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Los Angeles Society of Pathology
Interesting Case Presentation
Marnelli A. Bautista, PGY-1Loma Linda University Medical Center
June 9, 2009
47-year-old male with: Pruritic skin rash Oral ulcers and epistaxis Low-grade feverWeight lossCervical lymphadenopathy Splenomegaly
SPEP: hypergammaglobulinemia
UPEP: Elevated globulin fraction
Warm auto and cold autoantibodies
ANA and dsDNA negative
Rheumatoid factor negative
EBV via PCR (blood): 3,335 copies/mL
40x
CD3CD43
CD5 CD10
CD20
CD23CD34
CD30
IHC stains Result
Ki-67 Positive (50-70%)
PAX-5 and CD79a Scattered B cells and immunoblasts
Pancytokeratin Negative
Abnormal lymphocyte population
CD2+, CD3+, CD4+, CD5+, CD7+, CD10+, CD45+ CD8-, CD56- Negative for T cell receptors - and -
Angioimmunoblastic T-cell lymphoma
Diagnosis?
Angioimmunoblastic T-cell lymphoma (AILT) is a 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.
1-2% of non-Hodgkin lymphomas and ~15-20% of PTCL-u
Clinical Presentation
Skin rash Hepatosplenomegaly and
lymphadenopathy Cold agglutinins
Partial or complete effacement of normal nodal architecture by predominantly paracortical polymorphous infiltrate – small to medium sized neoplastic lymphoid cells with clear or pale cytoplasm, often forming small clusters around the follicles and HEV, admixed with small reactive lymphocytes, eosinophils, plasma cells, and histiocytes
There is marked proliferation of arborizing high endothelial venuels (HEV)
There are frequently associated follicular dendritic cell meshworks in the background
www.nature.com/modpathol/journal/v22/n6/pdf/modpathol200912a.pdf
www.ispub.com/journal/the_internet_journal_of_otorhinolaryngology/volume_9_number_2_11
Immunophenotype
Neoplastic T cells: CD3+, CD2+, CD5+, CD4+, CD10+, CXCL13+ and PD1 (60-100%)
Follicular dendritic cells: CD21+, CD23+, CD35 and CNA42
Lymphocytes, eosinophils, plasma cells, and histiocytes
EBV+ in immunoblasts or RS-like cells (DLBCL may co-exist or at relapse)
Path.upmc.edu/cases/case41/micro.html
Gene rearrangements
Cytogenetic abnormalities: Trisomy 3 Trisomy 5 Additional X chromosome Gains of 22q, 19, 11q13 and/or loss of 13q
TCR 75-90%
Immunoglobulin 25-30%
Molecular genetics
AITL: New pathoogical insights Putative cell of origin – CD4+ Follicular helper T
(TFH) cells expressing CD10, BCL6, CXCL13 (a chemokin produced by normal TFH cell following co-stimulation via CD28 and TCR
Gene expression profile in 16 cases of AITL showed characteristic genes (CXCL13, BCL6, PDCG1, CD40L and NFATC1) of normal TFH cells (De Leval et al: Blood 2007;109:4952)
The functions of CXCL13 include recruitment of B cells to LNs and follicles, induction and proliferation of FDCs, and B cell activation
Universal presence of EBV – proposes its role in the early pathogenesis of AITL by activating TFH cells
Dunleavy, et al: Curr Opin Hematol, Volume 14(4).July 2007.348–353
Aggressive clinical course with a median survival of less than 3 years Immunodeficiency state – succumb to
infectious complications, which makes delivery of aggressive chemotherapy difficult
Supervening large B-cell lymphomas (EBV variably +)
home.mweb.co.za/te/teknovis/images/T-M0009%20
Jaffe ES, Harris NL, et al (Eds.). (2008). World Health Organization Classification of Tumours: Tumours of Hematopoietic and Lymphoid Tissues (pp. 309-311). Lyon: International Agency for Research on Cancer.
Dunleavy K, Wilson WH, Jaffe ES. Angioimmunoblastic T cell lymphoma: pathobiological insights and clinical implications. Curr Opinion Hema. 2007; 14: 348-353.
Dupuis J, Boye K, Martin N. Expression of CXCL13 by neoplastic cells in angioimmunoblastic T-Cell lymphoma (AITL): A new diagnostic marker providing evidence that AITL derives from follicular helper T cells. Am J Surg Pathol. 2006; 30: 490 - 494.
Rodriguez-Justo, M, Attygale A, Munson P, et al. 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. Modern Pathol. 2009; 22: 753-761.
Attygale A, Al-Jehani R, Diss TC, et al. Neoplastic T cells in angioimmunoblastic T-cell lymphoma express CD10. Blood. 2002;99: 627-633.
Dr. J. Wang Dr. J. Cao Dr. E. Rowsell Dr. C. Zuppan Dr. T. Stevens
AcknowledgmentDr. J. WangDr. J. CaoDr. E. RowsellDr. C. ZuppanDr. T. Stevens