PMID- 34392269
OWN - NLM
STAT- MEDLINE
DCOM- 20220214
LR  - 20220217
IS  - 1532-0979 (Electronic)
IS  - 0147-5185 (Linking)
VI  - 46
IP  - 1
DP  - 2022 Jan 1
TI  - Mutational Landscape of TdT+ Large B-cell Lymphomas Supports Their Distinction 
      From B-lymphoblastic Neoplasms: A Multiparameter Study of a Rare and Aggressive 
      Entity.
PG  - 71-82
LID - 10.1097/PAS.0000000000001750 [doi]
AB  - In the current World Health Organization classification, terminal 
      deoxynucleotidyl transferase (TdT) expression in a high grade/large cell B-cell 
      lymphoma (LBCL) indicates a B-lymphoblastic lymphoma/leukemia (B-LBL), although 
      TdT expression in what appear to be mature LBCL or following mature B-cell 
      neoplasms is reported. The frequency of TdT+ LBCL, how to best categorize these 
      cases, and their clinicopathologic features, molecular landscape, and 
      relationship to classic B-LBL remain to be better defined. TdT expression was 
      therefore assessed in 258 LBCL and the results correlated with the cytologic, 
      phenotypic, and cytogenetic findings. Targeted mutational analysis, review of 
      prior biopsies, and assessment of clinical associations was performed in the 6 
      cases with >10% TdT+ cells. All 6 TdT+ LBCL were blastoid-appearing, CD34-, MYC+, 
      BCL2+, and had MYC rearrangements (R) (5/6 with BCL2 and/or BCL6-R). 5/6 had a 
      prior TdT- LBCL and/or follicular lymphoma and all had an aggressive course. 
      Fifteen nonsynonymous variants in 11 genes were seen in the 4/5 tested cases with 
      mutations. TdT+ and TdT- areas in 1 case showed identical mutations. The 
      mutational profiles were more like those reported in germinal center B-cell 
      type-diffuse LBCL rather than B-LBL. Evolution from preceding TdT- lymphomas was 
      nondivergent in 1/3 tested cases and partially divergent in 2. The 
      clinicopathologic and cytogenetic features of these 6 cases were similar to those 
      found in a meta-analysis that included additional cases of TdT+ LBCL or B-LBL 
      following follicular lymphoma. Thus, TdT+, CD34- large B-cell neoplasms with MYC 
      rearrangements and often a "double hit" are rare, frequently a transformational 
      event and aggressive but are distinct from classic B-LBL.
CI  - Copyright (c) 2021 Wolters Kluwer Health, Inc. All rights reserved.
FAU - Bhavsar, Shweta
AU  - Bhavsar S
AD  - Department of Pathology, UPMC.
FAU - Liu, Yen-Chun
AU  - Liu YC
AD  - Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, 
      PA.
FAU - Gibson, Sarah E
AU  - Gibson SE
AD  - Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, 
      PA.
FAU - Moore, Erika M
AU  - Moore EM
AD  - Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, 
      PA.
FAU - Swerdlow, Steven H
AU  - Swerdlow SH
AD  - Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, 
      PA.
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Meta-Analysis
PT  - Review
PL  - United States
TA  - Am J Surg Pathol
JT  - The American journal of surgical pathology
JID - 7707904
RN  - 0 (BCL2 protein, human)
RN  - 0 (BCL6 protein, human)
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (MYC protein, human)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (Proto-Oncogene Proteins c-bcl-6)
RN  - 0 (Proto-Oncogene Proteins c-myc)
RN  - EC 2.7.7.31 (DNA Nucleotidylexotransferase)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Biomarkers, Tumor/*genetics
MH  - DNA Mutational Analysis
MH  - DNA Nucleotidylexotransferase/genetics
MH  - Female
MH  - Gene Rearrangement
MH  - Genetic Predisposition to Disease
MH  - High-Throughput Nucleotide Sequencing
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Lymphoma, Large B-Cell, Diffuse/*genetics/immunology/mortality/pathology
MH  - Male
MH  - Middle Aged
MH  - *Mutation
MH  - Neoplasm Grading
MH  - Phenotype
MH  - Proto-Oncogene Proteins c-bcl-2/genetics
MH  - Proto-Oncogene Proteins c-bcl-6/genetics
MH  - Proto-Oncogene Proteins c-myc/genetics
MH  - Young Adult
COIS- Conflicts of Interest and Source of Funding: The authors have disclosed that they 
      have no significant relationships with, or financial interest in, any commercial 
      companies pertaining to this article.
EDAT- 2021/08/16 06:00
MHDA- 2022/02/15 06:00
CRDT- 2021/08/15 20:57
PHST- 2021/08/16 06:00 [pubmed]
PHST- 2022/02/15 06:00 [medline]
PHST- 2021/08/15 20:57 [entrez]
AID - 00000478-202201000-00015 [pii]
AID - 10.1097/PAS.0000000000001750 [doi]
PST - ppublish
SO  - Am J Surg Pathol. 2022 Jan 1;46(1):71-82. doi: 10.1097/PAS.0000000000001750.