Chaudhary Shweta, Brown Noah, Song Joo Y, Yang Lin, Skrabek Pamela, Nasr Michel R, Wong Jerry T, Bedell Victoria, Murata-Collins Joyce, Kochan Lindsay, Li Jie, Zhang Weiwei, Chan Wing C, Weisenburger Dennis D, Perry Anamarija M
Department of Pathology, University of Michigan, Ann Arbor, MI, 48109, USA.
Department of Pathology, City of Hope National Medical Center, Duarte, CA, 91010, USA.
Hum Pathol. 2021 Aug;114:19-27. doi: 10.1016/j.humpath.2021.04.014. Epub 2021 May 5.
MYC rearrangement is a relatively rare genetic abnormality in follicular lymphoma (FL). In this study, we evaluated the relative frequency of MYC rearrangement in 522 cases of FL and studied their clinicopathologic, cytogenetic, and molecular characteristics. Fluorescence in situ hybridization studies for MYC (break-apart probe), MYC/IGH, IGH/BCL2, and BCL6 rearrangements were performed on tissue microarrays. Immunohistochemical stains for CD10, BCL2, BCL6, and MYC were performed and scored on MYC-rearranged cases. On 4 FL cases, a custom targeted panel of 356 genes was used for mutation analysis. Ten cases (1.9%) were positive for MYC rearrangement. Histologically, 6 of 10 cases were grade 1-2, and 4 cases were grade 3A. By immunohistochemistry, 9 of 9 tested cases were CD10+, all cases were BCL6+, and 9/10 cases were BCL2+. MYC protein staining was low in all cases tested. IGH/BCL2 rearrangement was detected in 5 of 9 cases, whereas BCL6 rearrangement was detected in 3 of 7 tested cases and 4 of 10 cases showed MYC/IGH rearrangement. The most commonly detected mutations in the MYC-positive cases included HLA-B, TNFRSF14, and KMT2D. MYC and/or B2M abnormalities were detected in 2 cases. In conclusion, MYC rearrangement is uncommon in FL and these cases do not appear to have specific histologic characteristics. Molecular analysis showed abnormalities in genes associated with transformation, namely MYC and B2M. Larger studies are needed to evaluate if MYC-rearrangement in FL has prognostic significance.
MYC重排在滤泡性淋巴瘤（FL）中是一种相对罕见的基因异常。在本研究中，我们评估了522例FL中MYC重排的相对频率，并研究了它们的临床病理、细胞遗传学和分子特征。在组织微阵列上进行了针对MYC（断裂探针）、MYC/IGH、IGH/BCL2和BCL6重排的荧光原位杂交研究。对MYC重排的病例进行了CD10、BCL2、BCL6和MYC的免疫组织化学染色并评分。在4例FL病例中，使用定制的356个基因靶向面板进行突变分析。10例（1.9%）MYC重排呈阳性。组织学上，10例中有6例为1-2级，4例为3A级。通过免疫组织化学，9例检测病例中有9例CD10阳性，所有病例BCL6阳性，10例中有9例BCL2阳性。所有检测病例中MYC蛋白染色均较低。9例中有5例检测到IGH/BCL2重排，7例检测病例中有3例检测到BCL6重排，10例中有4例显示MYC/IGH重排。MYC阳性病例中最常检测到的突变包括HLA-B、TNFRSF14和KMT2D。2例检测到MYC和/或B2M异常。总之，MYC重排在FL中不常见，这些病例似乎没有特定的组织学特征。分子分析显示与转化相关的基因存在异常，即MYC和B2M。需要更大规模的研究来评估FL中的MYC重排是否具有预后意义。
