Flow Cytometric Aberrancies and Clinical Outcome in Low Grade, High Proliferation Index Follicular Lymphoma
Kirthi R Kumar, Sean G Yates, Venetia R Sarode, Nitin J Karandikar, Jacqueline Emmons. UT Southwestern Medical Center, Dallas, TX
Background: Follicular lymphoma (FL) is the second most common non-Hodgkin lymphoma, accounting for 20% of all lymphomas. FL grading is assessed on H&E-stained histologic sections and is based on the number of large centroblasts in neoplastic follicles. The proliferation index (PI) determined by Ki-67 immunohistochemistry (IHC) on tissue sections correlates with the grade of FL in most cases but is not included in the grading criteria defined by the World Health Organization. The purpose of this study was to determine the clinical significance of a high PI in low-grade (LG) FL (grade 1-2 FL) and to identify flow cytometric characteristics that would distinguish LG FL with a high PI (LG-HPI) from those with a low PI (LG-LPI).
Design: Cases of LG FL were identified in the institutional database. The available flow cytometric data were re-analyzed with Flow Jo software. Two 1-mm punches were performed on each diagnostic tissue block to create a tissue microarray (TMA). Ki-67 IHC was performed on the TMA using Ventana systems. Image Analysis software was used to obtain % Ki-67 positive cells. A cut off of 30% or higher was used to categorize cases as LG-HPI.
Results: Amongsy the 18 LG FL patients that were evaluated. 8 were found to have PI >30%, whilst the remaining 10 were categorized as LG-LPI. Medical records showed that only 2 of 10 (20%) LG-LPI FL patients had poor response to chemotherapy with relapse, whereas 4 of 8 (50%) LG-HPI patients had relapse following chemotherapy. Of the flow cytometric features evaluated, a significant difference was found in FMC7 expression between the two cohorts, as gauged by %positivity and mean fluorescence intensity (MFI), on CD19+ lymphoma cells. LG-HPI FL cases showed significantly higher FMC7 compared to LG-LPI FL (FMC7 MFI: 53.3 ± 14.8 vs 25.1 ± 5.1, p = 0.05; FMC7 %positive: 71.6 ± 8.5 vs 50.0 ± 8.4, p = 0.03). LG-HPI showed lower incidence of lambda LC usage (22%) compared to LG-LPI cases (50%). We did not identify any T-lymphocyte-related differences amongst the two groups of LG FL. The incidence of the (14;18) cytogenetic abnormality was found to be 50% in both groups, albeit the sample size for this data was small.
Conclusions: Our results indicate that LG-HPI FL patients display poor response to chemotherapy with relapse. LG-HPI FL is associated with higher level of FMC7 expression on the lymphoma cells. Recognition of this FC characteristic may prove to be useful screening tool to help identify FL cases that would benefit from Ki-67 evaluation, as LG-HPI is associated with poorer prognosis when compared to their LG-LPI counterparts.
Monday, March 19, 2012 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 220, Monday Morning