PTFL cells demonstrate positivity of the mature B cell markers CD20, CD79a, and PAX5
Germinal cell-associated markers BCL6, CD10, LLT1, and STMN1 are also strongly expressed in these cells
Nuclear FOXP1 transcription factor staining in >80% of PTFL cells
Although weak staining may be seen in few cases, BCL2 is typically negative, consistent with the absence of BCL2 rearrangement which distinguishes PTFL from other follicular lymphomas
IRF4/MUM1 is negative, distinguishing PTFL from large B-cell lymphoma with IRF4 rearrangement
The Ki67 proliferation index is moderate to high (>30% of PTFL cells)
Finding
Marker
Positive (universal)
CD20, CD79a, PAX5, BCL6, CD10, LLT1, STMN1, FOXP1
Negative
BCL2, IRF4/MUM1
Chromosomal Rearrangements (Gene Fusions)
Negative for BCL2, BCL6, IGF4, IG@, and MYC rearrangement[8][9][10][12]
Characteristic Chromosomal Aberrations / Patterns
No characteristic chromosomal aberrations or patterns are described
Genomic Gain/Loss/LOH
Copy number alterations are uncommon (~0.5% of the genome)[9]
Copy neutral loss of heterozygosity (cnLOH) of 1p36 is most frequently reported, commonly overlapping the TNFRSF14 gene and frequently in patients with concomitant TNFRSF14 non-synonymous variation[9][10][12][14]
Although alterations in chromatin-modifying genes, such as KMT2D, CREBBP, EP300, EZH2, are frequently described in adult follicular lymphoma[15][16], these genes are not recurrently altered in PTFL
PTFL frequently presents with somatic activating alterations in the MAPK signaling pathway[9][14]
Although IRF8 alterations in the C-terminal domain are described in adult follicular lymphoma and diffuse large B-cell lymphoma, the hotspot alteration p.K88R is specific to PTFL[9][11][14]
MAP2K1 encodes mitogen-activated protein kinase kinase 1 (also known as MEK1) involved in the MAPK signaling pathway. Oncogenic MAP2K1 alterations are predicted to constitutively activate the MAPK signaling pathway through ERK1/2 phosphorylation.[17]
TNFRSF14 encodes the tumor necrosis factor (TNF) superfamily member herpesvirus entry mediator (HVEM) involved in activating both inflammatory and inhibitory T-cell responses. TNFRSF14 alterations disrupt the interaction of TNFRSF14 and the immunoglobulin superfamily proteins B and T lymphocyte attenuator (BTLA) receptor, thereby abrogating B-cell receptor activation.[18][19]
IRF8 encodes interferon regulatory factor 8 primarily expressed in immune cells. In B cells, IRF8, in tandem with IRF4, plays a critical role in pre-B cell development.[20]
GNA13 encodes G protein subunit alpha 13 involved in signal transduction. GNA13 is expressed in germinal center B cells and is involved in sphingosine-1-phosphate signaling and germinal center confinement.[21][22]
Diagnostic Testing Methods
Histopathology and immunophenotyping
Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications)
No genomic findings currently assist in diagnosis.
No differences in overall survival between patients with and without genomic alterations[12]
Activating alterations within the MAPK pathway alterations are frequently reported in PTFL which demonstrate constitutive activation of MEK/ERK signaling. Currently, the utility of MEK inhibitors, such as trametinib, in PTFL is not established.[9]
Familial Forms
Not applicable
Other Information
Not applicable
Links
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↑ 3.03.13.23.33.43.5Jaffe ES, Harris NL, Siebert R et al (2017) Paediatric-type follicular lymphoma. In: Swerdlow SH, Campo E, Harris NL et al (eds) WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. IARC Press, Lyon, pp 278–279
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