Bcl-2 Maturation Pattern in T-Cells Distinguishes Thymic Neoplasm/Hyperplasia, T-Lymphoblastic Lymphoma and Reactive Lymph Nodes
Junaid Baqai, Marc Smith, James Huang. William Beaumont Hospital, Royal Oak, MI
Background: Evaluation of lymphoid tissue from mediastinal biopsies can be very challenging. In cases with predominantly T-cell infiltrates, the differential diagnosis includes thymic neoplasm/hyperplasia (THY), T-cell lymphoblastic lymphoma (T-LBL) and reactive lymph nodes (RLN), all of which contain of small lymphocytes. Previous studies of normal thymus have shown a triphasic bcl-2 expression pattern in thymic T-cells that corresponds with T-cell maturation. However the utility of this finding in distinguishing T-cells of THY, T-LBL and RLN has not been carefully evaluated.
Design: Using electronic medical records, we searched for cases of THY, LBL and RLN. Cases that lacked flow cytometry (FC) or bcl-2 in the antibody panel were excluded. The remaining cases were analyzed by 5 color FC for CD3 and bcl-2 expression in T-cells. Mean bcl-2 expression of total T-cells in the 3 groups was measured and compared using ANOVA. In addition, each case was then classified based on the number of T-cell maturation stages/phases present as heterogeneous (>2 stages) or non-heterogeneous. Groups were compared with Fisher's exact test.
Results: Altogether, 72 cases (17 THY, 6 T-LBL, 49 RLN) were analyzed. Overall, bcl-2 expression was significantly lower in THY (mean 2.318 ± 1.655) than T-LBL (4.350 ± 3.146 p<0.05) and RLN (4.247 ± 1.017 p<0.001). In THY, bcl-2 expression was heterogeneous in all cases (17/17), showing 4 distinct and reproducible stages of T cell maturation: stage 1 (CD3- bcl-2+), stage 2 (CD3+ dim, bcl-2-), stage 3 (CD3+ moderate, bcl-2-) and stage 4 (CD3+ bright, bcl-2+) [see fig.1]. This stepwise maturation pattern was diminished/absent in T-LBL and RLN as reflected by an absence of heterogeneous cases in both groups (0/6 p = <0.0001 and 0/49 <0.0001, respectively).
Conclusions: Using FC, we demonstrate that thymic T-cells in THY have a bcl-2 maturation pattern similar to that of normal thymus. Furthermore, this pattern can be divided into 4 stages based on CD3/bcl-2 coexpression. The presence of this maturation pattern in mediastinal biopsies can be used to distinguish normal thymus, thymic hyperplasia or thymoma from T-LBL and RLN, both of which show more homogeneity in CD3/bcl-2 coexpression and higher overall bcl-2 expression.
Monday, March 4, 2013 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 200, Monday Morning