Classical Hodgkin Lymphoma With Aberrant CD8 Expression: A Clinicopathologic Study of Five Cases

2018 ◽  
Vol 27 (2) ◽  
pp. 166-173
Author(s):  
Neda Mirzamani ◽  
Xinmin Zhang ◽  
Judith Brody ◽  
Silvia G. Spitzer ◽  
Filiz Sen ◽  
...  

Hodgkin/Reed-Sternberg (HRS) cells of classical Hodgkin lymphoma (CHL) are of B-cell origin. In a small number of CHL cases, the tumor cells can express T-cell antigens. CD8 expression in this setting is extremely rare. We identified 5 cases of CHL with aberrant CD8 expression from our database. The patients included 3 men and 2 women with a median age of 33 years (range = 20-59 years). All the patients initially presented with lymphadenopathy and variable number of RS cells. Two cases were classified as mixed cellularity type that showed prominent vascular proliferation mimicking peripheral T-cell lymphoma. Two cases represented nodular sclerosis type. The tumor cells in all cases were positive for CD8 and negative for CD2, CD3, CD4, and CD7 and carried germline T-cell receptor genes. Molecular studies revealed T-cell receptor genes to be in germline configuration in 4 cases with available information. Given the morphologic overlap with peripheral T-cell lymphoma and the rarity of this type of CHL, identifying more cases will help our better understanding of this entity.

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Koen Debackere ◽  
Lukas Marcelis ◽  
Sofie Demeyer ◽  
Marlies Vanden Bempt ◽  
Nicole Mentens ◽  
...  

AbstractPeripheral T-cell lymphoma (PTCL) is a heterogeneous group of non-Hodgkin lymphomas with poor prognosis. Up to 30% of PTCL lack distinctive features and are classified as PTCL, not otherwise specified (PTCL-NOS). To further improve our understanding of the genetic landscape and biology of PTCL-NOS, we perform RNA-sequencing of 18 cases and validate results in an independent cohort of 37 PTCL cases. We identify FYN-TRAF3IP2, KHDRBS1-LCK and SIN3A-FOXO1 as new in-frame fusion transcripts, with FYN-TRAF3IP2 as a recurrent fusion detected in 8 of 55 cases. Using ex vivo and in vivo experiments, we demonstrate that FYN-TRAF3IP2 and KHDRBS1-LCK activate signaling pathways downstream of the T cell receptor (TCR) complex and confer therapeutic vulnerability to clinically available drugs.


2010 ◽  
Vol 189 (4) ◽  
pp. i10-i10
Author(s):  
Konstanze Pechloff ◽  
Julian Holch ◽  
Uta Ferch ◽  
Marc Schweneker ◽  
Kristina Brunner ◽  
...  

Author(s):  
Koya Ono ◽  
Yasushi Onishi ◽  
Koichi Onodera ◽  
Daigo Michimata ◽  
Eijiro Furukawa ◽  
...  

2019 ◽  
Vol 60 (14) ◽  
pp. 3561-3564
Author(s):  
Katrin S. Huettl ◽  
Annette M. Staiger ◽  
Alexander Stehle ◽  
Irina Bonzheim ◽  
Heike Horn ◽  
...  

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 965-965
Author(s):  
Julie Teruya-Feldstein ◽  
Takahiro Maeda ◽  
Alexander Filatov ◽  
P.P. Pandolfi

Abstract Background: POKEMON (for POK, Erythroid, Myeloid ONtogenic factor) has recently been shown to be a novel proto-oncogene, playing a key role in cellular transformation and repression of ARF. Pokemon overexpression leads to overt oncogenic transformation both in vitro and in vivo in transgenic mice. Because these transgenic mice developed T-cell lymphoma we sought to expand our original screening analyses. We intially showed POKEMON expression in diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) and co-expression of BCL6 and POKMEON showed higher proliferation and predicted for better overall survival in DLBCL (Nature 433, 278–285). Nodular lymphocyte predominant Hodgkin Lymphoma (NLPHL) is another tumor that expresses BCL6 and shows localization to L&H tumor cells. We therefore sought to compare POKEMON protein expression in NLPHL and Classical Hodgkin Lymphoma (cHL) cases. Design: Stains for POKEMON were performed with the anti-POKEMON hamster monoclonal antibody (clone 13E9). Sections of reactive human tonsil were stained as controls showing localization to squamous epithelium and reactive germinal centers as well as paracortical regions. For NLPHL, the cohort comprised of 19 males, 2 females; for cHL 16 males, 14 females. 20 NLPHL and 30 cHL tissue biopsies were stained using whole sections. Intensity and percent positivity of malignant L&H cells and Reed-Sternberg (RS) cells as well as surrounding reactive lymphocytes was scored. Expression in T-cell lymphomas was expanded to include a total of 84 cases analyzed by tissue microarray (TMA) that included: 8 ALCL (Anaplastic Large Cell Lymphoma), 11 AILT (Angioimmunoblastic T-cell Lymphoma), 17 T-ALL (T Lymphoblastic Lymphoma), 43 PTCL (Peripheral T-cell Lymphoma), 3 T/NK (Nasal type T/NK cell Lymphoma), and 2 PTCL, NOS (Not Otherwise Subclassified). Tumor cells in T-cell lymphomas and HL were scored and defined as 0 (negative), 1 (scattered <50%, weak positive), and 2 (diffuse >50%, strong positive) with a nuclear localization pattern. Results: For NLPHL, 18/20 (90%) cases showed diffuse strong positivity in >50% of malignant L&H tumor cells whereas in cHL cases, 6/30 (20%) cases showed diffuse strong positivity in >50% of malignant RS tumor cells for POKEMON protein expression. In T-cell lymphomas, POKEMON expression was strongest in ALCL (6/8, 75%) and AILD (7/11, 74%) compared to the other subtypes. In contrast, BCL6 protein expression was positive in 12/20 (60%) cases which showed weak, scattered to diffuse strong positivity in L&H tumor cells and 1/30 (3%) with scattered weak reactivity in cHL malignant RS cells Conclusion: POKEMON is co-expressed with BCL6 in malignant L&H tumor cells in NLPHL but not in cHL. Pokemon’s critical role in cellular transformation makes it an attractive target for therapeutic intervention in NLPHL.


2021 ◽  
Author(s):  
Koen Debackere ◽  
Lukas Marcelis ◽  
Sofie Demeyer ◽  
Marlies Vanden Bempt ◽  
Nicole Mentens ◽  
...  

Abstract Peripheral T cell lymphoma (PTCL) is a heterogeneous group of non-Hodgkin lymphomas with poor prognosis. Up to 30% of PTCL lack distinctive features and are classified as PTCL, not otherwise specified (PTCL-NOS). To further improve our understanding of the genetic landscape and biology of PTCL-NOS, we performed RNA-sequencing of 18 cases and validated results in an independent cohort of 37 PTCL cases. We identified FYN-TRAF3IP2, KHDRBS1-LCK and SIN3A-FOXO1 as new in-frame fusion transcripts, with FYN-TRAF3IP2 as a recurrent fusion detected in 8 of 55 cases. Using ex vivo and in vivo experiments, we demonstrate that FYN-TRAF3IP2 and KHDRBS1-LCK activate signaling pathways downstream of the T cell receptor (TCR) complex and confer therapeutic vulnerability to clinically available drugs.


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