Characterization of t(2;5) Reciprocal Transcripts and Genomic Breakpoints in CD30+ Cutaneous Lymphoproliferations

Abstract

NPM-ALK chimeric transcripts, encoded by the t(2;5), lead to an aberrant expression of ALK by CD30+ systemic lymphomas. To determine if t(2;5) is involved in cutaneous lymphoproliferative disorders, we studied 37 CD30+ cutaneous lymphoproliferations, 27 mycosis fungoides (MF), and 16 benign inflammatory disorders (BID). NPM-ALK transcripts were detected by nested reverse transcription-polymerase chain reaction (RT-PCR) in 1 of 11 lymphomatoid papulosis (LyP), 7 of 15 CD30+ primary cutaneous T-cell lymphoma (CTCL), 3 of 11 CD30+ secondary cutaneous lymphoma, 6 of 27 MF, and 1 of 16 BID. However, the expression of NPM-ALK transcripts was not associated with ALK1 immunoreactivity in MF, LyP, or BID cases. Only 1 CD30+ primary CTCL and 3 CD30+ secondary cutaneous lymphoma were ALK1 immunoreactive. The ALK1+cases were also characterized by amplification of tumor-specific genomic breakpoints on derivative chromosome 5. These cases, except for 1 secondary cutaneous lymphoma, were also characterized by reciprocal breakpoints on derivative chromosome 2, leading to the expression of reciprocal ALK-NPM transcripts. Amplification of chromosomal breakpoints on both derivative chromosomes could represent an alternative to conventional cytogenetics for the diagnosis of t(2;5) and seems to be more reliable than the detection of cryptic NPM-ALK transcripts by nested RT-PCR.

WHO/EORTC classification of cutaneous lymphomas 2005: histological and molecular aspects

“…The findings of translocation studies for t(2;5) are controversial, showing translocation and the t(2;5)‐associated p80 NPM/ALK fusion protein in some CD30 + cutaneous lymphoma and LyP 98,99 whereas it is absent in most cases 100 . Furthermore, conflicting data on the detection of clonality among the large CD30 + tumor cells and small lymphocytes have been reported 101,102 .…”

Primary Cutaneous Anaplastic Large Cell Lymphoma of the Nasal Tip in a Child

“…The primary cutaneous form, characterized by the absence of nodal or visceral involvement at presentation, is uncommon below 20 years of age and usually runs an indolent course, as spontaneous remissions occur approximately in 25% of the cases, and dissemination is infrequent (18). Where more than 90% of systemic ALCLs in children are positive for ALK immunostaining, primary C‐ALCLs are almost always negative (19); likewise, ALK is expressed in S‐ALCL with cutaneous involvement (20). Epithelial membrane antigen is present in most cases of S‐ALCL and absent in most cases of C‐ALCL (21).…”

How I treat primary cutaneous CD30+ lymphoproliferative disorders

“…While ALK expression is unusual in pcALCL, the associated t(2;5) translocation can occasionally be detected in a minority of pcALCL cases and thus lacks specificity for differentiating pcALCL from systemic ALCL. 38,40,41 The majority of cases of pcALCL demonstrate monoclonal rearrangements of the T-cell receptor gene. 42 Numerous chromosomal aberrations are found in pcALCL, including genomic imbalances that lead to copy-number gains of known oncogenes.…”