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)

We investigated the representation of T cells in patients who had been treated for Hodgkin's disease (HD). We found a marked depletion in both CD4 and CD8 naive T-cell counts that persists up to 30 years after completion of treatment. In contrast, CD4 and CD8 memory T-cell subsets recovered to normal or above normal levels by 5 years posttreatment. Thus, the previously-reported long-term deficit in total CD4 T-cell counts after treatment for HD is due to specific depletion of naive T cells. Similarly, total CD8 T-cell counts return to normal by 5 years only because CD8 memory T cells expand to higher than normal levels. These findings suggest that the treatment (mediastinal irradiation) results in a longterm dysregulation of T-cell subset homeostasis. The profound depletion of naive T cells may explain the altered T-cell function in treated patients, including the poor response to immunization after treatment for HD. Further, in some individuals, we identified expansions of unusual subsets expressing low levels of CD8. Eight-color fluorescence-activated cell sorting analyses showed that these cells largely express CD8alphaalpha homodimers and CD57, consistent with the phenotype of potentially extrathymically derived T cells. In addition, these cells, both CD4+ and CD4-, are probably cytotoxic lymphocytes, as they express high levels of intracellular perforin. In adults treated for HD, an increased activity of extrathymic T-cell differentiation may partially compensate for the loss of thymic-derived T cells.
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PMID:Long-term depletion of naive T cells in patients treated for Hodgkin's disease. 934 51

The measurement of rhodamine 123 (Rho123) efflux in hematological malignancies, using flow-cytometry, provides an accurate assessment of multidrug resistance (MDR) of both P-glycoprotein and MRP. While their normal counterparts display high levels of PgP and Rho123 efflux, we investigated the MDR status of marked T/NK proliferations. When diagnosed according to natural killer (NK) markers (CD16, CD56, CD57) 8 of nine NK lymphoproliferative disorders (LPD) were markedly positive (3 NK non Hodgkin's lymphomas (NHL), 1 NK lymphoproliferative disease of large granular lymphocytes (LGL), and 5 T/NK LGL). These results are in accordance with the observed response to chemotherapy in the treated cases. Mature T LPD (prolymphocytic leukemia (PLL), and NHL) cells gave varying results, as did cells from Sezary syndromes. Marked Rho123 efflux was detected in the two cases of T-PLL suggesting the expression of MRP as previously described. Immature T-lymphomas or leukemias (6 cases) were all negative. These data should be considered in relation to NK proliferations which clearly display an MDR phenotype and therefore raise the question, of the relevance of this phenotype in normal cells, and secondly of the negativity of immature T-LPD. The latter could indicate that MDR inhibitors may be superfluous in the initial treatment of acute lymphoblastic leukemia (ALL). Finally the resistance to treatment of T-ALL or mature T cells LPD invokes the importance of exploring other mechanisms of drug resistance such as the lung resistance related protein (LRP).
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PMID:Multidrug resistance in aggressive lymphoproliferative disorders of T and natural-killer origin. 971 68

We report 2 cases of agranular CD2- CD4+ CD56+ non-Hodgkin lymphoma in which skin seemed to be the primary site. A 21-year-old woman's initial symptom was a skin nodule on the right cheek. She also had tumors in the nasopharynx, and the bone marrow subsequently became involved. No lymphadenopathy was present. She experienced complete remission after dose-intensified therapy with cyclophosphamide, hydroxydaunomycin, vincristine [Oncovin], and prednisone (CHOP), but the disease relapsed in the central nervous system 6 months later. An 81-year-old man experienced an 11-month history of skin nodules in the left forearm. On admission, he had a bone marrow infiltration of lymphoma cells. He died of pneumonia during chemotherapy. The malignant cells of the 2 patients had similar morphologic features, with a monocytoid nucleus and no cytoplasmic granules. The cells in both cases showed a unique phenotype: CD2-, CD3-, CD4+, CD8-, CD13-, CD14-, CD34-, CD16-, CD56+, CD57-, HLA-DR-positive. Staining for peroxidase and alpha-naphthyl butyrate esterase was negative. The T-cell receptor beta, gamma, delta, IgH, kappa, lambda genes were of germ line configurations. The DNA of Epstein-Barr virus was not detected from the bone marrow cells by polymerase chain reaction. Only 3 other cases with similar phenotypes have been reported; all had skin lesions. Although the origin of these cells remains unknown, we propose that this is a distinct clinicopathologic entity.
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PMID:A cutaneous agranular CD2- CD4+ CD56+ "lymphoma": report of two cases and review of the literature. 1043 11

There are significant difficulties in the differential diagnosis of lymphomas at the interface between classic Hodgkin's lymphoma and both paragranuloma and T-cell-rich B-cell lymphoma as well as at the interface between T-cell-rich B-cell lymphoma and paragranuloma. We therefore investigated 197 cases (155 classic Hodgkin's lymphomas, 32 T-cell-rich B-cell lymphomas, and 10 paragranulomas) by paraffin immunohistochemistry. Special interest was given to cases with a B-cell phenotype of tumor cells. The reactive inflammatory infiltrate in both classic Hodgkin's lymphoma and T-cell-rich B-cell lymphoma was rich in TIA-1-positive cytolytic lymphocytes, and CD57-positive cells were rarely encountered. In contrast, in paragranuloma CD57-positive cells and small B-lymphocytes predominated the background infiltrate. The tumor cells in cases of classic Hodgkin's lymphoma were positive for CD30 in 95%, for CD15 in 75%, and for CD20 in 22%. Apart from this, vimentin was expressed in >95% of the cases. All cases of T-cell-rich B-cell lymphoma were negative for vimentin, CD30, and CD15. The reactivity of the tumor cells for CD30, CD15, CD20, and vimentin together with the background reactivity for CD57 and TIA-1 seem to reliably discriminate between the entities and should therefore help to increase the interobserver reproducibility of diagnoses in the gray zone around Hodgkin's lymphoma.
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PMID:Differential diagnosis between classic Hodgkin's lymphoma, T-cell-rich B-cell lymphoma, and paragranuloma by paraffin immunohistochemistry. 977 80

The defects in lymphocyte apoptosis that underlie the autoimmune lymphoproliferative syndrome (ALPS) are usually attributable to inherited mutations of the CD95 (Fas) gene. In this report, we present the histopathological and immunophenotypic features seen in the lymph nodes (n = 16), peripheral blood (n = 10), bone marrow (n = 2), spleen (n = 3), and liver (n = 2) from 10 patients with ALPS. Lymph nodes showed marked paracortical hyperplasia. Interfollicular areas were expanded and populated by T cell receptor-alphabeta CD3+ CD4-CD8- (double-negative, DN) T cells that were negative for CD45RO. CD45RA+ T cells were increased in all cases studied. The paracortical infiltrate was a result of both reduced apoptosis and increased proliferation, as measured by in situ detection of DNA fragmentation and staining with MIB-1, respectively. The paracortical proliferation may be extensive enough to suggest a diagnosis of malignant lymphoma. Many of the paracortical lymphocytes expressed markers associated with cytotoxicity, such as perforin, TIA-1, and CD57. CD25 was negative. In addition, most lymph nodes exhibited florid follicular hyperplasia, often with focal progressive transformation of germinal centers; in some cases, follicular involution was seen. A polyclonal plasmacytosis also was present. The spleens were markedly enlarged, more than 10 times normal size. There was expansion of both white pulp and red pulp, with increased DN T cells. DN T cells also were observed in liver biopsies exhibiting portal triaditis. In the peripheral blood, the T cells showed increased expression of HLA-DR and CD57 but not CD25. CD45RA+ T cells were increased in the four cases studied. Polyclonal B cell lymphocytosis with expansion of CD5+ B cells was a characteristic finding. Taken together, the histopathological and immunophenotypic findings, particularly in lymph nodes and peripheral blood, are sufficiently distinctive to suggest a diagnosis of ALPS. Of note, two affected family members of one proband developed lymphoma (T-cell-rich B-cell lymphoma and nodular lymphocyte predominance Hodgkin's disease, respectively).
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PMID:Pathological findings in human autoimmune lymphoproliferative syndrome. 981 46

To determine whether there might be immunophenotypic differences between nodular lymphocyte predominance Hodgkin's disease (NLPHD) and progressive transformation of germinal centers (PTGC) to aid in the differential diagnosis, we compared 16 cases of NLPHD with 13 cases of florid PTGC and 2 cases of focal PTGC. Paraffin-section immunohistochemistry was performed for CD20, CD45RA, CD45RO, CD3, CD43, CD57, EMA, CD30, and CD21. All PTGC cases showed well-circumscribed nodules of confluent sheets of CD20+ CD45RA+ small cells. T cells were scattered singly or in small groups. In 5 patients with florid PTGC, the T cells in some of the nodules formed rings around a few large transformed lymphocytes. In contrast, the nodules in all NLPHD cases showed an irregular, "broken-up" pattern with CD20 and CD45RA, and there were prominent T cell rosettes around the CD20+ large cells in all nodules. Rosettes of CD57+ cells and staining of large cells for EMA were seen in 3 and 2 cases of NLPHD, respectively, but not in PTGC. There were no differences between NLPHD and PTGC with respect to staining for CD30 or CD21. Three of the eight patients with florid PTGC and a few T cell rosettes had had persistent or recurrent lymphadenopathy; NLPHD developed in 1 of these patients 13 years later. We conclude that a combination of pan-B and pan-T antigens can be a useful adjunct to morphology in distinguishing NLPHD from PTGC. In approximately one-third of florid PTGC cases, T cell rosettes may be present, but they are notably fewer than those in NLPHD. Close follow-up of such patients may be appropriate.
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PMID:Progressive transformation of germinal centers and nodular lymphocyte predominance Hodgkin's disease: a comparative immunohistochemical study. 988 1

Twenty-four years after apparently successful treatment for nodular lymphocyte predominant Hodgkin's disease (nLPHD), a 41-year old male developed "B" symptoms and extensive adenopathy. A right axillary lymph node biopsy showed two distinct regions including (1) histiocyte-rich B-cell lymphoma and (2) diffuse small T-cell lymphoma. A clonal rearrangement of the gene for the T-cell receptor beta chain confirmed the presence of a T-cell neoplasm, and this was further confirmed by selective polymerase chain reaction (PCR) on this morphologic zone. PCR on the morphologic B-cell lymphoma confirmed the presence of an immunoglobulin gene rearrangement. These two regions were separated by a less-defined zone containing a mixture of small CD57 positive T lymphocytes, small B lymphocytes, and rare lymphocytic and histiocytic (L&H) cells, highly suggestive of recurrent LPHD. The development of composite B-cell and T-cell lymphoma in this patient raises the speculation that nLPHD may be a neoplasm of lymphoid cells, which can differentiate in both B- and T-cell directions, with the "L&H" cells constituting their B-cell progeny.
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PMID:Composite B-cell and T-cell lymphoma arising 24 years after nodular lymphocyte predominant Hodgkin's disease. 999 Jan 10

Anaplastic large cell lymphomas (ALCL) are a heterogeneous group of CD30+ large cell lymphomas; the most characteristic type have a T or null cell phenotype, often express epithelial membrane antigen (EMA) and cytolytic lymphocyte markers, and often possess a nonrandom t(2;5)(p23;q35) chromosomal translocation. We studied 22 (19 T, 1 null, 2 B cell) ALCL, including four primary cutaneous ALCL (PC-ALCL), for the expression of TIA-1, the cytotoxic T lymphocyte (CTL) or natural killer (NK) cell-associated antigens CD4, CD8, betaF1, TCRdelta1, CD56, and CD57, the ALCL-associated antigens p80 and EMA, and the Hodgkin's disease-associated marker CD15 to better define the relationship of these markers to histological subtype, primary site, and patient clinical characteristics. TIA-1 expression was seen in 12 of 20 (60%) T or null cell ALCLs with a cytoplasmic, granular distribution. Ultrastructural studies showed cytotoxic-type granules (dense core, multivesicular, and intermediate types) with TIA-1 localized to granules on immunogold labeling. TIA-1 staining strongly correlated with young patient age (< or = 32 years, P < .05) and EMA expression (P < .05). Excluding the four PC-ALCL cases, TIA-1 staining also correlated with p80 expression (P < .05) in all of the T cell cases. Three CD15+ cases were TIA-1-. TIA-1 expression in T or null cell ALCL was seen in all morphological subtypes (2 of 2 small cell variant, 3 of 4 monomorphic variant, and 7 of 14 pleomorphic variant) and primary tumor sites (6 of 14 nodal, 2 of 4 primary cutaneous, 2 of 2 bone, and 2 of 2 soft tissue). TIA-1+ granules were seen in all subsets: 5 of 6 CD4+, 1 of 2 CD8+, 4 of 8 CD56+, and 1 of 2 CD57+ ALCL. Of note, 4 of 10 T or null cell ALCL expressed gammadelta T-cell receptors (TCR), whereas only 1 of 10 T or null cell ALCL was alphabeta TCR+; TCR were not detected in five cases. TIA-1 was expressed by 3 of 4 gammadelta TCR+ ALCL and 1 of 1 alphabeta TCR+ ALCL. These data support a cytotoxic lymphocyte phenotype in most T or null cell ALCL and suggest that some T cell ALCL are derived from cytolytic CD4+ T cells, gammadelta T cells, or NK-like (CD56+ or CD57+) T cells.
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PMID:The expression of TIA-1+ cytolytic-type granules and other cytolytic lymphocyte-associated markers in CD30+ anaplastic large cell lymphomas (ALCL): correlation with morphology, immunophenotype, ultrastructure, and clinical features. 1002 54

Immunoperoxidase markers are useful and often essential in distinguishing among lymphocyte-predominant Hodgkin's lymphoma, T-cell-rich B-cell lymphoma, and lymphocyte-rich classic Hodgkin's lymphoma. However, it is becoming increasingly clear that these "entities" are closely related clonal B-lineage neoplasms that may intertransform and/or coexist. We hypothesized that, just as there are cases with morphologic overlap, there would also be immunophenotypic overlap that would be found when a series of such cases is studied in detail. Eight cases of lymphocyte predominant Hodgkin's lymphoma, eight cases of lymphocyte-rich classic Hodgkin's lymphoma, seven cases of T-cell-rich B-cell lymphoma, and four cases of large B-cell lymphoma with focal features of T-cell-rich B-cell lymphoma were examined by the immunoperoxidase technique for expression of CD3, CD15, CD30, CD20, CD57, epithelial membrane antigen, and Epstein-Barr virus latent membrane protein (EBV LMP). All eight of the lymphocyte-predominant Hodgkin's lymphoma cases had CD20+ lymphocytic and histiocytic cells and CD57+ rosettes; however, in two cases, occasional lymphocytic and histiocytic cells were also weakly positive for CD15, CD30, and EBV LMP. Among the eight lymphocyte-rich classic Hodgkin's lymphoma cases, CD15+ Reed-Sternberg (R-S) cells were found in seven; however, in three of these cases rare rosettes of CD57+ cells surrounded the R-S or lacunar cells. In one case of large B-cell lymphoma the malignant cells resembled R-S cells and were CD20+, EBV LMP+, CD30+, CD15-, and surrounded by rosettes of CD57+ T cells. The majority of the cases exhibited the "expected" immunophenotypic patterns; however, the exceptional cases that were found serve to confirm the interrelationship among these clonal B-lineage neoplasms.
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PMID:Hodgkin's and non-Hodgkin's lymphoma: spectrum of morphologic and immunophenotypic overlap. 1055 72

Distinction of lymphocyte predominance Hodgkin's disease (LPHD) from other forms of lymphoma often requires immunohistochemistry (IHC). Most previously published recommended panels include markers to define the large neoplastic cells (for example, CD20, J chain, CD45) as well as the non-neoplastic background cells (CD21, CD45RO, CD57, TiA 1). In the present study we examine the practical use of a double IHC method designed to look simultaneously at two germinal center specific cell types: bcl6+ cells and [bc16+, CD57+] co-positive cells. All 10 nodular LPHD had bcl6+ large cells and numerous CD57+ small background cells, including [bcl6+CD57+] cells in rosettes. One case of LPHD with large cell transformation contained numerous bcl6+ large cells both singly (in areas of typical LPHD) and in sheets (in foci of large cell transformation), many CD57+ small cells but few [bcl6+CD57+] co-positive cells and no rosettes. In none of the five cases of florid progressive transformation of germinal centers were true rosettes seen, although all contained variable numbers of bcl6+ large cells and CD57+ cells. Lymphocyte-rich classic Hodgkin's disease LRCHD cases were notable for bcl6 reactivity in Reed-Sternberg cells in all cases, numerous background small bcl6+ lymphocytes, and rare CD57+ cells. Two phenotypic profiles were associated with the 10 cases of T cell-rich B cell large cell lymphoma (TCRBCL). In the first, group "A," six of six cases had bc16- large cells and few CD57+ small cells, and none had significant numbers of [bcl6+, CD57+] co-positive cells. In the second, group "B," four of four cases had bcl6+ large cells with numerous CD57+ and [bcl6+, CD57+] co-positive cells. These findings not only show that LPHD can be distinguished from its morphologic mimics through identification of specific germinal center cell types, but also identifies a second group of TCRBCL (group "B") whose phenotype suggests it might be an architectural variant of nodular LPHD.
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PMID:Lymphocyte predominance Hodgkin's disease: the use of bcl-6 and CD57 in diagnosis and differential diagnosis. 1093 47


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