Practice Patterns in the Diagnosis of Follicular Lymphoma (FL): Report from the National Lymphocare Study (NLCS).
Authors: Matasar Matthew J. , Saxena Rakhee , Wong Elaine K. , Filippa Daniel A. , Zelenetz Andrew D. 
Published: April 2020

Abstract
The National Comprehensive Cancer Network (NCCN) issues guidelines that define adequate pathologic evaluation of FL, but rates of adherence to these guidelines have not been reported. The NLCS is a multicenter, longitudinal observational study of patients (pts) with newly diagnosed FL. With over 2700 pts enrolled, the NLCS offers a unique opportunity to characterize patterns of care in the diagnosis of FL. From 9/06 to 3/07, 232 pts in the NLCS had complete pathology reports available for independent review by two oncologists [MJM, EKW]. Data collected included pathologic diagnosis; geographic region; anatomic site, tissue type, and biopsy technique; diagnostic evaluation (morphology, immunohistochemistry [IHC], flow cytometry [FCM], cytogenetics, molecular genetics); and adherence with NCCN guidelines [surgical or core biopsy; consistent morphology; and confirmation of immunophenotype (IP) by IHC [CD20, CD10, CD3, CD5, bcl–2] or FCM [CD19, CD20, CD10, CD5, CD23, κ/λ]]. Discrepant or ambiguous reports were reviewed by two hematopathologists [RS, DAF]. Diagnostically appropriate specimens were obtained in the majority of cases: 78% of pts underwent incisional/excisional biopsy, 18% core biopsy, and 4% fine needle aspiration (FNA). Thirty-two (14%) were enrolled without a diagnosis of FL. Eighteen had diagnoses of B-cell lymphoma (BCL) of follicular center cell origin (FCCO): 8 with diffuse large B-cell lymphoma (DLBCL) of FCCO, and 10 with BCL of FCCO not otherwise specified (NOS). Eight pts (3%) had diagnoses of BCL NOS with suspected FL, 3 (1%) aggressive BCL other than DLBCL of FCCO, and 3 indolent BCL other than FL. Pts with diagnoses other than FL were more likely to have been diagnosed by FNA or core biopsy (59% of non-FL vs. 16.5% of FL, P&lt;0.001). Of the 200 diagnoses of FL, only 5 were made without assessing IP. 76% of FL cases had IHC, 50% FCM, and 7% cytogenetic or molecular genetic testing. However, the overall rate of adherence to NCCN guidelines was only 65%. The most common omission was CD5 testing; when CD5 testing was disregarded, the overall rate of guideline adherence increased to 85%. Rates of guideline adherence differed by US Census region: diagnoses in the Northeast (NE) were more often adherent (90%) than those in the Midwest (55%), West (60%), or South (64%) (P&lt;0.01 for each pairwise comparison vs. NE). However, no impact on guideline adherence was seen by anatomic site, biopsy technique, tissue type, or type of practice (academic or community). In conclusion, adherence to NCCN guidelines is suboptimal, although improved when CD5 (of modest utility in otherwise typical FL) is disregarded; only geographic region predicts guideline adherence. Pts diagnosed by FNA or core biopsy were more likely to be enrolled without a diagnosis of FL, in most cases due either to confusion regarding terminology or to acceptance of suspicious (but non-diagnostic) specimens. Eighteen pts were enrolled with diagnoses of BCL of FCCO, eight of whom had DLBCL; it is likely that clinicians misinterpreted FCCO (describing the IP of a lymphoma) as a diagnosis of FL (a lymphoma with both FCCO phenotype and characteristic morphology). Surgical biopsy remains preferred for diagnosis according to NCCN guidelines, and consideration should be given to replacing “follicular center cell origin” with “germinal center phenotype” to reduce the risk of misinterpretation by clinicians. Future studies will investigate the impact of diagnostic adequacy on management and outcomes.