Improved Sensitivity of T-Cell Clonality Detection in Mycosis Fungoides by Hand Microdissection and Heteroduplex Analysis

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Abstract
MYCOSIS FUNGOIDES (MF), the most common cutaneous T-cell lymphoma (CTCL), is a proteiform entity in which a definite clinical and pathologic diagnosis may be difficult to establish in the initial stages. Molecular methods searching for a dominant T-cell clone in the infiltrate have been advocated, but a clear correlation between initial molecular data, final diagnosis, and patient outcome could not be established in ambiguous cutaneous lymphoid infiltrates.1 Conversely, in definite MF cases, the presence of a detectable dominant T-cell clone seems to be an independent risk factor for an unfavorable outcome and resistance to therapy.2 Another difficulty lies in the sensitivity of molecular methods, with the possibility of overlooking an authentic dominant T-cell clone when the percentage of neoplastic clonal cells falls below the threshold of the method's ability to detect them. Southern blot, the sensitivity of which is about 5% at best, has been superseded by more sensitive methods based on polymerase chain reaction (PCR) capable of detecting as few as 0.1% of clonal T cells in a mixed lymphocytic infiltrate.3-6

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