TY - JOUR
T1 - Blastoid and Pleomorphic Mantle Cell Lymphoma Demonstrate Distinct Clinicopathologic and Genetic Features
AU - Khanlari, Mahsa
AU - Mo, Huan
AU - Kim, Do Hwan
AU - Sakhdari, Ali
AU - Young, Ken H.
AU - Jain, Preetesh
AU - Wang, Michael
AU - Li, Shaoying
AU - Kanagal-Shamanna, Rashmi
AU - Miranda, Roberto N.
AU - Vega, Francisco
AU - Medeiros, L. Jeffrey
AU - Ok, Chi Young
N1 - Publisher Copyright:
© 2023 Lippincott Williams and Wilkins. All rights reserved.
PY - 2023/8/1
Y1 - 2023/8/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85165220931&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85165220931&partnerID=8YFLogxK
U2 - 10.1097/PAS.0000000000002068
DO - 10.1097/PAS.0000000000002068
M3 - Article
C2 - 37288826
AN - SCOPUS:85165220931
SN - 0147-5185
VL - 47
SP - 849
EP - 858
JO - American Journal of Surgical Pathology
JF - American Journal of Surgical Pathology
IS - 8
ER -