Limited Tissue Biopsies and Hematolymphoid Neoplasms

Success Stories and Cautionary Tales

Kimberly F. Ingersoll, MD; Yue Zhao, MD, PhD; Grant P. Harrison, MD; Yang Li, MD, PhD; Lian-He Yang, MD, PD; Endi Wang, MD, PhD


Am J Clin Pathol. 2019;152(6):782-798. 

In This Article

Abstract and Introduction


Objectives: Use of fine-needle aspiration/needle core biopsy (FNA/CNB) in evaluating hematolymphoid processes has been debated. We investigate its applicability in various clinicopathologic settings.

Methods: We retrospectively analyzed 152 cases of FNA/CNB.

Results: Of 152 FNA/CNBs, 124 (81.6%) resulted in diagnoses without excisional biopsies, while 28 required subsequent excisional biopsies. Of these, 43 FNA/CNBs performed for suspected lymphoma relapse demonstrated 95.4% diagnostic rate (41/43), which was significantly better than those without history of lymphoma (77/109, 71%; odds ratio [OR], 8.5; confidence interval, 1.9–37.4). Patients with immunodeficiency also showed a high rate of diagnosis by FNA/CNB (100%). When stratified by types of disease, diffuse large B-cell lymphoma/high-grade B-cell lymphoma demonstrated a higher success rate (92.7%) than small B-cell lymphoma (79.2%), though the difference was not statistically significant (OR, 3.3; P value = .07). A subsequent excisional biopsy was required in 28 cases, 23 of which resulted in diagnoses concordant with the FNA/CNB. Five cases showed diagnostic discordance, reflecting pitfalls of FNA/CNB in unusual cases with complex pathology.

Conclusions: FNA/CNB is practical in evaluating most hematolymphoid lesions, with high efficacy in recurrent disease and some primary neoplasms with homogeneous/aggressive histology, or characteristic immunophenotype.


Limited tissue biopsy, including both fine-needle aspiration biopsy and core needle biopsy (FNA/CNB), is a minimally invasive procedure that may be used as a primary diagnostic tool for a multitude of disease processes.[1] There are limited adverse effects associated with performing an FNA/CNB due to the small-caliber needle used as compared to the instruments used to perform an incisional biopsy or excisional biopsy, which may require anesthetic sedation in an operating room.[1–4] Additionally, FNA/CNB may allow for a more rapid pathologic evaluation compared to conventional histologic evaluation.[5] Therefore, FNA/CNB is the initial tool used for many disease processes when tissue procurement is required for diagnosis and treatment.[1,5] However, hematolymphoid neoplasms present a unique challenge to diagnosis by FNA/CNB as a number of ancillary studies, including flow cytometry, immunohistochemistry, florescence in situ hybridization, and molecular testing, are often required to render an accurate diagnosis and classification of these lesions. FNA/CNB may not provide sufficient tissue to perform all these tests.[2,6–19] Additionally, diagnoses of hematolymphoid neoplasms often hinge on architectural alterations, which may not be well represented in an FNA/CNB as compared to an incisional or excisional biopsy.[13]

Prior studies have demonstrated that FNA is effective in the assessment of approximately 70% to 90% of hematolymphoid neoplasms.[1,5,12,18,20–22] It has been reported that FNA demonstrates a lower yield in certain types of hematolymphoid neoplasms, including cases of mature T-cell lymphoma, T-cell–rich large B-cell lymphoma, and lymphomas that have sclerotic changes, such as mediastinal (thymic) large B-cell lymphoma and classic Hodgkin lymphoma (cHL).[12,23–25] These cases often pose a diagnostic challenge on the evaluation of smears or touch preparation slides; nonetheless, the addition of a cell block or core biopsy with immunohistochemical evaluation may enhance the diagnostic accuracy.[12,22,24] Thus, in the correct clinicopathologic context and with adequate sampling, FNA/CNB has been shown to be a useful tool in the evaluation of patients with lesions suspicious for hematolymphoid processes.[4,12,14,20,21,26] However, false-negative and false-positive cases have been noted in previous studies.[6,20,27] This leaves a cohort of patients with suspected hematolymphoid neoplasms who may be misdiagnosed and mistreated based on FNA/CNB analysis if a subsequent excisional biopsy is not performed. Therefore, for both pathologists and clinicians, it is imperative to understand the limitations of FNA/CNB in the evaluation of hematolymphoid neoplasms, and it is important to understand in which clinical scenarios FNA/CNB can provide a reliable diagnosis, and in which clinical situations and pathologic contexts an excisional biopsy is more appropriate.[12,14,20,26,27]

The purpose of this study is to expand upon prior studies that have identified situations in which FNA/CNB is unsuccessful in evaluating patients with suspected hematolymphoid neoplasms. This study aims to further stratify which patients may benefit from an FNA/CNB as the primary procedure in the diagnosis of a hematolymphoid neoplasm, and which cases carry potential pitfalls and may benefit from excisional biopsy for definitive diagnosis and precise classification.