Current Progress in Breast Implant-Associated Anaplastic Large Cell Lymphoma

Breast implant-associated anaplastic large-cell lymphoma (BIA-ALCL) is an uncommon type of T-cell lymphoma. Although with a low incidence, the epidemiological data raised the biosafety and health concerns of breast reconstruction and breast augmentation for BIA-ALCL. Emerging evidence confirms that genetic features, bacterial contamination, chronic inflammation, and textured breast implant are the relevant factors leading to the development of BIA-ALCL. Almost all reported cases with a medical history involve breast implants with a textured surface, which reflects the role of implant surface characteristics in BIA-ALCL. With this review, we expect to highlight the most significant features on etiology, pathogenesis, diagnosis, and therapy of BIA-ALCL, as well as we review the physical characteristics of breast implants and their potential pathogenic effect and hopefully provide a foundation for optimal choice of type of implant with minimal morbidity.

BRG1 and NPM-ALK Are Co-Regulated in Anaplastic Large-Cell Lymphoma; BRG1 Is a Potential Therapeutic Target in ALCL

Anaplastic large-cell lymphoma (ALCL) is a T-cell malignancy driven in many cases by the product of a chromosomal translocation, nucleophosmin–anaplastic lymphoma kinase (NPM-ALK). NPM-ALK activates a plethora of pathways that drive the hallmarks of cancer, largely signalling pathways normally associated with cytokine and/or T-cell receptor-induced signalling. However, NPM-ALK is also located in the nucleus and its functions in this cellular compartment for the most part remain to be determined. We show that ALCL cell lines and primary patient tumours express the transcriptional activator BRG1 in a NPM-ALK-dependent manner. NPM-ALK regulates expression of BRG1 by post-translational mechanisms dependent on its kinase activity, protecting it from proteasomal degradation. Furthermore, we show that BRG1 drives a transcriptional programme associated with cell cycle progression. In turn, inhibition of BRG1 expression with specific shRNA decreases cell viability, suggesting that it may represent a key therapeutic target for the treatment of ALCL.

The Leukemic Phase of ALK-Negative Anaplastic Large Cell Lymphoma Is Associated with CD7 Positivity, Complex Karyotype, TP53 Deletion, and a Poor Prognosis

Patients with anaplastic large cell lymphoma (ALCL) rarely develop a leukemic phase of the disease. The reported leukemic ALCL cases are almost all ALK-positive, which are frequently associated with small cell morphology, t(2;5)(p23;q35), and a poorer prognosis. Rare leukemic ALK-negative ALCL cases have been reported. In the present study, we investigated the clinical and pathologic features and outcomes of nine patients with leukemic ALK-negative ALCL and compared these features with 39 patients without leukemic disease. Compared with the non-leukemic ALK-negative ALCL group, patients with leukemic disease more often had absolute lymphocytosis (50% vs. 0%, p = 0.008), thrombocytopenia (60% vs. 11%, p = 0.03), bone marrow involvement (50% vs. 14%, p = 0.04), and CD7 positivity (71% vs. 19%, p = 0.02). Four of five (80%) patients with leukemic ALK-negative ALCL had a complex karyotype, which was significantly higher than that of the patients in the non-leukemic group. A fluorescence in situ hybridization for TP53 was performed on six leukemic ALK-negative ALCL cases and all (100%) had TP53 deletion. There were no significant differences in the other clinicopathologic features, treatment, and complete remission rates between patients in the leukemic versus non-leukemic group (all p > 0.05). The median follow-up of this cohort was 18 months with a range of 0.3–140 months. Eight of nine (90%) patients with leukemic ALK-negative ALCL died, and their overall survival was significantly shorter than that of the patients with non-leukemic disease (median 15.5 vs. 60 months, p = 0.001). In conclusion, we show that the leukemic phase of ALK-negative ALCL is associated with high-risk biologic features and, in particular, a complex karyotype and TP53 deletion. Compared with the non-leukemic ALK-negative ALCL patients, the patients with a leukemic phase of disease have poorer survival and may require more aggressive treatment.