PAX5-Positive T-Cell Anaplastic Large Cell Lymphomas Associated with Extra Copies of the PAX5 Gene Locus
AL Feldman, ME Law, DJ Inwards, A Dogan, RF McClure, WR Macon. Mayo Clinic, Rochester, MN
Background: The distinction of anaplastic large cell lymphoma (ALCL) from classical Hodgkin lymphoma (CHL) is critical because of differing therapy and prognosis. However, ALCL and CHL may show overlapping morphologic and phenotypic features. Weak expression of the transcription factor PAX5 (B-cell-specific activating protein/BSAP) by CHL but not ALCL has been suggested to help distinguish these entities. In this study we examined the clinicopathologic and molecular features of 4 ALCLs with weak PAX5 expression, similar to the staining intensity seen in CHL.
Design: Cases were classified using 2008 WHO criteria. We reviewed clinical data and morphologic features, and performed immunohistochemistry (IHC) for a broad panel of B- and T-cell antigens and PCR for T-cell receptor (TCR) and immunoglobulin (Ig) gene rearrangements. Fluorescence in situ hybridization (FISH) was performed using a home-brew PAX5 gene probe. IHC and FISH for PAX5 were performed on tissue microarrays containing 198 additional peripheral T-cell lymphomas (PTCLs).
Results: Four ALCLs showed weak nuclear staining for PAX5 (2 M, 2F; age range 31-87 y). Diagnoses were confirmed by a combination of morphologic, phenotypic, and molecular criteria. Hallmark cells were present in all cases. 3 were ALK-negative and 1 was ALK-positive. At least 1 T-cell antigen was seen in all cases. Cytotoxic markers were positive in 3/4; clusterin, EMA, and OCT2 were positive in 2/4 each; and BOB.1 was positive in 1/4. Clonal TCR rearrangments were detected in 2/3 evaluable cases; no clonal Ig rearrangements were detected. All (3/3) evaluable cases had extra (≥4) copies of the PAX5 gene. Patients presented with stage III-IV disease; 1 died, 2 had responses to CHOP, and 1 was lost to follow-up. Pax5 immunohistochemistry was negative in 198 additional peripheral T-cell lymphomas (PTCLs), including 66 ALCLs. Only 4% of PAX5 protein-negative PTCLs (all PTCLs, NOS) had extra copies of PAX5.
Conclusions: Aberrant PAX5 expression occurs rarely in T-cell ALCLs, and should not be considered definitive in distinguishing CHL from ALCL. Cases with overlapping features require thorough phenotypic and molecular evaluation to avoid diagnostic errors that could lead to inappropriate treatment. PAX5-positive ALCLs uniformly showed extra copies of PAX5. This event is otherwise rare in PTCLs. Since genetically induced PAX5 overexpression causes T-cell neoplasms in experimental models, PAX5 expression may have contributed to lymphomagenesis in our cases.
Tuesday, March 23, 2010 9:30 AM
Poster Session III # 196, Tuesday Morning