Comparison of Follicular Helper T-Cell Markers with the Expression of the Follicular Homing Marker CXCR5 in Peripheral T-Cell Lymphomas—A Reappraisal of Follicular Helper T-Cell Lymphomas
Abstract
:1. Introduction
2. Results
2.1. CXCR5 Staining Pattern in Non-Neoplastic and Neoplastic TFH Cells
2.2. Determination of TFH Cell Phenotype in PTCL Cases
2.3. Immunomorphology of TFHL
2.3.1. TFHL-AI-1
2.3.2. TFHL-AI-2
2.3.3. TFHL-AI-3
2.3.4. TFHL-F
2.3.5. TFHL-NOS
3. Discussion
4. Materials and Methods
4.1. Patients and Tissue Samples
4.2. Immunohistochemistry and Evaluation
4.3. Multiple Fluorescence Antigen Immunostaining
4.4. EBER In Situ Hybridization
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
PTCL | Peripheral T-cell lymphoma |
TFH | Follicular T helper |
TFHL | Follicular T helper cell lymphoma |
TFHL-AI | Follicular T helper cell lymphoma angioimmunoblastic-type |
TFHL-AI-1 | Follicular T helper cell lymphoma angioimmunoblastic-type, pattern 1 |
TFHL-AI-2 | Follicular T helper cell lymphoma angioimmunoblastic-type, pattern 2 |
TFHL-AI | Follicular T helper cell lymphoma angioimmunoblastic-type, pattern 3 |
TFHL-F | Follicular T helper cell lymphoma follicular-type |
TFHL-NOS | Follicular T helper cell lymphoma not otherwise specified-type |
CXCR5 | CXC chemokine receptor type 5 |
CXCL13 | CXC chemokine ligand 13 |
BCL6 | B-cell lymphoma 6 |
PD1 | Programmed cell death protein 1 |
ICOS | Inducible T-cell costimulator |
MEF2B | Myocyte enhancer binding factor 2 B |
EBV | Epstein-Barr virus |
EBER | EBV-encoded small RNA |
LMP1 | EBV-encoded latent membrane protein 1 |
DLBCL | Diffuse large B-cell lymphoma |
TCR | T-cell receptor |
GC | Germinal center |
B-IBs | B immunoblasts |
HRS-like | Hodgkin-Reed-Sternberg-like |
FDC | Follicular dendritic cell |
HEV | High endothelial venule |
IHC | Immunohistochemistry |
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Sensitivity | Specificity | Accuracy | |
---|---|---|---|
CXCR5 | 85% (67/79) (* 98% (62/63)) | 0.91 | 0.86 |
PD1 | 99% (77/78) | 0.73 | 0.96 |
BCL6 | 94% (67/71) | 1 | 0.95 |
CD134 | 94% (74/79) | 0.60 | 0.90 |
CXCL13 | 87% (69/79) | 0.91 | 0.88 |
ICOS | 83% (65/78) | 0.70 | 0.82 |
CD10 | 63% (50/79) | 1 | 0.67 |
TFHL-AI-1 | TFHL-AI-2 | TFHL-AI-3 | TFHL-F | TFHL-NOS | |
---|---|---|---|---|---|
Architectural alterations | Partial disarrangement; Follicular hyperplasia-like features | Partial or complete disarrangement in the LN architecture | Complete diffuse effacement of the LN architecture | Partial disarrangement; Follicle-like nodules mainly composed of abnormal T cells. | Type A, diffuse infiltrate of medium to large neoplastic cells; Type B, T-zone lymphoma pattern; Type C, polymorphic infiltrate without follicles |
Extrafollicular/paracortical compartment | Minimal paracortical alterations; HEVs may penetrate radially into GC; Scarce CD30+ (EBV+/−) large B-cells/HRS-like cells | Polymorphic infiltrate with HEV proliferation; CD30+ (EBV+/−) large B/HRS-like cells can be present | Polymorphic infiltrate with arborizing HEVs. CD30+ (EBV+/−) large BB/HRS-like cells often present | Disrupted paracortical tissue with mild HEV proliferation | Type A, diffuse infiltrate; Type B & C, polymorphic infiltrate with HEV proliferation; CD30+ (EBV+/−) large B cells/RS-like cells can be present |
Follicles/GC B cells | Largely retained GC B cell population; CD30+ (EBV+/−) intrafollicular large B/HRS-like cells can be present | Depleted follicles, scarce GC B cells | GC B cells absent | No residual GC B cells; CD30+ (EBV+/−) intrafollicular large B/HRS-like cells can be present | Type A & C, no follicles; Type B, atrophic follicles with residual GC B cells |
Mantle zone/small B-cell aggregates | Distorted mantle zones; Displaced small B-cell aggregates can be present | Displaced mantle zone-type small B cells pushed to the periphery of the LN | Haphazardly distributed sheets of small B cells adjacent to the FDC meshwork or confined to the periphery of the LN | Sheets of small B cells adjacent to the neoplastic T-cell nodules or pushed to the subcapsular region | Type A, few small B cells; Type B, almost intact mantle zones; Type C, sheets of mantle zone-type small B-cells |
FDC meshwork | Vanishing polarization; marginally expanded FDC meshwork | Dense, partly concentric, focally expanded, focally interconnected | Dense, markedly expanded, and widely interconnected; HEVs can be entrapped | Dense, irregular, marginally expanded, focally confluent FDC meshwork | Type A: no FDCs; Type B: atrophic FDC meshwork; Type C: absent or delicate traces of FDCs |
Neoplastic cells | Small to medium abnormal TFH cells with pale cytoplasm | Medium to large abnormal TFH cells often with pale cytoplasm | Medium to large abnormal TFH cells with pale cytoplasm | Small to medium abnormal TFH cells sometimes with pale cytoplasm | Type A, medium to large abnormal T cells with pale cytoplasm; Type B, medium-sized abnormal T cells; Type C, Medium to large abnormal T cells with pale cytoplasm |
TFH phenotype */localization of neoplastic T cells | Complete/Accumulated at the boundary of GCs, minimal paracortical population | Complete/Type A, mainly intra/perifollicular; Type B, mainly paracortical | Complete/Intrafollicular (within FDC meshwork) > paracortical | Complete/Dense intrafollicular aggregates and scattered extrafollicular | Type A, CXCR5+/CD10-; Type B, CXCR5-/CD10-; Type C, CXCR5-/CD10- > CXCR5+/CD10+; Exclusively paracortical localization |
Antibody/Clone | Origin | Source |
---|---|---|
BCL6/LN22 | Mouse | Leica/Novocastra |
CD3/H-12 | Mouse | Santa Cruz |
CD4/N1GU0 | Mouse | Thermofisher/eBioscience |
CD8/C8/144B | Mouse | Santa Cruz |
CD10/56C6 | Mouse | Leica |
CD20/L26 | Mouse | Leica |
CD21/ER3093 | Rabbit | Histopathology * |
CD23/1B12 | Mouse | Leica |
CD30/JCM182 | Mouse | Leica |
CD134/Ber-Act35 | Mouse | Santa Cruz |
CXCL13/polyclonal | Goat | Bio-Techne/R&D Systems |
CXCR5/polyclonal | Rabbit | Atlas Antibodies |
CXCR5/51505 | Mouse | Bio-Techne/R&D Systems |
EBV-LMP1/CS1-4 | Mouse | Agilent/DAKO |
ICOS/polyclonal | Goat | Bio-Techne/R&D Systems |
IgD/polyclonal | Rabbit | Agilent/DAKO |
MEF2B/polyclonal | Rabbit | Atlas Antibodies |
PD1/polyclonal | Goat | Bio-Techne/R&D Systems |
TIA-1/2G9A10F5 | Mouse | Beckman-Coulter |
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Krenács, L.; Krenács, D.; Borbényi, Z.; Tóth, E.; Nagy, A.; Piukovics, K.; Bagdi, E. Comparison of Follicular Helper T-Cell Markers with the Expression of the Follicular Homing Marker CXCR5 in Peripheral T-Cell Lymphomas—A Reappraisal of Follicular Helper T-Cell Lymphomas. Int. J. Mol. Sci. 2024, 25, 428. https://doi.org/10.3390/ijms25010428
Krenács L, Krenács D, Borbényi Z, Tóth E, Nagy A, Piukovics K, Bagdi E. Comparison of Follicular Helper T-Cell Markers with the Expression of the Follicular Homing Marker CXCR5 in Peripheral T-Cell Lymphomas—A Reappraisal of Follicular Helper T-Cell Lymphomas. International Journal of Molecular Sciences. 2024; 25(1):428. https://doi.org/10.3390/ijms25010428
Chicago/Turabian StyleKrenács, László, Dóra Krenács, Zita Borbényi, Erika Tóth, Anna Nagy, Klára Piukovics, and Enikő Bagdi. 2024. "Comparison of Follicular Helper T-Cell Markers with the Expression of the Follicular Homing Marker CXCR5 in Peripheral T-Cell Lymphomas—A Reappraisal of Follicular Helper T-Cell Lymphomas" International Journal of Molecular Sciences 25, no. 1: 428. https://doi.org/10.3390/ijms25010428