Angioimmunoblastic T-cell Lymphoma



Angioimmunoblastic T-cell Lymphoma


Sa A. Wang, MD





Key Facts


Terminology



  • Peripheral T-cell lymphoma derived from CD4(+) follicular helper T cells characterized by



    • Lymphadenopathy, systemic disease, and, usually, immunodysregulation and immunodeficiency


Clinical Issues



  • Advanced stage with generalized lymphadenopathy, hepatomegaly, &/or splenomegaly


  • Aggressive, with median survival of < 3 years


  • Anemia, hypereosinophilia, polyclonal hypergammaglobulinemia


Microscopic Pathology



  • Lymph node



    • Partial or complete effacement of architecture


    • Neoplastic T cells with clear/pale cytoplasm


    • Proliferation of arborizing high endothelial venules


    • Proliferation of follicular dendritic cells


Ancillary Tests



  • CD2(+), CD3(+), CD4(+) CD5(+), TCR-αβ(+)


  • CD10(+/−), Bcl-6(+/−), CXCL13(+/−), PD-1(+/−)


  • B immunoblasts(+) in variable numbers


  • Monoclonal T-cell receptor rearrangements


  • EBER(+) in ˜ 80-90% of cases


  • Neoplastic cells have gene expression profile of follicular helper T cells


Top Differential Diagnoses



  • Viral lymphadenitis or drug reaction


  • Classical Hodgkin lymphoma


  • T-cell/histiocyte-rich large B-cell lymphoma


  • Peripheral T-cell lymphoma, not otherwise specified







Lymph node involved by angioimmunoblastic T-cell lymphoma (AITL) shows residual follicles, expanded paracortical and interfollicular regions, and open subcapsular (peripheral) sinuses image.






AITL involving lymph node shows increased high endothelial venules (HEV) and a mixed cellular infiltrate. Around the HEV are clusters of neoplastic clear cells.


TERMINOLOGY


Abbreviations



  • Angioimmunoblastic T-cell lymphoma (AITL)


Synonyms



  • Angioimmunoblastic lymphadenopathy with dysproteinemia (AILD)



    • AILD-like (type) T-cell lymphoma


  • Immunoblastic lymphadenopathy


Definitions



  • Peripheral T-cell lymphoma (PTCL) derived from CD4(+) follicular helper T cells characterized by



    • Lymphadenopathy, systemic disease, and, usually, immunodysregulation and immunodeficiency


ETIOLOGY/PATHOGENESIS


Immunodysregulation



  • AITL is tumor of follicular helper T cells



    • Follicular helper T cells upregulate CXCR5 and CXCL13



      • CXCL13 promotes B-cell recruitment through adherence of B cells on high endothelial venules (HEV)


      • CD21(+) follicular dendritic cells expand from HEV


      • Leads to B-cell expansion, plasmacytic differentiation, and hypergammaglobulinemia


Viral Infection



  • EBV(+) B cells are detected in most cases of AITL



    • Most likely secondary event as result of host immunocompromise


  • Human herpesvirus 6B (HHV6B) is also detected by PCR in almost 1/2 of AITL cases


  • EBV and potentially HHV6B may



    • Modulate secretion of cytokines and chemokines or expression of membrane receptors


    • Influence development of tumor microenvironment, favoring disease progression


CLINICAL ISSUES


Epidemiology



  • Incidence



    • Rate: 0.5 per 100,000 person years in USA



      • More common in whites than in African-Americans or Asian-Americans


    • Represents 1.2% of all non-Hodgkin lymphomas and 18% of all PTCLs


    • AITL is more common in Europe than in North America or Asia


  • Age



    • Median: 59-65 years in various studies


  • Gender



    • Likely a slight male predominance (but varies in different studies)


Presentation



  • Subacute or acute systemic illness


  • Advanced stage with generalized lymphadenopathy, hepatomegaly, &/or splenomegaly


  • B symptoms are common (fever, weight loss, night sweats)


  • Skin rash in > 50% of patients



    • Generalized or predominantly truncal maculopapular eruption mimicking inflammatory dermatosis


    • Nodular lesions, plaques, purpura, and urticarial lesions also have been observed


    • Prior to, concurrent with, or following initial diagnosis of AITL


  • Other systemic manifestations



    • Arthralgias or arthritis


    • Pleural effusions, ascites, &/or edema



    • Lung, neurologic, or gastrointestinal involvement


  • Cases of AITL have been reported after administration of antibiotics



    • Most likely, patients with undetected AITL predisposed to infection requiring antibiotic therapy


Laboratory Tests



  • Complete blood cell count



    • Anemia



      • Cryoglobulins or cold agglutinins


      • Positive Coombs test in many patients


    • Hypereosinophilia


    • Lymphopenia (lymphocytosis is rare)


    • Thrombocytopenia


  • Polyclonal hypergammaglobulinemia



    • Hypoalbuminemia


  • ± autoantibodies



    • Rheumatoid factor, anti-nuclear factor, anti-smooth muscle


  • Elevated erythrocyte sedimentation rate


  • Elevated serum lactate dehydrogenase and β2-microglobulin levels


Treatment



  • No consensus on optimal therapeutic regimen


  • For medically eligible patients, combined chemotherapy followed by autologous hematopoietic cell transplantation after achieving remission


  • For nontransplant candidates, combined chemotherapy


  • Steroids have role for patients who are not candidates for chemotherapy


  • Novel, investigational therapies are needed for patients with AITL


Prognosis



  • Aggressive, with median survival of < 3 years


  • ˜ 30% of patients are long-term survivors


  • Adverse prognostic factors



    • Male sex, mediastinal lymphadenopathy, and anemia adversely affect overall survival


    • Overall immune status also influences survival


  • Histological features of AITL do not correlate with prognosis


IMAGE FINDINGS


Radiographic Findings



  • Generalized lymphadenopathy, organ involvement, body effusions



    • Cannot distinguish AITL from other lymphoma types with disseminated disease


MICROSCOPIC PATHOLOGY


Histologic Features



  • Lymph node



    • Partial or complete effacement of architecture; perinodal infiltration common



      • Paracortical distribution of neoplasm


      • Peripheral sinuses in lymph node cortex are often patent


    • Neoplastic cells are small- to medium-sized, with clear to pale cytoplasm, distinct cell membranes, and minimal atypia



      • Tumor cells often form small clusters around follicles and HEV


    • Background cells are polymorphous



      • Variable numbers of small reactive lymphocytes, eosinophils, plasma cells, and histiocytes


      • ± immunoblasts of B-cell lineage; number is variable and can be prominent


      • ± HRS-like cells of B-cell lineage; usually EBV(+)


    • Marked proliferation of arborizing high endothelial venules (HEV)


    • Increased proliferation of follicular dendritic cells (FDC), usually surrounding HEV


    • 3 patterns in lymph node have been described



      • I: Architecture is partially preserved and hyperplastic, or normal follicles are present


      • II: Architecture is mostly effaced with residual follicles present; ± follicles disrupted or irregular



      • III: Architecture is completely replaced; ± few regressed (“burned out”) follicles


  • Bone marrow



    • Nodular or interstitial aggregates in paratrabecular or nonparatrabecular distribution



      • Neoplastic cells are often small; ± clear cytoplasm; can be difficult to identify


      • Reactive cells include plasma cells, eosinophils, histiocytes, and B cells


      • Aggregates are associated with blood vessel proliferation


      • ± EBV(+) cells


    • Uninvolved bone marrow ± reactive changes associated with AITL



      • Erythroid hyperplasia, polyclonal plasmacytosis, eosinophilia, fibrosis, or hemophagocytosis


  • Peripheral blood



    • Lymphocytosis is uncommon


    • ± atypical lymphocytes or activated lymphocytes (so-called immunocytes)


    • CD10(+) T cells have been shown in many patients by flow cytometric immunophenotyping


  • Skin



    • Changes are variable, may not always result from direct tumor infiltration



      • Changes can range from nonspecific, mild perivascular dermal lymphocytic infiltrate to, more rarely, overt lymphoma


  • Body effusions



    • Nonneoplastic in nature and their cause is poorly understood


    • Mixture of small lymphocytes, histiocytes, ± eosinophils


  • Morphological variants of AITL

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Jul 8, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Angioimmunoblastic T-cell Lymphoma

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