MBN 2016 Aesthetic Breast Meeting BIA-ALCL Consensus Conference Report.

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Sir: GENETIC MARKERS FOR EARLY DETECTION OF BREAST IMPLANT–ASSOCIATED ANAPLASTIC LARGE CELL LYMPHOMA IN PLASTIC SURGERY PROCEDURES We read with great interest the article written by Nava et al.,1 recently published as a Special Topic article in Plastic and Reconstructive Surgery entitled “MBN 2016 Aesthetic Breast Meeting BIA-ALCL Consensus Conference Report.” This study focuses on the current pathogenesis, diagnosis, and therapy of breast implant–associated anaplastic large cell lymphoma (BIA-ALCL). Because BIA-ALCL is a rare type of lymphoma, the pathogenesis of this disease is still not clear, and few clinical data are available.2 A panel of experts in breast plastic surgery, to improve the production of reliable scientific data, emphasize the need for a consensus “patient registry” document of all new BIA-ALCL cases diagnosed, reporting safety, medical devices, follow-up, and other factors.1 We are confident that the actions proposed in the conference report will help the management of BIA-ALCL. Moreover, it is also important to differentiate a simple T-lymphocytosis with no malignant CD30+ lymphocytes from BIA-ALCL early. The early detection is finalized to prevent the risk of lymph node involvement and systemic spread. Currently, the diagnosis of BIA-ALCL is based on the characterization of serum cellular population by the cytologic smear and CD30 status detected by immunocytofluorimetric assays, but this information is not sufficient to support an early diagnosis of BIA-ALCL. Moreover, although the factors leading to anaplastic cell progression are still unclear, the identification of genetic markers underlying the development of neoplastic T-cell diseases is now possible.3 Here, we report a panel of somatic mutations, known to be associated with malignant transformation of normal T-lymphocytes in anaplastic large T cells (Table 1).Table 1.: Common Genetic Variants at the Molecular Level Found in ALCLThe majority of cases (74 to 90 percent) show clonal rearrangement of TCR genes and other genetic variants.3 Moreover, gene expression profiling studies suggest that ALCL-anaplastic lymphoma kinase–negative lymphoma is different from anaplastic lymphoma kinase–positive lymphoma. Recently, the translocation involving the DUSP22 gene, t(6;7)(p25.3;q32.3), was found in ALCL-anaplastic lymphoma kinase–negative BIA-ALCL cases. The 6p25.3 translocation inactivates DUSP22, a dual-specificity phosphatase that inhibits ERK1/2 signaling in T cells leading to loss of tumor-suppressor function.4 Specific evaluation of known genetic variants (mutations) in patients with a late onset, persistent peri-implant seroma will help to early differentiate patients with nonmalignant CD30+ T-lymphocytosis from those carrying potential neoplastic T cells.4 In case of BIA-ALCL patients, this platform must be able to detect low mutant T cells in the wide range of wild-type cells.5 Available methods for the detection of known point mutations and small deletions or insertions are summarized in Table 2.Table 2.: Widely Used Methods for Genotyping at the Molecular LevelWe believe that this diagnostic approach will contribute to early diagnosis of BIA-ALCL in seroma samples and to a better understanding of the transformation of normal T-lymphocytes into ALCL of patients with BIA-ALCL, and it may be helpful in designing the most appropriate approach for patient management and personalized therapy. In this scenario, the present process is a multifaceted task that needs the successful cooperation of the clinicians, surgeon, and laboratory manager to develop diagnostic strategies suitable for early diagnosis and eventually personalized therapy. DISCLOSURE Dr. Santorelli is a consultant and speaker for Allergan, Inc. (Irvine, Calif.). The other authors declare no potential conflicts of interest with respect to the research, authorship, and publication of this communication. Adriano Santorelli, M.D.Plastic SurgeryHealth ParkNaples, Italy Stefano Avvedimento, M.D.Plastic Surgery Clinica Villa dei FioriAcerra, Naples, Italy Antonio Abbadessa, M.D.CETAC Diagnostic and Research CenterCaserta, Italy