A Double-Positive CD4+CD8+ T-Cell Population Is Commonly Found in Nodular Lymphocyte Predominant Hodgkin Lymphoma

Harvard University, Cambridge, Massachusetts, United States
American Journal of Clinical Pathology (Impact Factor: 2.51). 12/2006; 126(5):805-14. DOI: 10.1309/Y8KD-32QG-RYFN-1XQX
Source: PubMed


Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is a distinct subtype of Hodgkin lymphoma in which T-cell subsets have not been studied specifically. We reviewed 24 cases of NLPHL and compared flow cytometric results with those of 13 progressively transformed germinal centers (PTGC) cases, 78 nonspecific reactive hyperplasia (RH) cases, and 31 classical Hodgkin lymphoma (CHL) cases. A double-positive (CD4+CD8+) T-cell population was present in 58% of NLPHL cases, constituting 10% to 38% of T cells. The cells were CD3+, CD5+, CD2+, CD7+, CD1a- and terminal deoxynucleotidyl transferase-. Similar CD4+CD8+ T cells were identified in 38% of PTGC cases (P = .31), 4% of RH specimens (P < .00001), and 6% of CHL specimens (P < .0001). The presence of a CD4+CD8+ T-cell population in NLPHL may reflect an activated or reactive T-cell subset and should not lead to a misdiagnosis of T-cell lymphoma. This population may be a clue to the diagnosis of NLPHL, particularly in cases with limited tissue.

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Available from: Kaaren K Reichard, Aug 13, 2014
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    • "A recent publication demonstrated that detection of significant proportions of CD4 and CD8 double-positive T cells may suggest a diagnosis of NLPHL by flow cytometry [24]. This study showed that many cases of NLPHL show T cells having CD4 expression at normal levels and variable, usually low level of CD8 [24]. "
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    ABSTRACT: Classical Hodgkin lymphoma (CHL) is a relatively uncommon B cell-derived neoplasm that presents with rare malignant cells in an abundant reactive background. The diagnosis of CHL currently relies on a combination of morphologic findings and immunohistochemical stains. With the exception of rare cases with dramatically increased malignant populations, isolation of pure viable tumor cells has not been historically possible. Recently, a reliable flow cytometric assay for direct detection and isolation of the malignant cells in this disease has been developed. This assay has proven useful diagnostically and has been clinically validated to have a very high sensitivity and nearly absolute specificity for the diagnosis of CHL in routine clinical samples. This paper describes the methodology for the flow cytometric detection of CHL in clinical samples as well as current state of evaluation of background lymphocytes as an adjunct diagnostic test. Also discussed are exciting research applications of the direct isolation of viable tumor cells in CHL. The current state of flow cytometric evaluation of nodular lymphocyte predominant Hodgkin lymphoma and T cell-rich large B cell lymphoma is also briefly discussed.
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    • "So, as we previously documented in breast cancer patients [10], this increase of DP T cells is associated with tumor microenvironment. Others studies also reported an increased number of DP T cells in lymphomas [16] and in other diseased individuals [18]–[20]. "
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    ABSTRACT: Double positive (DP) CD4CD8 Talphabeta cells have been reported in normal individuals as well as in different pathological conditions including inflammatory diseases, viral infections and cancer, but their function remains to be elucidated. We recently reported the increased frequency of DP Talphabeta cells in human breast pleural effusions. This manuscript addresses the question of the existence and above all the role of this non-conventional DP sub-population among tumor associated lymphocytes in melanomas. We analyzed the intratumoral cell infiltrate in solid metastasis (n = 6) and tumor invaded lymph nodes (n = 26) samples from melanomas patients by multiparametric cytometry. Here we documented for the first time significant increased frequency of DP T cells in about 60% of melanoma tumors compared to blood samples. Interestingly, a high proportion of these cells produced TNF-alpha in response to autologous melanoma cell lines. Besides, they are characterized by a unique cytokine profile corresponding to higher secretion of IL-13, IL-4 and IL-5 than simple positive T cells. In deep analysis, we derived a representative tumor-reactive DP T cell clone from a melanoma patient's invaded lymph node. This clone was restricted by HLA-A*2402 and recognized both autologous and allogeneic tumor cells of various origins as well as normal cells, suggesting that the target antigen was a ubiquitous self antigen. However, this DP T cell clone failed to kill HLA-A*2402 EBV-transformed B cells, probably due to the constitutive expression of immunoproteasome by these cells. In conclusion, we can postulate that, according to their broad tumor reactivity and to their original cytokine profile, the tumor associated DP T cells could participate in immune responses to tumors in vivo. Therefore, the presence of these cells and their role will be crucial to address in cancer patients, especially in the context of immunotherapies.
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    ABSTRACT: Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare indolent B-cell lymphoma. However, its morphology can resemble T-cell/histiocyte rich large B-cell lymphoma (T/HRBCL), a subtype of more aggressive diffuse large B-cell lymphoma. More and more studies suggest that these two entities are closely related. In this report, a 59-year-old man with nodal NLPHL and concomitant T/HRBCL in the bone marrow is presented, the current progress in our understanding of these two closely related B-cell lymphomas reviewed and the problems in the diagnosis and differentiation of NLPHL and T/HRBCL discussed.
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