Pathobiology of Anaplastic Large Cell Lymphoma

Abstract

The authors revise the concept of anaplastic large cell lymphoma (ALCL) in the light of the recently updated WHO classification of Tumors of Hematopoietic and Lymphoid Tissues both on biological and clinical grounds. The main histological findings are illustrated with special reference to the cytological spectrum that is indeed characteristic of the tumor. The phenotype is reported in detail: the expression of the ALK protein as well as the chromosomal abnormalities is discussed with their potential pathogenetic implications. The clinical features of ALCL are presented by underlining the difference in terms of response to therapy and survival between the ALK-positive and ALK-negative forms. Finally, the biological rationale for potential innovative targeted therapies is presented.

18F-FDG PET in Patients with Primary Systemic Anaplastic Large Cell Lymphoma: Differential Features According to Expression of Anaplastic Lymphoma Kinase

“…ALK-positive patients were significantly younger than ALK-negative patients, being consistent with the established correlation between ALK expression and young age [7][8][9][10].…”

“…Together these findings support the view that primary systemic ALK-positive and ALK-negative ALCL are different disease entities [7][8][9][10].…”

“…Depending on the expression of a protein called anaplastic lymphoma kinase (ALK), two different entities are recognized as systemic forms, the ALK-positive and ALK-negative ALCL [7].…”

Hypoxia-microRNA-16 downregulation induces VEGF expression in anaplastic lymphoma kinase (ALK)-positive anaplastic large-cell lymphomas

“…NPM-ALK and TPM3-ALK are the main translocations recorded in ALCL. 32 A direct role for NPM-ALK in cellular transformation has been shown both in vitro and in vivo, and such studies have shed light on the mechanisms of malignant transformation by this oncoprotein. 33,34 These mechanisms include activation of several downstream signal-transduction pathways, which regulate cell survival, proliferation, migration and, more recently, hypoxia.…”

Primary tonsilar ALK negative anaplastic large cell lymphoma – report of a rare entity with brief review of literature

“…In particular two different entities are recognized, the ALK positive and the ALK negative based on genetic features [5,6] . The most frequent genetic alteration in the classical ALK positive ALCL is the translocation t(2;5)p23;q35, between the ALK gene on chromosome 2 and the nucleophosmin (NPM) gene on chromosome 5, leading to the nuclear/cytoplasmic positivity for the protein, which is not seen in ALK negative cases.…”