Early cutaneous T-cell lymphoma (CTCL) remains challenging to diagnose, as it clinically and histologically may mimic inflammatory conditions such as eczematous dermatitis, pityriasis lichenoides, or psoriasis. The consequence is delay in time from symptom onset to diagnosis, which commonly spans years (median, 36 months; interquartile range, 12-90 months). Definitive diagnosis continues to hinge on careful clinicopathologic correlation, which is sometimes supported by detection of a clonal T-cell population in skin and/or blood. Yet, the polymerase chain reaction (PCR)–based T-cell receptor (TCR) γ and β gene rearrangement assays most widely available in practice have limited sensitivity and can yield false-negative results; conversely, clonal T-cell populations are not pathognomonic and may be detected in inflammatory conditions. However, detecting clonal T-cell populations is not only important in establishing diagnosis of CTCL, but also, the overall clonal burden or tumor clone frequency (TCF) is associated with prognosis. In patients with a TCF greater than 25%, there is a reduction in progression-free survival and overall survival. Against this backdrop, technologies that provide more sensitive and granular assessment of TCR repertoires are particularly salient, as they promise to refine diagnosis, quantify clonal burden, and potentially inform prognosis and management.
