The research, conducted at Fondazione IRCCS Istituto Nazionale dei Tumori in Milan, followed 1,059 consecutive patients, both adults and children, who were referred for biopsy between 2010 and 2022 with clinical suspicion of a lymphoproliferative disease, an umbrella term covering lymphomas and related disorders of the lymphoid tissues. Every one of these patients underwent imaging-guided core needle biopsy as their first diagnostic procedure, and the results, published in CVIR Oncology, are striking. In 96.6 percent of all referred patients, the needle biopsy alone delivered a conclusive histological diagnosis without any need for follow-up surgery. Among the 882 patients ultimately confirmed to have lymphoma, 95.9 percent received a complete, actionable diagnosis from the needle procedure alone.

Those numbers matter because of what they replace. Traditional excisional biopsy requires surgical pre-assessment, anesthesia, an incision, and recovery time, and carries risks of infection, scarring, and bleeding. It can also introduce delays at exactly the moment when speed matters most, since different lymphoma subtypes demand radically different treatment strategies, and treatment often cannot begin until the subtype is pinned down. Core needle biopsy, by contrast, is a minimally invasive procedure performed through a tiny puncture, typically under local anesthesia, in an outpatient or short-stay setting. For frail patients, for those needing urgent therapy, and for anyone with a deep-seated lesion that surgery would struggle to reach safely, the difference is not merely one of convenience but of clinical feasibility.

The technical backbone of the procedure is the semiautomated Tru-cut needle, a spring-loaded device available in gauges ranging from 14 to 18 Gauge in routine practice, with 16 Gauge being the workhorse in the Milan series. The operator pulls back a mandrel to load the spring, advances the needle into the target tissue while continuously visualizing the needle tip, and then fires the outer cutting cannula over the stylet, capturing a slender cylindrical core of tissue. At this institution, at least three or four passes through the lymph node or lesion are typically made, and the median number of samples in the recorded data was four. The cores are fixed in formalin, embedded in paraffin, stained with hematoxylin and eosin, and then classified according to the World Health Organization criteria using morphology, immunohistochemistry, and, when needed, FISH and molecular testing.

Equally important is how the target is chosen and how the needle finds its way there. Ultrasound guided the large majority of the procedures, 891 of the 1,059, and remains the technique of choice for superficial lymph nodes, soft tissues, salivary glands, liver, and kidney, thanks to its real-time visualization, low cost, and wide availability, often complemented by color Doppler mapping of the lesion’s vascular structure. Computed tomography took over for deep anatomical sites, accounting for 168 procedures, particularly retroperitoneal and mediastinal lesions nestled near vessels and organs. For these, the team used a coaxial technique, placing a larger introducer through which the biopsy needle could be advanced repeatedly, allowing multiple samples from a single puncture while reducing the risks of bleeding and tumor seeding. Contrast-enhanced CT scans helped identify viable tissue and avoid sampling necrotic or liquefied areas, and the technique proved its worth: CT-guided biopsies actually achieved a slightly higher diagnostic yield, 97.1 percent, than ultrasound-guided ones, at 95.8 percent.

A particularly sophisticated element of the workflow was the use of positron emission tomography, or PET-CT, for target selection. In 42.5 percent of lymphoma cases, a PET-CT scan performed within 30 days before the biopsy was available to guide the choice of where to sample. Because fluorodeoxyglucose uptake correlates with the histological grade and proliferative activity of lymphoma cells, hot spots on a PET image mark the metabolically active, viable regions of a tumor, allowing operators to aim the needle at the most informative tissue and steer clear of dead or fibrotic zones. The study found that PET-CT availability did not measurably raise the overall binary diagnostic yield, but the authors argue that its true value is qualitative: distinguishing active disease from post-treatment fibrosis, and selecting the clinically most informative target in cases of suspected relapse or transformation. In one illustrative case, a retroperitoneal mass showed poor enhancement on contrast CT, yet PET imaging revealed intense uptake in the same region, and the needle was placed precisely where the PET signal was strongest, yielding a conclusive diagnosis that conventional imaging alone might have missed.

Safety was another standout finding. Not a single patient in the entire cohort suffered a biopsy-related complication of grade 2 or higher on the standard CTCAE v5 scale, meaning no severe bleeding, infection, or event requiring unplanned intervention. Minor local bleeding occurred in roughly 5 percent of cases, and no patient required hospitalization beyond the planned 24 hours after deep-tissue biopsies. Standard precautions, including blood counts and coagulation testing, stopping anticoagulation at least 24 hours before the procedure, and platelet transfusion for patients with counts below 50,000 per microliter, kept the risk profile firmly in check. Even the 22 pediatric patients in the cohort were managed successfully, underscoring that minimally invasive image-guided biopsy can be appropriate even in children when multidisciplinary teams weigh anesthetic risk, lesion location, and protocol requirements.

The study is honest about where the needle falls short. Thirty-six lymphoma patients, 4.1 percent of the cohort, still required a subsequent excisional biopsy, either because the needle sample was inadequate or because it was suggestive but not conclusive. Notably, certain subtypes were overrepresented in this surgical group: half of the patients with nodular lymphocyte-predominant Hodgkin lymphoma and 15 percent of those with peripheral T-cell lymphoma needed surgery to reach a final diagnosis, a pattern consistent with pathological guidance suggesting that these entities are best assessed when an entire lymph node’s architecture can be examined. Among the 36 surgical cases, the excisional diagnosis differed from the needle-based impression in 9 patients, confirmed it in 12, and provided a new conclusive answer in 15, all of whom ended up with a definitive histological result. The authors stress that these figures argue not against needle biopsy, but for prompt surgical follow-up whenever the needle result does not inspire confidence for treatment decisions, ideally after early multidisciplinary discussion among hematologists, radiologists, and pathologists.

The broader picture emerging from more than a decade of data is one of a diagnostic landscape in transition. The Lugano classification, the standard framework for lymphoma management, still reserves core needle biopsy for situations where surgery is not possible or for relapse. Yet this Milanese experience, one of the largest single-center intent-to-diagnose cohorts ever assembled, shows that with careful patient selection, meticulous imaging guidance, judicious needle gauge choice tailored to lesion location, multiple sampling, and PET-informed targeting, the needle succeeds where the scalpel was once thought indispensable. Follicular lymphoma, diffuse large B-cell lymphoma, and classical Hodgkin lymphoma, the three most common diagnoses in the cohort, were reliably captured by needle sampling, and 177 patients with suspected lymphoma actually turned out to have entirely different conditions, including metastatic carcinoma, sarcoma, neurogenic tumors, and retroperitoneal fibrosis, all of which the needle correctly identified. In an era when medicine increasingly prizes precision with minimal invasiveness, this study makes a compelling case that for most patients with suspected lymphoma, the first and often only diagnostic procedure needed is one that fits through a needle’s eye.

Subject of Research: Diagnostic yield and procedural techniques of imaging-guided core needle biopsy in patients with suspected lymphoproliferative disease

Article Title: Core needle biopsy in patients with suspected lymphoproliferative disease: diagnostic yield in a large single-center cohort and procedural techniques

Article References: Core needle biopsy in patients with suspected lymphoproliferative disease: diagnostic yield in a large single-center cohort and procedural techniques. (n.d.). https://doi.org/10.1007/s44343-026-00051-5

Image Credits: AI Generated

DOI: 10.1007/s44343-026-00051-5

Keywords: core needle biopsy, lymphoma, lymphoproliferative disease, excisional biopsy, ultrasound-guided biopsy, CT-guided biopsy, PET-CT, interventional radiology, diagnostic yield, hematologic malignancies, Tru-cut needle, minimally invasive diagnosis