Department of Pathology and Laboratory Medicine, Weill Medical College of Cornell University, New York, NY 10065, USA.
Mod Pathol. 2009 Nov;22(11):1507-17. doi: 10.1038/modpathol.2009.106. Epub 2009 Jul 24.
Among the diffuse lymphomas of B-cell origin, we have encountered one variant displaying blastoid features that morphologically mimic lymphoblastic lymphoma, the blastoid variant of mantle cell lymphoma, and the so-called blastoid transformation of follicular lymphoma. To better characterize this entity, we studied eight cases morphologically, immunohistochemically, and by fluorescence in situ hybridization (FISH) for cytogenetic abnormalities commonly associated with follicular lymphoma and B-cell lymphomas exhibiting high-grade histological features. All eight cases were presented as de novo neoplasms, and displayed an entirely diffuse (five cases) or only minimal follicular (three cases) growth pattern. The neoplastic lymphoid cells were of medium size with round nuclei, fine chromatin, inconspicuous nucleoli, and high mitotic rate; they expressed CD10, BCL6, and BCL2-a phenotype consistent with follicle center cell origin. A proportion of cases expressed MUM1. Their lack of TdT and CYCLIN D1 distinguished them from lymphoblastic lymphoma and the blastoid mantle cell lymphoma, respectively. The neoplastic lymphoid cells consistently expressed CD43 (seven of eight cases) and occasionally other T-cell-associated antigens, including CD5, CD7, CD8, and CD57. Although all cases overexpressed BCL2, t(14;18) was not detected in any of the five cases examined by FISH; instead, extra copies of chromosome 18 were found in four of five cases. Finally, other cytogenetic abnormalities, including structural abnormalities of BCL6 (allelic loss/gain, rearrangement), monosomy 7, del(13)(q14), and MYC allelic loss, were frequently detected. The combination of a B-cell CD10+ BCL6+ BCL2+ phenotype in the presence of structural abnormalities of BCL6 is consistent with a follicular center cell derivation for our cases. The lack of t(14;18) seen in our cases, although rare in most cases of follicular lymphoma, has been nevertheless reported in cases of follicular lymphoma with a predominantly diffuse growth pattern. The molecular pathogenesis, clinical manifestations, and prognostic significance of these lesions remain to be elucidated.
在 B 细胞来源的弥漫性淋巴瘤中，我们遇到了一种具有母细胞淋巴瘤的母细胞样变体、所谓滤泡性淋巴瘤的母细胞样转化以及淋巴母细胞性淋巴瘤的母细胞样特征的变体。为了更好地描述这种实体，我们通过荧光原位杂交（FISH）研究了形态学、免疫组织化学和 8 例与滤泡性淋巴瘤和具有高级别组织学特征的 B 细胞淋巴瘤相关的细胞遗传学异常。所有 8 例均为初发性肿瘤，表现为完全弥漫性（5 例）或仅最小滤泡性（3 例）生长模式。肿瘤性淋巴样细胞为中等大小，圆形核，细染色质，不明显核仁，有丝分裂率高；它们表达 CD10、BCL6 和 BCL2-a，表现型与滤泡中心细胞起源一致。一部分病例表达 MUM1。它们缺乏 TdT 和 CYCLIN D1，分别与淋巴母细胞性淋巴瘤和母细胞样套细胞淋巴瘤相区别。肿瘤性淋巴样细胞一致表达 CD43（8 例中的 7 例），偶尔还表达其他 T 细胞相关抗原，包括 CD5、CD7、CD8 和 CD57。尽管所有病例均过度表达 BCL2，但在通过 FISH 检查的 5 例中均未检测到 t(14;18)；相反，在 5 例中的 4 例中发现了 18 号染色体的额外拷贝。最后，还经常检测到其他细胞遗传学异常，包括 BCL6 的结构异常（等位基因丢失/获得、重排）、7 号单体、del(13)(q14)和 MYC 等位基因丢失。我们病例中存在 B 细胞 CD10+BCL6+BCL2+表型，同时存在 BCL6 的结构异常，与滤泡中心细胞起源一致。尽管在大多数滤泡性淋巴瘤病例中很少见，但我们病例中未见 t(14;18)，但已在具有弥漫性生长模式为主的滤泡性淋巴瘤病例中报道。这些病变的分子发病机制、临床表现和预后意义仍有待阐明。
