Pediatric-type follicular lymphoma (PTFL)

Pediatric-type follicular lymphoma (PTFL) is a disease in which malignant B-cells accumulate and cause the expansion of the lymphoid follicles, enlargement of the lymph nodes in the head and neck regions and, less commonly, groin and armpit regions.

The disease accounts for 1.5% to 2% of all the lymphomas that occur in the pediatric age group.

PTFL differs from follicular lymphoma in its clinical manifestations, its pathophysiology including the genomic alterations which occur in the diseases malignant cells.

PTFL often presents histologically as a high-grade malignancy but unlike the small percentage of follicular lymphoma cases that similarly present as a high grade malignancy, it almost invariably takes an indolent, relapsing and remitting course without progressing to a more aggressive and incurable form.

The recognition of PTFL as a distinct disease from follicular lymphoms is critical to avoid mistaking it for a more aggressive lymphoma that requires potentially toxic chemotherapy treatments.

This appears to be particularly the case when PTFL occurs in children, adolescents, and perhaps very young adults.

PTFL occurs in male (male to female ratio ~10;1) children or adolescents (ages 1–17 years, median age ~13-14), less frequently in young adults (ages 18–30 years), and occasionally in older adults.

In ~90% of cases, the diseases is diagnosed in an early stage I or II, and localized to one or two adjacent lymph node chains.

Commonly presenting with swollen lymph nodes and/or tonsils in the head and neck regions,, and less commonly as swollen lymph nodes in the axillary and/or inguinal regions, and/or rarely as swollen lymph nodes in the abdomen and infiltrations of malignant cells into the testes, bone marrow, and/or central nervous system.

PTFL presents almost exclusively with enlargement of lymph nodes in the head, neck, axilla, or groin.[3][11]

PTFL is the proliferation of a clonal 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 increases in size, and spreads to other lymphoid tissues with increasing accumulation of numerous chromosome deletions and gene mutations.

These alterations 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 for development of other genomic alterations that have these pro-malignancy effects. 

The most common chromosome deletion is the 1p36 deletion.

This deletion occurs in 20-50% of PTFL cases that results in the loss of 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

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.

About 90% of cases occur in males, that are more often children, adolescents, or young adults who have enlargement of lymph nodes located in one or two nearby sites of the head or neck or less commonly, armpit or groin regions. 

Histopathological examination of the involved lymph nodes reveals medium- to large-sized lymphoblasts mixed with occasional macrophages and rare centrocytes and centroblasts

Cells form follicular structures that replace the nodes’ normal structure with irregularly shaped and follicles, attenuated mantle zones, and the presence of helper T-cells that are pushed to the periphery of the follicles. 

Histologically this lymphoma is often graded as high-grade/grade Roman

Its histology is most often rated as high grade and by this criterion defines the disease as an aggressive grade III lymphoma, yet almost always behaves as a non-aggressive or minimally, aggressive. Eoplasm.

The  malignant cells express CD20, CD10, and BCL6 but not BCL2 or interferon regulatory factor protein. 

Genomic analyses of these cells indicate that they have a clonal rearrangement  in the  IgH genes in all cases and in many cases the Ip6 deletion and gene mutations.

 These cells lack the t(14:18)(q32:q21.3) translocation which is characteristic of malignant cells in follicular lymphoma.

Differential diagnosis

Follicular lymphoma does not have a strong male-predominance; is most common in older adults; is usually associated with the involvement of other tissues (e.g. bone marrow) in addition to lymph nodes.

Histology that is usually dominated by centrocytes and centorblasts.

 There are >85-90% of cases with  t(14:18)(q32:q21.3) translocation; and in 10-40% of cases MAP2K1 mutations.

It has malignant cells that overexpress interferon regulatory factor protein in almost all cases, frequently express BC10, and in most cases exhibit overt rearrangements of the IRF4 gene.

The pediatric form of Marginal zone B-cell lymphoma has lymph node lesions consisting of a mixed population of monocyte-like cells, plasma cells, and lymphoblasts; its malignant cells do not to express CD10 and BCL6 and have relatively few genomic abnormalities except for trisomy 18 in up to 20% of cases.

Benign reactive lymph node and follicular hyperplasia’s lymph nodes do not exhibit irregularly shaped and merged follicles, abnormally attenuated mantle zones, or the presence of helper T-cells that are pushed to the periphery of the follicles.

Virtually all cases of PTFL  have have a relatively benign and sometimes remitting and relapsing course. 

All chemotherapeutic/immunologic treatments have yielded in pediatric patients overall survival rates of 100% and relapse rates of 0 to 6% as observed over variable observation periods of up to 5 years. 

Of 36 pediatric patients were treated with surgical resection alone followed by observation with all patients surviving and only one having a relapse.

The current recommendations for the treatment of pediatric PTFL patients is watch-and-wait following radiation therapy or complete surgical resection; 

In cases where surgical resection is incomplete, immuno-chemotherapy is added to the regimen.


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