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Case 38 - Discussion

Hematopathology Case



CD20 CD20
CD79a CD79a
CD15 CD30
  • Case Description: The lymph node structure show diffuse infiltration of lymphoid cells. There are many scattered large cells within a mixed background of small lymphocytes and histiocytes. The large cells reveal large irregular nucleus with prominent nucleoli and vesicular chromatin. Multiple nucleation is common. The large neoplastic cells are positive for CD45, CD20, and CD79a but negative for EBV-LMP1, CD15 and CD30. The vast majority (>90%) of the small lymphocytes are positive for T cell markers (CD3, CD5) and the rest of them are positive for B cell markers (CD20 and CD79a).
  • Flow cytometry did not detect an abnormal B-cell population. In addition, molecular studies did not detect a clonal immunoglobulin heavy chain gene rearrangement.
  • Discussion: this case was diagnosed as nodular lymphocyte predominant Hodgkin lymphoma (NLPHL). I cannot remember if there were other immunostains performed, particularly CD21/CD23 and CD57. The major differential diagnosis includes NLPHL and T-cell/histiocyte rich large B-cell lymphoma (THRLBL). NLPHL typically has at least focal nodular pattern with expanded follicular dendritic meshwork, and the lymphoma cells classically have rosettes, formed by CD4/CD57/PD1+ T-cells. THRLBL shows diffuse growth pattern with no nodular formation, and the tumor cells have no CD4/CD57/PD1+ T-cell rosettes. Both lymphomas are of germinal center B-cell origin, and express BCL6, BOB1 and OCT2.

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