Affiliation:
1. Hematopathology
2. Division of Hematopathology, Department of Pathology, Duke University School of Medicine, Durham, NC
3. Lymphoma, The University of Texas MD Anderson Cancer Center, Houston, TX
Abstract
The blastoid (B) and pleomorphic (P) variants of mantle cell lymphoma (MCL) are associated with aggressive clinical behavior. In this study, we collected 102 cases of B-MCL and P-MCL from untreated patients. We reviewed clinical data, analyzed morphologic features using an image analysis tool (ImageJ) and we assessed mutational and gene expression profiles. The chromatin pattern of lymphoma cells was assessed quantitatively by the pixel value. Cases of B-MCL showed a greater median pixel value with lower variation compared with P-MCL, indicating a homogeneously euchromatin-rich pattern in B-MCL. In addition, the Feret diameter of the nuclei was significantly smaller (median 6.92 vs. 8.49 µm per nucleus, P<0.001) and had a lesser degree of variation in B-MCL compared with P-MCL, indicating that B-MCL cells have smaller cells with a more monomorphic appearance. B-MCL showed a significantly higher median Ki-67 proliferation rate (60% vs. 40%, P=0.003), and affected patients had poorer overall survival compared with those with P-MCL (median overall survival: 3.1 vs. 8.8 y, respectively, P=0.038). NOTCH1 mutation was significantly more frequent in B-MCL compared with P-MCL (33% and 0%, respectively, P=0.004). Gene expression profiling showed 14 genes overexpressed in B-MCL cases and gene set enrichment assay for the overexpressed genes showed significant enrichment in the cell cycle and mitotic transition pathways. We also report a subset of MCL cases that has blastoid chromatin but a higher degree of pleomorphism in nuclear size and shape, designated here as hybrid MCL. Hybrid MCL cases had a similar Ki-67 proliferation rate, mutation profile, and clinical outcome to B-MCL and distinct from P-MCL. In summary, these data suggest biological differences between B-MCL and P-MCL cases justifying their separate designation when possible.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Subject
Pathology and Forensic Medicine,Surgery,Anatomy
Cited by
4 articles.
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