Compendium of Cancer Genome Aberrations

Testpage5

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Primary Author(s)*

Sara Akhavanfard, M.D., Ph.D.

Ruthann Pfau, Ph.D., FACMG

Cancer Category/Type

Angioimmunoblastic T-cell Lymphoma and Other Nodal Lymphomas of T Follicular Helper Cell Origin

Cancer Sub-Classification / Subtype

Angioimmunoblastic T-cell Lymphoma (AITL)

Definition / Description of Disease

  • A neoplasm of mature T follicular helper (TFH) cells
  • Characterized by systemic disease and a polymorphous infiltrate involving lymph nodes
  • Have prominent proliferation of high endothelial venules (HEVs) and folicular dentritic cells (FDCs)
  • EBV-positive B cells are nearly always present
  • Clinically aggressive and seen mainly in older adults

Synonyms / Terminology

  • Peripheral T-cell Lymphoma
  • Angioimmunoblastic Lymphadenopathy with Dysproteinaemia
  • Immunoblastic Lymphadenopathy
  • Lymphogranulomatosis X

[1]

Clinical Features[2][3][4][5]

Sign and Symptoms

  • Advanced-stage disease with systemic symptoms
  • Generalized lymphadenopathy
  • Hepathosplenomegaly
  • Polyclonal hypergammagloulinaemia
  • Skin rash, often with pruritus
  • Pleural effusion
  • Arthritis
  • Ascities

Laboratory Findings

  • Circulating Immune Complexes
  • Cold agglutinins with haemolytic anemia
  • Positive rheumatoid factor
  • Positive anti-smooth muscle antibody

Sites of Involvement

  • Primary site: Lymph node
  • Other involved sites: Spleen, Liver, Skin,and Bone marrow[6][7][8][9]

Morphologic Features[10][11]

Pattern-1 (Early involvement)

  • Bare, hyperplastic follicles, with Well-formed germinal centers, often lacking well-defined mantle cuffs[12]
  • Paracortical expansion
  • Marked Vascular Proliferation, associated with perifollicular or atypical lymphoid cells

Pattern-2

  • Remnant of follicles with regressive changes
  • Readily identified neoplastic cells in the expanded paracortex
  • Marked perifollicular expansion of clear cells

Pattern-3

  • Totally or sub-totally effacement of normal architecture
  • Marked vascular proliferation
  • Aggregates of atypical lymphoid cells

Immunophenotype[13][14][15][16][17]

Finding Marker
Positive (universal) CD3, CD2, CD5, CD4, CD10, CXCL13, ICOS, BCL6, PD1(CD279)
Positive (extrafollicular pattern) CD21, CD23, CD35

Chromosomal Rearrangements (Gene Fusions)

TMP REMOVED

Characteristic Chromosomal Aberrations / Patterns

  • Clonal rearrangement in T-Cell receptor gene in 75-90% of AITL cases[18] [19][20]
  • Clonal rearrangement in immunoglobulin genes in 25-30% of AITL cases[18][20]

Genomic Gain/Loss/LOH

Chromosome Number Gain/Loss/Amp/LOH Reference
3,5,21 Trisomy [21]
X Gain [21]
6q Loss [21]
22q Gain [22]
19 Gain [22]
11q13 Gain [22]
13q Loss [22]

Gene Mutations (SNV/INDEL)

Gene Mutation Oncogene/Tumor Suppressor/Other Presumed Mechanism (LOF/GOF/Other; Driver/Passenger) Prevalence (COSMIC/TCGA/Other)
IDH2 R172S; R172G;R172K Tumor Suppressor LOF 20-30%[23][24][25][26]
TET2 Widely distributed Tumor Suppressor LOF 50-80%[27][25]
DNMT3A W305* Tumor Suppressor LOF 20-30%[24][25]
RHOA G17V; G17E; C16R; T19I; D120Y Tumor Suppressor LOF 60-70%[28][29][30]
FYN L174R; R176C; Y531H Oncogene GOF up to 5-10%[31][30]
PLCG1 S345F; G869E Oncogene GOF up to 5-10%[31][24]
CD28 D124V; D124E; T195P Oncogene GOF up to 5-10%[31][32]
TNFRSF21 S428fs*S1 Tumor Suppressor LOF [24]
CCND3 Q280* Tumor Suppressor LOF [24]
SAMSN1 R153* Tumor Suppressor LOF [24]

Epigenomics (Methylation)

  • Frequent mutation in epigenetic modifiers like: [24][25][26][27]
    • IDH2 (20-30%)
    • TET2 (50-80%)
    • DNMT3A (20-30%)

Diagnostic Testing Methods

  • Clinical, morphological, and immunophenotypic findings are generally sufficient for diagnosis
  • IDH2 R172 mutations are specific to AITL
  • T-Cell receptor and immunoglobulin genes rearrangement detection by karyotyping and FISH analysis

Suggested Treatment Regimens based on NCCN Guideline Version 1.2020 (TCEL-B 3 of 5)

Second-line therapy (with intention to transplant) and subsequent therapy:

  • Clinical Trial preferred
  • Preferred regimens
    • Single Agents (alphabetical order)
      • Belinostat
      • Brentuximab Vedotin for CD30+ AITL
      • Romidepsin
    • Combination Regimens
      • DHAP(Dexamethasone, Cisplatin, Cytarabine)
      • ESHAP (Etoposide, Methylprednisolone, Citarabine, Cisplatin)
      • GDP (Gemcitabine, Dexamethasone, Cisplatin)
      • GemOx (Gemcitabine, Oxaliplatin)
      • ICE (Ifosfamide, Carboplatin, Etoposide)
  • Other recommended regimens
    • Single Agents (alphabetical order)
      • Bendamustine
      • Gemcitabine
      • Lenalidomide
      • Pralatrexate

Second-line or initial palliative intent therapy (no intention to transplant) and subsequent therapy:

  • Clinical Trial preferred
  • Preferred regimens
    • Single Agents (alphabetical order)
      • Belinostat
      • Brentuximab Vedotin for CD30+ AITL
      • Romidepsin
  • Other recommended regimen (alphabetical order)
    • Alemtuzumab
    • Bendamustine
    • Bertezomib (categort 2B)
    • Cyclophosphamide and/or Etoposide (IV or PO)
    • Cyclosporine
    • Gemcitabine
    • Lenalidomide
    • Pralatrexate
    • Radiation therapy

Other Information

N/A

Links

Angioimmunoblastic T-cell Lymphoma and Other Nodal Lymphomas of T Follicular Helper Cell Origin

References

(use "Cite" icon at top of page)

  1. ↑ Schmidt, J; et al. (1995). "Intravenous contrast medium aggravates the impairment of pancreatic microcirculation in necrotizing pancreatitis in the rat". Annals of Surgery. 221 (3): 257–264. doi:10.1097/00000658-199503000-00007. ISSN 0003-4932. PMC 1234567. PMID 7717779.
  2. ↑ A, Dogan; et al. (2003). "Angioimmunoblastic T-cell lymphoma". PMID 12780782.
  3. ↑ F, Lachenal; et al. (2007). "Angioimmunoblastic T-cell lymphoma: clinical and laboratory features at diagnosis in 77 patients". PMID 17873758.
  4. ↑ N, Mourad; et al. (2008). "Clinical, biologic, and pathologic features in 157 patients with angioimmunoblastic T-cell lymphoma treated within the Groupe d'Etude des Lymphomes de l'Adulte (GELA) trials". doi:10.1182/blood-2007-08-105759. PMC 2343588. PMID 18292286.CS1 maint: PMC format (link)
  5. ↑ W, Siegert; et al. (1995). "Angioimmunoblastic lymphadenopathy (AILD)-type T-cell lymphoma: prognostic impact of clinical observations and laboratory findings at presentation. The Kiel Lymphoma Study Group". PMID 8664186.
  6. ↑ L, de Leval; et al. (2010). "Advances in the understanding and management of angioimmunoblastic T-cell lymphoma". PMID 19961485.
  7. ↑ A, Dogan; et al. (2003). "Angioimmunoblastic T-cell lymphoma". PMID 12780782.
  8. ↑ M, Federico; et al. (2013). "Clinicopathologic characteristics of angioimmunoblastic T-cell lymphoma: analysis of the international peripheral T-cell lymphoma project". doi:10.1200/JCO.2011.37.3647. PMC 3532394. PMID 22869878.CS1 maint: PMC format (link)
  9. ↑ N, Mourad; et al. (2008). "Clinical, biologic, and pathologic features in 157 patients with angioimmunoblastic T-cell lymphoma treated within the Groupe d'Etude des Lymphomes de l'Adulte (GELA) trials". doi:10.1182/blood-2007-08-105759. PMC 2343588. PMID 18292286.CS1 maint: PMC format (link)
  10. ↑ A, Attygalle; et al. (2002). "Neoplastic T cells in angioimmunoblastic T-cell lymphoma express CD10". PMID 11781247.
  11. ↑ M, Rodriguez-Justo; et al. (2009). "Angioimmunoblastic T-cell lymphoma with hyperplastic germinal centres: a neoplasia with origin in the outer zone of the germinal centre? Clinicopathological and immunohistochemical study of 10 cases with follicular T-cell markers". PMID 19329936.
  12. ↑ Hj, Ree; et al. (1998). "Angioimmunoblastic lymphoma (AILD-type T-cell lymphoma) with hyperplastic germinal centers". PMID 9630171.
  13. ↑ A, Attygalle; et al. (2002). "Neoplastic T cells in angioimmunoblastic T-cell lymphoma express CD10". PMID 11781247.
  14. ↑ L, de Leval; et al. (2007). "The gene expression profile of nodal peripheral T-cell lymphoma demonstrates a molecular link between angioimmunoblastic T-cell lymphoma (AITL) and follicular helper T (TFH) cells". PMID 17284527.
  15. ↑ Dm, Dorfman; et al. (2006). "Programmed death-1 (PD-1) is a marker of germinal center-associated T cells and angioimmunoblastic T-cell lymphoma". doi:10.1097/01.pas.0000209855.28282.ce. PMC 3137919. PMID 16819321.CS1 maint: PMC format (link)
  16. ↑ Kl, Grogg; et al. (2005). "Angioimmunoblastic T-cell lymphoma: a neoplasm of germinal-center T-helper cells?". doi:10.1182/blood-2005-03-1083. PMC 1895208. PMID 16079436.CS1 maint: PMC format (link)
  17. ↑ G, Roncador; et al. (2007). "Expression of two markers of germinal center T cells (SAP and PD-1) in angioimmunoblastic T-cell lymphoma". PMID 17640856.
  18. ↑ 18.0 18.1 Ad, Attygalle; et al. (2007). "Distinguishing angioimmunoblastic T-cell lymphoma from peripheral T-cell lymphoma, unspecified, using morphology, immunophenotype and molecular genetics". PMID 17448026.
  19. ↑ L, de Leval; et al. (2010). "Advances in the understanding and management of angioimmunoblastic T-cell lymphoma". PMID 19961485.
  20. ↑ 20.0 20.1 Bt, Tan; et al. (2006). "The frequency of B- and T-cell gene rearrangements and epstein-barr virus in T-cell lymphomas: a comparison between angioimmunoblastic T-cell lymphoma and peripheral T-cell lymphoma, unspecified with and without associated B-cell proliferations". doi:10.2353/jmoldx.2006.060016. PMC 1867616. PMID 16931587.CS1 maint: PMC format (link)
  21. ↑ 21.0 21.1 21.2 B, Schlegelberger; et al. (1994). "Detection of aberrant clones in nearly all cases of angioimmunoblastic lymphadenopathy with dysproteinemia-type T-cell lymphoma by combined interphase and metaphase cytogenetics". PMID 7919378.
  22. ↑ 22.0 22.1 22.2 22.3 C, Thorns; et al. (2007). "Chromosomal aberrations in angioimmunoblastic T-cell lymphoma and peripheral T-cell lymphoma unspecified: A matrix-based CGH approach". PMID 17044049.
  23. ↑ Ra, Cairns; et al. (2012). "IDH2 mutations are frequent in angioimmunoblastic T-cell lymphoma". doi:10.1182/blood-2011-11-391748. PMC 3293643. PMID 22215888.CS1 maint: PMC format (link)
  24. ↑ 24.0 24.1 24.2 24.3 24.4 24.5 24.6 Cite error: Invalid <ref> tag; no text was provided for refs named :4
  25. ↑ 25.0 25.1 25.2 25.3 O, Odejide; et al. (2014). "A targeted mutational landscape of angioimmunoblastic T-cell lymphoma". doi:10.1182/blood-2013-10-531509. PMC 4260974. PMID 24345752.CS1 maint: PMC format (link)
  26. ↑ 26.0 26.1 C, Wang; et al. (2015). "IDH2R172 mutations define a unique subgroup of patients with angioimmunoblastic T-cell lymphoma". doi:10.1182/blood-2015-05-644591. PMC 4600014. PMID 26268241.CS1 maint: PMC format (link)
  27. ↑ 27.0 27.1 F, Lemonnier; et al. (2012). "Recurrent TET2 mutations in peripheral T-cell lymphomas correlate with TFH-like features and adverse clinical parameters". PMID 22760778.
  28. ↑ M, Sakata-Yanagimoto; et al. (2014). "Somatic RHOA mutation in angioimmunoblastic T cell lymphoma". PMID 24413737.
  29. ↑ Hy, Yoo; et al. (2014). "A recurrent inactivating mutation in RHOA GTPase in angioimmunoblastic T cell lymphoma". PMID 24584070.
  30. ↑ 30.0 30.1 T, Palomero; et al. (2014). "Recurrent mutations in epigenetic regulators, RHOA and FYN kinase in peripheral T cell lymphomas". doi:10.1038/ng.2873. PMC 3963408. PMID 24413734.CS1 maint: PMC format (link)
  31. ↑ 31.0 31.1 31.2 Sh, Lee; et al. (2015). "A highly recurrent novel missense mutation in CD28 among angioimmunoblastic T-cell lymphoma patients". doi:10.3324/haematol.2015.133074. PMC 4666342. PMID 26405154.CS1 maint: PMC format (link)
  32. ↑ J, Rohr; et al. (2016). "Recurrent activating mutations of CD28 in peripheral T-cell lymphomas". doi:10.1038/leu.2015.357. PMC 5688878. PMID 26719098.CS1 maint: PMC format (link)

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