort in terms of clinical outcome, histopathology and EBV association. Histopathologic changes of lymphoid malignancies were classified according to the Kiel classification. For detection of the EBV-encoded small RNAs EBER1 and EBER2, a method of non-isotopic in situ hybridization was established. The presence of EBNA-2 antigens was assessed by immunohistochemistry. Seven of 43 rhesus macaques developed highly malignant B-cell lymphomas of the centroblastic, immunoblastic and Burkitt subtypes within 18-29 months post-experimental SIV infection. In situ hybridization revealed the presence of small EBER1 and -2 RNAs in 6 of 7 disease cases. EBNA-2 antigens could be demonstrated in only 4 of 7 tissue specimens. As expected, the Burkitt-type of lymphoma was negative for EBNA-2 antigen staining. In accordance with findings on SIV-associated lymphomas of cynomolgus macaques, infection with an EBV-related herpesvirus could be demonstrated in almost 90% of lymphomas in SIV-infected rhesus macaques. In contrast, the presence of EBV in lymphomas had been documented previously in only 30-40% of HIV-infected patients. Further studies should thus define the precise role of herpesvirus infection for lymphomagenesis in SIV- and HIV-induced immunodeficiency.
 ...
PMID:Detection of Epstein-Barr virus small RNAs EBER1 and EBER2 in lymphomas of SIV-infected rhesus monkeys by in situ hybridization. 921 38

An increasing frequency of malignant lymphomas occurs among patients infected by human immunodeficiency virus. Because of the close similarities to human malignancies, we used a nonhuman primate model to study the pathogenesis of simian immunodeficiency virus (SIV)-associated malignancies. Specifically, we investigated (1) the presence of the SIV genome in tumor cells, (2) the presence of coinfecting viruses, and (3) the presence of a rearrangement of the immunoglobulin and c-myc genes. We observed 5 cases of non-Hodgkin's lymphomas (4 of B- and 1 of T-cell origin) among 14 SIV-infected cynomolgus monkeys. No c-myc translocation was observed in the tumors, whereas B-cell lymphomas were characterized either by a monoclonal (in 2 of 4) or by an oligoclonal (in 2 of 4) VDJ rearrangements of the immunoglobulin heavy chain gene. Molecular, biological, and immunological analyses did show the presence of infectious SIV in the tumor cells of 1 T-cell and 2 oligoclonal B-cell lymphomas. Neither Simian T-lymphotropic nor Epstein-Barr viruses were detectable, whereas Simian herpes virus Macaca fascicularis-1 was detectable at a very low copy number in 3 of 4 B-cell lymphomas; however, only 1 of these also harbored the SIV genome. These results support the possibility that SIV may be directly involved in the process of B or T lymphomagenesis occurring in simian acquired immunodeficiency syndrome.
 ...
PMID:Detection of infectious simian immunodeficiency virus in B- and T-cell lymphomas of experimentally infected macaques. 955 63

Epstein-Barr virus (EBV)-associated lymphoproliferative diseases are a frequent occurrence in immunodeficient patients. Most commonly seen are polymorphic B-cell lymphoproliferative disorders and malignant B-cell lymphomas. Classical Hodgkin's disease (HD), however, is rare in these patients. In the present study, we attempted to characterize cases resembling HD in patients with a variety of underlying immunodeficiency states using clinical aspects, immunohistochemistry, in situ hybridization, and polymerase chain reaction. All of the six cases that we investigated presented clinically with B symptoms and a short, devastating course. Histologically, they showed a lymphocytic depletion and multiple cells that resembled HD and Reed-Sternberg cells. Many of those were atypical blast cells that stained positively for B-cell surface antigens, such as CD20 and CD79a, whereas others were of the typical HD and Reed-Sternberg phenotype. Another frequent finding, especially in the extranodal sites, was a perivascular arrangement of large blast cells intermingled with small lymphoid cells. All of the cases were EBV-associated (proved latent membrane protein-1 immunohistochemical analysis, EBV-encoded RNA in situ hybridization, and polymerase chain reaction for subtypes A and B), with a frequent coinfection of type A and B. This was in contrast to ordinary HD, which is characterized by single infection of only one strain, i.e., the subtype A in Western countries. Three cases showed clonal B-cell populations, at least at terminal stages of the disease. We describe a lymphoproliferative disorder in immunodeficient patients with features of HD that, in some respects, resembles an EBV-driven lymphoproliferative disorder seen in cases of fatal infectious mononucleosis. We conclude that clinical and pathologic features of these disorders might cause some problems for histologic differential diagnosis and might represent a separate entity of their own in immunodeficient patients.
 ...
PMID:Hodgkin's disease-like lymphoproliferative disorders in patients with different underlying immunodeficiency states. 957 79

Methotrexate is the most widely used second-line treatment in rheumatoid arthritis because of its excellent efficacy and safety profile. However, since 1991, about 100 cases of lymphoproliferative disorders have been reported in rheumatoid arthritis patients under methotrexate therapy. Four characteristics similar to those in lymphomas associated with immunodeficiency were identified during a review of the 48 cases for which detailed information is available. (1) Most cases were non-Hodgkin's B-cell lymphomas of the large cell or diffuse mixed type. (2) Extranodal involvement (55% of cases) was unusually common. (3) Evidence of Epstein-Barr infection was found in 46% of tested patients. (4) Of the 14 patients treated by methotrexate withdrawal alone, eight achieved a full remission, with follow-ups ranging from one to five years. These characteristics suggest a role for two factors: (1) the abnormalities in cell-mediated immunity seen in rheumatoid arthritis may promote latent Epstein-Barr virus infection, which may in turn lead to proliferation of malignant lymphoid cells; (2) the immunomodulatory effects of methotrexate may promote the development not only of opportunistic infections but also of Epstein-Barr virus-related lymphoproliferative disorders. There is no firm evidence to date that methotrexate has a direct oncogenic effect and no excess in malignant diseases has been reported with this drug. In conclusion, the rate of occurrence of lymphoproliferative disorders induced by low-dose methotrexate therapy remains controversial, although the characteristics of the malignancies and the possibility of a complete remission after methotrexate withdrawal militate against a chance association. Epidemiologic and other studies are needed to clarify this issue.
 ...
PMID:Lymphoproliferative disorders in rheumatoid arthritis patients on low-dose methotrexate. 959 95

Lymphomas that occur in patients with human immunodeficiency virus (HIV) infection are predominantly of B-cell origin and subsets show evidence for Epstein-Barr virus (EBV) infection or chromosomal translocations in the c-myc locus. The only subset of lymphoma clearly related to the immunodeficiency caused by HIV infection (similar to transplantation-associated lymphomas) is the EBV+ primary central nervous system lymphoma. The systemic AIDS-related lymphomas (ARLs) represent a complex set of disease processes histologically categorized as large cell or small non-cleaved (Burkitt's-like) lymphomas. Molecular analyses of the ARLs have demonstrated polyclonal lymphomas as likely early representatives of monoclonal immunoglobulin (Ig)-expressing B-cell lymphomas. Variable region analysis of lymphoma-associated Ig has shown evidence for extensive somatic mutation with little evidence for appropriate affinity maturation. These observations suggest that abnormal control of B-cell maturation in response to polyclonal antigenic stimulation may play a central role in the pathogenesis of ARL. The recent finding of clonal HIV integrated within macrophages in a subset of early lymphomas also provides evidence for abnormalities outside the B-cell compartment playing roles in this disease. Overall, ARLs generally appear to be outgrowths of antigen-driven B-cells with significant growth control influence provided by abnormal T-cell and antigen-presenting cell processes.
 ...
PMID:The immunology of AIDS-associated lymphomas. 960 72

The association of Epstein-Barr virus (EBV) with B-cell lymphoma was examined in 72 human immunodeficiency virus-negative Japanese patients using the polymerase chain reaction (PCR) on DNA obtained from formalin-fixed paraffin-embedded tissues and an in situ hybridization (ISH) technique. EBV-encoded RNA 1 (EBER-1) was detected in 12 of 72 cases (17%); five of 33 cases (15%) of nodal B-cell lymphomas and seven of 39 cases (18%) of extranodal B-cell lymphomas. Three cases of post-bone marrow transplantation and one case of autoimmune disease (Evans syndrome) were included among seven EBER-1 positive extranodal lymphomas. A combined study of immunohistochemistry and EBER-1 revealed that some L26 positive cells were EBER-1 positive. A DNA band was also observed in 13 of 70 examined cases (19%) (four of 33 cases of nodal B-cell lymphomas (12%) and nine of 37 cases of extranodal B-lymphomas (24%)) in the PCR study using primers to detect the Bam HI-W fragment of EBV. In the immunohistochemical study using a monoclonal antibody to the latent membrane protein 1 (LMP-1) of the EBV, one of the EBV-encoded latent gene products, LMP-1, was expressed in six of 34 cases (18%) of extranodal B-lymphomas, but none of the cases with nodal B-cell lymphomas were shown to be LMP-1 positive. Oncoprotein bcl-2 was examined by immunohistochemistry and found to be expressed in seven cases of nodal lymphomas and three cases of extranodal lymphomas, and two of these nodal cases were EBER ISH positive. In EBV serology, only two cases of nodal and one case of extranodal EBER positive B-cell lymphomas revealed a reactivation pattern. In the PCR study using primers to detect the lymphocyte-determined membrane antigen (LYDMA), the same sized monoclonal bands were observed in case 36 in the PCR products from the nose and skin, suggesting the monoclonal proliferation of the tumor. These findings suggested a low incidence of EBV association with B-cell lymphomas unless patients were in an immunologically impaired condition such as post-organ transplantation or autoimmune diseases.
 ...
PMID:Determination of Epstein-Barr virus association with B-cell lymphomas in Japan: study of 72 cases--in situ hybridization, polymerase chain reaction, immunohistochemical studies. 963 83


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>