Immunophenotypic features and t(14;18) (q32;q21) translocation of Chinese follicular lymphomas helps to distinguish subgroups

Abstract

BackgroundThe revised 2008 World Health Organization classification maintains a histological grading system (grades 1–3) for follicular lymphoma (FL). The value of grading FL has been debated. This study will yield deeper insights into the morphologic, immunophenotypic characterization and t(14;18) translocation in FL and explore their significance of diagnosis of Chinese FL subgroups.MethodsWe retrospectively reviewed the FL diagnoses according to the 2008 WHO classification in all diagnostic specimens from a multicentric cohort of 122 Chinese patients. Upon review, 115 cases proved to be truly FL. CD10, BCL6, MUM1, BCL2 and t(14;18) (q32;q21) translocation were detected by Envision immunostaining technique and fluorescence in situ hybridization.ResultsFL1 has larger proportion of follicular pattern (93.0%) than that of FL2 (73.7%, P = 0.036), FL3B (63.6%, P = 0.003) and FL3A (77.4%, P = 0.053), although the last P value was more than 0.05 (Pearson’s chi-squared test). Areas of DLBCL were present in 25.8% (8/31) of FL3A and more frequent in FL3B (59.1%, 13/22; P = 0.015). The positivity of CD10 and BCL2 in FL1-2 were significantly higher than those in FL3 (P < 0.001, P = 0.043, respectively). The positivity of MUM1 in FL1-2 was significantly lower than that in FL3 (10.2% vs. 51.0%; P < 0.001). Furthermore the positivity of MUM1 in FL3A was significantly lower than that in FL3B (37.9% vs. 68.2%; P = 0.032). The positivity of t(14;18) was higher in FL1-2 than in FL3 (73.5% vs. 35.6%, P < 0.001), and was higher in FL3A than in FL3B (51.9% vs. 11.1%, P = 0.005). t(14;18) was significantly correlated with CD10+ (R = 0.453, P < 0.001) and MUM1+ (R = -0.482, P < 0.001).ConclusionsFL1 and FL2 were immunophenotypically and genomically similar, while FL3A and FL3B were partly immunophenotypically similar but morphologically, genomically distinct. FL3A was genomically closer to FL1-2, whereas FL3A was genomically closer DLBCL. Thus we hypothesize that FL may in fact be a heterogeneous indolent lymphoma encompassing entities with distinct molecular pathogenesis and genetic characteristics. Immunohistochemical and genetic characterization helps to distinguish subgroups of FLs.Virtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1334018129864616.

t(14;18)(q32;q21) in chronic lymphocytic leukemia patients: Report of two cases and a literature review

“…The t(14;18)(q32;q21) chromosomal abnormality involves the immunoglobulin heavy chain (IGH) gene on chromosome 14q32 and the B-cell CLL/BCL2 gene on chromosome 18q21, and results in BCL2 being placed under the regulatory control of the IgH promoter leading to overexpression of the BCL2 protein (7). It is considered the genetic hallmark of FL and is identified in ≤90% of FL cases (7).…”

“…It is considered the genetic hallmark of FL and is identified in ≤90% of FL cases (7). Although present in the majority of FL patients, using a standardized, highly sensitive quantitative polymerase chain reaction technique, t(14;18)(q32;q21) may be identified at low frequencies in ≤70% healthy individuals, suggesting that BCL2 overexpression is required but not sufficient for FL development (8).…”

“…Diagnosis of CLL is based on the typical morphology and characteristic immunophenotype of lymphocytes. Patients with CLL that harbor t(14;18)(q32;q21) and exhibit an atypical immune phenotype may present CD5-positive FL (6,7). However, CD5-positive FL is extremely rare and <40 cases have been reported in the literature to date (16).…”

Genetic characteristics of non-Hodgkin lymphoma in ethnic Uighur people, and their clinical significance

“…However, the change of chromosome karyotype is an important independent risk factor for NHL prognosis in addition to its histological implications (Chen et al, 2013). One study has shown multiple critical chromosome karyotype changes in NHL patients, and their significant effect on patient treatment efficacy and median survival period (Zhang et al, 2013). Certain complex changes in chromosome karyotype or rearrangement, and some special chromosome genesis abnormalities such as t(8:14)(q24:q32) translocation and +7, are unfavorable prognostic factors for NHL (Kahl and Yang, 2008;Zhang et al, 2010. Certain basic studies have shown no dysfunction of known genes located in the 6q21-25 region in NHL patients.…”