The role of molecular pathology in the diagnosis of cutaneous lymphomas

Abstract

Primary cutaneous lymphomas can be difficult to be distinguished from reactive mimics, even when integrating histologic, immunophenotypic, and clinical findings. Molecular studies, especially PCR-based antigen receptor gene rearrangement (ARGR) analysis, are frequently useful ancillary studies in the evaluation of cutaneous lymphoproliferations. The biologic basis of ARGR studies is discussed, as well as a comparison of various current protocols. The pitfalls and limitations of ARGR analysis are also highlighted. Recent advances in the understanding of the molecular pathogenesis of various cutaneous lymphomas are discussed. Some of these nascent discoveries may lead to the development of diagnostically useful molecular assays.

Figure 1

(a) IGH@ gene structure, VDJ rearrangement, and PCR primer annealing sites. The IGH@ gene is composed of ~45 V segments, ~23 D segments, and 6 J segments. DJ rearrangement occurs first, here combining D_H3 and J_H5. This is followed by V-DJ rearrangement, here combining V_H2 with the previously rearranged D_H3-J_H5. Multiple PCR primers are directed against the 3 FR regions in the V segment and a single primer to the J segment (FR4). N represents nucleotides inserted and deleted by TdT. Adapted with permission from [4]. (b) TRG@ gene structure, VJ rearrangement, and PCR primer annealing sites. The TRG@ gene is composed of 11 V segments and 5 J segments. VJ rearrangement here combines the Vγ6 and JγP2 segments. Multiple PCR primers are directed against Vγ segments and Jγ segments.

Figure 2

Capillary electropherograms of TRG@ PCR studies. Clonal (a) and polyclonal (b) rearrangements (from different samples) are shown, using Vγ9-11 primers and Vγ1-8 primers, respectively. The X axis is amplicon size (base pairs) and the Y axis is random fluorescent units.

Figure 3

Capillary electropherogram of TRG@ PCR study. Oligoclonal rearrangements using Vγ1-8 primers. Note the presence of multiple irregular peaks in a nonGaussian distribution. The X axis is amplicon size (base pairs) and the Y axis is random fluorescent units.