Molecular diagnosis of lymphocytic infiltrates of the skin

Advances in our understanding of the molecular genetics of lymphocyte antigen receptors (B-cell immunoglobulin and T-cell antigen receptor), have led to the application of molecular biologic techniques to molecularly characterize lymphocytic infiltrates of the skin. Molecular diagnosis refers to the application of these techniques as a diagnostic aid in the clinicopathologic evaluation of cutaneous lymphocytic infiltrates.

Molecular studies have clinical application in the determination of lineage and detection of retroviruses in cutaneous lymphoid neoplasms, distinguishing between lymphoproliferative and reactive infiltrates, and staging and monitoring response to therapy in cutaneous T-cell lymphoma. Southern blot analysis of immunoglobulin and T-cell antigen receptor gene rearrangements may fail to aid the clinician in establishing a diagnosis of a cutaneous malignancy due to the limits of detection sensitivity in minimally infiltrated lesions (eg, parapsoriasis and patch-stage mycosis fungoides) or the still uncertain prognostic significance of clonality in benign cutaneous diseases (eg, follicular mucinosis, pityriasis lichenoides et varioliformis acuta, lymphomatoid papulosis, and cutaneous lymphoid hyperplasia).

Molecular studies have enormous research value, providing new means to explore the pathogenesis and clonal evolution of lymphoproliferative skin diseases. Presently, however, they have limited applications as an independent diagnostic tool. As our understanding of the clinical and biologic significance of the molecular detection of clonal lymphocyte populations in the skin expands and as the application of polymerase chain reaction amplification provides us with greater detection sensitivity and specificity, the clinical utility of molecular diagnosis of lymphocytic infiltrates of the skin will be enhanced.