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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