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Case 14 - Discussion

Hematopathology Case

CD23, 4× CD3, 20×
CD20, 20× CD79a,40×
EMA, 40× CD15, 10×
CD30, 10×

CD57, 40×


The lymph node architecture is effaced by a nodular infiltrate with predominantly small lymphocytes and scattered LH cells. The LH cells are positive for EMA, CD45, CD20 and CD79a, and are negative for CD15 and CD30. The nodules are composed of  B-cell lymphocytes (CD20 and CD79a positive) and CD3+ T-cells, many of which are CD57+ with tendency to surround the LH cells. CD23 highlights expanded FDC meshworks. 

Nodular Lymphocyte Predominant Hodgkin Lymphoma (NLPHL)

  • Peak incidence in fourth decade, male preponderance, M:F=2.4:1

  • Typically at early-stage as isolated lymphadenopathy, often involve cervical and axillary nodes

  • Extremely rare marrow involvement, 2.5%

  • Histopathology:

    • Often complete obliteration of nodal architecture

    • Macronodules with loose FDC meshworks, rarely diffuse pattern

    • Scattered tumor cells in the large nodules, “moth-eaten” appearance

    • LH cells: large, complex lobation, popcorn cells; nucleoli medium-sized, generally basophilic, and smaller than those of classic HRS cells; relatively sparse cytoplasm

    • Predominant small lymphocytes in the nodules

    • Groups of epithelioid cells surrounding the nodules in some cases

    • Rarely diffuse pattern (D-LPHL): with cytologic characteristics of NLPHL but lacking evidence of a nodular growth pattern

  • Immunophenotype:

    • Positive: CD45, CD20, BCL6, AID, BSAP, OCT2, BOB1, PU.1, MUM-1, T-bet, GCET1, HGAL/GCET2, IgD, J chain

    • Negative: CD15, CD30, BCL2, CD10, CD138, EBV

    • Background CD4+ T cells: c-Maf+, CD57+, PD-1+, CXCL13+, with T-cell rosettes around LP cells; low ratio of TIA-1+ to CD57+

    • Most cases with reactive CD4+CD8+ cells in 10-38% of T cells

  • Associated with PTGC, preceding or following NLPHL

  • T/HRBCL, most common of lymphoma develops after NLPHL

  • Transformation to DLBCL, 3-10%; not transform to classic HL

  • Excellent outcome, overall event-free survival 90%

  • Differential diagnosis:

    • T-cell rich large B-cell lymphoma: similar immunoprofile, but no typical NLPHL nodules, no CD3+/CD57+ T-cell rosettes

    • Classic Hodgkin lymphoma: CD45-, CD20-, OCT2-, BOB1-, CD30+, CD15+, PAX5 weakly +, EBV+/-; may have T-cell rosettes, but T-cells CD57-

    • PTGC: lack of LH cells, be aware of reactive immunoblasts

    • ALCL: CD30+, CD2+, perforin/granzyme+, ALK+/-, CD43+/-, B-cell markers-.

    • Reactive lymphoid hyperplasia: especially when tumor cells are scant. Need to spend some time in higher power