LYMPHOPROLIFERATIVE DISORDER OF GRANULAR LYMPHOCYTES - 9 CASES INCLUDING ONE WITH FEATURES OF CD56 (NKH1)-POSITIVE AGGRESSIVE NATURAL-KILLER-CELL LYMPHOMA

Twelve cases of large granular lymphocytosis were examined by flow cyt ometry and Southern blot analysis to correlate immunophenotypic and mo lecular genetic markers with clinical features. Nine cases fulfilled c linical criteria for the lymphoproliferative disorder of granular lymp hocytes, and eight of these demonstrated the molecular features of T-c ell-type lymphoproliferative disorder of granular lymphocytes includin g surface expression of CD3, expression of one or more natural killer (NK)-cell antigens (CD11b, CD16, or CD57), and clonal rearrangement of both the T-cell receptor beta- and gamma-chain-joining genes. One of these cases demonstrated coexisting clonal rearrangement of the immuno globulin heavy-chain-joining genes, but none demonstrated kappa-light- chain-joining gene rearrangement, The eight T-cell lymphoproliferative disorder of granular lymphocytes cases all lacked expression of the N K antigen CD56 (NKH1). In contrast, the other case of lymphoproliferat ive disorder of granular lymphocytes rapidly evolved into an aggressiv e NK-cell lymphoma which did not express CD3, did express CD56, had ge rmline T-cell receptor gene configurations, and had multiple clonal ch romosomal abnormalities. This case demonstrated nasal cavity and cutan eous tumor infiltrates consistent with previously described CDS-negati ve, CDB6-positive NK-cell lymphoma of the upper aerodigestive tract. T hree cases of transient large granular lymphocytosis demonstrated germ line T-cell receptor gene configurations. This study demonstrates the usefulness of Southern blot analysis and flow cytometry in characteriz ing proliferations of large granular lymphocytes. The transformation o f a single case into an aggressive NK-cell lymphoma with blastic morph ology and tissue infiltration was associated with a fatal outcome.