Immunohistochemical Profile and Prognostic Significance in Chinese Primary Central Nervous System Lymphoma: Analysis of 132 Cases

Abstract

Primary central nervous system lymphoma (PCNSL) is aggressive and confined to the central nervous system, including the brain parenchyma, leptomeninges, spinal cord, eyes or cranial nervous. Morphologically, approximately 95% of these tumors are DLBCL according to the new World Health Organization (WHO) classification. However, PCNSL has treatment outcome distinct from those of systemic DLBCL, as well as dismal prognosis than systemic DLBCL. Our goal was to determine the immunohistochemical profile and prognostic significance for 132 Chinese PCNSL cases. The expression of CD20, CD10, BCL-6, MUM1, CD138, BCL-2, and Ki67 antigens were observed by immunohistochemical method. All cases expressed CD20. CD10, BCL-6, and MUM1 were positive in 15.2% (20/132), 86.4% (114/132), 90.2% (119/132). CD138 was negative in 100% (39/39). BCL-2 was positive in 89.3% (108/121). The Ki67 antigen, a proliferative index, ranging from 1% to 100% (median 85.3%) and 76.5% (101/132) PCNSLs showed Ki67 ≥ 90%. Among 132 cases, 25 (18.9%) were classified as germinal center B-cell-like (GCB); 107 (81.1%) were classified as activated B-cell-like (ABC). The Ki67 index in 25 GCB was similar to that in 107 ABC (p=0.663>0.05). No significant correlation was found between Ki67 index and BCL-2 (p=0.225>0.05). Significant positive correlation was found between Ki67 index and BCL-6 expression (p=.000<0.05). Among 132 cases, 43 had complete data of treatment that received chemotherapy regimens based on HD-MTX. GCB and ABC had similar OS (p=0.969) and PFS (p=0.070). These findings support that PCNSL predominantly express an ABC immunophenotype and express high Ki67 index, and suggest that the proliferative activity of GCB was similar to ABC and the expression of BCL-6 but not BCL-2 was positively correlated with the malignant degree of tumors. Table 1. Clinical characteristics. Characteristics Patients, n (%) Age (years); n=132 ≥60 y, n=53; <60 y, n=79 Median (range) 57 (21-85) Gender; n=132 Male 69 (52.3) Female 63 (47.7) ECOG; n=43 0-1 8 (18.6) 2-4 35 (81.4) LDH; n=43 Normal 25 (58.1) Elevated 18 (41.9) Numbers of lesions; n=132 1 48 (36.4) >2 84 (63.6) Involvement of deep structures; n=132 Absence 43 (32.6) Presence 89 (67.4) Table 2. Hans classification. CD10 BCL-6 MUM1 Immunoprofile PCNSL, n (%) + + + GCB 16 (12.1) + + - GCB 3 (2.3) + - + GCB 0 (0) + - - GCB 1 (0.7) - + - GCB 5 (3.8) - + + Non-GCB 90 (68.2) - - + Non-GCB 12 (9.1) - - - Non-GCB 5 (3.8) Table 3. Chang classification. CD10 BCL-6 MUM1 Immunoprofile PCNSL, n (%) + + - GCB (Pattern A) 3 (2.4) + - - GCB (Pattern A) 1 (0.8) - + - GCB (Pattern A) 5 (3.9) + + + activated GCB (Pattern B) 16 (12.6) + - + activated GCB (Pattern B) 0 (0) - + + activated GCB (Pattern B) 90 (70.9) - - + activated non-GCB (Pattern C) 12 (9.4) Figure 1. Immunohistochemical labeling. Figure 1. Immunohistochemical labeling. Figure 2. Kaplan-Meier curve shows clinical prognostic variables and their relationship to OS and/or PFS. Figure 2. Kaplan-Meier curve shows clinical prognostic variables and their relationship to OS and/or PFS. Figure 3. T1 axial, post-gadolinium magnetic resonance imaging of PCNSL. Figure 3. T1 axial, post-gadolinium magnetic resonance imaging of PCNSL. Disclosures No relevant conflicts of interest to declare.

Intratumor heterogeneity and T cell exhaustion in primary CNS lymphoma

“…2B, Additional file 6: Table S4). In accordance with flow cytometry, CD27 and CD38 expressions were increased in mBc and SDC1/CD138 was absent, as it is well known in PCNSL [32] (Fig. 2B).…”