The progression at 24 months ( <scp>POD24</scp> ) induces a high risk of transformation of follicular lymphoma: A systematic biopsy verification

Modern imaging-guided minimally invasive approaches enhance lymphadenopathy assessment.1, 2 New power Doppler (PD) ultrasonography (US) technology and biopsy needle devices enable an effective integrated diagnostic strategy, with precise assessment of lymph node lesions, accurate selection of the most suspicious target and real-time monitoring of the entire puncture process.1, 2 The modified-Menghini needle (16 G diameter) is recommended.3 Selected lymph nodes typically have ≥2 cm long axis and abnormal vascular patterns on intranodal PD assessment. In PDUS-selected lymph nodes, neoangiogenesis is the key finding, generating abnormal, structurally defective vessels. Driving tumour growth and spread, increased neoangiogenesis in lymphoma correlates with disease progression and greater aggressiveness.4 We read with great interest the study by Kalashnikov et al. published in the British Journal of Haematology in 20255 which describes the risk of transformation of follicular lymphoma (FL) in Finland from 1995 to 2018, with a cumulative incidence of transformation at 10 years of 8.4% (95% confidence interval [CI], 7.5–9.5). The authors noted that some transformed FL (t-FL) cases diagnosed clinically without biopsy may not have been captured in the analysis. Given favourable evidence supporting the efficacy and safety of PDUS-guided core needle biopsy (CNB) in the diagnostic work-up of lymphadenopathies,2, 3, 6 it has become a routine procedure for evaluating suspected transformation of indolent lymphomas in tertiary centres in southern Italy. We recently conducted a real-life multicentre analysis using registry databases of these units focusing on PDUS-guided CNB accuracy for diagnosing t-FL.7 In a 12-year period (July 2009 to January 2022), we identified a total of 182 consecutive patients with newly diagnosed grade 1–3A FL who underwent a wait & watch approach (n = 90), radiotherapy (n = 22) and/or immunochemotherapy (n = 70). Overall, 45 consecutive cases of t-FL were documented; in all cases, the diagnoses of t-FL were obtained by PDUS-guided CNB. The median age of transformed patients was 62 years (range, 22–91). Target lymph node lesions were superficial in 70% of cases and deep-seated in the remainder. The median number of core passes was 2 (range, 1–4), with a median sample length of 35 mm (range, 15–70) and an estimated volume of 250 mm3 (range, 92–430). All 45 nodal lesions were classified consistently by the reference standard (complete surgical excision for 5 patients, for the remaining 40 patients, consensus review by three blinded haematopathologists on CNB samples and/or confirmation by PCR/FISH studies on CNB samples) as they were by PDUS-guided CNB. According to the 5th Edition of the WHO classification,8 the specific histological diagnoses by CNB were the following: LBCL NOS (n = 40) and high-grade B-cell lymphoma with MYC and BCL2 rearrangements (n = 5). The median waiting time for biopsy was 4 days (range, 1–10) and the median turnaround time from PDUS-guided CNB to final histological diagnosis was 8 days (range, 7–10). No patients required general anaesthesia or hospitalization, and no biopsy-related complications were reported. Finally, based on the Italian National Healthcare System data,9 PDUS-guided CNB costs €181 versus €3.200 for surgical biopsy. In our series, systematic biopsy verification showed 27.7% (95% CI, 20.6–36.6) t-FL incidence at 10 years with markedly higher risk in progression at 24 months (POD24) patients, confirming POD24 as a strong predictor of transformation (Figure 1). MP designed the research. MP, AV, NP, CG, MM, EV, GT and PZ performed the research and wrote the paper. AV, NP, and CG collected and analyzed data. FP and MP performed the final revision of the manuscript. The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.