Anaplastic Large Cell Lymphoma: Molecular Pathogenesis and Treatment

Abstract

Anaplastic large cell lymphoma (ALCL) is an uncommon type of non-Hodgkin’s lymphoma (NHL), as well as one of the subtypes of T cell lymphoma, accounting for 1 to 3% of non-Hodgkin’s lymphomas and around 15% of T cell lymphomas. In 2016, the World Health Organization (WHO) classified anaplastic large cell lymphoma into four categories: ALK-positive ALCL (ALK+ALCL), ALK-negative ALCL (ALK−ALCL), primary cutaneous ALCL (pcALCL), and breast-implant-associated ALCL (BIA-ALCL), respectively. Clinical symptoms, gene changes, prognoses, and therapy differ among the four types. Large lymphoid cells with copious cytoplasm and pleomorphic characteristics with horseshoe-shaped or reniform nuclei, for example, are found in both ALK+ and ALK−ALCL. However, their epidemiology and pathogenetic origins are distinct. BIA-ALCL is currently recognized as a new provisional entity, which is a noninvasive disease with favorable results. In this review, we focus on molecular pathogenesis and management of anaplastic large cell lymphoma.

Current Understanding of Breast Implant-Associated Anaplastic Large Cell Lymphoma

“…This collection of T cells might be in close proximity to the silicone substance, which may eventually cause them to become sensitive to particles composed of silicones or their subsequent proteins, triggering a response to the antigen and its presentation in T cells [ 26 ]. Monocytes and T lymphocytes are mainly infiltrated close to the surface of biomaterials, where they release IL-4, IL-13, and other substances as a result [ 6 , 27 ]. Additionally, the immunological response involves T-helper cell activation of Th1 and Th17, which helps in drawing in macrophages and attracting neutrophils to extracellular infections, respectively.…”

“…However, any direct link between bacterial infection and the disease hasn't been established. BIA-ALCL being brought on by infections is thus a possibility [ 6 ]. Recent research indicates that antigenic stimulation may be responsible for prolonging an extended period of inflammation caused by several bacteria, including Staphylococcus and Ralstonia pickettii [ 19 , 30 , 31 ].…”

“…Because lymph node involvement indicates either progressive or chronic disorder, it has a significant impact on the prognosis of BIA-ALCL. Patients without lymph node involvement have a survival rate of 97.9 percent, but cases with lymph node involvement have a much lower survival rate of only 75% [ 6 , 35 ]. The depth of invasion, or the extent of the disease, seems to be the strongest prognostic factor.…”

“…When a clinical examination or imaging results point to the involvement of lymph nodes, the dissection of the axillary lymph nodes should be taken into account. To avoid a local recurrence, every effort should be taken to complete the surgical excision [ 6 ]. The mass should be fully removed, and the surgical margins should be examined for signs of cancer [ 13 ].…”

“…Less than 1,000 cases and 36 fatalities have been reported to date, and the average patient presents seven to 10 years after the initial insertion of the breast implants [3,5]. The American Food and Drug Administration (FDA) revealed a potential connection between breast implants and the emergence of BIA-ALCL in January 2011 [6,7]. It was introduced as a provisional entity to the WHO Classification of Tumors of Hematopoietic and Lymphoid Tissues [8][9][10].…”