Molecular Biology Techniques for the Diagnosis of Cutaneous T-Cell Lymphoma

Abstract

The molecular biologic analysis of TCR gene rearrangements by Southern blot analysis and various PCR-based assays has contributed significantly to the understanding of CTCL. It is now known that CTCL is a monoclonal T-cell disorder like other T-cell neoplasms and that the same tumor clone is generally present in all sites of tissue involvement. Relative to histopathologic examination, the enhanced sensitivity of molecular biologic assays has allowed the diagnosis of CTCL at an early stage in many cases. In fact, molecular biologic analysis of TCR gene rearrangements suggests that CTCL may contain a dominant monoclonal tumor cell population from the time of its earliest clinically recognizable lesions, such as the cutaneous patches once termed large plaque parapsoriasis and now generally regarded as early CTCL. Furthermore, available data indicate that, at least in some cases, tumor cells are distributed widely among cutaneous and extracutaneous tissues at a time long before this involvement can be appreciated morphologically. It is apparent that, in addition to their value in the early diagnosis and staging of cutaneous lymphomas, these molecular biologic assays are valuable in monitoring the response to therapy, detecting early relapse, and improving understanding of the compartmentalization and trafficking of tumor cells. In order to reap the full clinical benefit from this new information, however, it is important to perform prospective long-term studies designed to determine the clinical significance of molecular biologic data. In addition, the complexity of cutaneous lymphoproliferative disorders dictates that molecular biologic clonality data should never be interpreted in a vacuum. In skin disease, dominant clonality does not always equate with clinical malignancy. The proper diagnosis of CTCL and other cutaneous lymphoproliferative diseases requires the thoughtful integration of molecular biologic data with the clinicopathologic and immunophenotypic findings.