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Lymphoma - Non B cell neoplasms

T/NK cell disorders

Angioimmunoblastic T-cell lymphoma


Reviewer: Dragos Luca, M.D., Children's Hospitals & Clinics of Minnesota (see Reviewers page)
Revised: 31 July 2013, last major update September 2011
Copyright: (c) 2001-2013, PathologyOutlines.com, Inc.

Definition
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● Peripheral T-cell lymphoma characterized by systemic disease, a polymorphous infiltrate involving lymph nodes, with a prominent proliferation of high endothelial venules and follicular dendritic cells (WHO 2008)

Terminology
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● Formerly called angioimmunoblastic lymphadenopathy (with or without dysproteinemia, AILD), an atypical reactive process prone to lymphomatous transformation; currently considered a lymphoma from the outset
● Other names used in the past: AILD-type T-cell lymphoma, lymphogranulomatosis X, diffuse mixed small and large cell immunoblastic lymphoma

Epidemiology
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● 15-20% of peripheral T-cell lymphomas
● 1-2% of non-Hodgkin lymphomas
● Middle aged and elderly patients
● M:F ratio 1:1
● More common in Caucasians than in Africans or Asians

Sites
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● Lymph nodes are primary site
● Virtually all patients have generalized lymphadenopathy
● Frequent involvement of spleen (50-70%), liver (50-70%), skin (50%), pleuropulmonary (40%) and bone marrow (60-90%, Am J Clin Pathol 2006;126:29)

Etiology
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● EBV associated (B cells are EBV+), but the neoplastic T cells are EBV negative
● May occur after penicillin / drug administration (27% of cases in one study)

Clinical features
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● Usually presents with advanced stage disease
● Hepatosplenomegaly, polyclonal hypergammaglobulinemia, fever, weight loss, skin rash, often with pruritus, pleural effusion, arthritis, ascites

Laboratory
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● Circulating immune complexes, cold agglutinins with hemolytic anemia, positive rheumatoid factor, anti-smooth muscle antibodies
● Expansion of EBV+ B-cells is probably due to immunodeficiency

Case reports
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● 43 year old woman with pure red cell aplasia (Cancer Res Treat 2010;42:115)
● 48 year old woman with composite tumor with diffuse large B cell lymphoma (Am J Clin Pathol 2002;118:848)
● 67 year old woman with cutaneous trunk lesions with prominent granulomas (Am J Surg Pathol 2003;27:699)
● 67 year old man with nephrotic syndrome (Ann Hematol 2004;83:455)

Treatment and prognosis
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● Moderately aggressive; may respond to steroids, may progress to diffuse large B-cell lymphoma (most common), classical Hodgkin lymphoma, plasmacytoma, small B-cell lymphoma, peripheral T cell lymphoma
● Median survival <3 years; death usually due to infectious complications

Postulated normal counterpart
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● CD4+ follicular helper T cell

Micro description
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● Partial effacement of lymphonodular architecture, often with perinodal infiltration but with preservation of subcapsular and trabecular sinuses
● Prominent arborizing high endothelial venules with thickened, hyalinized PAS+ walls surrounded by CD21+ follicular dendritic cells and irregular homogenous eosinophilic material
● Burnt out germinal centers with increased follicular dendritic cell meshworks (mediated through expression of CXCL13 by neoplastic follicular helper T cells)
● Predominantly paracortical aggregates of polymorphic small to medium-sized cells with clear / pale cytoplasm, distinct cell membranes and minimal cytologic atypia
● Small clusters of neoplastic cells around follicles and high endothelial venules, variable numbers of small reactive lymphocytes, eosinophils, plasma cells, histiocytes
● Paracortical expansion of B immunoblasts linked to the functional properties of neoplastic follicular helper T cells
● Three different histologic patterns described, I-III, with increasing degrees of architectural effacement, commonly coexisting in the same specimen, arbitrary cut-offs

Bone marrow:
● Focal or diffuse marrow involvement
● Focal lesions have indistinct margins
● Contain polymorphous infiltrate of lymphocytes, immunoblasts, plasma cells, histiocytes, eosinophils and neutrophils
● Often vascular proliferation with prominent endothelial cells and fibroblasts
● Perivascular clustering of neoplastic clear cells in 41%
● Variable epithelioid histiocytes
● Usually no amorphous PAS+ material (found in nodal lesions)
● Uninvolved marrow may be hypercellular

Peripheral blood:
● Reactive lymphocytes, immunoblasts, immunocytes, increased eosinophils, various cytopenias, rouleaux
● May also see circulating lymphoma cells

Micro images
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Various images

Cytology description
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● Small to large cells with moderate to faint basophilic cytoplasm without azurophilic granules and sometimes with microvacuoles, often irregular or indented nuclei, moderately condensed chromatin

Cytology images
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Peripheral blood: atypical lymphocytes

Positive stains
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● EBV
● CD2, CD3, CD4, CD5, CD10 (Am J Surg Pathol 2004;28:54, may be negative in bone marrow)
● Also CXCL13, PD-1, bcl6, CD38, CD45
● CD21, CD23, CD35 and CNA42 in the follicular dendritic cells
● Reticulin increased in involved areas; polyclonal immunoblasts and plasma cells
● Characteristic phenotype of normal T helper cells CD10, CXCL13, PD-1 (60-100% of AITL), bcl6
● Numerous reactive CD8+ T cells

Negative stains
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● CD8, CD56, pan B cell markers, immunoglobulins, cytotoxic antigens, CD1a, CD99, TdT

Genetics and Molecular
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● Clonal rearrangement of T cell receptor genes (75-90%) or IgH (25-30%)
● Most frequent cytogenetic abnormalities: +3, +5, +X
● Other: +22q, +19, +11q13, -13q

Electron microscopy descriptions
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● Lymphocytes with cytoplasmic vacuoles thought to correspond to neoplastic cells
● High endothelial venules: swollen endothelial cells with walls thickened by basement membrane-like material and immunoglobulin deposition
● Intercellular collagen and immunoglobulins correspond to the eosinophilic PAS+ material

Differential diagnosis
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● Reactive lymphoid hyperplasia: may also have CD10+ T cells, Mod Pathol 2003;16:879)
● Peripheral T-cell lymphoma: CD10-, EBV-, no clear cells
● Classical Hodgkin lymphoma, mixed cellularity: no aberrant T cell phenotype, no TCR gene rearrangements
● Drug reactions
● Infectious mononucleosis
● Castleman disease

Additional references
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● Review articles: Br J Haematol 2003;121:681, Br J Haematol 2010;148:673

End of Lymphoma - Non B cell neoplasms > T/NK cell disorders > Angioimmunoblastic T-cell lymphoma


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