Anatomic Pathology, Foundation IRCCS Policlinico San Matteo and University of Pavia, 27100 Pavia, Italy.
Hum Pathol. 2011 Aug;42(8):1204-8. doi: 10.1016/j.humpath.2010.11.015. Epub 2011 Feb 21.
Increased expression of cyclin D1 is notoriously associated with mantle cell lymphoma because of translocation t(11;14)(q13;q32) or variants involving the cyclin D1 gene. We present an unusual case of CD5-negative diffuse large B-cell lymphoma expressing cyclin D1 in the absence of translocation by fluorescence in situ hybridization analysis. Using array-comparative genomic hybridization, we found a complex karyotype without the characteristic chromosomal aberrations accompanying cyclin D1 translocation in mantle cell lymphoma; instead, there was monoallelic deletion of AKT interacting protein and glycogen synthase kinase-3 β genes, both involved in the AKT/glycogen synthase kinase-3 β cascade-controlling nuclear levels of cyclin D1. These findings suggest that posttranslational events regulating cyclin D1 activity may take place also in a subset of diffuse large B-cell lymphomas and contribute to lymphomagenesis. As a consequence, the sole cyclin D1 positivity by immunohistochemistry may not be enough to distinguish pleomorphic/blastoid mantle cell lymphoma from diffuse large B-cell lymphoma. Search for t(11;14) with fluorescence in situ hybridization probes should always be performed in doubtful cases.
由于易位 t(11;14)(q13;q32)或涉及 cyclin D1 基因的变体，cyclin D1 的表达增加与套细胞淋巴瘤明显相关。我们提出了一个不寻常的 CD5 阴性弥漫性大 B 细胞淋巴瘤病例，该病例通过荧光原位杂交分析在没有易位的情况下表达 cyclin D1。使用阵列比较基因组杂交技术，我们发现了一种复杂的核型，没有伴随 cyclin D1 易位的套细胞淋巴瘤的特征染色体异常；相反，存在 AKT 相互作用蛋白和糖原合酶激酶-3β 基因的单等位基因缺失，这两个基因都参与 AKT/糖原合酶激酶-3β 级联反应，控制 cyclin D1 的核水平。这些发现表明，调节 cyclin D1 活性的翻译后事件也可能发生在弥漫性大 B 细胞淋巴瘤的亚群中，并有助于淋巴瘤的发生。因此，单凭免疫组织化学检测 cyclin D1 阳性可能不足以将多形性/成骨性套细胞淋巴瘤与弥漫性大 B 细胞淋巴瘤区分开来。在有疑问的情况下，应始终使用荧光原位杂交探针进行 t(11;14)搜索。
