Diagnostic Discrepancies in Small-volume Biopsy for the Initial Diagnosis, Recurrence, and Transformation of Follicular Lymphoma

Abstract

Small-volume biopsies (SVBs) including fine-needle aspiration (FNA), cell block, and needle core biopsies (NCB) are increasingly utilized to diagnose and guide the clinical management of lymphoma. We established a multi-institutional interdisciplinary collaboration of cytopathologists, hematopathologists, and oncologists focused on the role of SVB in the management of patients with follicular lymphoma (FL). To assess the performance characteristics of SVB in this setting, we evaluated all consecutive SVBs performed for clinical indications of initial diagnosis, recurrence, or transformation of FL over a 5-year period and focused on the 182 that had at least one subsequent biopsy within 3 months as part of the same clinical work-up. The most common outcome of a subsequent biopsy as part of the same clinical work-up was a more specific diagnosis usually assigning the pathologic grade (111/182, 61%), followed by a complete agreement with the SVB (24/182, 13%), and change from nondiagnostic on initial biopsy to diagnostic on subsequent biopsy (21/182, 12%). A minority resulted in a diagnostic change from benign to lymphoma (17/182, 9%), a change in FL grade (5/182, 3%), or change in the lymphoma diagnostic category (4/182, 2%). There were no cases where an initial diagnosis of lymphoma was overturned. The distribution of discrepancies was similar across initial SVB types (FNA, FNA + cell block, NCB with or without FNA). Tissue limitations were noted in a minority of cases (53/182, 29%) and were enriched among initially nondiagnostic biopsies (16/21, 76%). Flow cytometry immunophenotyping was performed in the majority of cases both at the first and last biopsy (147/182, 81%). SVB can be a powerful method to detect FL in various clinical indications, with discrepant cases mostly resulting from a refinement in the initial diagnosis.

Commentary on small‐volume biopsy of follicular lymphoma: Practical issues in the molecular era

“…2 Hematolymphoid neoplasms are diagnosed and evaluated more and more with small-volume biopsy (SVB) through fine-needle aspiration (FNA) with or without a cell block, flow cytometry, and needle core biopsy (NCB). 3 Because of FL's clinical and biological heterogeneity, SVB can play a role as a useful initial step for diagnosing and monitoring FL. 3,4 Figure 1 illustrates the principal workflow of SVB for evaluating FL.…”

“…3 Because of FL's clinical and biological heterogeneity, SVB can play a role as a useful initial step for diagnosing and monitoring FL. 3,4 Figure 1 illustrates the principal workflow of SVB for evaluating FL.…”

“…Despite SVB's advantages, a primary limitation is related to the size of the diagnostic tissue sample obtained: It sometimes may be too small to be representative of the lymphoma, and this may result in either a false-negative diagnosis or a diagnostic discrepancy. 3,5 This is especially frequent when SVB is applied to the initial diagnosis of FL. 3 Although flow cytometry does not affect the rate of repeat SVB, it does help to avoid nondiagnostic or false-negative results.…”

“…3,5 This is especially frequent when SVB is applied to the initial diagnosis of FL. 3 Although flow cytometry does not affect the rate of repeat SVB, it does help to avoid nondiagnostic or false-negative results. 3,4 In addition, flow cytometry can be helpful for grading FL in FNA samples by determining the percentage of large lymphoma cells; this is analogous to the histological grading scheme and avoids interobserver bias.…”

“…3 Although flow cytometry does not affect the rate of repeat SVB, it does help to avoid nondiagnostic or false-negative results. 3,4 In addition, flow cytometry can be helpful for grading FL in FNA samples by determining the percentage of large lymphoma cells; this is analogous to the histological grading scheme and avoids interobserver bias. 6,7 When SVB is used, cell blocks prepared from cellular FNA samples may increase sensitivity and aid in grading FL.…”