Introduction: Breast implant associated anaplastic large cell lymphoma (BIA-ALCL) was recently recognized by the WHO as a lymphoma presenting a median of 8 years after insertion of breast implants for reconstructive surgery following breast cancer, for prophylactic mastectomy due to high genetic risk of breast cancer, e.g. BRACA1/2 mutations, or for other cosmetic reasons. The American Society of Plastic Surgeons BIA-ALCL Global Network reports there are 1,158 known cases of BIA-ALCL and 35 deaths across 46 countries worldwide as of January 28, 2022. Approximately 80% of Australian women present with a peri-implant effusion whereas in the USA, 30% present with a mass +/- lymphadenopathy. Five-year overall survival is 90.1% when disease is confined to a peri-implant effusion and capsule but 72.4% when disease extends beyond the capsule. Therefore, we set out to develop a diagnostic test for early disease detection in peri-implant effusions. Experimental procedure: Our initial publications from the USA and Italy revealed higher mean concentrations of IL-9, IL-10 and IL-13 in BIA-ALCL than in more common benign effusions due to capsule contracture, leakage, trauma and infection. To validate these findings in a larger number of patients, mostly from another geographic region (Australia), we evaluated cryopreserved peri-implant effusions of 25 patients with BIA-ALCL and 30 patients with benign seromas collected at Macquarie University Medical School in Sydney AU and Rhode Island Hospital in the USA. Informed consent and Institutional approvals were obtained. Cytokine concentrations were determined with the Biolegend Human Th Cytokine 12 plex multianalyte flow assay kit (Cat. No. 741028), San Diego, USA. Results: The results show that mean levels of IL-9, IL-10 and IL-13 were elevated 72-, 716- and 22-fold, respectively, in BIA-ALCL compared to benign effusions, and each cytokine separated the two groups with little overlap (P < 0.0001), Mann-Whitney test. For IL-10, there was 92% sensitivity, 100% specificity, Youden Index (YIA08_92), cut-off value 150pg/ml; for IL-9, 96% sensitivity, 80% specificity (YI=76) cut-off value 88pg/ml; for IL-13, 76% sensitivity, 96.7% specificity, (YI= 72.7) cut-off value 714pg/ml. Furthermore, the geometric mean of the 3 cytokines has an area under the Receiver Operated Curve (AUROC) value of 0.9947 with 100% sensitivity and 96% specificity (Youden index of 96). Only one other cytokine, IFNgamma, showed significant diagnostic value.Conclusions: Measurement of a panel of 12 cytokines representing different T helper subsets discriminates with high sensitivity and specificity peri-implant effusions of BIA-ALCL from benign peri-implant effusions, facilitating early diagnosis with potential for curative surgery. The consistent cytokine profile of IL-9, IL-10 and IL-13 in malignant peri-implant effusions in this and 2 previous studies of 40 patients across 3 continents suggest that a specific immune response to unique etiologic agent(s) is an early event in the pathogenesis of BIA-ALCL.
Citation Format: Marshall E Kadin, Helen Hu, Elena Elena Shklovskaya, Anand Deva, Mark Dooner, Haiying Xu. Diagnosis of breast implant associated anaplastic large cell lymphoma by analysis of cytokines in peri-implant effusions [abstract]. In: Proceedings of the Third AACR International Meeting: Advances in Malignant Lymphoma: Maximizing the Basic-Translational Interface for Clinical Application; 2022 Jun 23-26; Boston, MA. Philadelphia (PA): AACR; Blood Cancer Discov 2022;3(5_Suppl):Abstract nr A08.