Stage, age, and EBV status impact outcomes of plasmablastic lymphoma patients: a clinicopathologic analysis of 61 patients

Abstract

Background: Plasmablastic lymphoma (PBL) is a rare aggressive neoplasm with lymphoid and plasmacytic differentiation that is commonly associated with immunodeficiency and an unfavorable prognosis. Clinicopathologic features have been largely derived from cases reports and small series with limited outcome analyses.

Patients and methods: The demographic, clinicopathologic features, and clinical outcomes of a cohort of 61 patients with PBL were reviewed and analyzed.

Results: Patients had a median age of 49 years (range 21-83 years) and most (49/61; 80%) were men. Human immunodeficiency virus (HIV) status was available for 50 patients: 20 were HIV-positive and 30 HIV-negative. Twenty-three patients were immunocompetent. Abdominal/gastrointestinal complaints were the most common presenting symptoms, reported in 14 of 47 (30%) of patients. At presentation, 24 of 43 (56%) patients had stage III or IV disease. Epstein-Barr virus (EBV) was detected in 40 of 57 (70%) cases. MYC rearrangement was identified in 10/15 (67%) cases assessed, and MYC overexpression was seen in all cases assessed regardless of MYC rearrangement status. HIV-positive patients were significantly younger than those who were HIV-negative (median 42 vs. 58 years; p = 0.006). HIV-positive patients were also significantly more likely to have EBV-positive disease compared with HIV-negative patients (19/19, 100% vs. 15/29, 52%; p = 0.002). Patients who received CHOP chemotherapy tended to have better overall survival (OS) compared with those who received hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (hyper-CVAD) (p = 0.078). HIV status had no impact on OS. Patients with EBV-positive PBL had a better event-free survival (EFS) (p = 0.047) but not OS (p = 0.306). Notably, OS was adversely impacted by age ≥ 50 years (p = 0.013), stage III or IV disease (p = <0.001), and lymph node involvement (p = 0.008).

Conclusions: The most significant prognostic parameters in patients with PBL are age, stage, and, to a lesser extent, EBV status. In this study, two-thirds of PBL cases assessed were associated with MYC rearrangement and all showed MYC overexpression.

Fig. 1

Representative case of plasmablastic lymphoma. a Neoplastic cells have plasmablastic morphology, with a prominent nucleolus and moderate amount of cytoplasm. Mitotic figures and tingible-body macrophages are abundant and impart a “starry-sky” pattern (H&E, ×200). b The neoplastic cells are diffusely positive for EBV-encoded RNA (EBER) by colorimetric in situ hybridization (×200). c CD20 expression is absent. This case was negative for CD19 and positive for CD38 by flow cytometry (data not shown) (×200). d MYC overexpression is positive by immunohistochemistry (×200). e Karyotype of case 30 (nasopharyngeal mass): 46, XY, del(6)(q23q29),t(8;14)(q24;q32), add(20)(p13). f Fluorescence in situ hybridization using a dual-color break-apart probe specific for the MYC locus on formalin-fixed paraffin-embedded tissue (case 30) showing split signals in ~80 % of nuclei (circle: fusion signal; arrow: split signal)

Fig. 2

Schematic representation of the immunophenotypic features of plasmablastic lymphoma cases in this study

Fig. 3

Overall survival of plasmablastic lymphoma patients showing a significant adverse impact of age >50 years (a) and lymph node involvement (b). Patients who presented with Ann Arbor stage III or IV disease had worse overall (c) and event-free survival (d) compared to patients who presented with stage I or II