Histopathologic-molecular Correlation in Early Mycosis Fungoides Using T-cell Receptor γ Gene Rearrangement by Polymerase Chain Reaction with Laser Capture Microdissection

Abstract

Early mycosis fungoides (MF) is difficult to distinguish from other benign inflammatory dermatoses. We evaluated clonal T-cell receptor (TCR) gamma gene rearrangement by polymerase chain reaction (PCR) as a surrogate to histologic diagnosis in early MF. Twenty paraffin-embedded skin biopsies from nine patients diagnosed with MF were included. Two multiplex PCR encompassing various Vgamma and Jgamma regions were used to detect TCRgamma gene rearrangements. Histologic diagnoses were categorized as "diagnostic", "consistent", "suggestive", or "nondiagnostic". We compared TCRgamma PCR results with histologic parameters to determine the differences between PCR-positive and PCR-negative groups. TCRgamma PCR was positive in 53% (8/15) of the patch stage, in 100% (2/2) of the plaque stage, and in 100% (3/3) of the tumor stage. TCRgamma PCR was positive in 50% (4/8) of the specimens in both the diagnostic and consistent of MF groups, 71% (5/7) in the suggestive of MF group. We found that inflammation was more severe in PCR-negative specimens. Papillary dermal fibrosis was common, and differed significantly between PCR-positive and PCR-negative groups (p = 0.01). T-cell monoclonality was detected in one nondiagnostic lesion in a patient with psoriasis and MF. TCRgamma PCR allows the diagnosis of MF in patients with lymphocyte-poor lesions, suggestive of MF pathologically. TCRgamma PCR is more likely to be negative with moderate to severe inflammation, particularly with papillary dermal fibrosis. We suggest that the ratio of malignant clonal to reactive T-cells is critical for MF diagnosis.