Introduction
Despite significant advances in radiological and molecular diagnostics, histological confirmation remains the most common approach for the diagnosis of neoplastic diseases, including both solid tumors and hematologic malignancies. In lymphoma, histological sampling of the affected tissue is required for comprehensive evaluation, including morphological assessment, immunohistochemistry and genetic profiling. Excisional biopsy remains the gold standard, allowing full evaluation of the nodal architecture and identification of histologic features unique to specific types (for example, grading in follicular lymphoma) (1). Repeat biopsy is often necessary to confirm disease recurrence or detect histologic transformation, particularly in the context of indolent lymphoma, where progression to high-grade histology is well recognized. By contrast, for the diagnosis of nodal metastatic disease in solid tumors, current guidelines recommend that the choice of biopsy technique should depend on the disease site, with lymph node evaluation performed using either non-invasive or invasive staging methods at the clinician's discretion (2,3).
In deep abdominal lymph nodes, a biopsy can be challenging due to limited accessibility, particularly in the retroperitoneum or sites close to major vessels and vital organs. In addition, surgical excisional biopsy of abdominal disease can be excessively invasive, commonly requiring hospitalization, general anesthesia, and carrying risks of infectious complications and delayed diagnosis. However, it may not be feasible in patients with high operative risk (4,5).
Ultrasound-guided needle biopsy (US-NB) represents a valuable diagnostic tool employed to diagnose abdominal masses, thus enabling preservation of tissue architecture and allowing multiple tissue sections for immunocytochemical or histochemical analyses (6,7). However, its application in assessing deeply located abdominal lymph nodes remains poorly investigated, with only a limited number of case studies reported (8–12).
Although US-NB is established for superficial or easily accessible lymph nodes, its role in deep abdominal lymph nodes remains poorly documented (13). It was hypothesized that US-NB could be considered a feasible and effective approach for diagnosing malignancies involving deep abdominal lymph nodes. Thus, the present study aimed to report a single-center, real-world experience with percutaneous US-NB for the diagnosis of abdominal lymph node malignancies.
Discussion
The literature on tissue sampling of suspected malignant abdominal lymph nodes primarily focuses on the diagnosis of lymphoma, due to both the anatomical site involved and the management of solid tumors, in which lymph nodes are commonly resected for histopathological analysis during surgery or are not biopsied in case of metastatic disease. The high diagnostic accuracy, safety, and cost-effectiveness of NB in the diagnosis of lymphoma have been widely reported, yielding a definitive diagnosis in >90% of cases (14). However, the majority of these studies mainly focus on specific imaging-guided techniques, including computed tomography (CT)-, PET/CT-, or US-guided NB), without taking into account whether the disease site is superficial or deep (4,5,10,14–17).
Evidence on percutaneous US-NB in deep abdominal lymph nodes remains limited (9,15,18–23), thus reflecting the need for experienced operators and a preference for CT-guided or echo-endoscopic approaches, which can provide improved lesion visualization (16,17). Needle selection is affected by lesion size and location. Therefore, larger core needles (14 G) are typically used for superficial lesions, while 16–18 G needles are preferred for deeper lesions. Although smaller needles are associated with lower complication rate, they can yield less informative samples. For example, small tissue samples could fail to detect histological transformation in lymphoma or could limit accurate assessment of features, such as the centroblast/centrocyte ratio in follicular lymphoma.
To the best of our knowledge, the current study represented one of the largest series evaluating the diagnostic yield and accuracy of percutaneous US-NB for suspected malignant disease, including both lymphomatous and solid, in deep abdominal lymph nodes (Table IV). The study demonstrated a high diagnostic yield (80.5%) and excellent diagnostic accuracy (98.4%), consistent with previous studies (9,11,12,16,19). Malignancy-negative results accounted for 8.1% of diagnostic samples and were all confirmed as true negatives on follow-up.
Despite the aforementioned encouraging results, 19.5% of biopsies were non-diagnostic, thus highlighting the challenges associated with sampling deep lymph nodes, particularly when lesions are small or necrotic. Although diagnostic biopsies showed a NPV of 100%, sensitivity could be overestimated due to the retrospective design and the exclusion of non-diagnostic cases from accuracy calculations.
As expected, the majority of biopsies were positive for lymphoma, with histological subtypes reflecting disease epidemiology. The most common diagnoses were follicular lymphoma, DLBCL and HL. Notably, no T-cell lymphomas were identified, which could be explained by their relative rarity and frequent extra-nodal involvement. Overall sample adequacy for clinical decision-making was 92.5%. However, in three cases the histological category could not be reliably established. Following repeat sampling, one patient was found to be free of lymphoma, while the remaining two were diagnosed with HL. Occasionally, distinguishing reactive lymphoid changes from low-grade non-HL on core biopsy could be challenging and could have contributed to the false positive result observed. Additionally, percutaneous biopsy yielding limited material could also lead to misclassification of lymphoma subtypes, particularly those with low tumor cell content or areas of sclerosis, such as HL. Notably, HL was subsequently diagnosed in the two cases with initially uncertain subtype. The vast majority of cases were newly diagnosed with lymphomas, while ~20% were repeat biopsies performed to confirm previous diagnoses. In this context, repeat biopsy at relapse is clinically valuable for excluding disease transformation and for evaluating antigen expression to guide targeted antibody-based salvage therapy (24,25). Notably, two non-diagnostic biopsies were carried out in patients with rapidly progressive disease following CAR-T cell therapy; both specimens were histologically characterized by extensive necrosis, suggesting that alternative or extensive tissue sampling strategies could be required in this setting.
Solid tumor diagnoses were less frequent, accounting for ~25% of all informative samples, with ~65% representing metastatic disease. Importantly, six of seven patients who underwent biopsy for suspected metastatic solid tumors were initially assessed for possible lymphoproliferative disease, underscoring the role of biopsy in excluding lymphoma. The most common solid tumor diagnoses were malignancies prone to abdominal nodal metastasis, particularly genitourinary, gastrointestinal, and neuroendocrine tumors.
In total, ~50% of the patients had available PET imaging to guide US biopsy, and 28 of 32 biopsies performed at sites of maximal PET uptake were diagnostic. Although no statistically significant association with biopsy outcome was obtained, likely due to the limited sample size, functional imaging could increase the likelihood of sampling representative malignant tissue, supporting an integrated approach to optimize sampling success (26).
Furthermore, the absence of procedure-related complications and the feasibility of performing US-NB in an outpatient setting further supported its safety, even among patients with significant comorbidities who were not candidates for more invasive approaches, such as surgery. These findings were consistent with previous oncologic reports.
However, the present study has certain limitations, including its retrospective design and relatively small sample size, which could introduce selection bias and limit generalizability. Additionally, the lack of procedural standardization, including variability in needle size and number of passes, could also affect outcomes. The risk of verification bias was considered low, as all five negative biopsies were closely monitored and no malignancies were identified. Finally, as diagnostic accuracy was calculated conditionally on diagnostic samples, the reported estimates may be subject to selection bias and could appear higher than those obtained with an intention-to-diagnose approach. The monocentric design of the present study represented a major strength, as procedures were performed by the same operators using consistent equipment and standardized techniques. Nevertheless, larger prospective studies are needed to confirm these findings.
In conclusion, our experience suggested that US-guided percutaneous NB could be a reliable, rapid and safe diagnostic tool for evaluating suspected malignant lymph node disease in the deep abdomen, applicable to both initial diagnosis and disease recurrence, with high diagnostic accuracy. However, caution is warranted in particular scenarios. In low-grade lymphoma, limited tissue samples could hinder differentiation between reactive and pathological tissues. In cases of suspected histological transformation or heterogeneous disease, NB could not fully capture full disease complexity. Furthermore, in rapidly proliferating lesions, extensive necrosis could reduce diagnostic yield, thus indicating that alternative sampling approaches capable of providing larger histological specimens should be considered.