Relative frequency and clinicopathologic characteristics of MYC-rearranged follicular lymphoma

• DOI: 10.1016/j.humpath.2021.04.014
• Publication Date: 2021-05-05T02:13:31Z
• Authors: Shweta Chaudhary; Noah Brown; Joo Y. Song; Lin Yang; Pamela Skrabek; Michel R. Nasr; Jerry T. Wong; Victoria Bedell; Joyce Murata-Collins; Lindsay Kochan; Jie Li; Weiwei Zhang; Wing C. Chan; Dennis D. Weisenb...; Anamarija M. Perry
• Keywords: Adult; Aged, 80 and over; Gene Rearrangement; Male; DNA Mutational Analysis; Manitoba; Middle Aged; Prognosis; Immunohistochemistry; United States; 3. Good health; Proto-Oncogene Proteins c-myc; 03 medical and health sciences; 0302 clinical medicine; Tissue Array Analysis; Mutation; Biomarkers, Tumor; Humans; Female; Lymphoma, Follicular; In Situ Hybridization, Fluorescence; Aged

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.