Peripheral T cell lymphoma, unspecified, is a lymphoma of mature T cells characterized by atypical morphology, antigenic loss and clonal T cell receptor gene rearrangement. T cell neoplasms can be diagnostically challenging on H&E stained sections. Cytologic morphology varies, especially within the subgroup of peripheral T cell lymphoma, unspecified. Reactive conditions, as well as some non-T cell lymphomas, may exhibit cytologic atypia within the T cells. Thus, immunophenotyping in the evaluation of a potential neoplastic process is essential.
Aberrant B cell antigen expression has also been described in mature T cell neoplasms. Although rare, aberrant expression of the CD20 B-cell marker has been observed on peripheral T cell lymphomas, and in some cases identified both by IHC and FC. Immunohistochemical analysis on one case report showed the neoplastic T cells to be positive for CD3, CD4, CD5, CD8, CD45RO and CD20 and negative for other B-cell markers such as CD79a and PAX-5 (5
). Flow cytometry showed expression of CD20 and FMC-7 with lack of expression for CD79a and TdT. Another report described a peripheral T cell lymphoma expressing CD3, CD4, CD5, CD45RO and CD20 (9
). By flow cytometry the cells were negative for CD19, CD22 and surface immunoglobulin. A clonal T cell receptor gamma chain gene rearrangement was detected. A review of the literature revealed 6 cases of CD20 positive T cell lymphomas that were negative for CD19 by flow cytometry (9
). All of these cases demonstrate that CD20 can be rarely expressed in T cell lymphomas. Additionally, CD20 expression has been identified by FC on a subset of normal T-cells, but no normal T-cell subsets have been described that express CD19 (10
). CD19 is an important and informative marker of B-cell lineage and maturation, and FC analysis relies heavily on the specificity of CD19 for defining B cell populations. CD19 is a transmembrane receptor protein which binds to CD21 for B cell activation. CD19 can be co-expressed in other neoplastic processes, such as acute myeloid leukemia harboring a t(8;21) translocation (1). However, to date, there have been no case reports in the literature describing co-expression of CD19 on a mature T-cell lymphoma.
The mechanism of aberrant CD19 expression may be related to expression of the transcription factor B-cell specific activator protein (BSAP), which is encoded by the PAX5 gene. In normal B-cell development, PAX5 plays a dual role in the commitment of bone marrow multipotent progenitor cells to the B lymphocyte lineage. PAX5 has a repressor role, inhibiting transcription of non- B cell hematopoietic differentiation. PAX5 also induces VH
recombination and transcriptional activation of CD19 and CD79a in B-cells(11
). Aberrant CD19 expression in t(8;21) AML is well documented, and more recently, expression of BSAP in this AML subtype has been described ((12
). In a recent series, CD19 expression was detected in 26/28 cases of t(8:21) AML, all of which expressed BSAP. Interestingly, this series also observed a case of CD19(+) T-cell ALL with expression of BSAP (13
). Furthermore, a rare case of a mature T-cell lymphoma with aberrant expression of BSAP has been described (14
). These findings would suggest a strong correlation between aberrant CD19 expression and PAX5. However, the mechanism of CD19 expression in our particular T-cell lymphoma case may fall outside of this potential mechanism, as immunohistochemistry for BSAP expression was negative in the neoplastic T-cells.
In our current case, the patient presented with diffuse superficial and deep lymphadenopathy, constitutional symptoms, hepatosplenomegaly and bone marrow and peripheral blood involvement by a neoplastic process. H&E stained sections showed effacement of the architecture by this atypical lymphoid proliferation. FC and IHC demonstrated an aberrant T cell lymphoid population in two separate lymph nodes and in the peripheral blood. The atypical lymphoid population consisted of a CD3 positive population expressing CD2, CD43, CD27, CD52, TCR alpha beta and partial expression of CD26 with loss of CD4, CD5, CD7 and CD8. The lack of staining for TdT and CD1a demonstrated that this was a mature T cell neoplasm. The clinical presentation and lack of additional markers such as CD30 and ALK-1 showed that this neoplasm was consistent with PTCL-NOS.
Molecular studies for T-cell receptor gene rearrangement were positive for a clonal process. CD16, CD56 and EBV in situ hybridization were negative, excluding an NK cell lymphoma. Immunohistochemical staining for specific B cell markers, CD20, CD79a and PAX-5 were negative, further excluding a neoplasm of B cell lineage. CD19 was attempted on the lymph node FNA specimen, but could not be successfully performed due to lack of viable cells remaining in the sample. Altogether, the immunophenoytpic and molecular findings confirmed the neoplasm’s T-cell lineage.
FC demonstrated unusual co-expression of CD19 in the neoplastic T-cells. In FC, CD19 is a key antigen used to define B cell populations; therefore, an FC panel with some redundancy built into its design is useful to confirm antigen expression and exclude an artifact of some kind. In this case, the CD19 co-expression on the aberrant T-cells was confirmed in two separate tubes containing CD19 and either CD3 or CD5, in both the FNA and peripheral blood specimens, and the findings were further supported in a 3rd tube, in which the aberrant CD19+ T-cell population was identified by its lack of surface kappa and lambda light chain immunoglobulin. The percentage of aberrant T cells of the total lymphoid cells was similar between the three separate tubes.
We also ruled out additional artifacts such as non-specific binding by monocyte Fc receptors by gating on the aberrant T cell population and demonstrating lack of CD14 expression. Non-specific binding by debris was excluded by analyzing the forward and side scatter characteristics of the aberrant T cell population, and confirming that the scatter properties were consistent with lymphoid cells, as the aberrant population fell within the lymphoid cell gate.
This is the first described case of a mature T cell neoplasm co-expressing CD19. This is an extremely rare event; however it is important to be aware of this rare phenomenon as it may cause a diagnostic dilemma.