Breast Implant Associated ALCL Closely Resembles Primary Cutaneous ALCL
Marshall E Kadin, Haiying Xu, Igor Pavlov, Alan L Epstein. Roger Williams Med Ctr, Providence, RI; U. Utah, Salt Lake City, UT; USC, Los Angeles, CA
Background: More than 60 cases of breast implant associated anaplastic large cell lymphoma (ALCL) are reported. Lymphoma is detected in seroma fluid or tissue around saline or silicone gel implants for breast augmentation or reconstructive surgery for breast cancer. Tumor cells express CD30 and T-cell antigens but are ALK negative. Case reports indicate an indolent course for most cases. These findings suggest the hypothesis that breast implant associated ALCL may closely resemble primary cutaneous ALCL.
Design: To test our hypothesis, we compared the morphology, immunophenotype, gene expression and cytokine profile of 6 cell lines derived from breast (3) and cutaneous (3) ALCL, and two non-anaplastic CTCL lines (HH and H9) and Jurkat, a lymphoblastic T cell lymphoma. Cells were grown in RPMI-1640 medium with 10% calf serum; cell conditioned media was harvested at 48 hours. Gene expression was examined by preparing cDNA from isolated RNA and hybridizing the cDNA to 96 well plates designed to detect 84 Th17 pathway genes, standardized with housekeeping genes, from Qiagen. Gene expression was compared with Qiagen software. A multianalyte assay was used to measure the following cytokines and cytokine receptors: CD30, IL-2R (CD25), IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, TNF-α and IFN-λ. A separate assay was used to measure VEGF. Results were compared to unconditioned media.
Results: Cytokine profiles for cutaneous and breast implant associated ALCL were similar but distinct from non-anaplastic CTCL and lymphoblastic T-cell lymphoma. ALCL cell lines secreted abundant CD30, CD25, IL-6, and IL-13, and low levels of IL-8, none of which were detected in non-ALCL lines. Breast implant ALCL lines also secreted IL-10. Amounts of VEGF did not differ significantly between breast implant and cutaneous ALCL lines or non-anaplastic T cell lines. Cutaneous and breast ALCL lines expressed RORC, the transcription factor for Th17 differentiation, and produced Th17 cytokines IL-17F and IL-22, not found in non-anaplastic CTCL or lymphoblastic T cell lymphoma.
Conclusions: The results support the hypothesis that breast implant associated ALCL resembles primary cutaneous ALCL with respect to morphology, immunophenotype and cytokine profile. This cytokine profile is not typical for Th1 or Th2 cells but more closely represents the Th17 type associated with inflammation and autoimmunity. Seroma fluid around breast implant associated ALCL is not explained by differential secretion of VEGF (formerly known as vascular permeability factor).
Wednesday, March 21, 2012 9:30 AM
Poster Session V # 190, Wednesday Morning