Indolent T cell lymphoproliferative disorder of the gastrointestinal tract

Last updated
Indolent T cell lymphoproliferative disorder of the gastrointestinal tract
Other namesIndolent lymphoma
Specialty Hematology and Oncology
Symptoms Common GI tract symptoms
CausesGrowth of benign T cells
Risk factors May progress to a lymphoma
Differential diagnosis Mimics certain lymphomas
TreatmentNone except routine follow-ups to detect malignant progression
Prognosis Guarded

Indolent T cell lymphoproliferative disorder of the gastrointestinal tract or Indolent T cell lymphoproliferative disorder of the GI tract (ITCLD-GT) is a rare and recently recognized disorder in which mature T cell lymphocytes accumulation abnormally in the gastrointestinal tract (GI tract). [1] This accumulation causes various lesions (e.g. polyps, thickened mucosal folds, small areas of redness, and superficial ulcerations) in the mucosal layer lining the GI tract. Individuals with ITCLD-GT commonly complain of chronic GI tract symptoms such as nausea, vomiting, diarrhea, abdominal pain, and rectal bleeding. [2]

Contents

Carbonnell et al. [3] first described a case of an indolent GI tract lymphoproliferation disorder in 1994 and defined the lymphocytes involved in it to be T cells expressing the CD4 glycoprotein on their surface membranes. Subsequent studies reported on patients who had a similar indolent GI tract disorder that involved T cells which expressed either the CD4, CD8, or neither surface membrane glycoprotein. The disorder resembled certain aggressive GI tract lymphomas and was variably termed indolent lymphoma or indolent T cell lymphoproliferative disorder of the gastrointestinal tract. [4] However, the disease differed from the aggressive lymphomas which it mimicked in having a prolonged and usually non-progressive course. Furthermore, the disorder's lesions consisted of normal-appearing T cells that proliferated very slowly and usually caused little or no tissue destruction. [5] In 2017, the World Health Organization provisionally classified ITCLD-GT as an extranodal (i.e. usually not involving lymph nodes), indolent disorder in which various subtypes of T cells proliferate in the GI tract. [6]

While usually acting like a benign disease, ITCLD-GT has malignant features: 1) its normal-appearing T cells are clonal in nature, i.e. descended from a single cell; [6] 2) these T cells may contain genetic abnormalities [7] that are known to occur in and contribute to the development of very aggressive lymphomas; [8] and 3) ITCLD-GI, after many years of indolent behavior, may progress to an aggressive lymphoma. [2] Thus, ITCLD-GT can act as a premalignat disorder. Nonetheless, most cases of it run an indolent, non-malignant course and when mistakenly treated as an aggressive lymphoma, do not responded to standard chemotherapy treatments. [5] The disorder has also been mistaken for, and found unresponsive to therapies that treat inflammatory or autoimmune bowel diseases. [1] [4] Clinically, ITCLD-GT must be distinguished from the malignant, inflammatory, and autoimmune bowel diseases that it mimics in order to avoid useless and potentially harmful therapies. [5]

Presentation

ITCLD-GT occurs more commonly in males of middle age (median age 48.4, range 15–77 years in one study). [2] Individuals with the disease present with GI tract symptoms which often are serious and/or debilitating [9] and may mimic those occurring in malignant lymphoproliferative, inflammatory, or autoimmune bowel diseases. [4] These symptoms include chronic epigastric pain, abdominal pain, heartburn, nausea, diarrhea, vomiting, weight loss, relapsing oral ulcers, relapsing colorectal ulcers, rectal bleeding, and/or night sweats. [4] Several patients presenting with these symptoms have been diagnosed with and unsuccessfully treated for peripheral T-cell lymphoma, [5] an inflammatory bowel disease (either Crohn disease or ulcerative colitis), [1] or the autoimmune GI tract disorder, celiac disease. [10] It has been shown or appears very likely that these patients had ITCLD-GT rather than the cited diagnoses. [1] [5] [10]

Natural course

Most patients with ITCLD-GT have chronic, relapsing and recurring GI tract symptoms that persist over many years. In one retrospective study, 19 of 23 patients with CD4+ ITCLD-GT had persistent disease over a follow-up period of 1–14 years (median 4.8 years), 2 of 23 patients had clinical and morphologic (i.e. negative GI tract evaluations) remissions enduring for at least 5–7 years, and 1 of 23 patients developed and died from a large-cell lymphoma of undetermined type. In the same study, 10 of 10 patients with CD8+ ITCLD-GT had persistent disease that had not progressed to a malignancy over an observation period of 1–18 years (median 2 years) although one patient had developed bone marrow involvement and therefore may have had disease which was in the process of transforming to a malignant state. [4] Other reports have found that the disorder in one patient with CD4-, CD8- ITCLD-GT disease progressed to involve the liver [5] and the disorder in two patients with CD4+ ITCLD-GT disease progressed to an undetermined type of large T-cell lymphoma. [9] In another retrospective analysis, 6 of 34 (17.6%) patients with ITCLD-GT progressed to a malignant state as evidenced by its spread to the blood or bone marrow: 2 (5.6%) patients died as a direct result of this spreading. [2]

Pathophysiology

The lesions in ITCLD-GT consists of slowly growing, mature, and benign-appearing T cells. The reasons for their accumulations in the GI tract are unclear. However, these cells often carry potentially oncogenic mutations. In a recent study, the T cells in 4 of 5 patients with CD4+ T-cell disease carried a STAT3-JAK2 fusion gene. [6] This gene consists of a fusion between the STAT3 gene at position 2.2 on the long (or "g") arm of chromosome 17 (location abbreviated 17q21.2) and the JAK2 gene at position 24.1 on the short ("q") of chromosome 9 (9p24.1). The disorder in two of the patients with this t(9;17)(p24.1;q21/2) fusion gene progressed to malignant lymphomas. [9] Abnormalities in the expression and/or activity of STAT3 and JAK2 [11] as well as various JAK2 fusion genes [9] are associated with the development and progression of various myeloproliferative and lymphoproliferative malignancies. These findings suggest that the STAT3-JAK2-fusion gene may contribute to the malignant progression and perhaps development of CD4+ ITCLD-GT. [9] Numerous other genetic abnormalities occur in the T-cells of ITCLD-GT but unlike the STAT3-JAK fusion gene have been limited to single cases. These abnormalities include trisomy of chromosome 5, a t(4;16)(q26;p13) fusion between interleukin-2 and B-cell maturation antigen genes, loses in the 4p26 and 16p13 chromosomal areas involved in formation of the t(4;16)9q26;p13) fusion gene, and one or more copy number variations in diverse areas of different chromosomes. [4] The role(s), if any, of these abnormalities in ITCLD-GT is unclear.[ citation needed ]

T cells In ITCLD-GT

The cells involved in all cases of ITCLD-GT are mature T cells [1] that exhibit a clonal rearrangement of their T-cell receptors and, therefore, are derived from a common ancestry cell. [4] They express the αβ as opposed to the γδ surface membrane T-cell receptor and therefore are αβ rather than γδ T-cells. In all reported cases, these T cells express the CD3 cluster of differentiation protein complex but vary in their expression of the CD4 cluster of differentiation glycoprotein as well as the CD8 glycoprotein component of the T cell receptor. Individuals with ITCLD-GT, therefore, have pathological accumulations of either CD4+, CD8+, or, very rarely, CD4-, CD8- T cells. [4] A single case of CD4+, CD8+ T cell disease has been reported recently. [9] There may be differences in the presentation, course, and malignant potential of ITCLD-GT based or these different expressions of CD4 and CD8 but this requires further study. Unlike certain types of T cell lymphomas for which it has been mistaken, the T cells in ITCLD-GT do not express the neutral cell adhesion molecule, CD56, and are not infected with the Epstein–Barr virus and therefore do not express this virus's latency proteins or latency ncRNAs. [1] The origin of these cells is unknown but it is thought that the CD4+ and CD8+ T-cells derive from mucosal T helper and cytotoxic T lymphocytes, respectively. The CD4-, CD8- T cells that may cause rare cases of the disorder exhibit cytology and morphology features of both of the latter two mucosal cell types. [4]

Histology

Histological analysis of tissues biopsied from the GI tract generally reveals dense infiltrates of small, mature lymphocytes in the mucosa that may displace [2] but usually do not invade [4] the epithelium; these cells sometimes extend through the muscularis mucosa to invade the submucosa. [4] The lesions may contain reactive plasma cells, eosinophils, granulomas (in CD4+ disease), and lymphoid follicles. [2] There is little or no tissue destruction. [1] Immunohistochemistry analyses indicate that the small lymphocytes are CD4+, [9] CD8+, [9] CD4-/CD8-, [4] or CD4+/CD8+ T-cells [9] that stain for CD3 [4] but not CD56 or Epstein-Barr virus products. [1] Notably, the affected T cells have an extremely low rate of proliferation as determined by examining their KI-67 protein using immunofluorescence analysis. [4]

Diagnosis

The diagnosis of indolent T cell lymphoproliferative disorder of the GI tract depends on identifying the presentation, clinical course, and laboratory and histological findings given in the previous four sections. [4] (Future studies may find that the diagnosis is supported by demonstrating the presence of the STAT3-JAK2 fusion gene in the CD4+ T cells of suspicious tissues. [6] )

Laboratory studies

Inspection of the entire GI tract by endoscopy and colonoscopy generally finds mucosal redness, erosions, small superficial ulcerations, occasional small polyps, [2] fissures, diverticula, and, rarely, tumor-like masses and deep ulcers. [4] These lesions may be localized, occur in multiple sites, or extend throughout the GI tract; [4] they are more common in the small intestine and colon [2] but can also occur in the stomach, esophagus, oral cavity (e.g. palate), and rectum. [4] Whole body computed tomography scans (i.e. CT scans) frequently find enlarged mesenteric lymph nodes (i.e. lymph nodes attached to the intestinal mesentery) and may show evidence of liver, spleen, and/or other organ involvement in cases which are advancing or have advanced to a malignant lymphoma. Positron emission tomography scans (i.e. PET scans) and positron emission tomography–computed tomography scans (i.e. PET-CT scans) likewise often show that the mesenteric lymph nodes in ITCLD-GT exhibit modestly increased metabolic or biochemical activity and, in cases of progressing or overt malignant disease, show increased activity in other organs. [4] Inspection of patients' peripheral blood smearss and bone marrow tissues may identify excessive numbers of ITCLD-GT's T cells and thereby likewise indicate progressing or malignant disease. [2]

Differential diagnosis

Because of the radical differences in their prognoses and treatments, ITCLD-GT should be distinguished from the malignant, inflammatory, autoimmune, and other diseases that it can mimic.[ citation needed ] Key findings that distinguish ITCLD-GT from the following major diseases which ITCLD-GT may mimic are:

Treatment

Studies indicate that patients with ITCLD-GT should be treated conservatively. Chemotherapy regimens directed at malignant lymphoma and treatment regimens used to treat celiac disease, Crohn's disease, or ulcerative colitis have had little or no beneficial effects on the course of the disease. [4] Patients should be follow regularly with peripheral blood and bone marrow examinations, GI tract endoscopic examinations [4] and PET scans [2] in order to detect the progression of ITCLD-GT to a malignant phase.

Prognosis

Studies to date[ when? ] indicate that most patients experience a prolonged course of persistent or recovering-relapsing GI tract symptoms. A small percentage of patients have had spontaneous and sustained recoveries or progressed to a malignant lymphoma. [4]

Related Research Articles

<span class="mw-page-title-main">Lymphoma</span> Hematologic cancer that affects lymphocytes

Lymphoma is a group of blood and lymph tumors that develop from lymphocytes. The name typically refers to just the cancerous versions rather than all such tumours. Signs and symptoms may include enlarged lymph nodes, fever, drenching sweats, unintended weight loss, itching, and constantly feeling tired. The enlarged lymph nodes are usually painless. The sweats are most common at night.

<span class="mw-page-title-main">Eosinophilia</span> Blood condition

Eosinophilia is a condition in which the eosinophil count in the peripheral blood exceeds 5×108/L (500/μL). Hypereosinophilia is an elevation in an individual's circulating blood eosinophil count above 1.5 × 109/L (i.e. 1,500/μL). The hypereosinophilic syndrome is a sustained elevation in this count above 1.5 × 109/L (i.e. 1,500/μL) that is also associated with evidence of eosinophil-based tissue injury.

Post-transplant lymphoproliferative disorder (PTLD) is the name given to a B cell proliferation due to therapeutic immunosuppression after organ transplantation. These patients may develop infectious mononucleosis-like lesions or polyclonal polymorphic B-cell hyperplasia. Some of these B cells may undergo mutations which will render them malignant, giving rise to a lymphoma.

<span class="mw-page-title-main">Tumors of the hematopoietic and lymphoid tissues</span> Medical condition

Tumors of the hematopoietic and lymphoid tissues or tumours of the haematopoietic and lymphoid tissues are tumors that affect the blood, bone marrow, lymph, and lymphatic system. Because these tissues are all intimately connected through both the circulatory system and the immune system, a disease affecting one will often affect the others as well, making aplasia, myeloproliferation and lymphoproliferation closely related and often overlapping problems. While uncommon in solid tumors, chromosomal translocations are a common cause of these diseases. This commonly leads to a different approach in diagnosis and treatment of hematological malignancies. Hematological malignancies are malignant neoplasms ("cancer"), and they are generally treated by specialists in hematology and/or oncology. In some centers "hematology/oncology" is a single subspecialty of internal medicine while in others they are considered separate divisions. Not all hematological disorders are malignant ("cancerous"); these other blood conditions may also be managed by a hematologist.

<span class="mw-page-title-main">Follicular lymphoma</span> Medical condition

Follicular lymphoma (FL) is a cancer that involves certain types of white blood cells known as lymphocytes. The cancer originates from the uncontrolled division of specific types of B-cells known as centrocytes and centroblasts. These cells normally occupy the follicles (nodular swirls of various types of lymphocytes) in the germinal centers of lymphoid tissues such as lymph nodes. The cancerous cells in FL typically form follicular or follicle-like structures (see adjacent Figure) in the tissues they invade. These structures are usually the dominant histological feature of this cancer.

Lymphoproliferative disorders (LPDs) refer to a specific class of diagnoses, comprising a group of several conditions, in which lymphocytes are produced in excessive quantities. These disorders primarily present in patients who have a compromised immune system. Due to this factor, there are instances of these conditions being equated with "immunoproliferative disorders"; although, in terms of nomenclature, lymphoproliferative disorders are a subclass of immunoproliferative disorders—along with hypergammaglobulinemia and paraproteinemias.

<span class="mw-page-title-main">Intravascular lymphomas</span> Medical condition

Intravascular lymphomas (IVL) are rare cancers in which malignant lymphocytes proliferate and accumulate within blood vessels. Almost all other tyes of lymphoma involve the proliferation and accumulation of malignant lymphocytes in lymph nodes, other parts of the lymphatic system, and various non-lymphatic organs but not in blood vessels.

X-linked lymphoproliferative disease is a lymphoproliferative disorder, usually caused by SH2DIA gene mutations in males. XLP-positive individuals experience immune system deficiencies that render them unable to effectively respond to the Epstein-Barr virus (EBV), a common virus in humans that typically induces mild symptoms or infectious mononucleosis (IM) in patients. There are two currently known variations of the disorder, known as XLP1 and XLP2. XLP1 is estimated to occur in approximately one in every million males, while XLP2 is rarer, estimated to occur in one of every five million males. Due to therapies such as chemotherapy and stem cell transplants, the survival rate of XLP1 has increased dramatically since its discovery in the 1970s.

<span class="mw-page-title-main">Enteropathy-associated T-cell lymphoma</span> Complication of coeliac disease

Enteropathy-associated T-cell lymphoma (EATL), previously termed enteropathy-associated T-cell lymphoma, type I and at one time termed enteropathy-type T-cell lymphoma (ETTL), is a complication of coeliac disease in which a malignant T-cell lymphoma develops in areas of the small intestine affected by the disease's intense inflammation. While a relatively rare disease, it is the most common type of primary gastrointestinal T-cell lymphoma.

<span class="mw-page-title-main">Marginal zone B-cell lymphoma</span> Group of lymphomas

Marginal zone B-cell lymphomas, also known as marginal zone lymphomas (MZLs), are a heterogeneous group of lymphomas that derive from the malignant transformation of marginal zone B-cells. Marginal zone B cells are innate lymphoid cells that normally function by rapidly mounting IgM antibody immune responses to antigens such as those presented by infectious agents and damaged tissues. They are lymphocytes of the B-cell line that originate and mature in secondary lymphoid follicles and then move to the marginal zones of mucosa-associated lymphoid tissue, the spleen, or lymph nodes. Mucosa-associated lymphoid tissue is a diffuse system of small concentrations of lymphoid tissue found in various submucosal membrane sites of the body such as the gastrointestinal tract, mouth, nasal cavity, pharynx, thyroid gland, breast, lung, salivary glands, eye, skin and the human spleen.

Monoclonal B-cell lymphocytosis (MBL) is an asymptomatic condition in which individuals have increased blood levels of particular subtypes of monoclonal lymphocytes. This increase must persist for at least 3 months. The lymphocyte subtypes are B-cells that share certain features with the abnormal clones of lymphocytes that circulate in chronic lymphocytic leukemia/small lymphocyte lymphoma (CLL/SLL) or, less frequently, other types of B-cell malignancies. Some individuals with these circulating B-cells develop CLL/SLL or the lymphoma types indicated by their circulating monoclonal B-cells. Hence, MBL is a premalignant disorder

<span class="mw-page-title-main">Extranodal NK/T-cell lymphoma, nasal type</span> Medical condition

Extranodal NK/T-cell lymphoma, nasal type (ENKTCL-NT) is a rare type of lymphoma that commonly involves midline areas of the nasal cavity, oral cavity, and/or pharynx At these sites, the disease often takes the form of massive, necrotic, and extremely disfiguring lesions. However, ENKTCL-NT can also involve the eye, larynx, lung, gastrointestinal tract, skin, and various other tissues. ENKTCL-NT mainly affects adults; it is relatively common in Asia and to lesser extents Mexico, Central America, and South America but is rare in Europe and North America. In Korea, ENKTCL-NT often involves the skin and is reported to be the most common form of cutaneous lymphoma after mycosis fungoides.

Lethal midline granuloma (LMG) is an historical term for a condition in which necrotic and highly destructive lesions develop progressively in the middle of the face, principally the nose and palate. Many cases presented with ulcerations in or perforations of the palate.

Lymphocyte-variant hypereosinophilia is a rare disorder in which eosinophilia or hypereosinophilia is caused by an aberrant population of lymphocytes. These aberrant lymphocytes function abnormally by stimulating the proliferation and maturation of bone marrow eosinophil-precursor cells termed colony forming unit-Eosinophils or CFU-Eos.

Epstein–Barr virus–associated lymphoproliferative diseases are a group of disorders in which one or more types of lymphoid cells, i.e. B cells, T cells, NK cells, and histiocytic-dendritic cells, are infected with the Epstein–Barr virus (EBV). This causes the infected cells to divide excessively, and is associated with the development of various non-cancerous, pre-cancerous, and cancerous lymphoproliferative disorders (LPDs). These LPDs include the well-known disorder occurring during the initial infection with the EBV, infectious mononucleosis, and the large number of subsequent disorders that may occur thereafter. The virus is usually involved in the development and/or progression of these LPDs although in some cases it may be an "innocent" bystander, i.e. present in, but not contributing to, the disease.

Natural killer cell enteropathy, also termed NK cell enteropathy (NKCE), and a closely related disorder, lymphomatoid gastropathy (LG), are non-malignant diseases in which one type of lymphocyte, the natural killer cell, proliferates excessively in the gastrointestinal tract. This proliferation causes red, sore-like spots, raised lesions, erosions, and ulcers in the mucosal layer surrounding the GI tract lumen. Both disorders cause either no or only vague symptoms of GI tract disturbances such as nausea, vomiting, and bleeding.

Monomorphic epitheliotropic intestinal T cell lymphoma (MEITL) is an extremely rare peripheral T-cell lymphoma that involves the malignant proliferation of a type of lymphocyte, the T cell, in the gastrointestinal tract. Over time, these T cells commonly spread throughout the mucosal lining of a portion of the GI tract, lead to GI tract nodules and ulcerations, and cause symptoms such as abdominal pain, weight loss, diarrhea, obstruction, bleeding, and/or perforation.

Duodenal-type follicular lymphoma (DFL) is a form of lymphoma in which certain lymphocyte types, the B-cell-derived centrocytes and centroblasts, form lymph node follicle-like structures principally in the duodenum and other parts of the small intestine. It is an indolent disease which on rare occasions progresses to a more aggressive lymphoma that spreads beyond these originally involved sites.

Primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT) is a cutaneous lymphoma skin disease that occurs mostly in elderly females. In this disease, B cells become malignant, accumulate in the dermis and subcutaneous tissue below the dermis to form red and violaceous skin nodules and tumors. These lesions typically occur on the lower extremities but in uncommon cases may develop on the skin at virtually any other site. In ~10% of cases, the disease presents with one or more skin lesions none of which are on the lower extremities; the disease in these cases is sometimes regarded as a variant of PCDLBL, LT termed primary cutaneous diffuse large B-cell lymphoma, other (PCDLBC-O). PCDLBCL, LT is a subtype of the diffuse large B-cell lymphomas (DLBCL) and has been thought of as a cutaneous counterpart to them. Like most variants and subtypes of the DLBCL, PCDLBCL, LT is an aggressive malignancy. It has a 5-year overall survival rate of 40–55%, although the PCDLBCL-O variant has a better prognosis than cases in which the legs are involved.

Fibrin-associated diffuse large B-cell lymphoma (FA-DLBCL) is an extremely rare form of the diffuse large B-cell lymphomas (DLBCL). DLBCL are lymphomas in which a particular type of lymphocyte, the B-cell, proliferates excessively, invades multiple tissues, and often causes life-threatening tissue damage. DLBCL have various forms as exemplified by one of its subtypes, diffuse large B-cell lymphoma associated with chronic inflammation (DLBCL-CI). DLBCL-CI is an aggressive malignancy that develops in sites of chronic inflammation that are walled off from the immune system. In this protected environment, the B-cells proliferate excessively, acquire malignant gene changes, form tumor masses, and often spread outside of the protected environment. In 2016, the World Health Organization provisionally classified FA-DLBCL as a DLBCL-CI. Similar to DLBCL-CI, FA-DLBCL involves the proliferation of EBV-infected large B-cells in restricted anatomical spaces that afford protection from an individual's immune system. However, FA-DLBCL differs from DLBCL-CI in many other ways, including, most importantly, its comparatively benign nature. Some researchers have suggested that this disease should be regarded as a non-malignant or pre-malignant lymphoproliferative disorder rather than a malignant DLBCL-CI.

References

  1. 1 2 3 4 5 6 7 8 Weindorf SC, Smith LB, Owens SR (November 2018). "Update on Gastrointestinal Lymphomas". Archives of Pathology & Laboratory Medicine. 142 (11): 1347–1351. doi: 10.5858/arpa.2018-0275-RA . PMID   30407861.
  2. 1 2 3 4 5 6 7 8 9 10 Foukas PG, de Leval L (January 2015). "Recent advances in intestinal lymphomas". Histopathology. 66 (1): 112–36. doi:10.1111/his.12596. PMID   25639480. S2CID   20669863.
  3. ↑ Carbonnel F, Lavergne A, Messing B, Tsapis A, Berger R, Galian A, Nemeth J, Brouet JC, Rambaud JC (February 1994). "Extensive small intestinal T-cell lymphoma of low-grade malignancy associated with a new chromosomal translocation". Cancer. 73 (4): 1286–91. doi: 10.1002/1097-0142(19940215)73:4<1286::AID-CNCR2820730425>3.0.CO;2-9 . PMID   8313332. S2CID   23237998.
  4. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 Matnani R, Ganapathi KA, Lewis SK, Green PH, Alobeid B, Bhagat G (March 2017). "Indolent T- and NK-cell lymphoproliferative disorders of the gastrointestinal tract: a review and update". Hematological Oncology. 35 (1): 3–16. doi: 10.1002/hon.2317 . PMID   27353398. S2CID   21364706.
  5. 1 2 3 4 5 6 Ganapathi KA, Pittaluga S, Odejide OO, Freedman AS, Jaffe ES (September 2014). "Early lymphoid lesions: conceptual, diagnostic and clinical challenges". Haematologica. 99 (9): 1421–32. doi:10.3324/haematol.2014.107938. PMC   4562530 . PMID   25176983.
  6. 1 2 3 4 Lemonnier F, Gaulard P, de Leval L (September 2018). "New insights in the pathogenesis of T-cell lymphomas" (PDF). Current Opinion in Oncology. 30 (5): 277–284. doi:10.1097/CCO.0000000000000474. PMID   30028743. S2CID   51704108.
  7. ↑ Matutes E (May 2018). "The 2017 WHO update on mature T- and natural killer (NK) cell neoplasms". International Journal of Laboratory Hematology. 40 Suppl 1: 97–103. doi: 10.1111/ijlh.12817 . PMID   29741263.
  8. ↑ Taylor J, Xiao W, Abdel-Wahab O (July 2017). "Diagnosis and classification of hematologic malignancies on the basis of genetics". Blood. 130 (4): 410–423. doi:10.1182/blood-2017-02-734541. PMC   5533199 . PMID   28600336.
  9. 1 2 3 4 5 6 7 8 9 Sharma A, Oishi N, Boddicker RL, Hu G, Benson HK, Ketterling RP, Greipp PT, Knutson DL, Kloft-Nelson SM, He R, Eckloff BW, Jen J, Nair AA, Davila JI, Dasari S, Lazaridis KN, Bennani NN, Wu TT, Nowakowski GS, Murray JA, Feldman AL (May 2018). "Recurrent STAT3-JAK2 fusions in indolent T-cell lymphoproliferative disorder of the gastrointestinal tract". Blood. 131 (20): 2262–2266. doi:10.1182/blood-2018-01-830968. PMC   5958657 . PMID   29592893.
  10. 1 2 Margolskee E, Jobanputra V, Lewis SK, Alobeid B, Green PH, Bhagat G (2013). "Indolent small intestinal CD4+ T-cell lymphoma is a distinct entity with unique biologic and clinical features". PLOS ONE. 8 (7): e68343. Bibcode:2013PLoSO...868343M. doi: 10.1371/journal.pone.0068343 . PMC   3701677 . PMID   23861889.
  11. ↑ Cahu X, Constantinescu SN (December 2015). "Oncogenic Drivers in Myeloproliferative Neoplasms: From JAK2 to Calreticulin Mutations". Current Hematologic Malignancy Reports. 10 (4): 335–43. doi:10.1007/s11899-015-0278-x. hdl: 2078.1/166223 . PMID   26370832. S2CID   28079297.
  12. ↑ Tse E, Kwong YL (April 2017). "The diagnosis and management of NK/T-cell lymphomas". Journal of Hematology & Oncology. 10 (1): 85. doi:10.1186/s13045-017-0452-9. PMC   5391564 . PMID   28410601.
  13. ↑ Ondrejka S, Jagadeesh D (December 2016). "Enteropathy-Associated T-Cell Lymphoma". Current Hematologic Malignancy Reports. 11 (6): 504–513. doi:10.1007/s11899-016-0357-7. PMID   27900603. S2CID   13329863.
  14. ↑ Khan N, Ozkaya N, Moskowitz A, Dogan A, Horwitz S (September 2018). "Peripheral T-cell lymphoma - are we making progress?". Best Practice & Research. Clinical Haematology. 31 (3): 306–314. doi:10.1016/j.beha.2018.07.010. PMC   8941989 . PMID   30213401. S2CID   52273670.
  15. ↑ Sandell RF, Boddicker RL, Feldman AL (April 2017). "Genetic Landscape and Classification of Peripheral T Cell Lymphomas". Current Oncology Reports. 19 (4): 28. doi:10.1007/s11912-017-0582-9. PMC   5517131 . PMID   28303495.
  16. ↑ Rezk SA, Zhao X, Weiss LM (June 2018). "Epstein—Barr virus—associated lymphoid proliferations, a 2018 update". Human Pathology. 79: 18–41. doi:10.1016/j.humpath.2018.05.020. PMID   29885408. S2CID   47010934.
  17. ↑ Xia D, Morgan EA, Berger D, Pinkus GS, Ferry JA, Zukerberg LR (January 2019). "NK-Cell Enteropathy and Similar Indolent Lymphoproliferative Disorders: A Case Series With Literature Review". American Journal of Clinical Pathology. 151 (1): 75–85. doi: 10.1093/ajcp/aqy108 . PMID   30212873. S2CID   52272766.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.