Low Stage Follicular Lymphoma: Biologic and Clinical Characterization According to Nodal or Extranodal Primary Origin

Abstract

Studies suggest that primary extranodal follicular lymphoma (FL) is not infrequent but it remains poorly characterized with variable histologic, molecular, and clinical outcome findings. We compared 27 extranodal FL to 44 nodal FL using morphologic, immunohistochemical, and molecular genetic techniques and evaluated the clinical outcome of these 2 similarly staged groups. Eight cases of primary cutaneous follicle center lymphoma were also studied. In comparison to nodal FL, a greater number of extranodal FL contained a diffuse growth pattern (P = 0.004) and lacked CD10 expression (P = 0.014). Fifty-four percent of extranodal and 42% of nodal FL cases showed evidence of t(14;18), with minor breakpoints (icr, 3′BCL2, 5′mcr) more commonly found in extranodal cases (P = 0.003). Outcome data showed no significant differences in overall survival (P = 0.565) and progression-free survival (P = 0.627) among extranodal, nodal, and primary cutaneous follicle center lymphoma cases. Analysis of all cases by t(14;18) status indicate that the translocation-negative group is characterized by a diffuse growth pattern (P = 0.043) and lower BCL2 expression (P = 0.018). The t(14;18)-positive group showed significantly better overall survival (P = 0.019) and disease-specific survival (P = 0.006) in comparison with the t(14;18)-negative group. In low stage FL, the status of t(14;18) seems to be more predictive of outcome than origin from an extranodal versus nodal site.

Translocation t(14;18)/IGH‐BCL2 in gastrointestinal follicular lymphoma

“…The translocation reportedly was associated with a favorable prognosis with regard to OS and EFS, [23][24][25] was unrelated to prognosis, [26][27][28] and even was associated with a poor prognosis. 12,29,30 With regard to prognosis, we observed that t(14;18)/IGH-BCL2-positive patients had a lower CR rate and tended to have a poorer EFS than t(14;18)-negative patients.…”

Biological characterization of stage I follicular lymphoma according to extranodal or nodal primary origin and t(14;18) status using high‐resolution array‐based comparative genomic hybridization

“…The IGH/BCL2 rearrangement is a relatively specific molecular marker of FL, frequently used for diagnosis and monitoring of disease [2]. We have recently shown that the incidence of t(14;18) is significantly lower in limited stage FL and the status of t(14;18) appears to be predictive of clinical outcome [2]. Little is known of the molecular genetics of t(14;18)-negative FL or of the genetic differences between nodal and extranodal FL.…”

“…The goal of the current study was to characterize stage I FL using high resolution array-based comparative genomic hybridization (aCGH). Validation of findings in aCGH were performed on 20 stage I FL as well as an additional 28 stage I and II FL cases by both RNA gene expression and DNA copy number.Twenty stage I FL were identified from the pathology database of Stanford University as previously described [2]. Agilent 60-mer oligonucleotide microarrays were used to analyze DNA copy number variations.…”

“…FLs are generally characterized by the presence of the t(14;18)(q32;q21), which causes a fusion of the BCL2 oncogene with the immunoglobulin heavy chain joining region. The IGH/BCL2 rearrangement is a relatively specific molecular marker of FL, frequently used for diagnosis and monitoring of disease [2]. We have recently shown that the incidence of t(14;18) is significantly lower in limited stage FL and the status of t(14;18) appears to be predictive of clinical outcome [2].…”

“…Twenty stage I FL were identified from the pathology database of Stanford University as previously described [2]. Agilent 60-mer oligonucleotide microarrays were used to analyze DNA copy number variations.…”