Randomized Comparison of Power Doppler Ultrasonography-Guided Core-Needle Biopsy with Open Surgical Biopsy for the Characterization of Lymphadenopathies in Patients with Suspected Lymphoma

Background

In case of clinical suspicion of lymphoma, the histological examination of lymphadenopathy is essential for defining a correct diagnosis and for developing a proper treatment plan. An open surgical biopsy (OSB) is still the "gold standard", owing to the large amount of tissue obtained. The sensitivity of lymph node core-needle biopsy under imaging guidance requires validation.

Aims

This randomized study compared the ultrasound-guided core-needle cutting biopsy (CNCB) approach with OSB approach.

Patient and methods

Institutional review board approval and informed consent were obtained. In a single center between 1 January 2009 and 31 December 2015, patients with lymph node enlargement suspected for lymphoma were randomly assigned (1:1) to biopsy with either OSB (standard group) or ultrasound-guided 16 gauge modified Menghini needle (core-needle group). In the core-needle group, the lymph node to undergone biopsy was determined by power Doppler US, in particular, the main criterion to select the node to be biopsied was the hypervascularization. The primary endpoint was to test the superiority of sensitivity for diagnosis of malignancy for ultrasound-guided CNCB compared with OSB. Secondary endpoints were negative predictive values, likelihood ratio of negative test, biopsy related complications, costs and times to biopsy.

Results

A total of 372 patients were randomized either to standard group (N= 187) or core-needle group (N= 185). Sensitivity for detection of malignancy was significantly better for US-guided CNCB [98.8%; 95% confidence interval (CI), 95.9-99.9] than standard biopsy [88.7%; 95% CI, 82.9-93] (P<0.001). Therefore, the study objective to show superiority of US-guided CNCB versus OSB was achieved, being the sensitivity rate of experimental approach significantly higher than standard approach. For all secondary endpoints, the comparison was significantly disadvantageous for standard approach. The negative predictive value was 50% (19 of 38; 95% CI, 33.4-66.6) for OSB and 84.6% (11 of 13; 95% CI, 54.5-98.1) for US-guided CNCB (P= 0.014). The negative likelihood ratio was 0.11 (95% CI: 0.07-0.17) for OSB and 0.01 (95% CI: 0.00-0.05) for US-guided CNCB, confirming the value of the US-guided CNCB for detecting malignancy. Patients who received standard biopsy had significantly more procedure-related complications (P<0.001). Furthermore, estimated cost per biopsy performed with standard surgery was 24-fold higher compared with that performed with US-guided CNCB (P<0.0001). The median waiting time for performance of biopsy (from procedure indication to perform itself), was 4 days with a range of 1 to 10 days in the core-needle group. By contrast, it was 16 days, with a range of 5 to 34 days in the standard group (P<0.0001).

Conclusions

This study is the first to compare in a randomized fashion the sensitivity of US-guided CNCB and OSB in detecting lymphoma. Power Doppler US and CNCB are diagnostic tools that enable effective, safe, fast and low-cost routine biopsy for patients with suspected lymphoma, avoiding psychological and physical pain of an unnecessary surgical intervention. We suggest this approach as first-line mini-invasive procedure for patients with a suspected lymphoma and not merely when surgical intervention is not possible, or to document relapse.