Table 2. Biological risk factors for... | American Society of Hematology

Table 2.

Biological risk factors for transformation reported in the literature

Category	Variable	Reported risk of transformation
Microanatomical structure	Disrupted CD21⁺ FDC meshworks	Increased^40,41
	Disrupted CD21⁺ FDC meshworks	Decreased⁴²
	Intrafollicular localization of CD14⁺ FDCs	Increased⁴³
FL grade	Grade 3A	Increased^17,38
	Grade 3A	No effect^39,40
	IRF4 tumor cell staining by IHC	Increased¹⁷
Tumor microenvironment	Predominantly intrafollicular localization of CD4⁺ T cells	Increased⁴⁰
	High numbers of PD1⁺ cells	Decreased⁴⁴
	Diffuse pattern of PD1⁺ cells	Increased⁴³
	Higher FOXP3 expression	Increased⁴²
	Higher FOXP3 expression	No effect⁴⁰
	Intra- or perifollicular distribution of FOXP3⁺ cells	Increased⁴⁵
	Intra- or perifollicular distribution of FOXP3⁺ cells	No effect⁴⁰
	Increased vessel density	Increased⁴⁶
Gene expression signatures	Embryonic stem cell–like signature	Increased⁴⁷
Gene expression signatures	NF-κB target signature scores	Increased⁴⁸
Germ line polymorphism	SNP rs6457327	Increased^49,50
Large-scale genetic alterations	eg, Deletions of chromosomes 1p or 6q; gain of chromosomes 2, 3q, or 5	Increased^51-54
Large-scale genetic alterations	Higher numbers of structural rearrangements	Increased²⁴
Single gene alterations	TP53 mutations, deletions	Inconclusive⁵⁵
	MYC translocations, mutations	Inconclusive
	FAS mutations	Increased²⁶
	BCL6 translocations	Increased^17,56
	BCL2 mutations	Increased⁵⁷
Circulating tumor DNA	Proportion of mutations uniquely found in plasma	Increased⁵⁸

Category	Variable	Reported risk of transformation
Microanatomical structure	Disrupted CD21⁺ FDC meshworks	Increased^40,41
	Disrupted CD21⁺ FDC meshworks	Decreased⁴²
	Intrafollicular localization of CD14⁺ FDCs	Increased⁴³
FL grade	Grade 3A	Increased^17,38
	Grade 3A	No effect^39,40
	IRF4 tumor cell staining by IHC	Increased¹⁷
Tumor microenvironment	Predominantly intrafollicular localization of CD4⁺ T cells	Increased⁴⁰
	High numbers of PD1⁺ cells	Decreased⁴⁴
	Diffuse pattern of PD1⁺ cells	Increased⁴³
	Higher FOXP3 expression	Increased⁴²
	Higher FOXP3 expression	No effect⁴⁰
	Intra- or perifollicular distribution of FOXP3⁺ cells	Increased⁴⁵
	Intra- or perifollicular distribution of FOXP3⁺ cells	No effect⁴⁰
	Increased vessel density	Increased⁴⁶
Gene expression signatures	Embryonic stem cell–like signature	Increased⁴⁷
Gene expression signatures	NF-κB target signature scores	Increased⁴⁸
Germ line polymorphism	SNP rs6457327	Increased^49,50
Large-scale genetic alterations	eg, Deletions of chromosomes 1p or 6q; gain of chromosomes 2, 3q, or 5	Increased^51-54
Large-scale genetic alterations	Higher numbers of structural rearrangements	Increased²⁴
Single gene alterations	TP53 mutations, deletions	Inconclusive⁵⁵
	MYC translocations, mutations	Inconclusive
	FAS mutations	Increased²⁶
	BCL6 translocations	Increased^17,56
	BCL2 mutations	Increased⁵⁷
Circulating tumor DNA	Proportion of mutations uniquely found in plasma	Increased⁵⁸

FDC, follicular dendritic cell; IHC, immunohistochemistry; SNP, single-nucleotide polymorphism.