scholarly journals Granzyme B-expressing peripheral T-cell lymphomas: neoplastic equivalents of activated cytotoxic T cells with preference for mucosa- associated lymphoid tissue localization

Blood ◽  
1994 ◽  
Vol 84 (11) ◽  
pp. 3785-3791 ◽  
Author(s):  
PC de Bruin ◽  
JA Kummer ◽  
P van der Valk ◽  
P van Heerde ◽  
PM Kluin ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Tumor Cells ◽  
Lymphoid Tissue ◽  
Cytotoxic T Cells ◽  
Granzyme B ◽  
Clinical Behavior ◽  
T Cell Lymphomas ◽  
Hodgkin's Lymphomas ◽  
Peripheral T Cell Lymphomas

T-cell non-Hodgkin's lymphomas can be considered the neoplastic equivalents of immunologically functional, site-restricted T lymphocytes. Little is known about the occurrence and clinical behavior of T-cell lymphomas that are the neoplastic equivalents of different functional T-cell subsets. Here, we investigated the prevalence, preferential site, immunophenotype, and clinical behavior of the neoplastic equivalents of activated cytotoxic T cells (CTLs) in a group of 140 nodal and extranodal T-cell lymphomas. Activated CTLs were shown immunohistochemically with a monoclonal antibody against granzyme B, a major constituent of the cytotoxic granules of activated T cells. Granzyme B-positive T-cell lymphomas were mainly found in mucosa- associated lymphoid tissue (MALT; nose, 63% of the cases; gastrointestinal tract, 46%; and lung, 33%). Granzyme B-positive cases with primary localization in MALT were more often associated with angioinvasion (P = .005), necrosis (P = .002), and histologic characteristics of celiac disease in adjacent mucosa not involved with lymphoma. Eosinophilia was more often observed in granzyme B-negative cases (P = .03). Most cases belonged to the pleomorphic medium- and large-cell group of the Kiel classification. CD30 expression was more often found in granzyme B-positive lymphomas of MALT (P = .04), whereas CD56 expression was exclusively found in nasal granzyme B-positive lymphomas. Immunophenotypically, most of the cases should be considered as neoplastic equivalents of activated CTLs based on the presence of T- cell markers on tumor cells. In two cases of nasal lymphoma, tumor cells probably were the neoplastic counterparts of natural killer cells. The prognosis of the granzyme B-positive gastrointestinal T-cell lymphomas was poor but did not differ from granzyme B-negative gastrointestinal T-cell lymphomas. This indicates that, in peripheral T- cell lymphomas, site of origin is more important as a prognostic parameter than derivation of activated CTLs.

Peripheral T-Cell Lymphomas with Follicular Growth Patterns Are Derived from Follicular Helper T Cells (TFH): A Link with Angioimmunoblastic T-Cell Lymphomas?.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3568-3568 ◽  
Author(s):  
Yenlin Huang ◽  
Anne Moreau ◽  
Jehan Dupuis ◽  
Berthold Streubel ◽  
Barbara Petit ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Tumor Cells ◽  
Growth Patterns ◽  
Helper T Cells ◽  
Follicular Growth ◽  
Follicular Helper T Cells ◽  
Follicular Helper ◽  
T Cell Lymphomas ◽  
Peripheral T Cell Lymphomas

Abstract Nodal peripheral T-cell lymphomas represent a heterogeneous category, composed of three entities: anaplastic large cell lymphomas, peripheral T-cell lymphomas unspecified (PTCLu) and angioimmunoblastic T-cell lymphomas (AITL). The later entity has been recently recognized to derive from follicular helper T cells (TFH). Among PTCLu - which represents an ill-defined entity - a peculiar form with follicular growth pattern (PTCL-F) has been recently reported, and one article stated their association with t(5 ;9)(q33 ;q22) involving ITK and SYK (Leukemia2006; 20: 313–318). However, the origin of tumor cells and clinical aspects of this group of PTCL-F are still unknown. The aim of this study was to analyse a series of PTCL-F to describe their clinical and histopathological aspects, to identify their cell of origin, and their relationship with AITL. Fourty-two patients from 32 to 85 years of age with 51 biopsies were selected from three Departments of Pathology (Creteil, n=24, Nantes n=13, Vienna n=14). All patients showed histopathologic features of PTCL-F in at least one biopsy. Biopsies were classified into three categories according to predominant morphological features at low power magnification: follicular lymphoma-like (n=7), progressive transformation of germinal center-like (n=22), and AITL-like features with follicular colonization (n=19). Several cases have combinations of patterns. The neoplastic population is characterized by medium-sized cells with clear cytoplasm surrounded by IgD+ B-cells. Tumor cells are of helper T-cell immunophenotype [CD2+ (33/33 = 100%), CD3+ (45/48 = 93%), CD4+ (35/42 = 83%), CD5+ (39/39 = 100%), CD7+ (7/37 = 19%)], with frequent expression of CD10 (29/43 = 67%) and of TFH markers [PDCD-1 (32/36 = 88%), CXCL13+ (33/38 = 87%), BCL6+ (15/25 = 60%), CD57+ (9/16 = 56%)]. Scattered CD20+ B-immunoblasts (27/28 = 96%) and EBV+ cells (18/30 = 60%) are also frequently observed. Seven out of 31 patients (22%) in the 3 morphological patterns have t(5 ;9)(q33 ;q22) detected by fluorescent in situ hybridization. At prentation and/or at relapse, most patients had multiple lymphadenopathies (19/23 = 83%) and disseminated disease (stages III–IV, 22/28 = 79%). Skin lesions and B symptoms were present in 7/19 (37%) and 6/22 (27%) patients, respectively. In addition, 2 patients with sequential biopsies disclosed typical clinical & histopathological features of AITL in one episode. Our results show that this rare form of PTCL has an immunophenotype indicative of TFH origin, is associated with t(5 ;9) in a proportion of cases, shows some similarities in morphology and immunophenotype with AITL, suggesting a relationship, and generates diagnostic pitfalls, especially with atypical reactive lymphoid lesions and some B-cell lymphomas. The use of immunohistochemistry with TFH markers and molecular studies can help to make a correct diagnosis.

Nodal peripheral T-cell lymphomas and, in particular, their lymphoepithelioid (Lennert?s) variant are often derived from CD8+ cytotoxic T-cells

2004 ◽  
Vol 445 (4) ◽  
pp. 334-343 ◽  
Author(s):  
Eva Geissinger ◽  
Tobias Odenwald ◽  
Seung-Sook Lee ◽  
Irina Bonzheim ◽  
Sabine Roth ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cytotoxic T Cells ◽  
T Cell Lymphomas ◽  
Peripheral T Cell Lymphomas

scholarly journals The expression of CD26 and CD40 ligand is mutually exclusive in human T- cell non-Hodgkin's lymphomas/leukemias

Blood ◽  
1995 ◽  
Vol 86 (12) ◽  
pp. 4617-4626 ◽  
Author(s):  
A Carbone ◽  
A Gloghini ◽  
V Zagonel ◽  
D Aldinucci ◽  
V Gattei ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
Mycosis Fungoides ◽  
Cell Lines ◽  
Critical Role ◽  
Cd40 Ligand ◽  
T Cell Lymphomas ◽  
Human T Cell ◽  
Hodgkin's Lymphomas

CD26 and CD40 ligand (CD40L) are surface molecules on human activated T lymphocytes that play a critical role in the regulation of lymphopoiesis. Both molecules are expressed on a restricted fraction of human T-cell non-Hodgkin's lymphomas (NHL)/leukemias; however, little is known about their functional and/or clinical significance in these disorders. In this study, the pattern of expression of CD40L was compared with that of the CD26 molecule. A series of 67 human T-cell NHL/leukemias and a panel of leukemia/lymphoma T-cell lines were evaluated by immunohistochemistry, flow cytometry, and RNA studies. The overall frequency of CD26+ and CD40L+ samples was rather similar (25/67 [37%] v 18/67 [27%]). However, the majority of CD26-expressing cases clustered in the lymphoblastic lymphomas (LBL)/T-acute lymphoblastic leukemias (ALL; 12/23) and CD30+ anaplastic large-cell (ALC) lymphomas (5/8), whereas CD40L+ lymphomas included a large fraction of mycosis fungoides (11/21 [52%]). CD26 and CD40L coexpression was found only in 2 myocosis fungoides cases and 1 small lymphocytic lymphoma. Thus, the expression of the two antigens was mutually exclusive in almost all T- cell lymphomas/leukemias. Accordingly, lymphoma cell lines expressed either one of the molecules or the relative amounts of CD26 and CD40L were inversely proportional. In contrast, reactive T lymphocytes from patients with non-neoplastic T-cell expansions and in vitro activated CD3+ or CD4+ normal T cells were found to coexpress CD40L and CD26. Results of a multivariate analysis showed that the expression of CD26 in T-cell LBL/ALL patients was associated to a worse outcome in terms of survival, as compared with patients with CD26- tumors (P < or = .0001). Based on our results, it can be concluded that, (1) as opposed to activated or reactive normal T cells, the expression of CD26 and of CD40L is mutually exclusive in human T-cell lymphomas/leukemias; (2) expression of CD26 is restricted to aggressive pathologic entities, such as T-cell LBL/ALL and T-cell CD30+ ALC lymphomas, whereas CD40L is expressed on slow progressing diseases such as mycosis fungoides; and (3) within the T-cell LBL/ALL group of tumors, CD26 may identify a subset of poor prognosis patients.

scholarly journals An overview of cutaneous T cell lymphomas

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 1882 ◽  
Author(s):  
Nooshin Bagherani ◽  
Bruce R. Smoller
Keyword(s):  
T Cell ◽  
T Lymphocytes ◽  
Mycosis Fungoides ◽  
Annual Incidence ◽  
Heterogeneous Group ◽  
Not Otherwise Specified ◽  
T Cell Lymphomas ◽  
Hodgkin's Lymphomas ◽  
Diagnosis Therapy ◽  
Peripheral T Cell Lymphomas

Cutaneous T cell lymphomas (CTCLs) are a heterogeneous group of extranodal non-Hodgkin’s lymphomas that are characterized by a cutaneous infiltration of malignant monoclonal T lymphocytes. They typically afflict adults with a median age of 55 to 60 years, and the annual incidence is about 0.5 per 100,000. Mycosis fungoides, Sézary syndrome, and primary cutaneous peripheral T cell lymphomas not otherwise specified are the most important subtypes of CTCL. CTCL is a complicated concept in terms of etiopathogenesis, diagnosis, therapy, and prognosis. Herein, we summarize advances which have been achieved in these fields.

Pathobiology of Peripheral T-cell Lymphomas

Hematology ◽  
2006 ◽  
Vol 2006 (1) ◽  
pp. 317-322 ◽  
Author(s):  
Elaine S. Jaffe
Keyword(s):  
T Cells ◽  
Immune System ◽  
T Cell ◽  
Clinical Features ◽  
Cell Lymphoma ◽  
Systemic Disease ◽  
T Cell Lymphoma ◽  
Adaptive Immune ◽  
T Cell Lymphomas ◽  
Peripheral T Cell Lymphomas

Abstract Peripheral T-cell lymphomas (PTLs) are uncommon, accounting for fewer than 10% of all non-Hodgkin lymphomas. Success in therapy of the PTLs has lagged behind that of aggressive B-cell lymphomas, and most PTLs have a poor prognosis. The molecular pathogenesis of most PTLs is also poorly understood. In the WHO classification, clinical features, in conjunction with morphological and immunophenotypic criteria, are relied on to define most disease entities. Functionally, T-cell lymphomas are related to the two major arms of the immune system, the innate and adaptive immune systems. NK cells and T cells of the innate immune system recognize antigen in the absence of MHC antigens and are involved in mucosal immunity. The lymphomas derived from these cells often involve cutaneous and mucosal sites. The expression of cytotoxic molecules in these lymphomas may predispose to apoptosis by tumor cells and normal bystander cells. Hepatosplenic T-cell lymphoma is a systemic disease derived from functionally immature innate effector cells, most often of γδ T-cell origin. In contrast, most nodal T-cell lymphomas belong to the adaptive immune system. Angioimmunoblastic T-cell lymphoma (AILT) is mostly likely derived from follicular helper T-cells (TFH), a finding that explains many of its pathological and clinical features. Studies of these neoplasms may assist in further unraveling the functional diversity of their normal counterparts.

PLZF Staining Identifies Peripheral T-Cell Lymphomas Derived From Non-Conventional T-Cells With Limited α-Chain Diversity

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4300-4300
Author(s):  
Stephanie McGregor ◽  
Anant Shah ◽  
Gordana Raca ◽  
Kamran Mirza ◽  
John Anastasi ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Nk Cells ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Peripheral T Cell Lymphoma ◽  
Innate T Cells ◽  
T Cell Lymphomas ◽  
Α Chain ◽  
Peripheral T Cell Lymphomas

Abstract Peripheral T-cell lymphomas are uncommon and account for 10-15% of all non-Hodgkin lymphomas (NHL). The current classification and treatment strategy of peripheral T-cell lymphomas relies on integrating morphology with immunophenotype, genetics and clinical presentation. However, the most common category of peripheral T-cell lymphomas remains peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) reflecting the lack of specific parameters to better define these lymphomas in a biologically relevant way. As our understanding of the biology of peripheral T-cell development continues to improve, several immunophenotypic markers have become available that can delineate peripheral T-cells into functional subsets. It is now recognized that peripheral T-cell lymphomas can arise from both conventional and innate-like T-cells. Classically, peripheral lymphomas with the γδ T-cell receptor (TCR) as well as lymphomas derived from true natural killer (NK) cells are considered to be arising from the innate T-cells whereas T-cell lymphomas with an αβ TCR are assumed to be derived from the adaptive, conventional T-cells. However, several recent studies have identified relatively rare populations of αβ T cells with extremely limited α chain diversity. These T-cells are characterized by the ability to mount immune responses by interacting with non-classical MHC class I antigen presenting molecules even in the absence of intentional priming. The cells within these populations express markers characteristic of NK cells and/or memory T-cells and include cells frequently labeled as “NKT” cells and mucosal-associated invariant T-cells (MAIT). Whether these cells contribute to peripheral T-cell lymphomas is not known. The transcription factor promyelocytic leukemia zinc finger (PLZF) is indispensable for development and maturation of these T-cells. We therefore asked the question whether PLZF expression could be used to identify peripheral T-cell lymphomas derived from these innate like non-conventional T-cells. To answer this question, we generated a tissue microarray that included biopsies from 26 PTCL-NOS, 11 anaplastic large cell lymphomas (ALCL), ALK-, and 13 ALCL, ALK+. Histologically normal tonsil, lymph node, thymus and gastrointestinal biopsies were used as controls. Immunohistochemistry with the PLZF antibody was performed in the clinical immunohistochemistry laboratory. Only rare PLZF positive cells were observed in uninvolved tonsils, lymph nodes, and thymus. In contrast, the intestinal mucosa, which is normally enriched in PLZF positive innate type T-cells showed a relative abundance with expression observed in 8-10% lymphocytes. Lymphomas were scored as positive when 20% or more of tumor cells showed expression with nuclear localization. Within the lymphomas, PLZF expression was observed in 2/26 PTCL-NOS and 2/13 ALCL, ALK+. PLZF expression was not observed in any of the ALCL, ALK- lymphomas included in the current study. PCR amplification followed by sequencing identified the Vα7.2-Jα33 TCR rearrangement characteristic of the MAIT cells in the two PLZF positive PTCL-NOS lymphomas confirming the origin of these lymphomas from bona fide innate-like T-cells. Sequencing of the TCR in the remaining three PLZF positive lymphomas is currently in progress. Cytogenetic analysis was available in three of the 4 cases. While t(2;5) was the sole cytogenetic abnormality in one ALCL, ALK+ lymphoma, the remaining two cases, including one ALCL, ALK+ had a complex karyotype that included t(2;5). In view of the relatively small number of patients available for analysis and the heterogeneous therapy administered to patients included retrospectively in the study, an outcome analysis was not performed. In conclusion, we demonstrate that PLZF expression identifies lymphomas derived from non-conventional innate-like T-cells and likely represent a biologically unique group of peripheral T-cell lymphoma. It is well known that innate T-cells are highly resistant to xenobiotics due to high expression of the transporter ATP binding cassette B1 (MDR). Prospective evaluation for PLZF expression may therefore be useful in identifying patients who will benefit from therapy that specifically targets this pathway of drug resistance. Disclosures: No relevant conflicts of interest to declare.

Pathobiology and Molecular Profiling of Peripheral T-Cell Lymphomas

Hematology ◽  
2008 ◽  
Vol 2008 (1) ◽  
pp. 272-279 ◽  
Author(s):  
Laurence de Leval ◽  
Philippe Gaulard
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Lymphoma ◽  
Clinical Manifestations ◽  
Large Cell ◽  
Molecular Profiling ◽  
Good Prognosis ◽  
Molecular Features ◽  
T Cell Lymphomas ◽  
Peripheral T Cell Lymphomas

Abstract Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of rare diseases, usually manifesting clinical aggressiveness. Although important novel insights into the pathobiology of nodal PTCL have been gained recently from molecular profiling studies and clinico-pathological analyses, the pathogenetic molecular lesions remain to be deciphered for most entities. Angioimmunoblastic T-cell lymphoma (AITL) comprises CD4+ CXCL13+ neoplastic cells displaying overlapping immunophenotypical and molecular features with normal follicular helper T cells. This derivation might account for the presence of a prominent non-neoplastic component in AITL tissues and the clinical manifestations of the disease reflective of an immunological dysfunction. ALK+ anaplastic large cell lymphoma (ALCL), defined by ALK gene translocation with various gene partners, is composed of CD30+ ALK+ cells with a cytotoxic phenotype and usually carries a good prognosis. ALK– ALCL, now considered as a distinct disease entity, is morphologically and immunophenotypically similar to ALK+ ALCL, except for ALK expression, but has distinctive molecular features. PTCL, not otherwise specified (PTCL, NOS), the largest PTCL category, which is derived from activated CD4+ (or CD8+) T cells, is markedly heterogeneous, including at the molecular level. Gene expression profiling approaches have identified novel biomarkers of potential therapeutic interest, and suggest the existence of molecularly distinct PTCL, NOS subgroups.

scholarly journals Natural killer-like T-cell lymphomas: aggressive lymphomas of T-large granular lymphocytes [see comments]

Blood ◽  
1996 ◽  
Vol 87 (4) ◽  
pp. 1474-1483 ◽  
Author(s):  
WR Macon ◽  
ME Williams ◽  
JP Greer ◽  
RD Hammer ◽  
AD Glick ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Natural Killer ◽  
Nk Cell ◽  
Cytotoxic T Cells ◽  
Cell Receptor ◽  
Lymphoproliferative Disease ◽  
Cell Subpopulation ◽  
T Cell Lymphomas ◽  
Lgl Leukemia

Natural killer (NK)-like T cells are major histocompatibility complex- unrestricted cytotoxic T cells that are surface CD3-positive, express NK-cell antigens, and rearrange their T-cell receptor. Most neoplasms arising from this T-cell subpopulation have been a chronic lymphoproliferative disease referred to as T-large granular lymphocyte (LGL) leukemia. Only 10 NK-like T-cell lymphomas have been described in detail previously; this study presents the clinicopathologic features of six others and distinguishes these lymphomas from T-LGL leukemia. All patients presented with B-symptoms and often had marked hepatosplenomegaly without significant peripheral lymphadenopathy. Four of the six patients were immunosuppressed. All had CD3, CD8, CD56- positive tumors, presumably of hepatosplenic (n = 3), intestinal (n = 1), pulmonary (n = 1), or nodal (n = 1) origin. Three patients had lymphomatous bone marrow infiltrates, and four had peripheral blood involvement by neoplastic large lymphocytes, some of which had a blastic appearance or resembled virocytes. Azurophilic granules, ultrastructurally corresponding to cytoplasmic dense core and/or double density granules, were seen in all cases. T-cell clonality was shown in five tumors by Southern blot analysis, and three had abnormal karyotypes. Two untreated patients died 20 days after presentation, and three patients who received combination chemotherapy died within 5 months of presentation. One patient remains in complete remission 22 months after treatment. These findings suggest NK-like T-cell lymphomas are aggressive, are clinicopathologically distinct from T-LGL leukemia, and should be in the differential diagnosis of extranodal T-cell lymphoproliferations, including those in immunosuppressed patients. Furthermore, the LGL morphology, phenotype, and tissue distribution of some NK-like T-cell lymphomas suggest they arise from thymic- independent T cells of the hepatic sinusoids and intestinal mucosa.

scholarly journals Pralatrexate in patients with recurrent or refractory peripheral T-cell lymphomas: a multicenter retrospective analysis

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Jung Yong Hong ◽  
Dok Hyun Yoon ◽  
Sang Eun Yoon ◽  
Seok Jin Kim ◽  
Ho Sup Lee ◽  
...  
Keyword(s):  
T Cell ◽  
Retrospective Analysis ◽  
Real World ◽  
Dose Intensity ◽  
Progression Free Survival ◽  
Complete Response ◽  
Efficacy And Safety ◽  
T Cell Lymphomas ◽  
Hodgkin's Lymphomas ◽  
Peripheral T Cell Lymphomas

AbstractPeripheral T-cell lymphomas (PTCL) are a heterogeneous group of non-Hodgkin’s lymphomas with poor clinical outcomes. Pralatrexate showed efficacy and safety in recurrent or refractory PTCLs. The purpose or this study was to investigate the efficacy and safety of pralatrexate in relapsed or refractory PTCLs in real-world practice. This was an observational, multicenter, retrospective analysis. Between December 2012 and December 2016, a total of 38 patients with relapsed or refractory PTCLs were treated with pralatrexate at 10 tertiary hospitals in Korea. Patients received an intravenous infusion of pralatrexate at a dose of 30 mg/m2/week for 6 weeks on a 7-week schedule. Modified dosing and/or scheduling was allowed according to institutional protocols. Median patient age was 58 years (range, 29–80 years) and the most common subtype was peripheral T-cell lymphoma, not otherwise specified (n = 23, 60.5%). The median dosage of pralatrexate per administration was 25.6 mg/m2/wk (range, 15.0–33.0 mg/m2/wk). In intention-to-treat analysis, 3 patients (7.9%) showed a complete response and 5 patients (13.2%) showed a partial response, resulting in an overall response rate (ORR) of 21.1%. The median duration of response was 7.6 months (range, 1.6–24.3 months). The median progression-free survival (PFS) was 1.8 months (95% confidence interval [CI], 1.7–1.8 months) and the median overall survival was 7.7 months (95% CI, 4.4–9.0 months). The most common grade 3/4 adverse events were thrombocytopenia (n = 13, 34.2%), neutropenia (n = 7, 23.7%), and anemia (n = 7, 18.4%). Our study showed relatively lower ORR and shorter PFS in patients with recurrent or refractory PTCLs treated with pralatrexate in real-world practice. The toxicity profile was acceptable and manageable. We also observed significantly lower dose intensity of pralatrexate in real-world practice.

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