Diagnostic Performance and Safety of Stereotactic Frame-Based Biopsy for Sub centimeter Intracranial Lesions: A Matched Cohort Analysis

Diagnostic Performance and Safety of Stereotactic Frame-Based Biopsy for Sub centimeter Intracranial Lesions: A Matched Cohort Analysis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Diagnostic Performance and Safety of Stereotactic Frame-Based Biopsy for Sub centimeter Intracranial Lesions: A Matched Cohort Analysis Charles-Henry MALLEREAU, Lucia Nichelli, karima Mokhtari, Alexandre Carpentier, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8047246/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 22 Jan, 2026 Read the published version in Neurosurgical Review → Version 1 posted 10 You are reading this latest preprint version Abstract Introduction Stereotactic brain biopsy is a standard neurosurgical procedure for diagnosing intracranial lesions. Lesion size is often considered a limiting factor; however, the safety and diagnostic yield of biopsies in lesions < 10 mm remain poorly defined. This study evaluated the outcomes of frame-based stereotactic biopsies for lesions < 10 mm in size compared with larger lesions. Methods. We retrospectively analyzed all consecutive adult patients who underwent frame-based stereotactic biopsy for targeted lesions < 10 mm in maximum diameter between April 2009 and April 2024 at our institution. Each case was matched (1:3) with patients with lesions ≥ 10 mm based on age, lesion location, and contrast enhancement. The primary endpoint was diagnostic yield, and the secondary endpoints included complications graded using a validated severity scale. Results. Of the 2,347 patients who underwent frame-based stereotactic biopsy during the inclusion period, 74 patients (3.2%) with lesions < 10 mm were compared with 222 controls. Among the 296 patients, the overall diagnostic yield was 95%. The diagnostic yields did not significantly differ between the small and large lesion groups (91.9% vs. 96.0%, p = 0.2). Non-tumoral pathology was the main factor associated with non-diagnostic results. Symptomatic complications occurred in 4.1% of patients, with no significant difference between the groups (1.4% vs. 4.9%; p = 0.3). No severe complications occurred in the < 10 mm group. The overall mortality rate was 1.3%, with no mortality in the small-lesion cohort. Conclusion. Frame-based stereotactic biopsy of lesions < 10 mm is safe and effective, with a diagnostic yield comparable to that of larger lesions and no excess risk of complications. These findings challenge long-standing assumptions discouraging the biopsy of small lesions and support its use when clinically indicated. stereotactic techniques brain biopsy safety diagnostic yield brain tumor small lesions Figures Figure 1 Figure 2 1. INTRODUCTION Stereotactic brain biopsy is a standard neurosurgical procedure for diagnosing various intracranial pathologies, including tumors, infections, and inflammatory or systemic diseases[ 36 ]. In neuro-oncology, histopathological diagnosis remains essential, particularly given the growing importance of molecular profiling in therapeutic decision-making[ 30 , 41 ]. Beyond oncology, brain biopsy has become increasingly common in the investigation of infectious, inflammatory, and systemic conditions[ 10 , 25 , 27 ]. The procedure is technically feasible in nearly all brain regions, with few anatomical limitations[ 1 , 28 ] , [ 21 ]. However, lesion size remains one of the few constraints, although the exact threshold below which biopsy becomes less effective or safe has not been clearly established. A commonly cited lower limit is 1 cm3, although it remains poorly defined in the literature[ 32 ]. To date, no dedicated studies have specifically assessed the diagnostic yield and safety of stereotactic biopsies of small brain lesions. This study aimed to evaluate the diagnostic yield and safety of frame-based stereotactic brain biopsy for lesions < 10 mm in maximum diameter and to compare these outcomes with those from a cohort of patients with lesions ≥ 10 mm. 2. METHODS 2.1. Design This retrospective single-center cohort study included all consecutive adult patients who underwent frame-based stereotactic brain biopsy for a newly diagnosed intracranial lesion measuring less than 10 mm in maximum diameter between April 2009 and April 2024 at our institution. Each case was matched in a 1:3 ratio with patients selected from a cohort of 2,347 individuals who underwent frame-based stereotactic biopsies during the same period. All procedures were performed using a frame-based stereotactic technique with a Leksell stereotactic frame (Elekta, Stockholm, Sweden). 2.2. Biopsy procedures Pre-biopsy evaluation Patients were eligible for biopsy procedures if they met the following institutional safety criteria: platelet count greater than 100,000/L, International Normalized Ratio (INR) between 0.8 and 1.1, and activated partial thromboplastin time (aPTT) less than 1.20. Oral anticoagulants and antiplatelet medications were discontinued 5–7 days before the biopsy, with the exact timing depending on the specific medication used. Frame-based biopsy Biopsies were performed under local anesthesia with or without intravenous conscious sedation or general anesthesia in rare cases[ 4 ]. The patients were positioned in a Leksell stereotactic frame. Preoperative imaging included three-dimensional gadolinium-enhanced and FLAIR sequences acquired using a 1.5-T MRI system (Signa; General Electric). In rare instances, contrast-enhanced CT was used instead of MRI because of technical constraints. In the latter case, stereotactic CT images were co-registered with prebiopsy MRI. The biopsy trajectory and depth were planned based on the location of the target lesion. Stereotactic coordinates were calculated using the Framelink software (Medtronic, Minneapolis, MN, USA). The biopsy trajectory was carefully selected to avoid critical, superficial, and deep vascular structures. Trajectory planning was confirmed millimeter by millimeter using three-dimensional visualization, including perpendicular and parallel oblique views of the intended needle path. The entry site was shaved, and the procedure was performed under standard aseptic surgical conditions without any antibiotic prophylaxis. The patients were placed in a semi-recumbent position, and a stereotactic arc was used to determine the incision site. A small stab incision was made, followed by the creation of a 3.2-mm twist-drill burr hole at predetermined coordinates. An intracerebral biopsy needle was then inserted through the burr hole and advanced along the planned trajectory to the lesion. Tissue samples (approximately 1 × 10 mm) were collected, and an intraoperative smear examination was performed[ 22 , 41 ]. Upon completion of the biopsy, the needle was withdrawn, and the incision site was closed with a single 3/0 absorbable suture. Post-biopsy management All patients were monitored in the recovery unit for at least two hours following the procedure. A postoperative CT scan was performed after completion of the biopsy to rule out complications before transferring patients to either the neurosurgical ward or the day surgery unit[ 24 , 34 , 36 ]. 2.3. Variables and Outcomes The primary and secondary endpoints were as follows: (1) to assess the diagnostic yield and post-biopsy complications of stereotactic brain biopsies targeting lesions < 10 mm, and (2) to compare these outcomes with biopsies targeting lesions ≥ 10 mm. The following variables were analyzed: patient age, sex, lesion location (cortical, subcortical, deep [e.g., insular region, basal ganglia], brainstem, cerebellar, or pineal), lesion size, contrast enhancement on post-gadolinium imaging, and histopathological diagnosis (WHO classification[ 19 ]: grade 1–4 gliomas, metastases, primary CNS lymphoma, pyogenic abscesses, radionecrosis, toxoplasmosis, inflammatory lesions, or other etiologies). In view of the existing literature on complications in stereotactic neurosurgery, we used a previously published grading severity scale tailored for diagnostic intracerebral procedures[ 3 , 13 , 25 , 26 , 35 , 36 ]: grade 1A: complication visible only on postoperative CT scan (i.e., asymptomatic hemorrhage); grade 1B: transient symptomatic complication that did not require treatment; grade 2: transient symptomatic complication that resolved completely but required treatment; grade 3: persistent neurological deficit > 6 months post-biopsy; grade 4: biopsy-related death. Complications of grade 1B or higher were symptomatic and included hemorrhage, edema-related neurological decompensation, infection, seizures, and new neurological deficits. Two independent investigators reviewed the patients’ charts and imaging and graded post-biopsy complications. Disagreements between the classifications were resolved by a third investigator. 2.4. Matching Methodology Patients who underwent frame-based stereotactic biopsy for lesions measuring < 10 mm in maximum diameter were individually matched with patients who underwent biopsy for lesions measuring ≥ 10 mm. Matching was performed based on the lesion location, presence of contrast enhancement, and patient age (± 5 years). These criteria were chosen based on established risk factors for (i) non-diagnostic biopsy outcomes and (ii) biopsy-related complications[ 13 , 34 , 36 ]. To improve the statistical power of the analysis, each patient in the < 10 mm group was matched with three patients in the ≥ 10 mm group (Fig. 1 ). 2.5. Statistical Analysis The results for categorical variables, expressed as number (%), were compared using χ2 tests; those for continuous variables, expressed as mean ± standard deviation or median [25th–75th percentile interquartile range (IQR)], were compared using the Student’s t-test or Wilcoxon’s rank test. Statistical significance was set at p < 0.05. Analyses were performed using R software (version 4.1.1). R Core Team (2021). 2.6. Ethical Considerations This study was conducted according to the Ethical Principles for Medical Research Involving Human Subjects stated in 2004 and further revisions made in 2008 and 2013 of the Declaration of Helsinki. According to French law, the need for signed patient consent was waived because of the retrospective nature of the study. However, patients were informed about the study and their right to refuse participation in it. To report our results, we followed the recommendations of the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement for observational studies[ 5 ]. The study was approved by the IRB Review Board of the French National Neurosurgery Society (Ref n° blinded for review). 3. RESULTS 3.1. Study population Of the 2,347 patients who underwent frame-based stereotactic biopsy during the inclusion period, 74 (3.2%) underwent biopsy for lesions measuring < 10 mm in maximum diameter. During the same timeframe, 222 patients were successfully matched to the cohort in a 3:1 ratio for the analysis of diagnostic yield and complications. Sex distribution (61.17% vs. 47.3%; p = 0.03) and histological diagnosis, particularly glioblastoma (WHO grade 4) and inflammatory diseases, differed significantly between the two groups (p < 0.001), as did the distribution of tumoral lesions (p = 0.01). Patient characteristics are summarized in Table 1 . Lesions were predominantly located in the subcortical (45.9%) and deep regions (43.6%), with a supratentorial distribution in 93.2% of the cases. Histopathological diagnoses were mainly tumoral (84.8%), with a high representation of grade 4 gliomas (45.9%). Table 1 Comparison of diagnostic yield and post-biopsy complications in patients with lesions < 10 mm and ≥ 10 mm in size. Lesions < 10 mm (N = 74) Lesions ≥ 10 mm (N = 222) Overall population (N = 296) p value Sex (male) 35 (47.3%) 137 (61.1%) 172 (58.1%) p = 0.03 Mean Age* +/ SD 55.6 +/- 17.2 56.1 +/- 17 55.9+/-17 p = 0.8 Leison localization* p = 1.0 Cortical 3 (4.1%) 9 (4.1%) 12 (0.4%) sub-cortical 34 (45.9%) 102 (45.9%) 136 (45.9%) deep 32 (43.2%) 96 (43.2%) 129 (43.6%) brainstem 3 (4.0%) 9 (4.0%) 12 (0.4%) Cerebellar 2 (2.7%) 6 (2.7%) 8 (2.7%) Pineal region 0 (0%) 1 (0.4%) 1 (0.1%) Tumor size Mean size +/- SD 6.7 +/-1.8 38.2 +/-16.9 30.4 +/-20 p < 0.001 Gadolinium enhancement* 55 (74.3%) 166 (74.3%) 221 (74.7%) p = 1.0 Histology Glioma grade 1 1 (1.3%) 0 (0%) p = 0.2 grade 2 6 (8.1%) 8 (3.6%) 14 (4.7%) p = 0.1 grade 3 10 (13.5%) 16 (7.1%) 26 (8.8%) p = 0.1 grade 4 18 (24.3%) 118 (52.7%) 136 (45.9%) p < 0.001 Metastasis 2 (2.7%) 11 (4.9%) 13 (4.3%) p = 0.5 Lymphoma 13 (17.6%) 25 (11.3%) 38 (12.8%) p = 0.1 Abscess 0 (0%) 6 (2.2%) 6 (2%) p = 0.3 Others 5 (6.7%) 17 (7.6%) 22 (7.4%) p = 0.8 Radionecrosis 0 (0%) 0 (0%) 0 (0%) NA Toxoplasmosis 0 (0%) 4 (1.8%) 4 (1.3%) p = 0.6 Inflammatory 13 (17.6%) 8 (3.6%) 21 (7%) p < 0.001 Tumoral lesions 56 (75.7%) 195 (87.8%) 251 (84.8%) p = 0.01 No diagnosis 6 (8.1%) 9 (4.0%) 15 (5%) p = 0.2 Complications ≥ Grade 1B 1 (1.4%) 11 (4.9%) 12 (4%) p = 0.3 ≥ Grade 2 0 (0%) 9 (4.0%) 9 (3.0%) p = 0.1 Grade 3 0 (0%) 1 (0.4%) 1 (0.1%) p = 0.6 Grade 4 0 (0%) 4 (1.8%) 4 (1.3%) p = 0.6 Symptomatic hematoma 0 (0%) 7 (3.1%) 7 (2.4%) p = 0.2 Non-hemorrhagic neurological aggravations 0 (0%) 3 (1.3%) 3 (1.0%) p = 0.8 Infection 0 (0%) 1 (0.4%) 1 (0.1%) p = 1 Seizure 1 (1.3%) 0 (0%) 1 (0.1%) p = 0.2 *Matching criteria. Post-biopsy complication grades were as follows: grade 1A, complication visible only on postoperative CT scan (i.e., asymptomatic hemorrhage); grade 1B, transient symptomatic complication that did not require treatment; grade 2, transient symptomatic complication that resolved completely but required treatment; grade 3, persistent neurological deficit > 6 months post-biopsy; and grade 4, biopsy-related death. 3.2. Diagnostic Yield In the cohort of 296 patients, 15 (5.1%) had nondiagnostic (negative) biopsies (Table 2 ). Univariate analysis revealed that non-neoplastic pathology was significantly associated with negative biopsy results (46.7%; p < 0.001). Negative biopsies were most often obtained in cases initially suspected to be lymphoma (26.7%), high-grade glioma (20%), or infectious disease (20%); granulomatous disease (0.7%), metastasis (0.7%), and inflammatory lesions (0.7%) were also observed (Table 3 ). In 20% of the cases, the lesions remained undetermined without a definitive diagnosis. Management of non-diagnostic biopsies included repeat stereotactic brain biopsy in 33.3% of patients, diagnosis via a non-cerebral procedure identifying systemic disease in 13.3%, empiric treatment in 33.3%, and observation in 13.3%. Concordance between the intended target and postoperative imaging was satisfactory in 80% of the cases. Table 2 Comparisons of Lesion Characteristics Between Diagnostic and Nondiagnostic Biopsies (Univariate Analysis) Nondiagnostic biopsy (N = 15) Diagnostic biopsy (N = 282) Overall population (N = 296) p-value Sex (M) 8 (53.3%) 164 (58.3%) 172 (58.1%) p = 0.7 Mean age 53.1 +/-18.9 56.1+/-16.8 55.9+/-16.9 p = 0.6 Location cortical 2 (13.3%) 10 (3.5%) 12 (4.0%) p = 0.1 sub-cortical 8 (53.3%) 128 (45.5%) 136 (45.9%) p = 0.1 deep 4 (26.7%) 124 (44.1%) 128 (43.2%) p = 0.18 brainstem 11 (3.9%) 1 (6.7%) 12 (4.0%) p = 0.5 cerebellar 0 (0%) 8 (2.9%) 8 (2.7%) p = 1 pineal region 0 (0%) 0 (0%) 0 (0%) NA Supratentorial 14 (93.3%) 262 (93.2%) 276 (93.2%) p = 1 Gadolinium enhancement 12 (80%) 208 (74.1%) 220 (74.3%) p = 0.7 Tumoral lesions 7 (46.7%) 244 (86.8%) 251 (84.8%) p < 0.001 Period 1 (2009–2016) 9 (60%) 125 (44.4%) 15 (5.0%) p = 0.2 Table 3 Histologic, Radiologic, and Management Characteristics of Nondiagnostic Lesions Non diagnostic biopsy (N = 15) Sex (M) 8 (53.3%) Mean age 53.1 +/-18.9 Histology suspected Lymphoma 4 (26.7%) High grade glioma 3 (20%) Infectious lesions 3 (20%) Granulomatosis 1 (0.7%) Metastasis 1 (0.7%) Inflammatory lesions 1 (0.7%) unknown 3 (20%) Strategy 2nd biopsy 5 (33.3%) Extracranial biopsy 2 (13.3%) Empirical treatment 5 (33.3%) Observation 2 (13.3%) Biopsy target–CT match 12 (80%) Among the 296 patients included in the study, 6 (8.1%) and 9 (4.0%) had non-diagnostic biopsies in the < 10 mm and ≥ 10 mm groups, respectively, with no statistically significant difference between the groups (p = 0.2). 3.3. Complications Twelve patients (4.1%) experienced complications of grade ≥ 1B (i.e., symptomatic) (Table 4 ). Hemorrhagic events were the most frequent (58.3%), followed by non-hemorrhagic neurological aggravations (25%), and less commonly, infectious (8.3%) and epileptic (8.3%) events. On univariate analysis, older age (65.8 ± 11.7 years; p = 0.03) and subcortical (p = 0.01) or deep lesion location (p < 0.001) were significantly associated with complications, whereas the study period (2009–2016 vs. 2017–2024) showed no temporal differences. Comparing the lesion size groups, the rates of grade ≥ 1B complications did not differ significantly (< 10 mm: 1.4% vs. ≥10 mm: 4.9%; p = 0.30). Likewise, grade ≥ 2 complications were similar (0% vs. 4.0%; p = 0.10), as were grade 3 events (p = 0.60). No significant between-group differences were observed in symptomatic hemorrhage, seizures, or new neurological deficits. Overall mortality was 1.3% (4/296) without a significant difference by lesion size (0% in < 10 mm vs. 1.8% in ≥ 10 mm; p = 0.60). Table 4 Comparison of Biopsies According to the Occurrence of Symptomatic Complications (Grade ≥ 1B) – Univariate Analysis Symptomatic complications (N = 12) No symptomatic complications (N = 284) Overall population (N = 296) p-value Sex (M) 9 (75%) 163 (57.4%) 172 (58.1%) p = 0.2 Mean age (ys) 65.8 +/-11.7 55.5+/-17 55.9+/-16.9 p = 0.03 Location cortical 1 (8.3%) 11 (3.9%) 12 (4.0%) p = 0.4 sub-cortical 1 (8.3%) 135 (47.5%) 136 (45.9%) p = 0.01 deep 10 (83.3%) 118 (41.5%) 128 (43.2%) p < 0.001 brainstem 0 (0%) 12 (4.2%) 12 (4.0%) p = 1 cerebellar 0 (0%) 8 (2.8%) 8 (2.7%) p = 1 pineal 0 (0%) 0 (0%) 0 (0%) NA Supratentorial 0 (0%) 20 (7.0%) 20 (6.7%) p = 1 Mean size (mm) 35.4+/-18.3 30.1+/-20 30.3+/-20 p = 0.3 Gadolinium enhancement 11 (91.6%) 209 (73.6%) 220 (74.3%) p = 0.3 Histology Glioma grade 1 0 (0%) 1 (0.3%) 1 (0.3%) p = 1 Glioma grade 2 0 (0%) 14 (4.9%) 14 (4.7%) p = 1 Glioma grade 3 0 (0%) 26 (9.1%) 26 (8.8%) p = 0.6 Glioma grade 4 6 (50%) 130 (45.7%) 136 (45.9%) p = 0.7 Metastasis 0 (0%) 13 (4.6%) 13 (4.4%) p = 1 Lymphoma 1 (8.3%) 37 (13.0%) 38 (12.8%) p = 1 Abscess 1 (8.3%) 5 (1.7%) 6 (2.0%) p = 0.2 No diagnosis biopsy 1 (8.3%) 14 (4.9%) 15 (5.0%) p = 0.4 Toxoplasmosis 1 (8.3%) 3 (1.0%) 4 (1.3%) p = 0.1 Inflammatory lesions 0 (0%) 21 (7.4%) 21 (7.0%) p = 1 Others 2 (16.7%) 20 (7.0%) 22 (7.4%) p = 0.2 Tumoral lesions 9 (75.0%) 242 (85.2%) 251 (84.8%) p = 0.4 Period 1 (2009–2016) 5 (41.7%) 129 (45.4%) 134 (45.3%) p = 0.8 Post-biopsy complication grades were as follows: grade 1A, complication visible only on postoperative CT scan (i.e., asymptomatic hemorrhage); grade 1B, transient symptomatic complication that did not require treatment; grade 2, transient symptomatic complication that resolved completely but required treatment; grade 3, persistent neurological deficit > 6 months post-biopsy; and grade 4, biopsy-related death. 4. DISCUSSION 4.1. Key results Seventy-four patients with lesions < 10 mm in maximum diameter were compared with 222 matched controls who underwent frame-based stereotactic biopsy. The diagnostic yield did not differ between the groups (91.9% vs. 96%, p = 0.2). Overall complication rates were low (4.1%), with no increased risk in the < 10 mm group and no severe (≥ grade 2) events reported in this subgroup. No significant differences were observed between the groups in terms of the rates of symptomatic hemorrhage, seizures, new neurological deficits, or mortality. 4.2. Comparisons with Literature Our findings challenge the long-standing empirical principles that have advised against performing biopsies of small intracranial lesions[ 32 ]. Recent literature has highlighted lesion size, both on gadolinium-enhanced imaging and FLAIR sequences, as a significant factor associated with non-diagnostic biopsy outcomes[ 37 ] , [ 16 ]. Our results demonstrate that these assumptions are not confirmed and that stereotactic biopsy, when clinically indicated, is entirely feasible for lesions smaller than 10 mm in maximum diameter without any added risk of complications. The diagnostic yield in this subgroup reached 91.9%, which appears broadly comparable to the rates reported in large stereotactic biopsy series (84.3%–99.3%)[ 2 , 8 , 11 , 13 , 18 , 33 , 39 ]. However, in our cohort, the large proportion of biopsied lesions of unknown (non-tumoral) etiology reduces the diagnostic yield, since biopsy is demonstrably less informative in these cases than in biopsies performed for brain tumors[ 10 , 14 , 23 , 25 , 27 ]. Importantly, the occurrence of severe (grade 2 or higher) complications was 0%, highlighting the safety of the procedure and aligning with previous studies[ 2 , 8 , 11 , 13 , 18 , 33 , 39 ] that identified predictors of complications, such as lesion location, histopathological diagnosis, and patient age, but not lesion size[ 3 , 6 , 26 , 34 – 36 ]. In the context of increasingly widespread access to advanced neuroimaging, the growing role of molecular diagnostics, and the contribution of neurosurgery to the work-up of infectious, inflammatory, and systemic diseases, our findings support the consideration of stereotactic biopsy, even in the setting of small-volume lesions. Several techniques can enhance the diagnostic yield and should be employed whenever possible, particularly in challenging cases, such as biopsies of small lesions. Although an established technique, intraoperative histopathological analysis significantly increases diagnostic yield, reducing the rate of non-diagnostic biopsies from 11.1% to 3.7%[ 18 ],, or even eliminating them entirely[ 22 ]. When performed near the operating room and interpreted by an experienced neuropathologist, intraoperative smears provide a reliable tool for minimizing non-diagnostic biopsies and the need for repeat procedures. Stimulated Raman Histology (SRH) is a label-free optical imaging technique that enables near-real-time hematoxylin–eosin–like digital histology directly in the operating room[ 40 ][ 29 , 40 ]. Early studies have demonstrated its seamless integration into the neurosurgical workflow, producing excellent image quality and high diagnostic accuracy (87.7%)[ 29 ]. When combined with artificial intelligence, SRH achieves a performance comparable to that of conventional histopathology (94.6%)[ 7 ]. Fluorescence-guided imaging using 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX or intravenous sodium fluorescein allows real-time visualization of tumor tissue during stereotactic brain biopsies. Multiple studies have demonstrated a strong correlation between fluorescence and the presence of tumor tissue, with high sensitivity and specificity (up to 85–100%), thereby improving the diagnostic yield and reducing the number of samples required[ 12 , 45 ]. 4.3. Stereotactic considerations Performing a stereotactic biopsy of a small intracranial lesion poses significant technical constraints[ 9 ]. As the target volume decreases, the ability to adjust the intracranial target point becomes increasingly limited, which, in turn, restricts the range of feasible trajectories[ 15 ]. In this setting, the target itself cannot be modified without risking sampling errors or exiting the lesion, thereby compromising diagnostic yield. Consequently, the only variable that can be adjusted is the entry point, which must be selected in strict adherence to the principles of stereotaxy: avoidance of eloquent cortical areas and vascular structures, optimization of trajectory safety, and preservation of targeting accuracy[ 15 , 28 ] (Fig. 2 ). The results of the present study apply specifically to frame-based stereotactic biopsies, as all procedures were performed using the Leksell frame. Therefore, extrapolation to other guidance systems should be approached with caution. Although robot-assisted systems have emerged as promising and reliable alternative[ 21 ] , [ 39 , 44 ], particularly in terms of precision and stability, the applicability of our findings to these systems remains to be validated. However, frameless neuronavigation raises more concerns in this context[ 21 ]. The existing literature suggests that its accuracy is inferior to that of frame-based and robotic systems[ 20 ]. Moreover, published studies using frameless neuronavigation report larger average lesion diameters—typically ranging from 36 to 38 mm—with reported volumes as low as 18 cm³, making direct comparison to our cohort of sub-10 mm lesions difficult[ 17 , 31 , 38 , 42 , 43 ]. Further dedicated studies are necessary to assess the diagnostic yield and safety of frameless approaches in this specific subset of patients. 4.4. Strengths and Limitations This study has several strengths. First, it directly addresses a long-standing evidence gap by focusing on frame-based stereotactic biopsies of lesions < 10 mm and comparing them with a rigorously matched cohort of larger lesions. Matching (1:3) was performed on clinically relevant covariates—age, lesion location, and contrast enhancement—drawn from a large institutional series of 2,347 biopsies, which helped mitigate confounding. The procedures were homogeneous (all Leksell frame–based) with standardized pre- and postoperative imaging, and complications were graded using a predefined validated severity scale. Outcome adjudication by two independent investigators (with third-party resolution of disagreements) further strengthened the internal validity. This study also has some limitations. Its retrospective, single-center design is susceptible to selection and information biases and may limit its external generalizability, particularly to frameless or robotic systems. Baseline imbalances, most notably sex distribution and histopathologic mix, with a higher proportion of non-neoplastic diagnoses in the < 10 mm group, could depress diagnostic yield in that subgroup despite matching. The sample size for very small lesions, while substantial for this niche (n = 74), still limits the power to detect rare adverse events; consequently, the absence of severe complications in the < 10 mm cohort should be interpreted cautiously. Finally, the results pertain to frame-based techniques and may not be extrapolated to alternative guidance platforms without dedicated evaluation. 5. Conclusion Frame-based stereotactic biopsy of intracranial lesions smaller than 10 mm is both safe and diagnostically effective, with outcomes comparable to those of larger lesions. In this matched cohort study, small lesion size did not compromise the diagnostic yield or increase the risk of complications, including symptomatic hemorrhage, seizures, neurological deficits, or mortality. Notably, no severe complications occurred in the < 10 mm group. These findings directly challenge long-standing assumptions that discourage biopsy of very small targets and suggest that lesion size alone should not preclude histopathological sampling when clinically indicated. As the role of tissue and molecular characterization continues to expand in neuro-oncology and neuroinflammatory disorders, the evidence provided here supports the integration of stereotactic biopsy into the diagnostic workup of small-volume brain lesions. Further studies are warranted to validate these results across alternative biopsy platforms, including frameless and robotic systems, and to explore strategies for optimizing tissue yield in non-neoplastic cases. Declarations Conflict of Interests : The authors declare no competing interests. Funding: The authors received no funding for this work. Ethical approval: This study was approved by the Institutional Review Board committee of the French National Neurosurgery Society. Data availability: Anonymized original data from this manuscript will be made available upon reasonable request to the corresponding author. Acknowledgements: None Consent to participate: According to the French law, the need for signed patient consent was waived given the retrospective nature of the study. However, patients were informed about the study and their right to refuse participation. Author contributions: All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Charles-Henry MALLEREAU. The first draft of the manuscript was written by Charles-Henry MALLEREAU and Bertrand MATHON and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript. Clinical trial number: not applicable References Bex A, Mathon B (2022) Advances, technological innovations, and future prospects in stereotactic brain biopsies. 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Springer US, New York, NY, pp 247–257 Mathon B, Riche M, Lombard A, Chabaane M, Roblot P, Boetto J, Marlier B, Mezjan I, Engelhardt J, Delaunois J, Benzagmout M, Corsino da Costa A, Iacoangeli F, Póczoš P, Rizzi M (2025) Technical Aspects of Frame-Based Stereotactic Brain Biopsy, Neuronavigation-Assisted Brain Biopsy, and Open Brain Biopsy. In: Mathon B (ed) Brain Biopsies. Springer US, New York, NY, pp 3–12 Neidert N, Straehle J, Erny D, Sacalean V, El Rahal A, Steybe D, Schmelzeisen R, Vlachos A, Reinacher PC, Coenen VA, Mizaikoff B, Heiland DH, Prinz M, Beck J, Schnell O (2022) Stimulated Raman histology in the neurosurgical workflow of a major European neurosurgical center - part A. Neurosurg Rev 45:1731–1739. doi: 10.1007/s10143-021-01712-0 Overcast WB, Davis KM, Ho CY, Hutchins GD, Green MA, Graner BD, Veronesi MC (2021) Advanced imaging techniques for neuro-oncologic tumor diagnosis, with an emphasis on PET-MRI imaging of malignant brain tumors. Curr Oncol Rep 23:34. doi: 10.1007/s11912-021-01020-2 Paleologos TS, Dorward NL, Wadley JP, Thomas DG (2001) Clinical validation of true frameless stereotactic biopsy: analysis of the first 125 consecutive cases. Neurosurgery 49:830–835; discussion 835-837. doi: 10.1097/00006123-200110000-00009 Pasternak KA, Schwake M, Warneke N, Masthoff M, Zawy Alsofy S, Suero Molina E, Stummer W, Schipmann S (2021) Evaluation of 311 contemporary cases of stereotactic biopsies in patients with neoplastic and non-neoplastic lesions-diagnostic yield and management of non-diagnostic cases. Neurosurg Rev 44:2597–2609. doi: 10.1007/s10143-020-01394-0 Pennlund A, Jakola AS, Skoglund T, Ljungqvist J (2022) A single-centre study of frame-based stereotactic brain biopsies. Br J Neurosurg 36:213–216. doi: 10.1080/02688697.2020.1867704 Riche M, Amelot A, Peyre M, Capelle L, Carpentier A, Mathon B (2021) Complications after frame-based stereotactic brain biopsy: a systematic review. Neurosurg Rev 44:301–307. doi: 10.1007/s10143-019-01234-w Riche M, Lavé A, Malaizé H, Mathon B (2025) Complications Associated with Stereotactic Brain Biopsies. In: Mathon B (ed) Brain Biopsies. Springer US, New York, NY, pp 293–304 Riche M, Marijon P, Amelot A, Bielle F, Mokhtari K, Chambrun MP de, Joncour AL, Idbaih A, Touat M, Do C-H, Deme M, Pasqualotto R, Jacquens A, Degos V, Shotar E, Chougar L, Carpentier A, Mathon B (2022) Severity, timeline, and management of complications after stereotactic brain biopsy. J Neurosurg 136:867–876. doi: 10.3171/2021.3.JNS21134 Schumacher X, Hudelist B, Paun L, Benzakoun J, Demasi M, Hamza M, Roux A, Moiraghi A, Elia A, Parraga E, Dezamis E, Chretien F, Varlet P, Oppenheim C, Pallud J, Zanello M (2025) Prevalence and risk factors of nonyield brain biopsy: a 21-year experience with robot-assisted stereotactic biopsies. J Neurosurg 1–11. doi: 10.3171/2025.2.JNS242273 Sciortino T, Fernandes B, Conti Nibali M, Gay LG, Rossi M, Lopci E, Colombo AE, Elefante MG, Pessina F, Bello L, Riva M (2019) Frameless stereotactic biopsy for precision neurosurgery: diagnostic value, safety, and accuracy. Acta Neurochir (Wien) 161:967–974. doi: 10.1007/s00701-019-03873-w Spyrantis A, Woebbecke T, Constantinescu A, Cattani A, Quick-Weller J, Willems LM, Marquardt G, Seifert V, Freiman TM (2021) Comparison of frame-less robotic versus frame-based stereotactic biopsy of intracranial lesions. Clin Neurol Neurosurg 207:106762. doi: 10.1016/j.clineuro.2021.106762 Straehle J, Erny D, Neidert N, Heiland DH, El Rahal A, Sacalean V, Steybe D, Schmelzeisen R, Vlachos A, Mizaikoff B, Reinacher PC, Coenen VA, Prinz M, Beck J, Schnell O (2022) Neuropathological interpretation of stimulated Raman histology images of brain and spine tumors: part B. Neurosurg Rev 45:1721–1729. doi: 10.1007/s10143-021-01711-1 Tran S, Bielle F (2025) Management of Brain Biopsy Samples: From Histological Examination to Biobanking and Multi-omic Analysis. In: Mathon B (ed) Brain Biopsies. Springer US, New York, NY, pp 117–144 Vychopen M, Wach J, Borger V, Schneider M, Eichhorn L, Maciaczyk J, Bara G, Vatter H, Banat M, Hamed M (2022) Patient Safety Comparison of Frameless and Frame-Based Stereotactic Navigation for Brain Biopsy-A Single Center Cohort Study. Brain Sci 12:1178. doi: 10.3390/brainsci12091178 Woodworth GF, McGirt MJ, Samdani A, Garonzik I, Olivi A, Weingart JD (2006) Frameless image-guided stereotactic brain biopsy procedure: diagnostic yield, surgical morbidity, and comparison with the frame-based technique. J Neurosurg 104:233–237. doi: 10.3171/jns.2006.104.2.233 Wu S, Wang J, Gao P, Liu W, Hu F, Jiang W, Lei T, Shu K (2021) A comparison of the efficacy, safety, and duration of frame-based and Remebot robot-assisted frameless stereotactic biopsy. Br J Neurosurg 35:319–323. doi: 10.1080/02688697.2020.1812519 Xu R, Rösler J, Teich W, Radke J, Früh A, Scherschinski L, Onken J, Vajkoczy P, Misch M, Faust K (2022) Correlation of Tumor Pathology with Fluorescein Uptake and MRI Contrast-Enhancement in Stereotactic Biopsies. J Clin Med 11:3330. doi: 10.3390/jcm11123330 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 22 Jan, 2026 Read the published version in Neurosurgical Review → Version 1 posted Editorial decision: Revision requested 10 Dec, 2025 Reviews received at journal 27 Nov, 2025 Reviewers agreed at journal 25 Nov, 2025 Reviews received at journal 24 Nov, 2025 Reviewers agreed at journal 14 Nov, 2025 Reviewers agreed at journal 13 Nov, 2025 Reviewers invited by journal 11 Nov, 2025 Editor assigned by journal 08 Nov, 2025 Submission checks completed at journal 07 Nov, 2025 First submitted to journal 06 Nov, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8047246","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":547501291,"identity":"ffc404c6-39c9-4d12-b6c1-24912f1f7437","order_by":0,"name":"Charles-Henry 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11:37:49","extension":"png","order_by":6,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":55940,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-8047246/v1/d93d5d4bd98d85fa428a30e9.png"},{"id":96555084,"identity":"3a4e465d-1f0e-49e2-88f5-2d5fe7365db5","added_by":"auto","created_at":"2025-11-23 11:37:49","extension":"xml","order_by":7,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":175519,"visible":true,"origin":"","legend":"","description":"","filename":"abec6ce0b9114e19a1a0286093c4e25e1structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-8047246/v1/cb2fc01872a61458b5b6e12b.xml"},{"id":96555083,"identity":"290bfcd2-ee3f-4b41-b4c3-368ccbdeee66","added_by":"auto","created_at":"2025-11-23 11:37:49","extension":"html","order_by":8,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":182963,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-8047246/v1/9dea6b5f5351a303ddcaeeff.html"},{"id":96604718,"identity":"5890633a-c6c2-48db-8c3e-3ef146333469","added_by":"auto","created_at":"2025-11-24 09:14:42","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":572628,"visible":true,"origin":"","legend":"\u003cp\u003eComparative imaging examples illustrating small (\u0026lt;10 mm) versus larger (≥10 mm) lesions. (A) Glioblastoma \u0026lt;10 mm with three matched ≥10-mm controls (B–D: glioblastomas). (E) Toxoplasmosis \u0026lt;10 mm with three matched controls (F: toxoplasmosis; G: abscess; H: neuro-Behçet disease).\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-8047246/v1/5b4761504427723bccb73219.png"},{"id":96555076,"identity":"e7d4ab6e-95b1-4ade-b659-c5ee276a0b69","added_by":"auto","created_at":"2025-11-23 11:37:49","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":127922,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of small (\u0026lt;10 mm) and large (≥10 mm) lesions across the three orthogonal planes and representative biopsy trajectories. A small lesion (\u0026lt;10 mm) is shown in the axial, coronal, and sagittal views (A-C) with limited feasible trajectories (D), contrasted with a larger lesion (≥10 mm) in the same planes (E–G), permitting multiple potential trajectories (H).\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-8047246/v1/75de41cb7c11f4434634be12.png"},{"id":101152395,"identity":"e26168c1-f2de-42fe-bd54-1e27c084f9ea","added_by":"auto","created_at":"2026-01-26 16:11:30","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2220182,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8047246/v1/83ae743c-d9e0-4d61-a3f5-12cadb6d7293.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Diagnostic Performance and Safety of Stereotactic Frame-Based Biopsy for Sub centimeter Intracranial Lesions: A Matched Cohort Analysis","fulltext":[{"header":"1. INTRODUCTION","content":"\u003cp\u003eStereotactic brain biopsy is a standard neurosurgical procedure for diagnosing various intracranial pathologies, including tumors, infections, and inflammatory or systemic diseases[\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]. In neuro-oncology, histopathological diagnosis remains essential, particularly given the growing importance of molecular profiling in therapeutic decision-making[\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e]. Beyond oncology, brain biopsy has become increasingly common in the investigation of infectious, inflammatory, and systemic conditions[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. The procedure is technically feasible in nearly all brain regions, with few anatomical limitations[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]\u003csup\u003e,\u003c/sup\u003e[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. However, lesion size remains one of the few constraints, although the exact threshold below which biopsy becomes less effective or safe has not been clearly established. A commonly cited lower limit is 1 cm3, although it remains poorly defined in the literature[\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. To date, no dedicated studies have specifically assessed the diagnostic yield and safety of stereotactic biopsies of small brain lesions. This study aimed to evaluate the diagnostic yield and safety of frame-based stereotactic brain biopsy for lesions\u0026thinsp;\u0026lt;\u0026thinsp;10 mm in maximum diameter and to compare these outcomes with those from a cohort of patients with lesions\u0026thinsp;\u0026ge;\u0026thinsp;10 mm.\u003c/p\u003e"},{"header":"2. METHODS","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003e2.1. Design\u003c/h2\u003e\u003cp\u003eThis retrospective single-center cohort study included all consecutive adult patients who underwent frame-based stereotactic brain biopsy for a newly diagnosed intracranial lesion measuring less than 10 mm in maximum diameter between April 2009 and April 2024 at our institution. Each case was matched in a 1:3 ratio with patients selected from a cohort of 2,347 individuals who underwent frame-based stereotactic biopsies during the same period. All procedures were performed using a frame-based stereotactic technique with a Leksell stereotactic frame (Elekta, Stockholm, Sweden).\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e\u003ch2\u003e2.2. Biopsy procedures\u003c/h2\u003e\u003cp\u003e\u003cem\u003ePre-biopsy evaluation\u003c/em\u003e\u003c/p\u003e\u003cp\u003ePatients were eligible for biopsy procedures if they met the following institutional safety criteria: platelet count greater than 100,000/L, International Normalized Ratio (INR) between 0.8 and 1.1, and activated partial thromboplastin time (aPTT) less than 1.20. Oral anticoagulants and antiplatelet medications were discontinued 5\u0026ndash;7 days before the biopsy, with the exact timing depending on the specific medication used.\u003c/p\u003e\u003cp\u003e\u003cem\u003eFrame-based biopsy\u003c/em\u003e\u003c/p\u003e\u003cp\u003eBiopsies were performed under local anesthesia with or without intravenous conscious sedation or general anesthesia in rare cases[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. The patients were positioned in a Leksell stereotactic frame. Preoperative imaging included three-dimensional gadolinium-enhanced and FLAIR sequences acquired using a 1.5-T MRI system (Signa; General Electric). In rare instances, contrast-enhanced CT was used instead of MRI because of technical constraints. In the latter case, stereotactic CT images were co-registered with prebiopsy MRI. The biopsy trajectory and depth were planned based on the location of the target lesion. Stereotactic coordinates were calculated using the Framelink software (Medtronic, Minneapolis, MN, USA). The biopsy trajectory was carefully selected to avoid critical, superficial, and deep vascular structures. Trajectory planning was confirmed millimeter by millimeter using three-dimensional visualization, including perpendicular and parallel oblique views of the intended needle path. The entry site was shaved, and the procedure was performed under standard aseptic surgical conditions without any antibiotic prophylaxis. The patients were placed in a semi-recumbent position, and a stereotactic arc was used to determine the incision site. A small stab incision was made, followed by the creation of a 3.2-mm twist-drill burr hole at predetermined coordinates. An intracerebral biopsy needle was then inserted through the burr hole and advanced along the planned trajectory to the lesion. Tissue samples (approximately 1 \u0026times; 10 mm) were collected, and an intraoperative smear examination was performed[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e]. Upon completion of the biopsy, the needle was withdrawn, and the incision site was closed with a single 3/0 absorbable suture.\u003c/p\u003e\u003cp\u003e\u003cem\u003ePost-biopsy management\u003c/em\u003e\u003c/p\u003e\u003cp\u003eAll patients were monitored in the recovery unit for at least two hours following the procedure. A postoperative CT scan was performed after completion of the biopsy to rule out complications before transferring patients to either the neurosurgical ward or the day surgery unit[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e, \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e].\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\u003ch2\u003e2.3. Variables and Outcomes\u003c/h2\u003e\u003cp\u003eThe primary and secondary endpoints were as follows: (1) to assess the diagnostic yield and post-biopsy complications of stereotactic brain biopsies targeting lesions\u0026thinsp;\u0026lt;\u0026thinsp;10 mm, and (2) to compare these outcomes with biopsies targeting lesions\u0026thinsp;\u0026ge;\u0026thinsp;10 mm. The following variables were analyzed: patient age, sex, lesion location (cortical, subcortical, deep [e.g., insular region, basal ganglia], brainstem, cerebellar, or pineal), lesion size, contrast enhancement on post-gadolinium imaging, and histopathological diagnosis (WHO classification[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]: grade 1\u0026ndash;4 gliomas, metastases, primary CNS lymphoma, pyogenic abscesses, radionecrosis, toxoplasmosis, inflammatory lesions, or other etiologies). In view of the existing literature on complications in stereotactic neurosurgery, we used a previously published grading severity scale tailored for diagnostic intracerebral procedures[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e, \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]: grade 1A: complication visible only on postoperative CT scan (i.e., asymptomatic hemorrhage); grade 1B: transient symptomatic complication that did not require treatment; grade 2: transient symptomatic complication that resolved completely but required treatment; grade 3: persistent neurological deficit\u0026thinsp;\u0026gt;\u0026thinsp;6 months post-biopsy; grade 4: biopsy-related death. Complications of grade 1B or higher were symptomatic and included hemorrhage, edema-related neurological decompensation, infection, seizures, and new neurological deficits. Two independent investigators reviewed the patients\u0026rsquo; charts and imaging and graded post-biopsy complications. Disagreements between the classifications were resolved by a third investigator.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e\u003ch2\u003e2.4. Matching Methodology\u003c/h2\u003e\u003cp\u003ePatients who underwent frame-based stereotactic biopsy for lesions measuring\u0026thinsp;\u0026lt;\u0026thinsp;10 mm in maximum diameter were individually matched with patients who underwent biopsy for lesions measuring\u0026thinsp;\u0026ge;\u0026thinsp;10 mm. Matching was performed based on the lesion location, presence of contrast enhancement, and patient age (\u0026plusmn;\u0026thinsp;5 years). These criteria were chosen based on established risk factors for (i) non-diagnostic biopsy outcomes and (ii) biopsy-related complications[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e, \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]. To improve the statistical power of the analysis, each patient in the \u0026lt;\u0026thinsp;10 mm group was matched with three patients in the \u0026ge;\u0026thinsp;10 mm group (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e\u003ch2\u003e2.5. Statistical Analysis\u003c/h2\u003e\u003cp\u003eThe results for categorical variables, expressed as number (%), were compared using χ2 tests; those for continuous variables, expressed as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation or median [25th\u0026ndash;75th percentile interquartile range (IQR)], were compared using the Student\u0026rsquo;s t-test or Wilcoxon\u0026rsquo;s rank test. Statistical significance was set at p\u0026thinsp;\u0026lt;\u0026thinsp;0.05. Analyses were performed using R software (version 4.1.1). R Core Team (2021).\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003e2.6. Ethical Considerations\u003c/h2\u003e\u003cp\u003e This study was conducted according to the Ethical Principles for Medical Research Involving Human Subjects stated in 2004 and further revisions made in 2008 and 2013 of the Declaration of Helsinki. According to French law, the need for signed patient consent was waived because of the retrospective nature of the study. However, patients were informed about the study and their right to refuse participation in it. To report our results, we followed the recommendations of the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement for observational studies[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. The study was approved by the IRB Review Board of the French National Neurosurgery Society (Ref n\u0026deg; blinded for review).\u003c/p\u003e\u003c/div\u003e"},{"header":"3. RESULTS","content":"\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e\u003ch2\u003e3.1. Study population\u003c/h2\u003e\u003cp\u003eOf the 2,347 patients who underwent frame-based stereotactic biopsy during the inclusion period, 74 (3.2%) underwent biopsy for lesions measuring\u0026thinsp;\u0026lt;\u0026thinsp;10 mm in maximum diameter. During the same timeframe, 222 patients were successfully matched to the cohort in a 3:1 ratio for the analysis of diagnostic yield and complications. Sex distribution (61.17% vs. 47.3%; p\u0026thinsp;=\u0026thinsp;0.03) and histological diagnosis, particularly glioblastoma (WHO grade 4) and inflammatory diseases, differed significantly between the two groups (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), as did the distribution of tumoral lesions (p\u0026thinsp;=\u0026thinsp;0.01). Patient characteristics are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Lesions were predominantly located in the subcortical (45.9%) and deep regions (43.6%), with a supratentorial distribution in 93.2% of the cases. Histopathological diagnoses were mainly tumoral (84.8%), with a high representation of grade 4 gliomas (45.9%).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003e\u003cb\u003eComparison of diagnostic yield and post-biopsy complications in patients with lesions\u0026thinsp;\u0026lt;\u0026thinsp;10 mm and \u0026ge;\u0026thinsp;10 mm in size.\u003c/b\u003e\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"6\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eLesions\u0026thinsp;\u0026lt;\u0026thinsp;10 mm (N\u0026thinsp;=\u0026thinsp;74)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eLesions\u0026thinsp;\u0026ge;\u0026thinsp;10 mm (N\u0026thinsp;=\u0026thinsp;222)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eOverall population (N\u0026thinsp;=\u0026thinsp;296)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003ep value\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSex (male)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003e35 (47.3%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003e137 (61.1%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003e172 (58.1%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.03\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eMean Age* +/ SD\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e55.6 +/- 17.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e56.1 +/- 17\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e55.9+/-17\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eLeison localization*\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003ep\u0026thinsp;=\u0026thinsp;1.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCortical\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3 (4.1%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e9 (4.1%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e12 (0.4%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003esub-cortical\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e34 (45.9%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e102 (45.9%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e136 (45.9%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003edeep\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e32 (43.2%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e96 (43.2%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e129 (43.6%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ebrainstem\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3 (4.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e9 (4.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e12 (0.4%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCerebellar\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2 (2.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6 (2.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e8 (2.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePineal region\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0 (0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1 (0.4%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1 (0.1%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eTumor size\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMean size +/- SD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003e6.7 +/-1.8\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e38.2 +/-16.9\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e30.4 +/-20\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003ep\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eGadolinium enhancement*\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e55 (74.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e166 (74.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e221 (74.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003ep\u0026thinsp;=\u0026thinsp;1.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eHistology\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGlioma\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003egrade 1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1 (1.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0 (0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003egrade 2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6 (8.1%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e8 (3.6%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e14 (4.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003egrade 3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e10 (13.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e16 (7.1%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e26 (8.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003egrade 4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003e18 (24.3%)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e118 (52.7%)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e136 (45.9%)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003ep\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMetastasis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2 (2.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e11 (4.9%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e13 (4.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLymphoma\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e13 (17.6%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e25 (11.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e38 (12.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAbscess\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0 (0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6 (2.2%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e6 (2%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOthers\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5 (6.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e17 (7.6%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e22 (7.4%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRadionecrosis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0 (0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0 (0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0 (0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eToxoplasmosis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0 (0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4 (1.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e4 (1.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eInflammatory\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003e13 (17.6%)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e8 (3.6%)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e21 (7%)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003ep\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eTumoral lesions\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003e56 (75.7%)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e195 (87.8%)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e251 (84.8%)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003ep\u0026thinsp;=\u0026thinsp;0.01\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eNo diagnosis\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6 (8.1%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e9 (4.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e15 (5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eComplications\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026ge; Grade 1B\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1 (1.4%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e11 (4.9%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e12 (4%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026ge; Grade 2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0 (0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e9 (4.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e9 (3.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGrade 3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0 (0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1 (0.4%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1 (0.1%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGrade 4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0 (0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4 (1.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e4 (1.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSymptomatic hematoma\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0 (0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e7 (3.1%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e7 (2.4%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNon-hemorrhagic neurological aggravations\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0 (0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3 (1.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3 (1.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eInfection\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0 (0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1 (0.4%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1 (0.1%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003ep\u0026thinsp;=\u0026thinsp;1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSeizure\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1 (1.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0 (0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1 (0.1%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"6\"\u003e\u003cb\u003e*Matching criteria.\u003c/b\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e\u003cp\u003e\u003cstrong\u003ePost-biopsy complication grades were as follows:\u0026nbsp;\u003c/strong\u003egrade 1A, complication visible only on postoperative CT scan (i.e., asymptomatic hemorrhage); grade 1B, transient symptomatic complication that did not require treatment; grade 2, transient symptomatic complication that resolved completely but required treatment; grade 3, persistent neurological deficit \u0026gt; 6 months post-biopsy; and grade 4, biopsy-related death.\u003c/p\u003e\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\u003ch2\u003e3.2. Diagnostic Yield\u003c/h2\u003e\u003cp\u003eIn the cohort of 296 patients, 15 (5.1%) had nondiagnostic (negative) biopsies (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Univariate analysis revealed that non-neoplastic pathology was significantly associated with negative biopsy results (46.7%; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Negative biopsies were most often obtained in cases initially suspected to be lymphoma (26.7%), high-grade glioma (20%), or infectious disease (20%); granulomatous disease (0.7%), metastasis (0.7%), and inflammatory lesions (0.7%) were also observed (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). In 20% of the cases, the lesions remained undetermined without a definitive diagnosis. Management of non-diagnostic biopsies included repeat stereotactic brain biopsy in 33.3% of patients, diagnosis via a non-cerebral procedure identifying systemic disease in 13.3%, empiric treatment in 33.3%, and observation in 13.3%. Concordance between the intended target and postoperative imaging was satisfactory in 80% of the cases.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eComparisons of Lesion Characteristics Between Diagnostic and Nondiagnostic Biopsies (Univariate Analysis)\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"6\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNondiagnostic biopsy (N\u0026thinsp;=\u0026thinsp;15)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eDiagnostic biopsy (N\u0026thinsp;=\u0026thinsp;282)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eOverall population (N\u0026thinsp;=\u0026thinsp;296)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003ep-value\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eSex (M)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e8 (53.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e164 (58.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e172 (58.1%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eMean age\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e53.1 +/-18.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e56.1+/-16.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e55.9+/-16.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eLocation\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ecortical\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2 (13.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e10 (3.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e12 (4.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003esub-cortical\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e8 (53.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e128 (45.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e136 (45.9%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003edeep\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4 (26.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e124 (44.1%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e128 (43.2%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.18\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ebrainstem\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e11 (3.9%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1 (6.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e12 (4.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ecerebellar\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0 (0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e8 (2.9%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e8 (2.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003ep\u0026thinsp;=\u0026thinsp;1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003epineal region\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0 (0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0 (0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0 (0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eSupratentorial\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e14 (93.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e262 (93.2%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e276 (93.2%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003ep\u0026thinsp;=\u0026thinsp;1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eGadolinium enhancement\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e12 (80%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e208 (74.1%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e220 (74.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eTumoral lesions\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003e7 (46.7%)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e244 (86.8%)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e251 (84.8%)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003ep\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003ePeriod 1 (2009\u0026ndash;2016)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e9 (60%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e125 (44.4%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e15 (5.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eHistologic, Radiologic, and Management Characteristics of Nondiagnostic Lesions\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"2\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNon diagnostic biopsy (N\u0026thinsp;=\u0026thinsp;15)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eSex (M)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e8 (53.3%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eMean age\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e53.1 +/-18.9\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eHistology suspected\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLymphoma\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4 (26.7%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHigh grade glioma\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3 (20%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eInfectious lesions\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3 (20%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGranulomatosis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1 (0.7%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMetastasis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1 (0.7%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eInflammatory lesions\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1 (0.7%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eunknown\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3 (20%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eStrategy\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e2nd biopsy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5 (33.3%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eExtracranial biopsy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2 (13.3%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEmpirical treatment\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5 (33.3%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eObservation\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2 (13.3%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eBiopsy target\u0026ndash;CT match\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e12 (80%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eAmong the 296 patients included in the study, 6 (8.1%) and 9 (4.0%) had non-diagnostic biopsies in the \u0026lt;\u0026thinsp;10 mm and \u0026ge;\u0026thinsp;10 mm groups, respectively, with no statistically significant difference between the groups (p\u0026thinsp;=\u0026thinsp;0.2).\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\u003ch2\u003e3.3. Complications\u003c/h2\u003e\u003cp\u003eTwelve patients (4.1%) experienced complications of grade\u0026thinsp;\u0026ge;\u0026thinsp;1B (i.e., symptomatic) (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). Hemorrhagic events were the most frequent (58.3%), followed by non-hemorrhagic neurological aggravations (25%), and less commonly, infectious (8.3%) and epileptic (8.3%) events. On univariate analysis, older age (65.8\u0026thinsp;\u0026plusmn;\u0026thinsp;11.7 years; p\u0026thinsp;=\u0026thinsp;0.03) and subcortical (p\u0026thinsp;=\u0026thinsp;0.01) or deep lesion location (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) were significantly associated with complications, whereas the study period (2009\u0026ndash;2016 vs. 2017\u0026ndash;2024) showed no temporal differences. Comparing the lesion size groups, the rates of grade\u0026thinsp;\u0026ge;\u0026thinsp;1B complications did not differ significantly (\u0026lt;\u0026thinsp;10 mm: 1.4% vs. \u0026ge;10 mm: 4.9%; p\u0026thinsp;=\u0026thinsp;0.30). Likewise, grade\u0026thinsp;\u0026ge;\u0026thinsp;2 complications were similar (0% vs. 4.0%; p\u0026thinsp;=\u0026thinsp;0.10), as were grade 3 events (p\u0026thinsp;=\u0026thinsp;0.60). No significant between-group differences were observed in symptomatic hemorrhage, seizures, or new neurological deficits. Overall mortality was 1.3% (4/296) without a significant difference by lesion size (0% in \u0026lt;\u0026thinsp;10 mm vs. 1.8% in \u0026ge;\u0026thinsp;10 mm; p\u0026thinsp;=\u0026thinsp;0.60).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eComparison of Biopsies According to the Occurrence of Symptomatic Complications (Grade\u0026thinsp;\u0026ge;\u0026thinsp;1B) \u0026ndash; Univariate Analysis\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"6\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eSymptomatic complications\u003c/p\u003e\u003cp\u003e(N\u0026thinsp;=\u0026thinsp;12)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eNo symptomatic complications (N\u0026thinsp;=\u0026thinsp;284)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eOverall population (N\u0026thinsp;=\u0026thinsp;296)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003ep-value\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"1\" nameend=\"c6\" namest=\"c6\"\u003e\u0026nbsp;\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eSex (M)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e9 (75%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e163 (57.4%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e172 (58.1%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eMean age (ys)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003e65.8 +/-11.7\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e55.5+/-17\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e55.9+/-16.9\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003ep\u0026thinsp;=\u0026thinsp;0.03\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eLocation\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ecortical\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1 (8.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e11 (3.9%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e12 (4.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003esub-cortical\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003e1 (8.3%)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e135 (47.5%)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e136 (45.9%)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003ep\u0026thinsp;=\u0026thinsp;0.01\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003edeep\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003e10 (83.3%)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e118 (41.5%)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e128 (43.2%)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003ep\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ebrainstem\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0 (0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e12 (4.2%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e12 (4.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003ep\u0026thinsp;=\u0026thinsp;1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ecerebellar\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0 (0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e8 (2.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e8 (2.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003ep\u0026thinsp;=\u0026thinsp;1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003epineal\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0 (0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0 (0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0 (0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eSupratentorial\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0 (0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e20 (7.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e20 (6.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003ep\u0026thinsp;=\u0026thinsp;1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eMean size (mm)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e35.4+/-18.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e30.1+/-20\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e30.3+/-20\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eGadolinium enhancement\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e11 (91.6%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e209 (73.6%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e220 (74.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eHistology\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGlioma grade 1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0 (0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1 (0.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1 (0.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003ep\u0026thinsp;=\u0026thinsp;1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGlioma grade 2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0 (0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e14 (4.9%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e14 (4.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003ep\u0026thinsp;=\u0026thinsp;1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGlioma grade 3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0 (0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e26 (9.1%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e26 (8.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGlioma grade 4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6 (50%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e130 (45.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e136 (45.9%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMetastasis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0 (0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e13 (4.6%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e13 (4.4%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003ep\u0026thinsp;=\u0026thinsp;1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLymphoma\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1 (8.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e37 (13.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e38 (12.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003ep\u0026thinsp;=\u0026thinsp;1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAbscess\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1 (8.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5 (1.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e6 (2.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNo diagnosis biopsy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1 (8.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e14 (4.9%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e15 (5.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eToxoplasmosis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1 (8.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3 (1.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e4 (1.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eInflammatory lesions\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0 (0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e21 (7.4%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e21 (7.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003ep\u0026thinsp;=\u0026thinsp;1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOthers\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2 (16.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e20 (7.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e22 (7.4%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eTumoral lesions\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e9 (75.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e242 (85.2%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e251 (84.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003ePeriod 1 (2009\u0026ndash;2016)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5 (41.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e129 (45.4%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e134 (45.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e\u003cp\u003e\u003cstrong\u003ePost-biopsy complication grades were as follows:\u0026nbsp;\u003c/strong\u003egrade 1A, complication visible only on postoperative CT scan (i.e., asymptomatic hemorrhage); grade 1B, transient symptomatic complication that did not require treatment; grade 2, transient symptomatic complication that resolved completely but required treatment; grade 3, persistent neurological deficit \u0026gt; 6 months post-biopsy; and grade 4, biopsy-related death.\u003c/p\u003e\n"},{"header":"4. DISCUSSION","content":"\u003cdiv id=\"Sec14\" class=\"Section2\"\u003e\u003ch2\u003e4.1. Key results\u003c/h2\u003e\u003cp\u003eSeventy-four patients with lesions\u0026thinsp;\u0026lt;\u0026thinsp;10 mm in maximum diameter were compared with 222 matched controls who underwent frame-based stereotactic biopsy. The diagnostic yield did not differ between the groups (91.9% vs. 96%, p\u0026thinsp;=\u0026thinsp;0.2). Overall complication rates were low (4.1%), with no increased risk in the \u0026lt;\u0026thinsp;10 mm group and no severe (\u0026ge;\u0026thinsp;grade 2) events reported in this subgroup. No significant differences were observed between the groups in terms of the rates of symptomatic hemorrhage, seizures, new neurological deficits, or mortality.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec15\" class=\"Section2\"\u003e\u003ch2\u003e4.2. Comparisons with Literature\u003c/h2\u003e\u003cp\u003eOur findings challenge the long-standing empirical principles that have advised against performing biopsies of small intracranial lesions[\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. Recent literature has highlighted lesion size, both on gadolinium-enhanced imaging and FLAIR sequences, as a significant factor associated with non-diagnostic biopsy outcomes[\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e]\u003csup\u003e,\u003c/sup\u003e[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Our results demonstrate that these assumptions are not confirmed and that stereotactic biopsy, when clinically indicated, is entirely feasible for lesions smaller than 10 mm in maximum diameter without any added risk of complications. The diagnostic yield in this subgroup reached 91.9%, which appears broadly comparable to the rates reported in large stereotactic biopsy series (84.3%\u0026ndash;99.3%)[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e, \u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e]. However, in our cohort, the large proportion of biopsied lesions of unknown (non-tumoral) etiology reduces the diagnostic yield, since biopsy is demonstrably less informative in these cases than in biopsies performed for brain tumors[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. Importantly, the occurrence of severe (grade 2 or higher) complications was 0%, highlighting the safety of the procedure and aligning with previous studies[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e, \u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e] that identified predictors of complications, such as lesion location, histopathological diagnosis, and patient age, but not lesion size[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan additionalcitationids=\"CR35\" citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]. In the context of increasingly widespread access to advanced neuroimaging, the growing role of molecular diagnostics, and the contribution of neurosurgery to the work-up of infectious, inflammatory, and systemic diseases, our findings support the consideration of stereotactic biopsy, even in the setting of small-volume lesions.\u003c/p\u003e\u003cp\u003eSeveral techniques can enhance the diagnostic yield and should be employed whenever possible, particularly in challenging cases, such as biopsies of small lesions. Although an established technique, intraoperative histopathological analysis significantly increases diagnostic yield, reducing the rate of non-diagnostic biopsies from 11.1% to 3.7%[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e],, or even eliminating them entirely[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. When performed near the operating room and interpreted by an experienced neuropathologist, intraoperative smears provide a reliable tool for minimizing non-diagnostic biopsies and the need for repeat procedures. Stimulated Raman Histology (SRH) is a label-free optical imaging technique that enables near-real-time hematoxylin\u0026ndash;eosin\u0026ndash;like digital histology directly in the operating room[\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e][\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e]. Early studies have demonstrated its seamless integration into the neurosurgical workflow, producing excellent image quality and high diagnostic accuracy (87.7%)[\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. When combined with artificial intelligence, SRH achieves a performance comparable to that of conventional histopathology (94.6%)[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Fluorescence-guided imaging using 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX or intravenous sodium fluorescein allows real-time visualization of tumor tissue during stereotactic brain biopsies. Multiple studies have demonstrated a strong correlation between fluorescence and the presence of tumor tissue, with high sensitivity and specificity (up to 85\u0026ndash;100%), thereby improving the diagnostic yield and reducing the number of samples required[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e].\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec16\" class=\"Section2\"\u003e\u003ch2\u003e4.3. Stereotactic considerations\u003c/h2\u003e\u003cp\u003ePerforming a stereotactic biopsy of a small intracranial lesion poses significant technical constraints[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. As the target volume decreases, the ability to adjust the intracranial target point becomes increasingly limited, which, in turn, restricts the range of feasible trajectories[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. In this setting, the target itself cannot be modified without risking sampling errors or exiting the lesion, thereby compromising diagnostic yield. Consequently, the only variable that can be adjusted is the entry point, which must be selected in strict adherence to the principles of stereotaxy: avoidance of eloquent cortical areas and vascular structures, optimization of trajectory safety, and preservation of targeting accuracy[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e] (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eThe results of the present study apply specifically to frame-based stereotactic biopsies, as all procedures were performed using the Leksell frame. Therefore, extrapolation to other guidance systems should be approached with caution. Although robot-assisted systems have emerged as promising and reliable alternative[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]\u003csup\u003e,\u003c/sup\u003e[\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e, \u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e], particularly in terms of precision and stability, the applicability of our findings to these systems remains to be validated. However, frameless neuronavigation raises more concerns in this context[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. The existing literature suggests that its accuracy is inferior to that of frame-based and robotic systems[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Moreover, published studies using frameless neuronavigation report larger average lesion diameters\u0026mdash;typically ranging from 36 to 38 mm\u0026mdash;with reported volumes as low as 18 cm\u0026sup3;, making direct comparison to our cohort of sub-10 mm lesions difficult[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e, \u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e, \u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e]. Further dedicated studies are necessary to assess the diagnostic yield and safety of frameless approaches in this specific subset of patients.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec17\" class=\"Section2\"\u003e\u003ch2\u003e4.4. Strengths and Limitations\u003c/h2\u003e\u003cp\u003eThis study has several strengths. First, it directly addresses a long-standing evidence gap by focusing on frame-based stereotactic biopsies of lesions\u0026thinsp;\u0026lt;\u0026thinsp;10 mm and comparing them with a rigorously matched cohort of larger lesions. Matching (1:3) was performed on clinically relevant covariates\u0026mdash;age, lesion location, and contrast enhancement\u0026mdash;drawn from a large institutional series of 2,347 biopsies, which helped mitigate confounding. The procedures were homogeneous (all Leksell frame\u0026ndash;based) with standardized pre- and postoperative imaging, and complications were graded using a predefined validated severity scale. Outcome adjudication by two independent investigators (with third-party resolution of disagreements) further strengthened the internal validity. This study also has some limitations. Its retrospective, single-center design is susceptible to selection and information biases and may limit its external generalizability, particularly to frameless or robotic systems. Baseline imbalances, most notably sex distribution and histopathologic mix, with a higher proportion of non-neoplastic diagnoses in the \u0026lt;\u0026thinsp;10 mm group, could depress diagnostic yield in that subgroup despite matching. The sample size for very small lesions, while substantial for this niche (n\u0026thinsp;=\u0026thinsp;74), still limits the power to detect rare adverse events; consequently, the absence of severe complications in the \u0026lt;\u0026thinsp;10 mm cohort should be interpreted cautiously. Finally, the results pertain to frame-based techniques and may not be extrapolated to alternative guidance platforms without dedicated evaluation.\u003c/p\u003e\u003c/div\u003e"},{"header":"5. Conclusion","content":"\u003cp\u003eFrame-based stereotactic biopsy of intracranial lesions smaller than 10 mm is both safe and diagnostically effective, with outcomes comparable to those of larger lesions. In this matched cohort study, small lesion size did not compromise the diagnostic yield or increase the risk of complications, including symptomatic hemorrhage, seizures, neurological deficits, or mortality. Notably, no severe complications occurred in the \u0026lt;\u0026thinsp;10 mm group. These findings directly challenge long-standing assumptions that discourage biopsy of very small targets and suggest that lesion size alone should not preclude histopathological sampling when clinically indicated. As the role of tissue and molecular characterization continues to expand in neuro-oncology and neuroinflammatory disorders, the evidence provided here supports the integration of stereotactic biopsy into the diagnostic workup of small-volume brain lesions. Further studies are warranted to validate these results across alternative biopsy platforms, including frameless and robotic systems, and to explore strategies for optimizing tissue yield in non-neoplastic cases.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eConflict of Interests\u003c/strong\u003e: The authors declare no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u003c/strong\u003e The authors received no funding for this work.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical approval:\u003c/strong\u003e This study was approved by the Institutional Review Board committee of the French National Neurosurgery Society.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability:\u003c/strong\u003e Anonymized original data from this manuscript will be made available upon reasonable request to the corresponding author.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements:\u003c/strong\u003e None\u003c/p\u003e\nConsent to participate:\n\nAccording to the French law, the need for signed patient consent was waived given the retrospective nature of the study. However, patients were informed about the study and their right to refuse participation.\n\nAuthor contributions:\n\nAll authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Charles-Henry MALLEREAU. The first draft of the manuscript was written by Charles-Henry MALLEREAU and Bertrand MATHON and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.\n\nClinical trial number: not applicable"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eBex A, Mathon B (2022) Advances, technological innovations, and future prospects in stereotactic brain biopsies. Neurosurg Rev 46:5. doi: 10.1007/s10143-022-01918-w\u003c/li\u003e\n\u003cli\u003eDammers R, Haitsma IK, Schouten JW, Kros JM, Avezaat CJJ, Vincent AJPE (2008) Safety and efficacy of frameless and frame-based intracranial biopsy techniques. 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J Neurosurg Pediatr 1\u0026ndash;8. doi: 10.3171/2020.4.PEDS19783\u003c/li\u003e\n\u003cli\u003eLeksell L, Leksell D, Schwebel J (1985) Stereotaxis and nuclear magnetic resonance. J Neurol Neurosurg Psychiatry 48:14\u0026ndash;18. doi: 10.1136/jnnp.48.1.14\u003c/li\u003e\n\u003cli\u003eLi Y, Wu D, Yan F, Wei P, Wang W, Wang Y, Shan Y, Zhao G (2025) Analysis of factors influencing diagnostic yield and target point error in robot-assisted stereotactic brain biopsy: a single-center experience. Neurosurg Rev 48:317. doi: 10.1007/s10143-025-03463-8\u003c/li\u003e\n\u003cli\u003eLim DH, Kim SY, Na YC, Cho JM (2023) Navigation Guided Biopsy Is as Effective as Frame-Based Stereotactic Biopsy. J Pers Med 13:708. doi: 10.3390/jpm13050708\u003c/li\u003e\n\u003cli\u003eLivermore LJ, Ma R, Bojanic S, Pereira EAC (2014) Yield and complications of frame-based and frameless stereotactic brain biopsy--the value of intra-operative histological analysis. Br J Neurosurg 28:637\u0026ndash;644. doi: 10.3109/02688697.2014.887657\u003c/li\u003e\n\u003cli\u003eLouis DN, Perry A, Wesseling P, Brat DJ, Cree IA, Figarella-Branger D, Hawkins C, Ng HK, Pfister SM, Reifenberger G, Soffietti R, von Deimling A, Ellison DW (2021) The 2021 WHO Classification of Tumors of the Central Nervous System: a summary. Neuro Oncol 23:1231\u0026ndash;1251. doi: 10.1093/neuonc/noab106\u003c/li\u003e\n\u003cli\u003eMallereau C-H, Chibbaro S, Ganau M, Benmekhbi M, Cebula H, Dannhoff G, Santin M-N, Ollivier I, Chaussemy D, Hugo Coca A, Proust F, Todeschi J (2022) Pushing the boundaries of accuracy and reliability during stereotactic procedures: A prospective study on 526 biopsies comparing the frameless robotic and Image-Guided Surgery systems. 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Springer US, New York, NY, pp 247\u0026ndash;257\u003c/li\u003e\n\u003cli\u003eMathon B, Riche M, Lombard A, Chabaane M, Roblot P, Boetto J, Marlier B, Mezjan I, Engelhardt J, Delaunois J, Benzagmout M, Corsino da Costa A, Iacoangeli F, P\u0026oacute;czo\u0026scaron; P, Rizzi M (2025) Technical Aspects of Frame-Based Stereotactic Brain Biopsy, Neuronavigation-Assisted Brain Biopsy, and Open Brain Biopsy. In: Mathon B (ed) Brain Biopsies. Springer US, New York, NY, pp 3\u0026ndash;12\u003c/li\u003e\n\u003cli\u003eNeidert N, Straehle J, Erny D, Sacalean V, El Rahal A, Steybe D, Schmelzeisen R, Vlachos A, Reinacher PC, Coenen VA, Mizaikoff B, Heiland DH, Prinz M, Beck J, Schnell O (2022) Stimulated Raman histology in the neurosurgical workflow of a major European neurosurgical center - part A. Neurosurg Rev 45:1731\u0026ndash;1739. doi: 10.1007/s10143-021-01712-0\u003c/li\u003e\n\u003cli\u003eOvercast WB, Davis KM, Ho CY, Hutchins GD, Green MA, Graner BD, Veronesi MC (2021) Advanced imaging techniques for neuro-oncologic tumor diagnosis, with an emphasis on PET-MRI imaging of malignant brain tumors. Curr Oncol Rep 23:34. doi: 10.1007/s11912-021-01020-2\u003c/li\u003e\n\u003cli\u003ePaleologos TS, Dorward NL, Wadley JP, Thomas DG (2001) Clinical validation of true frameless stereotactic biopsy: analysis of the first 125 consecutive cases. Neurosurgery 49:830\u0026ndash;835; discussion 835-837. doi: 10.1097/00006123-200110000-00009\u003c/li\u003e\n\u003cli\u003ePasternak KA, Schwake M, Warneke N, Masthoff M, Zawy Alsofy S, Suero Molina E, Stummer W, Schipmann S (2021) Evaluation of 311 contemporary cases of stereotactic biopsies in patients with neoplastic and non-neoplastic lesions-diagnostic yield and management of non-diagnostic cases. Neurosurg Rev 44:2597\u0026ndash;2609. doi: 10.1007/s10143-020-01394-0\u003c/li\u003e\n\u003cli\u003ePennlund A, Jakola AS, Skoglund T, Ljungqvist J (2022) A single-centre study of frame-based stereotactic brain biopsies. Br J Neurosurg 36:213\u0026ndash;216. doi: 10.1080/02688697.2020.1867704\u003c/li\u003e\n\u003cli\u003eRiche M, Amelot A, Peyre M, Capelle L, Carpentier A, Mathon B (2021) Complications after frame-based stereotactic brain biopsy: a systematic review. Neurosurg Rev 44:301\u0026ndash;307. doi: 10.1007/s10143-019-01234-w\u003c/li\u003e\n\u003cli\u003eRiche M, Lav\u0026eacute; A, Malaiz\u0026eacute; H, Mathon B (2025) Complications Associated with Stereotactic Brain Biopsies. In: Mathon B (ed) Brain Biopsies. Springer US, New York, NY, pp 293\u0026ndash;304\u003c/li\u003e\n\u003cli\u003eRiche M, Marijon P, Amelot A, Bielle F, Mokhtari K, Chambrun MP de, Joncour AL, Idbaih A, Touat M, Do C-H, Deme M, Pasqualotto R, Jacquens A, Degos V, Shotar E, Chougar L, Carpentier A, Mathon B (2022) Severity, timeline, and management of complications after stereotactic brain biopsy. J Neurosurg 136:867\u0026ndash;876. doi: 10.3171/2021.3.JNS21134\u003c/li\u003e\n\u003cli\u003eSchumacher X, Hudelist B, Paun L, Benzakoun J, Demasi M, Hamza M, Roux A, Moiraghi A, Elia A, Parraga E, Dezamis E, Chretien F, Varlet P, Oppenheim C, Pallud J, Zanello M (2025) Prevalence and risk factors of nonyield brain biopsy: a 21-year experience with robot-assisted stereotactic biopsies. J Neurosurg 1\u0026ndash;11. doi: 10.3171/2025.2.JNS242273\u003c/li\u003e\n\u003cli\u003eSciortino T, Fernandes B, Conti Nibali M, Gay LG, Rossi M, Lopci E, Colombo AE, Elefante MG, Pessina F, Bello L, Riva M (2019) Frameless stereotactic biopsy for precision neurosurgery: diagnostic value, safety, and accuracy. Acta Neurochir (Wien) 161:967\u0026ndash;974. doi: 10.1007/s00701-019-03873-w\u003c/li\u003e\n\u003cli\u003eSpyrantis A, Woebbecke T, Constantinescu A, Cattani A, Quick-Weller J, Willems LM, Marquardt G, Seifert V, Freiman TM (2021) Comparison of frame-less robotic versus frame-based stereotactic biopsy of intracranial lesions. Clin Neurol Neurosurg 207:106762. doi: 10.1016/j.clineuro.2021.106762\u003c/li\u003e\n\u003cli\u003eStraehle J, Erny D, Neidert N, Heiland DH, El Rahal A, Sacalean V, Steybe D, Schmelzeisen R, Vlachos A, Mizaikoff B, Reinacher PC, Coenen VA, Prinz M, Beck J, Schnell O (2022) Neuropathological interpretation of stimulated Raman histology images of brain and spine tumors: part B. Neurosurg Rev 45:1721\u0026ndash;1729. doi: 10.1007/s10143-021-01711-1\u003c/li\u003e\n\u003cli\u003eTran S, Bielle F (2025) Management of Brain Biopsy Samples: From Histological Examination to Biobanking and Multi-omic Analysis. In: Mathon B (ed) Brain Biopsies. Springer US, New York, NY, pp 117\u0026ndash;144\u003c/li\u003e\n\u003cli\u003eVychopen M, Wach J, Borger V, Schneider M, Eichhorn L, Maciaczyk J, Bara G, Vatter H, Banat M, Hamed M (2022) Patient Safety Comparison of Frameless and Frame-Based Stereotactic Navigation for Brain Biopsy-A Single Center Cohort Study. Brain Sci 12:1178. doi: 10.3390/brainsci12091178\u003c/li\u003e\n\u003cli\u003eWoodworth GF, McGirt MJ, Samdani A, Garonzik I, Olivi A, Weingart JD (2006) Frameless image-guided stereotactic brain biopsy procedure: diagnostic yield, surgical morbidity, and comparison with the frame-based technique. J Neurosurg 104:233\u0026ndash;237. doi: 10.3171/jns.2006.104.2.233\u003c/li\u003e\n\u003cli\u003eWu S, Wang J, Gao P, Liu W, Hu F, Jiang W, Lei T, Shu K (2021) A comparison of the efficacy, safety, and duration of frame-based and Remebot robot-assisted frameless stereotactic biopsy. Br J Neurosurg 35:319\u0026ndash;323. doi: 10.1080/02688697.2020.1812519\u003c/li\u003e\n\u003cli\u003eXu R, R\u0026ouml;sler J, Teich W, Radke J, Fr\u0026uuml;h A, Scherschinski L, Onken J, Vajkoczy P, Misch M, Faust K (2022) Correlation of Tumor Pathology with Fluorescein Uptake and MRI Contrast-Enhancement in Stereotactic Biopsies. J Clin Med 11:3330. doi: 10.3390/jcm11123330\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"neurosurgical-review","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"nrev","sideBox":"Learn more about [Neurosurgical Review](https://www.springer.com/journal/10143)","snPcode":"10143","submissionUrl":"https://submission.nature.com/new-submission/10143/3","title":"Neurosurgical Review","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"stereotactic techniques, brain biopsy, safety, diagnostic yield, brain tumor, small lesions","lastPublishedDoi":"10.21203/rs.3.rs-8047246/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8047246/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eIntroduction\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eStereotactic brain biopsy is a standard neurosurgical procedure for diagnosing intracranial lesions. Lesion size is often considered a limiting factor; however, the safety and diagnostic yield of biopsies in lesions \u0026lt; 10 mm remain poorly defined. This study evaluated the outcomes of frame-based stereotactic biopsies for lesions \u0026lt; 10 mm in size compared with larger lesions.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe retrospectively analyzed all consecutive adult patients who underwent frame-based stereotactic biopsy for targeted lesions \u0026lt; 10 mm in maximum diameter between April 2009 and April 2024 at our institution. Each case was matched (1:3) with patients with lesions ≥ 10 mm based on age, lesion location, and contrast enhancement. The primary endpoint was diagnostic yield, and the secondary endpoints included complications graded using a validated severity scale.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOf the 2,347 patients who underwent frame-based stereotactic biopsy during the inclusion period, 74 patients (3.2%) with lesions \u0026lt; 10 mm were compared with 222 controls. Among the 296 patients, the overall diagnostic yield was 95%. The diagnostic yields did not significantly differ between the small and large lesion groups (91.9% vs. 96.0%, p = 0.2). Non-tumoral pathology was the main factor associated with non-diagnostic results. Symptomatic complications occurred in 4.1% of patients, with no significant difference between the groups (1.4% vs. 4.9%; p = 0.3). No severe complications occurred in the \u0026lt; 10 mm group. The overall mortality rate was 1.3%, with no mortality in the small-lesion cohort.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFrame-based stereotactic biopsy of lesions \u0026lt; 10 mm is safe and effective, with a diagnostic yield comparable to that of larger lesions and no excess risk of complications. These findings challenge long-standing assumptions discouraging the biopsy of small lesions and support its use when clinically indicated.\u003c/p\u003e","manuscriptTitle":"Diagnostic Performance and Safety of Stereotactic Frame-Based Biopsy for Sub centimeter Intracranial Lesions: A Matched Cohort Analysis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-11-23 11:37:44","doi":"10.21203/rs.3.rs-8047246/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-12-10T23:37:21+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-11-27T18:33:34+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"93763090541477164507000671996132289486","date":"2025-11-25T07:29:52+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-11-24T17:18:01+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"22500914195879938999381477886441233856","date":"2025-11-14T14:44:36+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"92266500639302726168624016995040631208","date":"2025-11-13T19:55:00+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-11-11T21:54:06+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-11-08T23:09:14+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-11-07T08:11:39+00:00","index":"","fulltext":""},{"type":"submitted","content":"Neurosurgical Review","date":"2025-11-06T11:03:06+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"neurosurgical-review","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"nrev","sideBox":"Learn more about [Neurosurgical Review](https://www.springer.com/journal/10143)","snPcode":"10143","submissionUrl":"https://submission.nature.com/new-submission/10143/3","title":"Neurosurgical Review","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"654ad85f-59a2-422c-8d55-f15ef8aac2f2","owner":[],"postedDate":"November 23rd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2026-01-26T16:06:46+00:00","versionOfRecord":{"articleIdentity":"rs-8047246","link":"https://doi.org/10.1007/s10143-025-04079-8","journal":{"identity":"neurosurgical-review","isVorOnly":false,"title":"Neurosurgical Review"},"publishedOn":"2026-01-22 15:58:12","publishedOnDateReadable":"January 22nd, 2026"},"versionCreatedAt":"2025-11-23 11:37:44","video":"","vorDoi":"10.1007/s10143-025-04079-8","vorDoiUrl":"https://doi.org/10.1007/s10143-025-04079-8","workflowStages":[]},"version":"v1","identity":"rs-8047246","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8047246","identity":"rs-8047246","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}