title: PAX5-positive T-cell anaplastic large cell lymphomas associated with extra copies of the PAX5 gene locus.
abstract: Cell lineage is the major criterion by which lymphomas are classified. Immunohistochemistry has greatly facilitated lymphoma diagnosis by detecting expression of lineage-associated antigens. However, loss or aberrant expression of these antigens may present diagnostic challenges. Anaplastic large cell lymphoma is a T-cell lymphoma that shows morphologic and phenotypic overlap with classical Hodgkin's lymphoma, which is a tumor of B-cell derivation. Staining for the B-cell transcription factor, paired box 5 (PAX5), has been suggested to be helpful in this differential, as it is positive in most classical Hodgkin's lymphomas, but absent in anaplastic large cell lymphomas. In this study we report four systemic T-cell anaplastic large cell lymphomas that were positive for PAX5 by immunohistochemistry, with weak staining intensity similar to that observed in classical Hodgkin's lymphoma. All diagnoses were confirmed by a combination of morphologic, phenotypic, and molecular criteria. Three cases were anaplastic lymphoma kinase (ALK) negative and one was ALK positive. PAX5 immunohistochemistry was negative in 198 additional peripheral T-cell lymphomas, including 66 anaplastic large cell lymphomas. Unexpectedly, although PAX5 translocations were absent, all evaluable PAX5-positive anaplastic large cell lymphomas showed extra copies of the PAX5 gene locus by fluorescence in situ hybridization (FISH). In contrast, only 4% of PAX5-negative peripheral T-cell lymphomas had extra copies of PAX5. We conclude that aberrant expression of PAX5 occurs rarely in T-cell anaplastic large cell lymphomas, and may be associated with extra copies of the PAX5 gene. PAX5-positive lymphomas with morphologic features overlapping different lymphoma types should be evaluated with an extensive immunohistochemical panel and/or molecular studies to avoid diagnostic errors that could lead to inappropriate treatment. As PAX5 overexpression causes T-cell neoplasms in experimental models, PAX5 may have contributed to lymphomagenesis in our cases.
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA. feldman.andrew@mayo.edu
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Feldman
authors.forename: Mark E
authors.initials: ME
authors.lastname: Law
authors.forename: David J
authors.initials: DJ
authors.lastname: Inwards
authors.forename: Ahmet
authors.initials: A
authors.lastname: Dogan
authors.forename: Rebecca F
authors.initials: RF
authors.lastname: McClure
authors.forename: William R
authors.initials: WR
authors.lastname: Macon
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D018628:Gene Dosage; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D017728:Lymphoma, Large-Cell, Anaplastic / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D051757:PAX5 Transcription Factor / Q000235:genetics*; D016133:Polymerase Chain Reaction
chemical_list: D051757:PAX5 Transcription Factor; C497281:PAX5 protein, human