Angioimmunoblastic T-cell lymphoma
{{For|avian infectious laryngotracheitis|Gallid alphaherpesvirus 1}}
{{Infobox medical condition (new)
| name = Angioimmunoblastic T-cell lymphoma
| synonyms = immunoblastic lymphadenopathy (Lukes-Collins Classification), AILD-type (lymphogranulomatosis X) T-cell lymphoma (Kiel Classification){{cite book |last1=Swerdlow |first1=S.H. |last2=Campo |first2=E. |last3=Harris |first3=N.L. |last4=Jaffe |first4=E.S. |last5=Pileri |first5=S.A. |last6=Stein |first6=H. |last7=Thiele |first7=J. |last8=Vardiman |first8=J.W |chapter=11 Mature T- and NK-cell neoplasms: Angioimmunoblastic T-cell lymphoma |title=WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues |edition=4th |series=IARC WHO Classification of Tumours |volume=2 |publisher=IARC |year=2008 |isbn=978-9283224310 |chapter-url=http://apps.who.int/bookorders/anglais/detart1.jsp?codlan=1&codcol=70&codcch=4002&content=1}}
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| field = Hematology and oncology
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Angioimmunoblastic T-cell lymphoma (AITL, sometimes misspelled AILT, formerly known as "angioimmunoblastic lymphadenopathy with dysproteinemia"{{cite book |last1=James |first1=William D. |last2=Berger |first2=Timothy G. |title=Andrews' Diseases of the Skin: Clinical Dermatology |publisher=Saunders Elsevier |year=2006 |isbn=0-7216-2921-0 |display-authors=etal}}{{rp|747}}) is a mature T-cell lymphoma of blood or lymph vessel immunoblasts characterized by a polymorphous lymph node infiltrate showing a marked increase in follicular dendritic cells (FDCs) and high endothelial venules (HEVs) and systemic involvement.
Signs and symptoms
Patients with AITL usually present at an advanced stage and show systemic involvement. The clinical findings typically include a pruritic skin rash and possibly edema, ascites, pleural effusions, and arthritis.{{cite journal |vauthors=Siegert W, Nerl C, Agthe A |title=Angioimmunoblastic lymphadenopathy (AILD)-type T-cell lymphoma: prognostic impact of clinical observations and laboratory findings at presentation. The Kiel Lymphoma Study Group |journal=Ann. Oncol. |volume=6 |issue=7 |pages=659–64 |date = September 1995|pmid=8664186 |display-authors=etal|doi=10.1093/oxfordjournals.annonc.a059281 |doi-access=free }}
Causes
AITL was originally thought to be a premalignant condition, termed angioimmunoblastic lymphadenopathy, and this atypical reactive lymphadenopathy carried a risk for transformation into a lymphoma. It is postulated that the originating cell for AITL is a mature (post-thymic) CD4+ T-cell that arises de novo, or that the disease has a premalignant subtype.{{cite journal |vauthors=Frizzera G, Kaneko Y, Sakurai M |title=Angioimmunoblastic lymphadenopathy and related disorders: a retrospective look in search of definitions |journal=Leukemia |volume=3 |issue=1 |pages=1–5 |date = January 1989|pmid=2642571 }}{{cite journal |vauthors=Smith JL, Hodges E, Quin CT, McCarthy KP, Wright DH |title=Frequent T and B Cell Oligoclones in Histologically and Immunophenotypically Characterized Angioimmunoblastic Lymphadenopathy |journal=Am. J. Pathol. |volume=156 |issue=2 |pages=661–9 |date = February 2000|pmid=10666395 |pmc=1850038 |doi=10.1016/S0002-9440(10)64770-0 }} The Epstein–Barr virus (EBV) is observed in the majority of cases, being identified in the reactive (i.e. non-malignant) B-cells that comprise part of the polymorphous infiltrate of AITL.{{cite journal |vauthors=Weiss LM, Jaffe ES, Liu XF, Chen YY, Shibata D, Medeiros LJ |title=Detection and localization of Epstein–Barr viral genomes in angioimmunoblastic lymphadenopathy and angioimmunoblastic lymphadenopathy-like lymphoma |journal=Blood |volume=79 |issue=7 |pages=1789–95 |date = April 1992|doi=10.1182/blood.V79.7.1789.1789 |pmid=1373088 |url=http://www.bloodjournal.org/content/79/7/1789.full|doi-access=free }} These EBV+ B cells have numerous non-malignant crippling mutations, often proliferate excessively, and in some cases may transform into EBV+ B cell lymphomas. The other cell types in these infiltrates, including the malignant TFH cells, are EBV negative. While the World Health Organization (2016) has classified these EBV-associated cases as one of the Epstein–Barr virus-associated lymphoproliferative diseases (see EBV+ angioimmunoblastic T cell lymphoma, the role of the virus in the development and progression of EBV+ angioimmunoblastic T cell lymphoma is unclear.{{cite journal | vauthors = Rezk SA, Zhao X, Weiss LM | title = Epstein–Barr virus (EBV)-associated lymphoid proliferations, a 2018 update | journal = Human Pathology | volume = 79 | pages = 18–41 | date = September 2018 | pmid = 29885408 | doi = 10.1016/j.humpath.2018.05.020 | s2cid = 47010934 }} Immunodeficiency is also seen with AITL, but it is a sequela and not a predisposing factor.
Diagnosis
=Laboratory findings=
The classical laboratory finding is polyclonal hypergammaglobulinemia, and other immunoglobulin derangements are also seen, including hemolytic anemia with cold agglutinins, circulating immune complexes, anti-smooth muscle antibodies, and positive rheumatoid factor.
=Lymph node=
The normal architecture of a lymph node is partially effaced by a polymorphous infiltrate and residual follicles are commonly seen. The polymorphous infiltrate consists of lymphocytes of moderate size with pale/clear cytoplasm and smaller reactive lymphocytes, eosinophils, histiocytes, plasma cells, and follicular dendritic cells. In addition, blast-like B-cells are occasionally seen. A classic morphological finding is the aborization and proliferation of high endothelial venules. Hyperplastic germinal centers and Reed-Sternberg-like cells can also be seen.{{cite journal |vauthors=Quintanilla-Martinez L, Fend F, Moguel LR |title=Peripheral T-cell lymphoma with Reed–Sternberg-like cells of B-cell phenotype and genotype associated with Epstein–Barr virus infection |journal=Am. J. Surg. Pathol. |volume=23 |issue=10 |pages=1233–40 |date = October 1999|pmid=10524524 |doi=10.1097/00000478-199910000-00008 |display-authors=etal}}
=Immunophenotype=
AITL typically has the phenotype of a mixture of CD4+ and CD8+ T-cells, with a CD4:CD8 ratio greater than unity. Polyclonal plasma cells and CD21+ follicular dendritic cells are also seen.
=Molecular findings=
Clonal T-cell receptor gene rearrangements are detected in 75% of cases,{{cite journal |vauthors=Feller AC, Griesser H, Schilling CV |title=Clonal gene rearrangement patterns correlate with immunophenotype and clinical parameters in patients with angioimmunoblastic lymphadenopathy |journal=Am. J. Pathol. |volume=133 |issue=3 |pages=549–56 |date = December 1988|pmid=2849301 |pmc=1880823 |display-authors=etal}}
and immunoglobin gene rearrangements are seen in 10% of cases, and these cases are believed to be due to expanded EBV-driven B-cell populations.{{cite journal |vauthors=Lipford EH, Smith HR, Pittaluga S, Jaffe ES, Steinberg AD, Cossman J |title=Clonality of angioimmunoblastic lymphadenopathy and implications for its evolution to malignant lymphoma |journal=J. Clin. Invest. |volume=79 |issue=2 |pages=637–42 |date = February 1987|pmid=3805286 |pmc=424152 |doi=10.1172/JCI112860 }}
Similarly, EBV-related sequences can be detected in most cases, usually in B-cells but occasionally in T-cells.{{cite journal |vauthors=Anagnostopoulos I, Hummel M, Finn T |title=Heterogeneous Epstein–Barr virus infection patterns in peripheral T-cell lymphoma of angioimmunoblastic lymphadenopathy type |journal=Blood |volume=80 |issue=7 |pages=1804–12 |date = October 1992|doi=10.1182/blood.V80.7.1804.1804 |pmid=1327284 |display-authors=etal |url=http://www.bloodjournal.org/content/80/7/1804.full|doi-access=free }}
Trisomy 3, trisomy 5, and +X are the most frequent chromosomal abnormalities found in AITL cases.{{cite journal |vauthors=Kaneko Y, Maseki N, Sakurai M |title=Characteristic karyotypic pattern in T-cell lymphoproliferative disorders with reactive "angioimmunoblastic lymphadenopathy with dysproteinemia-type" features |journal=Blood |volume=72 |issue=2 |pages=413–21 |date = August 1988|doi=10.1182/blood.V72.2.413.413 |pmid=3261178 |display-authors=etal |url=http://www.bloodjournal.org/content/72/2/413.full|doi-access=free }}{{cite journal |vauthors=Schlegelberger B, Zhang Y, Weber-Matthiesen K, Grote W |title=Detection of aberrant clones in nearly all cases of angioimmunoblastic lymphadenopathy with dysproteinemia-type T-cell lymphoma by combined interphase and metaphase cytogenetics |journal=Blood |volume=84 |issue=8 |pages=2640–8 |date = October 1994|doi=10.1182/blood.V84.8.2640.2640 |pmid=7919378 |url=http://www.bloodjournal.org/content/84/8/2640.full|doi-access=free }}
Treatment
There is a subset of AITL that can remit with immunosuppression with agents like glucocorticoids or methotrexate. Most patients, however, will need combination chemotherapy like CHOP-like chemotherapy backbone- either CHOP alone or CHOP in combination with etoposide (CHOEP). Median response duration is short and median OS is only 15–36 months. Relapsed disease is treated similar to the relapsed PTCL, NOS.[17]
Epidemiology
The typical patient with angioimmunoblastic T-cell lymphoma (AITL) is either middle-aged or elderly, and no gender preference for this disease has been observed. AITL comprises 15–20% of peripheral T-cell lymphomas and 1–2% of all non-Hodgkin lymphomas.{{cite journal |title=A clinical evaluation of the International Lymphoma Study Group classification of non-Hodgkin's lymphoma. The Non-Hodgkin's Lymphoma Classification Project |journal=Blood |volume=89 |issue=11 |pages=3909–18 |date = June 1997|pmid=9166827 |url=http://www.bloodjournal.org/content/89/11/3909.full |doi=10.1182/blood.V89.11.3909|doi-access=free }}
See also
References
{{Reflist}}
17. Harrison Principle Of Internal Medicine. Edition:21st page no.850–51
External links
{{Medical resources
| DiseasesDB =
| ICD10 = {{ICD10|C|86|5|c|81}} (ILDS C84.460)
| ICD9 =
| ICDO = {{ICDO|9705|3}}
| OMIM =
| MedlinePlus =
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| MeshID = D007119
| SNOMED CT = 413537009
| Orphanet = 86886
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{{Hematological malignancy histology}}