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. 2015 Aug 13;126(7):863-72.
doi: 10.1182/blood-2015-02-630632. Epub 2015 May 21.

EBV-positive large B-cell lymphomas in young patients: a nodal lymphoma with evidence for a tolerogenic immune environment

Alina Nicolae  1 , Stefania Pittaluga  1 , Shahed Abdullah  1 , Seth M Steinberg  2 , Thu Anh Pham  3 , Theresa Davies-Hill  1 , Liqiang Xi  3 , Mark Raffeld  3 , Elaine S Jaffe  1
Affiliations

EBV-positive large B-cell lymphomas in young patients: a nodal lymphoma with evidence for a tolerogenic immune environment

Alina Nicolae et al. Blood. .

Abstract

Few studies have reported Epstein-Barr virus-positive (EBV(+)) large B-cell lymphomas (LBCLs) in young patients without immunodeficiency. We identified 46 such cases in patients ≤45 years of age and analyzed the clinical and pathological characteristics. EBV(+) LBCLs affected predominantly males (male:female = 3.6:1), with a median age of 23 years (range, 4-45 years). All patients presented with lymphadenopathy and 11% also had extranodal disease. Morphologically, 3 patterns were identified: T-cell/histiocyte-rich large B-cell lymphoma-like (n = 36), gray zone lymphoma (n = 7), and diffuse LBCL-not otherwise specified (n = 3). Tumor cells (EBV(+) in >90% of cells) expressed B-cell antigens, were often CD30 and PD-L1 positive, and showed a nongerminal center immunophenotype. A total of 93% expressed EBV latency type II and 7% latency type III. Indoleamine 2,3-dioxygenase was expressed on background accessory cells. The most common treatment regimen was rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (58%), with local radiation therapy added in 21%. With a median follow-up of 22 months, 82% of patients are in clinical remission and only 8% died of disease. Younger patients achieved a significantly higher overall survival than prior series of EBV(+) LBCLs reported in the elderly (P < .0001). In conclusion, EBV(+) LBCLs are not restricted to the elderly. Young patients present with nodal disease and have a good prognosis.

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Figures

Figure 1
Figure 1
THRLBCL-like cases (case 13 [A-C,G,H,J-L], case 11 [D-F], and case 16 [I]). (A) The lymph node shows effacement of the architecture. (B) Scattered mono- or multilobated tumor cells, some HRS-like, are observed in a lymphohistiocytic microenvironment. (C) Bone marrow biopsy shows similar morphology. (D) Case 11 shows a diffuse proliferation, rich in histiocytes with sparse tumor cells, morphologically indistinguishable from THRLBCL. (E) Foci of necrosis are present. (F) The tumor cells are positive for CD20, with rare small B cells in the background. Most cases expressed CD79a (G), CD30 (H), PD-L1 (I), LMP1 (J), and EBER (K). (L) Numerous dendritic cells/histiocytes IDO positive are present in the microenvironment. Original magnifications: ×40 (A), ×100 (E), ×200 (D,F), and ×400 (B,C,D inset, G-L).
Figure 2
Figure 2
GZL (case 43). (A) The lymph node architecture is altered by nodular proliferation divided by collagen bands. (B) Sheets of large cells resembling HRS cells and variants—admixed with small lymphocytes, eosinophils, and granulocytes—are identified. (C) Foci of necrosis are present. The tumor cells are strongly and uniformly positive for CD20 (D), PAX5 (E), and Oct-2 (F). They are also positive for CD30 (G), CD15 (H), LMP1 (I), and EBER (J). Original magnifications: ×40 (A); ×200 (C), and ×400 (B,D-J).
Figure 3
Figure 3
DLBCL-NOS (case 45). (A) Diffuse lymphoid proliferation of medium to large cells that dissects the skeletal muscle of chest wall. (B) Mitotic figures were readily seen. The tumor cells are positive for CD79a focal (C), PAX5 strong (D), MUM1 (E), LMP1 (F), and EBNA2 (G). This was 1 of 3 cases that expressed a latency III phenotype. Original magnifications: ×200 (A) and ×400 (B-G).
Figure 4
Figure 4
Distribution of EBV+ LBCLs per age group. The age distribution followed a Gaussian curve, with a peak in the third decade of life (n = 19).
Figure 5
Figure 5
Kaplan-Meier curves of EBV+ LBLCs in young patients. (A) Overall survival of morphological subgroups of EBV+ LBCLs in young patients (≤45 years); overall survival THRLBCL-like vs GZL at 3 years is 95.8% and 75%, respectively (P = .17). (B) Overall survival of EBV+ LBCL in young patients, all groups, regardless of morphological pattern and EBV+ DLBCL in elderly patients (>45 years of age) including all causes of death, is 89.0% and 24.4% at 5 years, respectively (P < .0001).
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