[1483] Pediatric-Type Follicular Lymphoma Occurs in Both Children and Adults and Is Characterized by a High Proliferation Index and the Absence of a BCL2 Gene Rearrangement

Abner Louissaint, Adam Ackerman, Judith A Ferry, A John Iafrate, Lawrence R Zukerberg, Nancy L Harris, Robert P Hasserjian. Massachusetts General Hospital, Boston, MA

Background: Despite its excellent prognosis, pediatric-type follicular lymphoma (PFL) remains challenging to define; it is uncertain if this indolent lymphoma is merely defined by age or may also occur in adult patients. In an effort to better define the morphologic, immunophenotypic, and genetic characteristics of PFL, we performed a comprehensive retrospective analysis of clonal B-cell proliferations with follicular pattern (CFPs) occurring in patients <40 years of age.
Design: We reviewed 42 cases of CFPs, in patients ranging from 8 to 38y of age (median 17y, 35M/7F). 36 were Stage 1, and 6 were Stage 3 or 4. We evaluated histologic and immunohistochemical features (including Ki67 proliferation index, PI) as well as FISH and/or molecular genetic analysis for BCL2, BCL6, MYC, and MUM1 rearrangements. We then used parameters associated with Stage 1 disease to interrogate an independent group of 60 similarly characterized FLs occurring in patients ≥ 18 y of age.
Results: None of the 36 stage 1 CFP cases had progressive/recurrent disease; 5/6 of the stage 3 or 4 cases had progressive/recurrent disease, all of whom were treated with chemotherapy.

Table 1: Features of Stage 1 vs. Stage 3/4 Clonal Follicular Proliferations
 Stage 1 (n=36)Stage 3-4 (n=6)P-value
Age (median)1825p=0.02
M:F31:54:2NS
LN size (median)2.2 cm2.3 cmNS
BCL2 rearrangement0/273/4p=0.0009
BCL2 protein expression4/335/5p=0.0003
PI >40% (Ki-67)28/280/4p=0.0005
Complete Architectural effacement7/304/5p=0.03
Follicles > 2mm27/340/5p=0.001
Grade †22:6:73:2:0NS
† Grade 1: Grade 2 : Grade 3

No patients had BCL6, MYC, or MUM1 rearrangement. Several features, in particular both lack of BCL2 gene rearrangement (BCL2R-) and high (>40%) PI (HPI), correlated with stage 1 disease.
Applying these criteria to a separate cohort of 60 FL cases, 3 cases (ages 18, 49 and 61 y) were both BCL2R- and had HPI. All 3 BCL2R-/HPI cases were Stage 1 and had no evidence of residual disease at the latest followup (median 135 months). In contrast, only 3/57 of the 'adult-type' FL patients (with BCL2 rearrangement and/or low PI) had no residual disease at latest followup (p=0.001).
Conclusions: PFL may be defined as an indolent clonal proliferation with a follicular pattern and variable histologic grade and BCL2 protein expression, but that both lacks BCL2 gene rearrangement and has HPI (>40%); large expansile follicles and lack of complete architectural effacement are morphologic clues to identify PFL. Similar indolent clonal follicular proliferations can occur in adults.
Category: Hematopathology

Monday, March 19, 2012 1:00 PM

Poster Session II # 209, Monday Afternoon

 

Close Window