The googly of CD3 in Plasmablastic Lymphomas

Introduction / Background / Significance: Plamablastic lymphomas (PBL) are a type of B-cell lymphomas with aggressive biology seen mainly in the elderly and immunocompromised. While aberrant expression of CD3, which is a pan T-cell Immunohistochemistry (IHC) marker, is sometimes seen in B cell lymphomas, it's occurrence in PBL is very rare and creates a major diagnostic dilemma. This is further complicated due to expression of overlapping markers like MUM1 and CD56 along with expression of Epstein-Barr Virus (EBV) encoded mRNAs (EBER) on RNA in-situ hybridization (RISH) in both PBL and certain T-cell lymphomas. We herein present three such interesting cases of aberrant expression of CD3 in PBL, one of which was particularly tricky and was referred to us due to poor treatment response after earlier being diagnosed as T/NK cell lymphoma at another center. While careful and systematic IHC evaluation suffices in most cases, molecular testing for immunoglobulin heavy chain (IGH) and T-cell receptor Gamma (TRG) gene rearrangements should be done for confirmation wherever needed.

Materials and Methods / Case Presentation / Objective: The first case was of an eighty-year-old, HIV positive male patient, who presented with pain and swelling in posterior chest wall caused by a progressively increasing mass measuring 5.5 x 4 x 3 cm. The mass did not involve the underlying bone. Biopsy was sent to a local diagnostic center where it was reported as a poorly differentiated malignant neoplasm and was referred to our center for IHC evaluation and further work up. The second case was of a 60 year old female patient, who presented with a rapidly increasing nasal mass with aggressive local invasion measuring 3 x 2.2 x 2 cm. Biopsy was reported as T/NK cell lymphoma at another center and treatment was initiated. The blocks were sent to our center for review due to poor treatment response. The third case was of a 62-year-old male patient who presented with pneumonia and a large perianal mass measuring 7 x 6.2 x 5 cm with few enlarged inguinal lymph nodes. HIV status was not known for the second and the third case. Histopathology in all the cases showed sheets of monotonous intermediate to large sized atypical lymphoid cells with immunoblastic features. Individual cells had basophilic cytoplasm, pleomorphic nuclei with prominent nucleoli. Few cells showed plasmablastic morphology. Numerous mitotic figures and areas of necrosis were seen. The third case showed more cells with plasmacytoid morphology.

Results / Description / Main Outcome Measure(s): The neoplastic cells in all cases expressed CD138, CD3, CD56, MUM1, EMA and were positive for expression of EBER on RISH. Light chain restriction was noted in all the cases, while Kappa restriction was noted for the first two cases, Lambda restriction was seen in the third case. CD79a was positive but expression in the second case was weak and focal. The cells were largely negative for CD45 in first two cases but showed expression for the same in the third. In all three instances, the neoplastic cells were negative for CD20 and other pan T-cell markers which included CD2, CD5 and CD7. The second case which was also confirmed on molecular testing with PCR assays, showed clonal IGH gene rearrangement but was negative for TRG gene rearrangement. Since the HIV status was unknown for the second and third case at the time of receiving the blocks, it was sought once the diagnosis of PBL was established. It was found to be negative in the second case but positive in the third.

Conclusion(s): Aberrant expression of CD3 poses a major diagnostic challenge in cases of PBL. This is further complicated due to the loss of one or more pan T-cell markers in T-cell lymphomas along with expression of CD56 and EBER in certain T- cell lymphomas like the T/NK cell lymphomas. A careful clinical and histopathological evaluation with use of appropriate IHC markers for B cell and plasmablastic differentiation, can in most cases obliviate the need for Molecular testing, which should be resorted to for confirmation wherever deemed necessary. Differentiating the two entities is of paramount importance in these scenarios given the different treatment involved, a lapse in which could be detrimental for the patient.

References

1. Pan, Z., Chen, M., Zhang, Q. et al. CD3-positive plasmablastic B-cell neoplasms: a diagnostic pitfall. Mod Pathol 31: 718–731, 2018.

2. Valera A, Balagué O, Colomo L, et al. IG/MYC rearrangements are the main cytogenetic alteration in plasmablastic lymphomas. Am J Surg Pathol 34(11):1686-1694, 2010.