Lymphoproliferative disorder of granular lymphocytes. A heterogeneous disease

Lymphoproliferative disorders of granular lymphocytes (LDGLs) represent a family of diseases that are morphologically similar but diverse with regard to immunophenotype, function, and clonality. In this article, we report three informative cases and propose a modification of the current classification of LDGLs. Our first case is an example of natural killer cell LDGLs (CD2+, CD3-, CD16+, CD57+/-). Based on a review of the literature, we suggest that natural killer cell LDGLs can be divided into two subgroups (types 1 and 2) according to the expression of CD57. Reduced expression of CD57 may distinguish between patients with a poorer prognosis. The remaining two cases illustrate examples of T-cell LDGLs (CD2+, CD3+, CD8+, CD57+) that differ mainly in their expression of CD16. The CD16+ T-cell LDGLs (type 1) usually show a clonal rearrangement of the T-cell receptor-beta chain gene, whereas CD16- T-cell LDGLs (type 2) may show a germline configuration, suggesting a reactive rather than a neoplastic process. Pathologists should differentiate LDGLs from other chronic lymphoproliferative diseases, since most cases evolve slowly and aggressive cytoreductive therapy is usually unwarranted.