Matsumoto, Nana

Abstract Objectives Per National Comprehensive Cancer Network guidelines for acute myeloid leukemia (AML), bone marrow (BM) evaluation is recommended after starting induction chemotherapy at 14 to 21 days (mid-induction) and 30 to 35 days (postinduction). Timely assessment of residual morphologic and molecular disease is challenging at these time points, given the low cellularity, the lack of CD34 or CD117 expression by blasts in most NPM1-mutated (NPM1mut) AML, and the longer turnaround time for molecular testing. Methods NPM1 mut AML undergoing BM evaluation at mid- and postinduction with concurrent flow cytometry and NPM1 real-time polymerase chain reaction or next-generation sequencing was evaluated. Different cell types positive by NPM1 immunohistochemistry (IHC) were enumerated, and the results were compared with flow cytometry and molecular findings. Results NPM1 IHC demonstrated a sensitivity of 78% and 41% for detecting residual mutation at mid- and postinduction, respectively, with a positive predictive value ranging from 88% to 100%. Of 16 IHC-negative cases, 3 had no residual NPM1 mutation, 12 had very low-level mutation at a variant allele frequency of less than or equal to 21 transcripts, and only 1 had a high-level mutation in a markedly hypocellular BM. Of 24 IHC-positive cases, 22 had residual NPM1 mutation, and 2 showed false-positive staining in only a single cell with no residual NPM1 mutation. The level of IHC staining was mostly proportional to the level of residual mutation. Conclusions Mutation-specific NPM1 IHC is a valuable tool for a rapid assessment of residual morphologic and molecular disease in mid- and postinduction NPM1mut AML.

Abstract Objective Rare large B-cell lymphomas (LBCLs) present with concurrent or subsequent lymphomatous effusion (solid-effusion LBCL, SE-LBCL), which may have an inferior prognosis compared with their noneffusion counterpart. In addition, the relationship between SE-LBCL and human herpesvirus 8–negative effusion-based LBCL (EB-LBCL) remains unclear. Methods We collected 141 cases of SE-LBCL and a control cohort of 101 cases of stage IV solid-only LBCL. The clinicopathologic features were analyzed and compared between SE-LBCL and solid-only LBCL. Results Patients with SE-LBCL had a median age of 67 years with a male-to-female ratio of 1.3:1. Eighty-six patients had concurrent solid lymphoma and lymphomatous effusion, whereas 55 developed lymphomatous effusion subsequently. Most cases involved the pleural cavities (79%, 112/141), followed by the peritoneal (21%, 29/141) and pericardial (11%, 16/141) cavities. BCL6, CD10, and MUM1 were expressed in 77% (90/117), 46% (60/130), and 61% (58/95) of cases, respectively, and 58% (71/123) were subclassified into the germinal center B-cell (GCB) subtype. Rearrangements of BCL2, BCL6, and MYC were detected in 42% (31/73), 35% (22/63), and 40% (35/88), respectively, and 22% (19/87) had both MYC and BCL2 rearrangements. The patients with SE-LBCL had a dismal prognosis, with a median survival of 5.7 months, which was significantly worse than solid-only LBCL (147.5 months; P < .0001). Conclusions The pathologic features of SE-LBCL were similar to those of solid-only LBCL but distinct from those of EB-LBCL; in particular, lymphomatous effusion was an independently adverse prognostic factor in LBCL. Our study underscores the need for surveillance of lymphomatous effusion during LBCL staging and development of effective therapeutic regimens for SE-LBCL.