Morphological, phenotypical and molecular characterization of canine lymphomas with dual T- and B-cell markers expression

IntroductionRecent investigations have identified rare, phenotypically complex lymphoma variants, including cases exhibiting concurrent expression of T- and B-cell markers. These atypical presentations suggest perturbations in lymphoid differentiation programs or clonal evolution, necessitating more...

Full description

Saved in:
Bibliographic Details
Main Authors: Giorgia Mezzalira, Valeria Martini, Francesca Abramo, Selina Iussich, Margherita Orlandi, Luca Pazzini, Barbara Banco, Anna Maria Rambaldi, Alessandro Bisognoso, Filippo Arena, Giulio Cocciolo, Michele Marino, Maria Massaro, Luca Aresu
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-04-01
Series:Frontiers in Veterinary Science
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fvets.2025.1578425/full
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1850156425838329856
author Giorgia Mezzalira
Valeria Martini
Francesca Abramo
Selina Iussich
Margherita Orlandi
Luca Pazzini
Barbara Banco
Anna Maria Rambaldi
Alessandro Bisognoso
Filippo Arena
Giulio Cocciolo
Michele Marino
Maria Massaro
Luca Aresu
author_facet Giorgia Mezzalira
Valeria Martini
Francesca Abramo
Selina Iussich
Margherita Orlandi
Luca Pazzini
Barbara Banco
Anna Maria Rambaldi
Alessandro Bisognoso
Filippo Arena
Giulio Cocciolo
Michele Marino
Maria Massaro
Luca Aresu
author_sort Giorgia Mezzalira
collection DOAJ
description IntroductionRecent investigations have identified rare, phenotypically complex lymphoma variants, including cases exhibiting concurrent expression of T- and B-cell markers. These atypical presentations suggest perturbations in lymphoid differentiation programs or clonal evolution, necessitating more sophisticated diagnostic approaches. The concurrent expression of CD3 and CD20 in canine lymphomas represents a particularly compelling phenomenon documented across various anatomical sites. Molecular diagnostics, particularly PCR for Antigen Receptor Rearrangements (PARR), have provided crucial insights into these phenotypically complex cases, revealing concurrent clonal rearrangements of both TCRγ and IgH in selected cases, further challenging traditional classification paradigms.MethodsHere, we report 33 cases of canine double-positive lymphoma, retrieved with a retrospective analysis of the MyLAV Diagnostic Laboratory electronic database. Specifically, we report results of an integrated approach combining WHO-based morphological classification, comprehensive immunohistochemical immunophenotyping with T-cell (CD3 and CD5) and B-cell markers (CD20 and PAX5), and PARR analysis.ResultsThe skin, oral/nasal mucosa and mucocutaneous junction were the most commonly affected sites, accounting for 24 cases (72.7%). All cases stained positive for CD3 and CD20 (100%), 32 (97%) for CD5, and only 12 (36.4%) for PAX5. Aberrant cytoplasmic localization of CD20 was found in 29 (87.9%) cases. Molecular analysis revealed rearrangement signals of TCR gene in 23 of 33 cases (69.7%) and of CBmajor or CBminor gene in 9 (27.3%).DiscussionThe findings emphasize that while immunohistochemistry remains a fundamental diagnostic tool, it may be insufficient in isolation for definitive lineage determination in these cases. PARR analysis emerges as an essential complementary technique for distinguishing between aberrant marker expression and true biphenotypic differentiation.
format Article
id doaj-art-77cadd3e1cec4d2e97a5d18a0863e8a0
institution OA Journals
issn 2297-1769
language English
publishDate 2025-04-01
publisher Frontiers Media S.A.
record_format Article
series Frontiers in Veterinary Science
spelling doaj-art-77cadd3e1cec4d2e97a5d18a0863e8a02025-08-20T02:24:33ZengFrontiers Media S.A.Frontiers in Veterinary Science2297-17692025-04-011210.3389/fvets.2025.15784251578425Morphological, phenotypical and molecular characterization of canine lymphomas with dual T- and B-cell markers expressionGiorgia Mezzalira0Valeria Martini1Francesca Abramo2Selina Iussich3Margherita Orlandi4Luca Pazzini5Barbara Banco6Anna Maria Rambaldi7Alessandro Bisognoso8Filippo Arena9Giulio Cocciolo10Michele Marino11Maria Massaro12Luca Aresu13MYLAV La Vallonea Veterinary Diagnostic Laboratory, Milan, ItalyDepartment of Veterinary Medicine and Animal Sciences, University of Milan, Lodi, ItalyDepartment of Veterinary Sciences, University of Pisa, Pisa, ItalyMYLAV La Vallonea Veterinary Diagnostic Laboratory, Milan, ItalyMYLAV La Vallonea Veterinary Diagnostic Laboratory, Milan, ItalyMYLAV La Vallonea Veterinary Diagnostic Laboratory, Milan, ItalyMYLAV La Vallonea Veterinary Diagnostic Laboratory, Milan, ItalyMYLAV La Vallonea Veterinary Diagnostic Laboratory, Milan, ItalyMYLAV La Vallonea Veterinary Diagnostic Laboratory, Milan, ItalyMYLAV La Vallonea Veterinary Diagnostic Laboratory, Milan, ItalyMYLAV La Vallonea Veterinary Diagnostic Laboratory, Milan, ItalyMYLAV La Vallonea Veterinary Diagnostic Laboratory, Milan, ItalyMYLAV La Vallonea Veterinary Diagnostic Laboratory, Milan, ItalyDepartment of Veterinary Sciences, University of Turin, Turin, ItalyIntroductionRecent investigations have identified rare, phenotypically complex lymphoma variants, including cases exhibiting concurrent expression of T- and B-cell markers. These atypical presentations suggest perturbations in lymphoid differentiation programs or clonal evolution, necessitating more sophisticated diagnostic approaches. The concurrent expression of CD3 and CD20 in canine lymphomas represents a particularly compelling phenomenon documented across various anatomical sites. Molecular diagnostics, particularly PCR for Antigen Receptor Rearrangements (PARR), have provided crucial insights into these phenotypically complex cases, revealing concurrent clonal rearrangements of both TCRγ and IgH in selected cases, further challenging traditional classification paradigms.MethodsHere, we report 33 cases of canine double-positive lymphoma, retrieved with a retrospective analysis of the MyLAV Diagnostic Laboratory electronic database. Specifically, we report results of an integrated approach combining WHO-based morphological classification, comprehensive immunohistochemical immunophenotyping with T-cell (CD3 and CD5) and B-cell markers (CD20 and PAX5), and PARR analysis.ResultsThe skin, oral/nasal mucosa and mucocutaneous junction were the most commonly affected sites, accounting for 24 cases (72.7%). All cases stained positive for CD3 and CD20 (100%), 32 (97%) for CD5, and only 12 (36.4%) for PAX5. Aberrant cytoplasmic localization of CD20 was found in 29 (87.9%) cases. Molecular analysis revealed rearrangement signals of TCR gene in 23 of 33 cases (69.7%) and of CBmajor or CBminor gene in 9 (27.3%).DiscussionThe findings emphasize that while immunohistochemistry remains a fundamental diagnostic tool, it may be insufficient in isolation for definitive lineage determination in these cases. PARR analysis emerges as an essential complementary technique for distinguishing between aberrant marker expression and true biphenotypic differentiation.https://www.frontiersin.org/articles/10.3389/fvets.2025.1578425/fulldoglymphomaimmunohistochemistryPARRdouble phenotype
spellingShingle Giorgia Mezzalira
Valeria Martini
Francesca Abramo
Selina Iussich
Margherita Orlandi
Luca Pazzini
Barbara Banco
Anna Maria Rambaldi
Alessandro Bisognoso
Filippo Arena
Giulio Cocciolo
Michele Marino
Maria Massaro
Luca Aresu
Morphological, phenotypical and molecular characterization of canine lymphomas with dual T- and B-cell markers expression
Frontiers in Veterinary Science
dog
lymphoma
immunohistochemistry
PARR
double phenotype
title Morphological, phenotypical and molecular characterization of canine lymphomas with dual T- and B-cell markers expression
title_full Morphological, phenotypical and molecular characterization of canine lymphomas with dual T- and B-cell markers expression
title_fullStr Morphological, phenotypical and molecular characterization of canine lymphomas with dual T- and B-cell markers expression
title_full_unstemmed Morphological, phenotypical and molecular characterization of canine lymphomas with dual T- and B-cell markers expression
title_short Morphological, phenotypical and molecular characterization of canine lymphomas with dual T- and B-cell markers expression
title_sort morphological phenotypical and molecular characterization of canine lymphomas with dual t and b cell markers expression
topic dog
lymphoma
immunohistochemistry
PARR
double phenotype
url https://www.frontiersin.org/articles/10.3389/fvets.2025.1578425/full
work_keys_str_mv AT giorgiamezzalira morphologicalphenotypicalandmolecularcharacterizationofcaninelymphomaswithdualtandbcellmarkersexpression
AT valeriamartini morphologicalphenotypicalandmolecularcharacterizationofcaninelymphomaswithdualtandbcellmarkersexpression
AT francescaabramo morphologicalphenotypicalandmolecularcharacterizationofcaninelymphomaswithdualtandbcellmarkersexpression
AT selinaiussich morphologicalphenotypicalandmolecularcharacterizationofcaninelymphomaswithdualtandbcellmarkersexpression
AT margheritaorlandi morphologicalphenotypicalandmolecularcharacterizationofcaninelymphomaswithdualtandbcellmarkersexpression
AT lucapazzini morphologicalphenotypicalandmolecularcharacterizationofcaninelymphomaswithdualtandbcellmarkersexpression
AT barbarabanco morphologicalphenotypicalandmolecularcharacterizationofcaninelymphomaswithdualtandbcellmarkersexpression
AT annamariarambaldi morphologicalphenotypicalandmolecularcharacterizationofcaninelymphomaswithdualtandbcellmarkersexpression
AT alessandrobisognoso morphologicalphenotypicalandmolecularcharacterizationofcaninelymphomaswithdualtandbcellmarkersexpression
AT filippoarena morphologicalphenotypicalandmolecularcharacterizationofcaninelymphomaswithdualtandbcellmarkersexpression
AT giuliococciolo morphologicalphenotypicalandmolecularcharacterizationofcaninelymphomaswithdualtandbcellmarkersexpression
AT michelemarino morphologicalphenotypicalandmolecularcharacterizationofcaninelymphomaswithdualtandbcellmarkersexpression
AT mariamassaro morphologicalphenotypicalandmolecularcharacterizationofcaninelymphomaswithdualtandbcellmarkersexpression
AT lucaaresu morphologicalphenotypicalandmolecularcharacterizationofcaninelymphomaswithdualtandbcellmarkersexpression