Analysis of clonality in cutaneous T cell lymphoma and associated diseases

The T cell receptor (TCR) is the antigen-specific receptor for T cells. During its differentiation, each T cell undergoes rearrangement of its TCR genes. This results in novel nucleotide sequences that constitute a unique signature or fingerprint for each T cell and all its clonal progeny. Analysis of TCR gene rearrangements in cutaneous T cell lymphoma (CTCL) has lead to several findings concerning CTCL tumor biology. First, like most other lymphomas, CTCL is a monoclonal lymphoproliferative disorder. Second, rather than being truly a cutaneous lymphoma, CTCL is actually a lymphoma of the skin-associated lymphoid tissue (SALT). Even when disease appears confined to the skin clinically, there can be low-level trafficking of tumor cells through the peripheral lymph nodes via the lymphatics and blood vessels. Furthermore, CTCL is a mature SALT lymphoma capable of trafficking to sites of cutaneous inflammation analogous to normal SALT T cells. Third, the earliest manifestation of CTCL may be "clonal dermatitis." This is a form of chronic dermatitis that harbors a dominant T cell clone but lacks histologic features diagnostic for CTCL. About 25% of clonal dermatitis cases progress to overt CTCL within five years. Fourth, other lymphoproliferative disorders that are associated with CTCL share the same TCR gene rearrangements and therefore arise as subclones of the original tumor. These include lymphomatoid papulosis, large-cell lymphoma, and Hodgkin's disease.