PTFL is the proliferation of a clone (i.e. a group of genetically identical cells that share a common ancestry) of B-cells that act non-physiologically by invading and disrupting the structure and function of lymphoid tissues. This cell clone forms, increases in size, and spreads to other lymphoid tissues in association with its progressively increasing accumulation of numerous chromosome deletions and gene mutations, although different sets of these alterations occur in different individuals with the disease. These alterations are thought to promote the survival of the malignant cells by inhibiting their programmed cell death, blocking their maturation, increasing their ability to evade the immune system, and/or creating conditions favorable for the development of other genomic alterations that have these pro-malignancy effects. The most common chromosome deletion is the 1p36 deletion which occurs in 20-50% of PTFL cases. This alteration is a deletion in the q arm of chromosome 1 at position 36 that results in the lose of TNFAIP3, a gene that encodes tumor necrosis factor, alpha-induced protein 3. This protein functions to inhibit the activation of NF-κB, to block programmed cell death, and to regulate lymphocyte-based immune responses through its ubiquitin ligase activity. Other alterations repeatedly seen in PTFL include mutations in the following genes: 1) TNFRSF14 (30-50% of cases) which encodes tumor necrosis factor receptor superfamily, member 14, a receptor that stimulates immune responses in T-cells, a set of non-B-cell lymphocytes; 2) IRF8 (10-50% of cases) which encodes the interferon regulatory factor 8 protein, a protein that contributes to the maturation and function of B-cells; 3) MAP2K1 (10-40% of cases), which encodes mitogen-activated protein kinase kinase 1, an enzyme which activates the MAPK/ERK cell signaling pathway that regulates cell proliferation and the expression of various genes; and 4) scores of other genes that are found in up to 15% of cases. Recent Whole exome sequencing studies in children and adolescents with PTFL have confirmed these results, found that many of these genomic alterations result in suppressing either the MAPK/ERK or G protein-coupled receptor signaling pathways, and suggest that the suppression of these pathways contributes to the development of PFFL.
Pediatric-type follicular lymphoma
Nodal marginal zone B cell lymphoma
Duodenal-type follicular lymphoma
Marginal zone B-cell lymphoma
Nodular lymphocyte predominant Hodgkin lymphoma
Follicular lymphoma
Indolent lymphoma
AIDS-related lymphoma