Indolent T cell lymphoproliferative disorder of the gastrointestinal tract

Add links
Source: Wikipedia, the free encyclopedia.
Indolent T cell lymphoproliferative disorder of the gastrointestinal tract
Other namesIndolent lymphoma
progress to a lymphoma
Differential diagnosisMimics certain lymphomas
TreatmentNone except routine follow-ups to detect malignant progression
PrognosisGuarded

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

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]

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

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).

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

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

cytology and morphology features of both of the latter two mucosal cell types.[4]

Histology

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

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:

  • NK rather than T cells; d) commonly causes tissue-destructive lesions that are spread through multiple layers of the GI tract; and e) has lesions consisting of rapidly proliferating lymphocytes which express Epstein-Barr virus products, CD56, and one or more of various specific genetic abnormalities (see Genetic abnormalities in ENKTCL-NT).[12]
  • Monomorphic epithelieotropic intestinal lymphoma (MEITL) (formerly termed Type II enteropathy-associate T-cell lymphoma): Unlike ITCLD-GT, MEITL a) is a highly aggressive lymphoma of the GI tract that usually takes a short, lethal course; b) has lesions in which rapidly proliferating T cells accumulate in the mucosa and epithelium of the GI tract; and c) involves T cells that are CD4-, CD56-, and MAKT+, often express the γδ rather than the αβ T cell receptor,[13] and in rare cases are infected with, and express products made by, the Epstein-Barr virus.[14]
  • genetic abnormalities in PTCL, NOS), and in ~30% of cases are infected with, and express products made by, the Epstein-Barr virus.[16]
  • celiac disease serology blood tests such as anti-transglutaminase antibodies; c) has infiltrating clonal T cells which do not express HLA-DQ2 or HLA-DQ8 human leukocyte antigens; and d) have lesions populated by mature, slowly proliferating clonal T cells which are CD56- and either CD4+, CD8+, CD4+/CD8+, or CD4-/CD8-. However, rare patients have been inflicted with both celiac disease and ITCLD-GT.[4]
  • Crohn's disease: Crohn's disease has been diagnosed in cases which were later diagnosed as ITCLD-GT perhaps because some patients with ITCLD-GT have histopathologic features (particularly the presence of granulomas)) that are characteristic of Crohn's disease. Awareness of ITCLD-GT and the histologic, clinical, and endoscopic differences between it and Crohn's disease should point to the proper diagnosis.[4]
  • Ulcerative colitis: Rare wcases of ITCLD-GT appear to have been diagnosed as ulcerative colitis. Awareness of ITCLD-GT and the histologic, clinical, and endoscopic differences between it and ulcerative colitis should point to the proper diagnosis.[4]
  • NK cell rather than T cell lymphocytes; b) does now show evidence of mesenteric lymph node or other organ involvement; and c) does not progress to a malignant disease.[17]

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]

References

  1. ^
    PMID 30407861
    .
  2. ^
    S2CID 20669863
    .
  3. S2CID 23237998
    .
  4. ^
    S2CID 21364706
    .
  5. ^
    PMID 25176983
    .
  6. ^
    S2CID 51704108
    .
  7. PMID 29741263
    .
  8. PMID 28600336
    .
  9. ^
    PMID 29592893
    .
  10. ^
    PMID 23861889
    .
  11. S2CID 28079297
    .
  12. PMID 28410601
    .
  13. S2CID 13329863
    .
  14. S2CID 52273670
    .
  15. PMID 28303495
    .
  16. S2CID 47010934
    .
  17. S2CID 52272766
    .
Retrieved from "https://en.wikipedia.org/w/index.php?title=Indolent_T_cell_lymphoproliferative_disorder_of_the_gastrointestinal_tract&oldid=1188075552"