IRF4 Translocations Are Specific for Cutaneous Anaplastic Large Cell Lymphoma in Skin Biopsies Involved by T-Cell Lymphoproliferative Disorders
D Wada, ME Law, A de Souza, R Weenig, N Comfere, WR Macon, LA Erickson, A Dogan, AL Feldman. Mayo Clinic, Rochester, MN
Background: Reliable pathologic criteria are lacking to differentiate cutaneous anaplastic large cell lymphoma (cALCL) from other T-cell lymphoproliferative disorders (TLPDs) involving skin, particularly lymphomatoid papulosis (LyP) and systemic ALK-negative ALCL with secondary cutaneous involvement. Using fluorescent in situ hybridization (FISH), we recently showed that some cALCLs have translocations involving IRF4 (interferon regulatory factor-4, or multiple myeloma oncogene-1 [MUM1]). We undertook the current study to see if IRF4 translocations are specific for cALCL in skin biopsies involved by TLPDs.
Design: Skin biopsies involved by TLPDs from 68 patients were classified by WHO/EORTC criteria. Clinicopathologic data for classification included progression/regression of lesions, history of mycosis fungoides (MF) or other cutaneous TLPD, anatomic site and timing of extracutaneous disease, morphology, immunophenotype, and T-cell clonality if needed. Cases that could not be classified definitively were excluded. FISH for IRF4 was performed using a home-brew breakapart probe. Most positive cases also were screened for T-cell receptor (TCRA, TCRB, and TCRG) rearrangements. FISH was scored by a cytogeneticist using previously established normal ranges based on 95% confidence intervals.
Results: Among cALCLs, 9 of 22 (41%) demonstrated abnormal separation of the IRF4 breakapart probe, indicating an IRF4 translocation. None of the 46 remaining TLPDs showed IRF4 translocations, including: 12 LyPs; 6 systemic ALK-negative ALCLs; 3 systemic ALK-positive ALCLs; 12 cases of MF (2 transformed); 2 cases of Sezary syndrome; 1 CD4-positive small/medium-sized pleomorphic T-cell lymphoma; 2 extranodal NK/T-cell lymphomas, nasal type; 1 subcutaneous panniculitis-like T-cell lymphoma; and 7 peripheral T-cell lymphomas, unspecified. No rearrangements of TCRA, TCRB, or TCRG were identified in cases with IRF4 translocations.
Conclusions: Our findings suggest IRF4 translocations are specific for cALCL in skin biopsies involved by TLPDs, and support the utility of clinical FISH testing in such cases. Because not all cALCLs harbor IRF4 translocations, and because such translocations rarely occur in extracutaneous peripheral T-cell lymphomas, FISH results should be interpreted in the context of morphology, phenotype, and clinical features. The gene partner(s) and biologic significance of IRF4 translocations in cALCL remain unknown and merit further study.
Monday, March 9, 2009 2:45 PM
Platform Session: Section D, Monday Afternoon