Table 2.
Recommended immunohistochemistry panels for the diagnosis of NLPHL and differential diagnostic considerations.
| Priority/Use | Panel of Markers | Utility |
|---|---|---|
| 1st tier (Recommended) | CD20, CD3, CD30, CD21 or CD23, PAX5 or OCT2, PD1 | Standard panel for initial diagnosis of NLPHL; may vary with biopsy type, practice setting and differential diagnostic considerations. |
| 2nd tier (Desirable) | IgD, EBV (EBER) | Perform if available. |
| 3rd tier (Optional) | CD79a, CD19, BOB1, BCL6, MUM1, CD15, ALK1, Kappa, Lambda | Perform if necessary to confirm or exclude other considerations in the differential diagnosis. |
| Core needle biopsy for initial diagnosis | CD20, CD3, CD30, PAX5 or OCT2, CD21 or CD23, EBV (EBER); additional B markers, CD15 and ALK1 as necessary | Differential diagnosis includes CHL; if NLPHL is suspected, a surgical biopsy should be performed for definitive diagnosis. |
| Core needle biopsy in patients with prior NLPHL | OCT2, CD3, CD21 or CD23, IgD, PD1 | Primary purpose is to assess for recurrence and/or progression; CD20 may be negative due to prior rituximab therapy. Use another pan-B marker if OCT2 is unavailable. |
| Separation from classic Hodgkin lymphoma | CD30, CD15, EBER, B-cell transcription factors, IgD, J-chain, MEF2B, STAT6 and BCL6 FISH | NLPHL can mimic lymphocyte-rich CHL. Awareness of aberrant phenotypes should prompt additional workup. |
| PTCL, AITL and other lymphomas of T follicular helper cells | PD1, ICOS, additional T-cell markers, molecular TCR rearrangement and/or mutational profiling | NLPHL with increased T cells can mimic T cell lymphoma; lack of an aberrant T cell phenotype and TCR rearrangements confirm NLPHL. |
| CD20-negative NLPHL | Additional B-cell markers, including CD79a, CD19, OCT2, BOB1, MUM1 | Awareness of aberrant phenotypes should prompt additional workup. |
| Progressive transformation of germinal centers | OCT2, IgD, CD21 | Presence of PTGC should prompt a search for NLPHL given the known co-occurrence. |
| EBV+ large atypical cells | Additional B-cell markers, including transcription factors, CD30 and CD15 | EBV+ NLPHL is rare; exclude CHL, EBV+ DLBCL and lymphoproliferative disorders arising in infectious or immunodeficiency settings. |