Table 7 Recommended liquid biopsy detection assays for main T-cell lymphoma subtypes concerning pathological and genetic features

nTFHL-AI

1. Pan T-cell antigens: CD2, CD3, and CD5;

2. TFH cell-associated markers, such as PD1, ICOS, CXCL13, CD10, and BCL6;

3. EBV-positive B cells are nearly always present

IDH2^R172, RHOA^G17V, TET2, DNMT3A, T-cell receptor (TCR) signaling and activation (eg, RHOA, VAV1, CD28, ICOS, FYN, LCK), TCR clonal rearrangements (most cases)

1.cfDNA/ctDNA (★★★)

2. CTCs (★★)

3. EBV DNA (★)

ALK-positive ALCL

CD30 + ; ALK + ; EMA + ; CD25 + ; cytotoxic granules + /–, CD4 + /–;

CD3–/ + ; CD43 + 

ALK rearrangement, NOTCH1, TP53, EP300, KMT2D, TCR clonal rearrangements (Approximately 90% of ALK-positive ALCLs)

1. Antibodies (★★★)

2. CTCs (★★)

3.cfDNA/ctDNA (★★)

ALK-negtive ALCL

CD30 + ; EMA + ; CD25 + ; cytotoxic granules + /–; CD4 + /–; CD3–/ + ;

CD43 + ; PAX5/BSAP–

DUSP22 and TP63 rearrangement, TP53 loss, JAK1, JAK3, STAT3, TCR clonal rearrangements (most cases)

1. CTCs (★★)

2.cfDNA/ctDNA (★★)

PTCL, NOS

CD4 > CD8; antigen loss frequent (CD7, CD5, CD4/CD8, CD52);

GATA3–/ + ; TBX21–/ + ; cytotoxic granules–/ + ; CD30-/ + ; CD56–/ + ;

rare cases EBV + 

PTCL-GATA3: TP53, CDKN2A/B, PRDM1, RB1, PTEN, STAT3, MYC;

PTCL-TBX21: low genomic complexity and few recurrent specific genetic changes;

TCR clonal rearrangements (most cases)

1.cfDNA/ctDNA (★★)

2. CTCs (★)

3. EBV DNA (★)

ENKTL

Lymphoma of NK-cell or T-cell lineage, has a very strong association with EBV

ENKTL: TP53, DDX3X, STAT3, JAK3, STAT5B, TET2, KMT2D, KMT2C;

Nodal EBV-positive T and NK-cell lymphoma: TET2;

TCR clonal rearrangements (10%-40% cases)

1. EBV DNA (★★)

2.cfDNA/ctDNA (★)