University of Pittsburgh School of Medicine, Pittsburgh, PA.
Am J Surg Pathol. 2018 Mar;42(3):342-350. doi: 10.1097/PAS.0000000000001015.
Myocyte enhancer binding factor 2B (MEF2B) is a transcriptional activator of the BCL6 proto-oncogene in normal germinal center (GC) B-cells. Limited data exists concerning its expression in B-cell lymphomas, and comparison with other GC-associated antigens is lacking. Its role in the differential diagnosis of B-cell lymphomas, particularly in the distinction of follicular lymphoma (FL) versus marginal zone lymphoma (MZL), remains to be determined. We evaluated MEF2B expression, in comparison with additional GC markers, LIM domain-only transcription factor 2 (LMO2), and human GC-associated lymphoma (HGAL), in a variety of B-cell lymphomas, with particular emphasis on their utility in differentiating FL from MZL. MEF2B was positive in all FL and Burkitt lymphomas, 8/9 mantle cell lymphomas, 2/24 splenic MZL, 1/10 chronic lymphocytic leukemia/small lymphocytic lymphomas, and 38/44 diffuse large B-cell lymphoma (DLBCL), but was negative in all extranodal MZL of mucosa-associated lymphoid tissue, nodal MZL, and B-lymphoblastic lymphomas. Focusing on low-grade FL versus MZL, MEF2B was 100% sensitive and 95% specific for FL, which was similar to BCL6, but superior to LMO2 (sensitivity 87%, specificity 86%) and HGAL (sensitivity 97%, specificity 86%). Importantly, MEF2B was positive in 4/4 FL with plasmacytoid differentiation, which were CD10, only weakly BCL6, and included 1 case that lacked both LMO2 and HGAL expression. MEF2B was positive in 22/25 (88%) GC-type DLBCL, but was also positive in 16/19 (61%) non-GC-type DLBCL. MEF2B shows superior sensitivity and specificity than LMO2 and HGAL in the differential diagnosis of FL versus MZL and is particularly useful in FL with plasmacytoid differentiation, which may have morphologic and immunophenotypic overlap with MZL. MEF2B, however, is not specific for GC-derived B-cell lymphomas as it is also apparently positive in most mantle cell lymphoma and many non-GC-type DLBCL.
肌细胞增强因子 2B（MEF2B）是正常生发中心（GC）B 细胞中 BCL6 原癌基因的转录激活因子。关于其在 B 细胞淋巴瘤中的表达的数据有限，并且缺乏与其他 GC 相关抗原的比较。其在 B 细胞淋巴瘤鉴别诊断中的作用，特别是在滤泡性淋巴瘤（FL）与边缘区淋巴瘤（MZL）的鉴别诊断中的作用仍有待确定。我们评估了 MEF2B 的表达，与其他 GC 标志物（LIM 结构域仅转录因子 2（LMO2）和人 GC 相关淋巴瘤（HGAL）进行比较，用于各种 B 细胞淋巴瘤，特别强调其在区分 FL 与 MZL 中的作用。MEF2B 在所有 FL 和伯基特淋巴瘤、8/9 例套细胞淋巴瘤、2/24 例脾 MZL、1/10 例慢性淋巴细胞白血病/小淋巴细胞淋巴瘤和 38/44 例弥漫性大 B 细胞淋巴瘤（DLBCL）中均为阳性，但在所有结外黏膜相关淋巴组织 MZL、结内 MZL 和 B 淋巴细胞白血病中均为阴性。在关注低级别 FL 与 MZL 时，MEF2B 对 FL 的敏感性为 100%，特异性为 95%，与 BCL6 相似，但优于 LMO2（敏感性 87%，特异性 86%）和 HGAL（敏感性 97%，特异性 86%）。重要的是，MEF2B 在 4/4 例具有浆母细胞分化的 FL 中为阳性，这些 FL 为 CD10、仅弱 BCL6，包括 1 例既缺乏 LMO2 又缺乏 HGAL 表达的病例。MEF2B 在 22/25 例（88%）GC 型 DLBCL 中为阳性，但在 16/19 例（61%）非 GC 型 DLBCL 中也为阳性。MEF2B 在 FL 与 MZL 的鉴别诊断中的敏感性和特异性优于 LMO2 和 HGAL，并且在具有浆母细胞分化的 FL 中特别有用，其可能与 MZL 在形态学和免疫表型上重叠。然而，MEF2B 不是 GC 衍生 B 细胞淋巴瘤的特异性标志物，因为它在大多数套细胞淋巴瘤和许多非 GC 型 DLBCL 中也明显阳性。
