The world health organization who classification of tumours of haematopoietic and lymphoid tissues stratifies neoplasms according to lineage and state of differentiation of the neoplastic cells. Ebv is also associated with diseases of t and nkcell origin, such as extranodal nk tcell lymphomanasal type enktl, aggressive nkcell leukemia ankl, and ebvt nklpds as already mentioned. Nivolumab in treating patients with relapsed or refractory. An approach to diagnosis of tacell lymphoproliferative disorders by. What are the treatment recommendations for primary. The first session focused on the clinical and pathological features of primary gastrointestinal t cell and nkcell lymphoproliferative disorders. Ebvpositive tcell and nkcell lymphoproliferative disorders of childhood 4 subtypes extranodal nktcell lymphoma, nasal type. Type, and posttransplant lymphoproliferative disorder tracy t. Overview of ebvassociated tnkcell lymphoproliferative.
Systemic t and nkcell lymphoma of childhood overlaps with chronic. In most reported cases, these cause b cell lymphoproliferative disorders. Indolent t and nkcell lymphoproliferative disorders of the. Chronic active ebv infection of t and nkcell type i. Ebvpositive t or natural killer nkcell lymphoproliferative disorders ebvtnklpds comprise chronic active ebv disease. T cell and nk cell lymphoproliferative disorders hematology. Anticcr4 monoclonal antibody mogamulizumab for the treatment. Theres considerable debate among scientists regarding this condition. There are reportedly ebvnegative cases, but data regarding clinical outcome of these cases is limited. Ko2 1department of pathology, ewha womans university school of medicine, and 2department of pathology, samsung medical center. Tcell and nkcell posttransplantation lymphoproliferative disorders. Review article epsteinbarr virusassociated t natural killer cell lymphoproliferative disorders sanghui park,1 young h. Mature t and nk cell lymphoproliferations mature t cell leukemias chronic lymphoproliferative disorders of nk cells published date.
The utility of flow cytometric immunophenotyping in the classification of mature t. Some types of primary immunodeficiencies are well known because their main feature is the development of ebvassociated disease. The cutaneous nasal type nktcell lymphomas occur more often in females, have a higher frequency of a tcell rather than a nkcell phenotype and less association with ebv. Following the screening of 57 clpd nk patients, only five. Tcell lymphoproliferative disorders are among the most challenging. The diagnosis and management of nktcell lymphomas journal. As for many other types of tcell and nkcell neoplasms. Subcutaneous, blastic natural killer nk, nktcell, and other cytotoxic lymphomas of the skin. B cells, t cells, nk cells, and histiocyticdendritic cells, are infected with the epsteinbarr virus ebv.
Primary gastrointestinal tcell and nkcell lymphoproliferative disorders enteropathyassociated t cell lymphoma eatl and precursor lesions type 2 refractory coeliac disease, rcd monomorphic epitheliotropic intestinal t cell lymphoma indolent t cell lymphoproliferative disorders of the gastrointestinal tract nk cell enteropathy. Expression of cytotoxic proteins in peripheral tcell and natural killer cell nk lymphomas. None of the 59 enrolled patients was reported to have an episode of hypersensitivity to mosquito bites. An unusual case report of indolent tcell lymphoproliferative. Epsteinbarr virus ebv infects not only b cells but also t cells and natural killer nk cells, and t and nkcell lymphoproliferative diseases tnklpd that are refractory to conventional chemotherapies may develop. Epsteinbarr virusassociated lymphoproliferative diseases.
Oct 11, 2012 the current world health organization who separates chronic proliferations of lgl according to their cell lineage into 2 entities. Although understanding of the heterogeneous landscape of natural killer nkcell malignancies remains limited, extranodal nk tcell lymphoma enktl stands out globally as a distinct disease entity. Ebvpositive tcell and nk cell lymphoproliferative diseases of childhood a. However, our understanding of ebvdriven t cell and nk cell proliferations has greatly expanded in recent years. Epsteinbarr viruspositive tnkcell lymphoproliferative. The distribution of progressionfree survival will be estimated using the method of kaplanmeier. Flow cytometry of t cell lymphoproliferative disorders.
Lymphoproliferative disorders lpds refer to several conditions in which lymphocytes are produced in excessive quantities. Primary gastrointestinal tcell and nk cell lymphoproliferative disorders enteropathyassociated t cell lymphoma eatl and precursor lesions type 2 refractory coeliac disease, rcd monomorphic epitheliotropic intestinal t cell lymphoma indolent t cell lymphoproliferative disorders of the gastrointestinal tract nk cell enteropathy. Currently only 2 lymphoma types, both cutaneous, mandate evaluation of tcr expression. The molecular pathogenesis of chronic lymphoproliferative disorder of natural killer nk cells clpd. They are sometimes equated with immunoproliferative disorders, but technically lymphoproliferative disorders are a subset of immunoproliferative disorders, along with hypergammaglobulinemia and. Gene mutations in lymphoproliferative disorders of t and nkt. Habermann, md overview primary central nervous system lymphoma, natural killer tcell lymphoma nasal type, and posttransplant lymphoproliferative disorder are uncommon and complex lymphoproliferative disorders. Mar 09, 2017 nivolumab in treating patients with relapsed or refractory peripheral t cell lymphoma the safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Extranodal natural killer nktcell lymphoma, nasal type nnktl has very. Massone c, chott a, metze d, kerl k, citarella l, vale e, et al. Lymphoproliferative disorders lpds are disorders in which there is uncontrolled production of excess lymphocytes due to several reasons. Extranodal nkt cell lymphoma and aggressive nk cell. The distinction between precursor lesions rcd type 2 and enteropathyassociated t cell lymphoma were stressed, including the discussion of new diagnostic markers for the identification of aberrant. The definition of the disease allows for a true nk or true t.
The 2016 revised world health organization classification recognizes the following ebvpositive lymphoproliferative disorders lpd. Ebvassociated t and nkcell lymphoproliferative diseases ebvtnk lpds are characterized by the transformation and proliferation of ebvinfected t or nk cells. Review article epstein barr virusassociated tnatural. Some patients also exhibit skinrelated symptoms, such as hvlike eruptions or hypersensitivity to mosquito bites. To identify a moleculartargeted therapy for ebvassociated tnklpds, we investigated whether cc chemokine receptor 4 ccr4 was expressed on ebvinfected t andor. The tcell lymphoproliferative disorders comprise a variety of entities that result from the clonal expansion of a mature tlymphocyte. Indolent t and nkcell lymphoproliferative disorders of. Ebvassociated tcell and natural killer cell lpds ebv is a ubiquitous herpes virus with tropism for b cells, but the infection of t cells and natural killer nk cells may lead to several ebvrelated lpds. Spectrum of t and nk lymphoproliferative disorders in. The t cell lymphoproliferative disorders comprise a variety of entities that result from the clonal expansion of a mature t lymphocyte. A high definition picture of somatic mutations in chronic. Ebv has been involved in the occurrence of a wide range of bcell lymphoproliferative disorders lpds, including burkitt lymphoma, classic hodgkins lymphoma, and immunedeficiency associated lpds posttransplant and human immunodeficiency virusassociated lpds. Abstractsystemic epsteinbarr virus ebvpositive tcell lymphoproliferative disorders lpds of childhood is a highly aggressive ebvpositive t natural killer nkcell lpd, which emerges in the background of chronic active ebv infection caebv or shortly after primary acute ebv infection.
Flow cytometry applications in the diagnosis of tnk. What are the treatment recommendations for primary cutaneous. Review article epstein barr virusassociated tnatural killer. Kinney gives a general overview of the diagnosis of ptcl and nk cell neoplasms. T cell and nk cell lymphoproliferative disorders request pdf. Significant geographic variation is noted with increased prevalence of select subtypes i. Mature t and nk cell lymphoproliferations mature tcell leukemias chronic lymphoproliferative disorders of nk cells published date.
Lgl is a chronic clonal lymphoproliferative disorder that can be phenotypically subdivided into tcell lgl and natural killer lgl. Cd16 is positive in approximately 75% of cases, but the immunophenotype is otherwise identical to that of extranodal nktcell lymphoma figure 2. The disease is associated with the ebv and most commonly seen in men with a median age in the mid40s. The t cell variations are usually caused by the prolonged use of t cell suppressant drugs, such as sirolimus, tacrolimus, or ciclosporin. Ebvpositive lymphoproliferations of b t and nkcell derivation.
They typically occur in people who have a compromised immune system. Chronic tcell lymphoproliferative disorders request pdf. The who classification considers lymphoproliferative disorders under three broad groupings of b cell neoplasms, tcell and nkcell neoplasms, and hodgkin lymphoma. Extranodal nk t cell lymphoma, nasal and nasal type is more prevalent in asia and south and central america. The first session focused on the clinical and pathological features of primary gastrointestinal t cell and nk cell lymphoproliferative disorders. Ebvpositive systemic tcell lymphoproliferative disease stlpd of childhood, and chronic active ebv caebv infection may develop after primary ebv infection. Biological functions of t and nk cells and ebv infection. Publications home of jama and the specialty journals of. Hematopoietic stem cell transplantation for adults with ebvpositive t or nk cell lymphoproliferative disorders. Epsteinbarr virusassociated t and nkcell lymphoproliferative.
Hematopoietic stem cell transplantation for adults with. Anticcr4 monoclonal antibody mogamulizumab for the. In addition, the progressionfree survival rate will be reported. Although the cell of origin is often a nk cell, particularly in patients in the far east. Hematopoietic stem cell transplantation for adults with ebv. T and nkcell lymphomas and systemic lymphoproliferative. And patient has primary cutaneous anaplastic large cell lymphoma alcl with. Batchelor, md, mph, lim soon thye, md, and thomas m. Listing a study does not mean it has been evaluated by the u. Indolent t cell lymphoproliferative disorder of the gastrointestinal tract or indolent t cell lymphoproliferative disorder of the gi tract itcldgt is a rare and recently recognized disorder in which mature t cell lymphocytes accumulation abnormally in the gastrointestinal tract gi tract. Tcell posttransplantation lymphoproliferative disorders after cardiac transplantation.
Gene mutations in lymphoproliferative disorders of t and. The tumour nk cells usually express brightly the cd56 adhesion molecule and cd94 lectin type killer receptor, and have an activationrelated cytoplasmic cd3. These cells play critical roles in the immune system and in the regulation of immune responses. Epsteinbarr virusassociated t and nkcell lymphoproliferative diseases. Immunodeficiency plays a key role in the pathogenesis of some lymphoproliferative disorders lpds.
Indolent t cell lymphoproliferative disorder of the. Eber can easily exclude nasal type aggressive extranodal nktcell lymphoma. Mature tcell and natural killer nkcell neoplasms represent a heterogeneous spectrum of postthymic tcell and nkcellderived malignancies. Tcell lymphoproliferative disorders that have been reported to be ebv associated include a subset of peripheral tcell lymphomas, angioimmunoblastic tcell lymphoma, extranodal nasal type natural killer tcell lymphoma, and other rare histotypes. Jan 04, 2019 ebv t nk lpds include chronic active ebv infection, ebvassociated hemophagocytic lymphohistiocytosis, hydroa vacciniformelike lymphoproliferative disease, and severe mosquito bite allergy. Posttransplant lymphoproliferative disorders fact sheet highlights y system. Overview of ebvassociated tnkcell lymphoproliferative diseases. Caebv is defined as an ebvrelated illness characterized by symptoms such as fever, persistent hepatitis, lymphadenopathy, hepatosplenomegaly, pancytopenia, uveitis, and interstitial pneumonia lasting for more than 3 months 3, 12. Apr 14, 2017 extranodal natural killer nktcell lymphoma is an aggressive malignancy of putative nkcell origin, with a minority deriving from the tcell lineage. Tcell and nkcell posttransplantation lymphoproliferative. Ebvpositive tnk lpd encompasses disease entities with a. Chronic lymphoproliferative disorders of nk cells clpdnk, provisional entity are characterized by a persistent 6 months increase in peripheral blood nk cells usually. It consists of the tissues and organs that a lymphoproliferative disorder is a disease in which cells of the lymphatic system grow uncontrollably. Posttransplant tcell lymphoproliferative disordersan aggressive, late complication of solidorgan transplantation.
Ebvpositive t cell and nk cell lymphoproliferative disorders of childhood 4 subtypes extranodal nk t cell lymphoma, nasal type. Extranodal natural killer nktcell lymphoma is an aggressive malignancy of putative nkcell origin, with a minority deriving from the tcell lineage. Nov 26, 2019 this paper summarizes two sessions of the workshop during the xix meeting of the european association for haematopathology eahp held in edinburgh in september 2018 dedicated to lymphomas of the gastrointestinal tract. Primary gastrointestinal tcell and nkcell lymphoproliferative disorders. Extranodal nk t cell lymphomanasal type and aggressive nk cell leukemia can also be included in this broad spectrum. Posttransplantation lymphoproliferative disorders ptlds of tcell or natural killer nk cell origin are an uncommon heterogeneous group of lymphoid proliferations that fulfill the criteria for one of the t or nkcell lymphomas leukemias. Extranodal nktcell lymphoma, nasal type and other types of peripheral tcell lymphomas may also occasionally occur in the gi tract 7,8. Mar 15, 2019 ebvassociated t and nk cell lymphoproliferative diseases ebv t nk lpds are characterized by the transformation and proliferation of ebvinfected t or nk cells. Jun 28, 2019 other iatrogenic immunodeficiencyassociated lymphoproliferative disorders oiialpds with a t or nk cell phenotype are markedly rare, with only a limited number of cases having been reported thus far.
Lymphoma occur most commonly 80% in the nose and upper aerodigestive tract, less commonly 20% in nonnasal. Cldnk, which has also been known as the nktype lymphoproliferative disorder of granular lymphocytes, is generally considered indolent. The pathogenesis of tcell and nkcell caebv is uncertain. Chronic lymphoproliferative disorder of natural killer cells or chronic nkcell lymphocytosis is a rare type of potentiallycancerous condition that is generally asymptomatic. Primary cutaneous nktcell lymphoma of nasal type pcnktl was reported. Posttransplantation lymphoproliferative disorder ptlpd is characterized by lymphoid proliferation after organ or bone marrow transplantation. Immunodeficiency is caused by aging, primary immune disorders, hiv infection, and immunosuppressive drugs. T and nkcell lymphoproliferative disorders annals of. Nk t proliferations are very rare and only a few cases have been described in children, most of them nktcell lymphoma or leukemia, but not nasaltype nk tcell lymphoma. Pcnktl affected face, neck, or limbs but not trunk, with a better outcome.
Frontiers epsteinbarr virusassociated t and nkcell. Background extranasal natural killer nktcell lymphoma and aggressive nkcell leukemia are strongly associated with epsteinbarr virus ebv and most often occur in middleaged individuals. Nkt proliferations are very rare and only a few cases have been described in children, most of them nktcell lymphoma or leukemia, but not nasaltype nktcell lymphoma. Intestinal t cell lymphomas 4 subtypes hepatosplenic t. Pathologically, the malignancy occurs in two forms, extranodal nktcell lymphoma, nasal type. Epsteinbarr virusassociated lymphoproliferative disorders. Refractory coeliac disease type 2 precursor of eatl clonal proliferation of aberrant iels. Indolent tcell proliferative disorder of the git is a rare and. However, the specific t or nk cell receptors that contribute to the disease state are not known. Chronic lymphoproliferative disorder of natural killer cells. In addition, pathologic findings for these 2 diagnoses are typically notable for necrosis, apoptosis, angioinvasion, and angiodestruction. Ebvpositive tnkcell lymphoproliferative disease of.
Aug, 2018 chronic lymphoproliferative disorder of natural killer cells is a rare type of cancer that is generally asymptomatic. Ebvpositive t cell and nk cell lymphoproliferative diseases of childhood c systemic ebvpositive t cell lymphoma of childhood c chronic active ebv infection of t and nk cell type, systemic form c hydroa vacciniformelike lymphoproliferative disorder c severe mosquito bite allergy extranodal nk t cell lymphoma, nasal type intestinal t cell. Ebvpositive tnk cells have been identified in the tonsils and peripheral blood from patients with infectious mononucleosis 17, and the virus has been shown to infect nk cells in vitro18. Emphasis will be placed on extranodal t cell and natural killer nk cell lymphomas such as hepatosplenic lymphoma, subcutaneous panniculitislike lymphoma and nasalnasal type tnkcell lymphoma. Epsteinbarr viruspositive tnkcell lymphoproliferative disorders. Tcell large granular lymphocytic leukemia tcell prolymphocytic leukemia sezary syndrome adult tcell leukemia chronic lymphoproliferative disorders of natural killer nk cells and aggressive nk cell leukemias are the focus of chapter 26 t22. Tcell lymphoproliferative disorders post thymic tdt ve as compared to prethymic disorders tall tdt positive. The most common types reported are peripheral tcell lymphoma, unspecified, and hepatosplenic tcell lymphoma. Chronic lymphoproliferative disorder of nk cells 1856. The immunophenotypic attributes of nk cells and nkcell. Intestinal tcell lymphomas 4 subtypes hepatosplenic t. Extranodal nktcell lymphoma, nasal type and other types of peripheral tcell lymphomas may.
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