Reactive hyperplasia in lymph nodes can be difficult to distinguish from a lymphoproliferative disorder. Sections show follicular hyperplasia with preservation of the lymph node architecture. In some areas, large follicles with irregularly shaped/ill-demarcated germinal centers and thick mantle zones are seen. Large atypical cells indicative of Reed-Sternberg cells or variants are not identified.

Immunohistochemistry studies (not shown) demonstrated a mixed population of CD20 positive B-cells and CD3+/CD5+/ CD43+ T cells in normal distribution. The germinal centers were negative for BCL-2 but positive for BCL-6 and CD10. CD30 stained scattered activated lymphoid cells. CD15 was negative. Few CD57 positive cells were randomly distributed; however, CD57 rosettes were not seen. ALK-1 and cyclinD1 were negative.

In situ hybridization for Epstein Barr-encoded RNA (EBER) was negative (not shown).

Overall, the combined morphologic and immunophenotypic features are most consistent with a reactive process, more specifically, progressive transformation of germinal centers (PTGC). PTGC can be associated with nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) in rare cases. However, in the great majority of cases there is no connection with Hodgkin lymphoma and can be seen with reactive lymphadenopathies. Thus, clinical correlation and re-biopsy for persistent or recurrent disease is recommended.

Features that would help distinguish PTGC from NLPHL include: presence of residual germinal centers, absence of PAX5+/OCT2+/BCL-6+ LP/popcorn cells, and absence of T-cell (CD3+/C057+) rosettes around large CD20+ cells.

Reference:
Christopher D. M. Fletcher Diagnostic Histopathology of Tumors, 4th Edition Elsevier Saunders, Philadelphia, 2013: p 1365-66.