Immunophenotypic Characterization of Canine Nodal T-Zone Lymphoma

2020 ◽  
pp. 030098582097407
Author(s):  
Leah Stein ◽  
Cynthia Bacmeister ◽  
Matti Kiupel

T-zone lymphoma (TZL) is an indolent nodal T-cell lymphoma most commonly observed in submandibular lymph nodes in dogs. The diagnosis is based on its distinct morphology and expression of CD3. TZL has been reported to have a low Ki67 index and to lack expression of CD45. The latter feature has been used to diagnose this type of lymphoma via fine needle aspirate and flow cytometry without confirmation of the characteristic tissue architecture. The goal of this study was to characterize the immunophenotype of canine nodal TZL in greater detail. Twenty-seven TZLs were selected based on their characteristic morphology. A tissue microarray was generated, and immunohistochemical expression of CD3, CD5, CD20, CD21, CD25, CD45, Bcl-6, and Ki67 was evaluated. Neoplastic T cells in all cases were positive for CD3, CD5, and CD25, and negative for CD20, CD21, and Bcl-6. Positive labelling for CD45 was detected in 2 of the 27 cases with the remaining 25 cases being negative. All cases had a low Ki67 index with an average index of 19.56%. For the CD45-positive TZLs, clonality of the T-cell antigen receptor gamma gene was confirmed in only one of these cases. The observed immunophenotype of canine TZL is similar to previous publications with the exception that 2 cases expressed CD45. Expression of CD45 in TZLs in this study emphasizes the importance of interpreting immunophenotypic findings in conjunction with histopathology to reach an accurate diagnosis and not to use lack of expression of a particular antigen as the sole diagnostic criterion.

2011 ◽  
Vol 204 (2) ◽  
pp. 103-107 ◽  
Author(s):  
Swarna Mandava ◽  
Reshma Sonar ◽  
Firoz Ahmad ◽  
Anil K. Yadav ◽  
Pratiksha Chheda ◽  
...  

Author(s):  
Elizabeth Kuczynski ◽  
Giulia Morlino ◽  
Alison Peter ◽  
Dinis Calado ◽  
Charles Sinclair ◽  
...  

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2332-2332
Author(s):  
Shinsuke Suzuki ◽  
Stefan Nagel ◽  
Bjoern Schneider ◽  
Maren Kaufmann ◽  
Dorothea Anders ◽  
...  

Abstract Activating mutations and deletions affecting specific NOTCH1 protein domains have been recently shown to occur widely in T-cell neoplasia, e.g. in T-acute lymphoblastic leukemia (T-ALL). However, knowledge of NOTCH1 chromosomal alterations is largely based on a single cell line model (SUP-T1) with t(7;9)(q35;q34) in which NOTCH1 truncated at exon 24 is juxtaposed with TCRB. We describe the characterization of a novel rearrangement, t(9;14)(q34.3;q11) in two T-cell lymphoma cell lines, HD-MAR and HT-1. FISH analysis using fosmid clones and sequencing of fragments identified by long distance inverse PCR showed that in both cases t(9;14) effected tail-to-tail juxtaposition of intron 27 of NOTCH1 with TCRA genes, namely 5′-TRAV40 in HD-MAR, and intron 2 of TRAV5 in HT-1. Thus, in both cell lines t(9;14) places NOTCH1, truncated immediately 3′ of the HD-domain, under transcriptional control of TCRA. The 14q11.2 breakpoints in HD-MAR and HT-1 lie, respectively, near the proximal E-delta enhancer and amid a cryptic enhancer region represented by a cluster of T-cell specific DNase-I hypersensitive sites. Western blotting revealed prominent expression of truncated activated NOTCH1 polypeptides, ranging in size from 100 to 115 kDa in both cell lines. Antibodies recognizing ANK and TAD domains, believed essential for inducing T-ALL, detected the aberrant polypeptides. Moreover, treatment with gamma-secretase inhibitor (GSI) altered expression patterns of NOTCH1 polypeptides and induced growth inhibition due to G0/G1 cell cycle arrest in both t(9;14) cell lines, in stark contrast to GSI-resistant SUP-T1 cells wherein truncation occurs before the heterodimerization (HD) domain. (Another recently described t(7;9) cell line (CUTLL1) which is GSI-sensitive also carries a NOTCH1 breakpoint at intron 27.) The same protein species were not detectable by antibodies recognizing the transmembrane domain of NOTCH1 which requires GS for exposure suggesting nuclear access requires GS-cleavage. Immunostaining confirmed extranuclear blocking of NOTCH1 in response to GSI in HD-MAR/HT-1 but not in SUP-T1. In contrast, repression of HES1 occurred in response to GSI irrespective of NOTCH1 breakpoint location, suggesting its non-involvement in growth signaling. In addition to providing cell line models for a new NOTCH1 disease translocation, these data suggest that the sensitivities of T-cell neoplasias bearing NOTCH1 translocations may critically depend on whether 9q34 breakpoints lie upstream or downstream of the HD domain.


2008 ◽  
Vol 130 (3) ◽  
pp. 343-351 ◽  
Author(s):  
Erich J. Schwartz ◽  
Hernan Molina-Kirsch ◽  
Shuchun Zhao ◽  
Robert J. Marinelli ◽  
Roger A. Warnke ◽  
...  

1990 ◽  
Vol 45 (5) ◽  
pp. 928-934 ◽  
Author(s):  
Riccardo Dolcetti ◽  
Antonino Carbone ◽  
Sergio Barlati ◽  
Roberta Maestro ◽  
Silvana Rizzo ◽  
...  

Haematologica ◽  
2007 ◽  
Vol 92 (2) ◽  
pp. e24-e25 ◽  
Author(s):  
R.P. Falcao ◽  
E.G. Rizzatti ◽  
F.P. Saggioro ◽  
A.B. Garcia ◽  
A.F. Marinato ◽  
...  

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