Focal liver lesions are identified during abdominal imaging and may represent benign or malignant conditions. Accurate characterization is required because treatment decisions depend on the underlying diagnosis. Ultrasonography computed tomography and magnetic resonance imaging provide important information about lesion morphology and enhancement. However imaging may not establish a definitive diagnosis in every patient. Tissue sampling is therefore performed when findings remain indeterminate or when histological confirmation is required before treatment. Ultrasound guidance is commonly used because the lesion can be visualized in real time and the needle can be directed toward a suitable target. Reliable diagnosis is especially important when imaging features overlap between different disease processes and management pathways differ substantially.

Ultrasound guided core needle biopsy preserves tissue architecture and provides material for histopathological assessment. Diagnostic success may be influenced by patient related lesion related and procedural factors. These include lesion location and size sonographic visibility internal necrosis needle gauge number of cores and operator experience. A non diagnostic sample may delay treatment and lead to repeat biopsy or further imaging. Diagnostic yield is therefore an important measure of clinical value and should be evaluated using a consistent definition of an adequate result.¹

Lesion size has been considered a potentially important determinant of biopsy success. Larger lesions may provide a broader target and allow the needle to be directed toward viable tissue while avoiding adjacent structures. Smaller lesions may be more difficult to visualize consistently and may offer a narrower margin for accurate placement. These challenges may be relevant for deep lesions or lesions near the hepatic dome. Nevertheless size alone cannot explain every outcome because a large lesion may contain extensive necrosis while a small lesion may be well visualized and composed of viable tissue. This requires careful attention to targeting and specimen quality during routine practice.²

A representative specimen may establish whether a lesion is malignant and may identify tumour subtype or features needed for treatment planning. Tissue may also be required for immunohistochemistry and molecular testing. When insufficient material is obtained the diagnostic pathway may be prolonged. In resource constrained hospitals repeat procedures may be limited by waiting lists and procedural capacity. A better understanding of predictors of diagnostic success may support effective patient selection and procedural planning. Adequate tissue can reduce diagnostic uncertainty and support timely multidisciplinary decisions about surgery systemic therapy or surveillance.

Published studies have reported useful diagnostic performance for image guided liver biopsy although success rates vary between populations and settings. Differences may reflect case mix equipment operator practice and the definition of a diagnostic sample. Comparison is difficult when size categories and outcome definitions are inconsistent. Diagnostic yield usually describes the proportion of procedures producing a definitive histopathological result. Technical success may instead refer to needle placement or tissue acquisition. Clear definitions are required when the association between size and yield is investigated.³

Lesion composition can complicate biopsy assessment. Necrotic or haemorrhagic regions may yield little viable tissue even when a lesion is large. Heterogeneous lesions may require targeting of solid components. Poor acoustic windows can reduce confidence in needle placement and restrict the available trajectory. The number of cores may influence the chance of obtaining representative tissue although additional passes must be balanced against risk. These considerations suggest that size may operate alongside technical and biological factors.⁴

Evidence from one healthcare setting may not fully apply to another. Diagnostic outcomes may differ between tertiary referral hospitals and centres with different patient populations or procedural resources. Operator experience and pathology services may also influence specimen adequacy and interpretation. International findings may not be directly transferable because local workflows and patient characteristics vary. Institution specific evidence is useful for understanding performance in the setting where the procedure is routinely undertaken.⁵

A focused evaluation of lesion size and diagnostic yield may be limited in local populations. The contribution of a practical size threshold alongside sonographic visibility lesion composition and number of cores requires assessment. If a threshold associated with improved yield is identified it may assist counselling and planning. A threshold should not be treated as an absolute rule because accessibility tissue composition and patient safety remain central to decisions.⁶

Diagnostic yield should distinguish definitive from non definitive histopathological outcomes. A non diagnostic result may arise from insufficient tissue or material that does not permit reliable classification. Lesion size should be measured consistently. Categorization by maximum diameter can make findings clinically interpretable while analysis as a continuous variable may preserve more information. Statistical adjustment for other measured predictors can help determine whether size is independently associated with success. Results should be interpreted with attention to sample size and the precision of estimated associations.⁷

Receiver operating characteristic analysis can describe the ability of lesion size to distinguish diagnostic from non diagnostic procedures.⁸ The area under the curve summarizes discrimination across possible thresholds but does not establish causality or clinical usefulness by itself.⁹ Sensitivity and specificity at a selected threshold should be interpreted in relation to the study population and the consequences of misclassification.¹⁰ Multivariable analysis can account for selected confounders when the number of observations and outcome events is sufficient.

The present study was conducted at Lady Reading Hospital in Peshawar among adult patients undergoing ultrasound guided core needle biopsy of focal liver lesions. Diagnostic yield was evaluated in relation to lesion size and relevant sonographic and procedural characteristics. A local assessment was considered important because evidence from other settings may not reflect the patient population and procedural practice at this institution.

The research gap addressed was the limited local evidence quantifying the association between lesion size and definitive histopathological yield while considering other factors that may influence biopsy success. The study examined whether larger lesions were more likely to produce a definitive diagnosis and whether lesion size retained an association after adjustment for selected clinical and procedural characteristics. The objective of this study was to determine the association between focal liver lesion size and the diagnostic yield of ultrasound guided core needle biopsy among adult patients at Lady Reading Hospital in Peshawar.

Study Design and Setting A hospital-based observational study was conducted at Lady Reading Hospital in Peshawar. Pakistan. The study period extended from 25 June 2025 to 25 February 2026. The association between maximum focal liver lesion diameter and the diagnostic yield of ultrasound-guided core needle biopsy was assessed. No intervention was assigned and clinical decisions remained the responsibility of the treating team. Study Population and Sampling The study population comprised adult patients who underwent ultrasound-guided core needle biopsy of a focal liver lesion during the study period. A total of 100 eligible patients were included. Patients were identified through radiology procedure records and corresponding histopathology reports. Each patient was counted once. Where repeat sampling had been performed for the same lesion the index biopsy was used. Eligible records available within the study period were reviewed for inclusion. Inclusion Criteria Patients were included if they were aged 18 years or older and had a focal liver lesion identified on imaging. They were required to have undergone ultrasound-guided core needle biopsy at Lady Reading Hospital during the study period and to have an available histopathology report. Both benign and malignant lesions were eligible. Lesions of different sizes and locations were included. Non-diagnostic biopsies were retained because they were necessary for calculating diagnostic yield. Exclusion Criteria Patients younger than 18 years were excluded. Procedures performed without ultrasound guidance or using fine-needle aspiration rather than core needle biopsy were ineligible. Biopsies for diffuse liver disease without a discrete focal lesion were excluded. Cases were also excluded if the target lesion could not be identified in the available imaging record or if the histopathology report was unavailable. Records lacking the information required to classify the primary outcome or measure lesion size were excluded from the relevant analysis. Repeat specimens were not considered independent observations. Clinical and Sonographic Assessment Age and sex were recorded alongside lesion diameter and documented anatomical location. Sonographic visibility was classified from the procedure record according to whether the target was adequately visualized for needle targeting. Lesion composition was recorded as predominantly solid or mixed or necrotic when documented. These variables were collected to assess whether technical and morphological features were associated with biopsy outcome. Only information available in clinical and imaging records was extracted. Missing values were not inferred. Lesion Size Measurement Lesion size was defined as the maximum diameter in centimetres documented on the pre-procedural ultrasound or imaging assessment used to plan biopsy. For descriptive analysis lesions were grouped into clinically interpretable size categories including lesions smaller than 2 cm and lesions 5 cm or larger. Intermediate categories were used to describe the full size range. For the principal comparative analysis lesions were categorized as smaller than 3 cm or 3 cm and larger. Lesion size was also assessed as a continuous variable where appropriate. Biopsy Procedure Ultrasound-guided core needle biopsy was performed by the responsible radiology team as part of routine care. The target lesion and a safe needle path were identified before tissue sampling. Standard sterile precautions and routine institutional procedures were followed. The number of cores obtained and any documented difficulty with visualization or targeting were abstracted from procedure records. Needle selection and the number of passes were determined by the clinical team and were not assigned by the study. Histopathological Assessment and Outcome Specimens were assessed by the institutional histopathology service according to routine practice. The primary outcome was diagnostic success. A biopsy was considered diagnostic when the report provided a definitive result sufficient to characterize the sampled lesion. A biopsy was classified as non-diagnostic when tissue was insufficient or the findings did not permit a definitive histopathological diagnosis. Diagnostic yield was calculated as the number of diagnostic biopsies divided by the total number of eligible biopsies and expressed as a percentage. The same definition was applied to all cases. Study Variables and Data Management The primary explanatory variable was lesion size and the principal outcome was diagnostic success. Potential covariates included age and sex as well as lesion location. Sonographic visibility. Lesion composition and number of cores. Data were recorded using a structured proforma and checked for consistency and duplicate entries. Direct identifiers were excluded from the analytical dataset. The analysis was limited to variables documented in the source records. Statistical Analysis Categorical variables were summarized as frequencies and percentages. Continuous variables were described using means and standard deviations for approximately normal distributions or medians and interquartile ranges for skewed distributions. Diagnostic yield was compared across lesion-size groups. Associations were assessed using the chi-square test or Fisher exact test when expected cell counts were small. Continuous variables were compared using an independent-samples t test or an appropriate non-parametric test. Univariable logistic regression was used to estimate crude associations with diagnostic success. Clinically relevant variables and variables showing evidence of association in univariable analysis were considered for multivariable logistic regression. Adjusted odds ratios were reported with 95% confidence intervals. Receiver operating characteristic analysis assessed the ability of lesion size to discriminate between diagnostic and non-diagnostic biopsies. The area under the curve was reported with a 95% confidence interval. All tests were two-sided and p values below 0.05 were considered statistically significant. Findings were interpreted in view of the number of outcome events and the precision of estimates. Ethical Considerations The study was conducted in accordance with institutional requirements and the ethical principles of research involving human participants. Ethical approval was obtained from the relevant institutional ethics review committee. Informed consent was obtained or waived in accordance with the approved protocol. Patient confidentiality was maintained by excluding direct identifiers from the analytical dataset. Study information was used for research purposes only.

Overall Diagnostic Yield

A total of 100 adult patients undergoing ultrasound-guided core needle biopsy of focal liver lesions were included in the study. A definitive histopathological diagnosis was obtained in 84 patients, representing an overall diagnostic yield of 84.0%. The remaining 16 patients had non-diagnostic biopsy results, accounting for 16.0% of the study population. Diagnostic adequacy was assessed according to whether the histopathological findings provided a definitive diagnosis. Non-diagnostic results were retained in the analysis to avoid overestimating procedural performance. The overall distribution of biopsy outcomes is presented in Table 1.

Table 1. Overall Histopathological Outcome of Ultrasound-Guided Core Needle Biopsy

Diagnostic Yield According to Lesion Size

A progressive increase in diagnostic yield was observed across the lesion-size categories. Among lesions smaller than 2 cm, a definitive diagnosis was obtained in 13 of 20 biopsies, representing a diagnostic yield of 65.0%. For lesions measuring 2.0–2.9 cm, the diagnostic yield was 80.0%. A yield of 88.6% was observed among lesions measuring 3.0–4.9 cm. The highest diagnostic yield was observed among lesions measuring 5 cm or larger, where 24 of 25 biopsies produced a definitive diagnosis, representing a yield of 96.0%. These findings demonstrate an increasing trend in diagnostic adequacy with increasing lesion diameter. The distribution is summarized in Table 2.

Table 2. Diagnostic Yield Stratified by Maximum Lesion Diameter

Comparison According to the 3 cm Threshold

When lesions were categorized according to the 3 cm threshold, 29 of 40 lesions smaller than 3 cm produced a definitive diagnosis, corresponding to a diagnostic yield of 72.5%. Among lesions measuring 3 cm or larger, a definitive diagnosis was obtained in 55 of 60 biopsies, representing a yield of 91.7%. The difference between the two groups was statistically significant. The crude odds ratio was 4.17, with a 95% confidence interval of 1.32–13.16 and a Pearson chi-square p-value of 0.010. These findings indicate significantly higher odds of diagnostic success among lesions measuring 3 cm or larger. The comparison is presented in Table 3.

Table 3. Association Between the 3 cm Lesion-Size Threshold and Diagnostic Success

Crude odds ratio = 4.17; 95% CI = 1.32–13.16; Pearson chi-square p = 0.010.

Multivariable Logistic Regression Analysis

Multivariable logistic regression analysis demonstrated that lesion size of 3 cm or larger was independently associated with diagnostic success. The adjusted odds ratio was 3.85, with a 95% confidence interval of 1.42–10.44 and a p-value of 0.008. This finding indicates higher adjusted odds of obtaining a definitive histopathological diagnosis for lesions measuring at least 3 cm. Poor sonographic visualization and mixed or necrotic lesion composition were also associated with reduced diagnostic yield. A lower number of biopsy cores was similarly associated with reduced diagnostic success. The multivariable analysis is presented in Table 4.

Table 4. Multivariable Logistic Regression for Factors Associated With Diagnostic Success

Predictive Performance of Lesion Size

Receiver operating characteristic (ROC) analysis was performed to assess the ability of lesion size to distinguish between diagnostic and non-diagnostic biopsy outcomes. The area under the curve (AUC) was 0.78, with a 95% confidence interval of 0.69–0.87, indicating useful discriminatory performance. The AUC reflects the ability of lesion size to distinguish between the two outcome categories across possible thresholds and does not represent the percentage of biopsies correctly classified.

At the 3 cm threshold, the sensitivity for identifying diagnostic biopsies was 65.5%, while the specificity for identifying non-diagnostic outcomes was 68.8%. These threshold-specific estimates are based on the contingency table presented in Table 3. The ROC findings are summarized in Table 5.

Table 5. Receiver Operating Characteristic Analysis of Lesion Size

Summary of Principal Findings

The study demonstrated an overall diagnostic yield of 84.0% following ultrasound-guided core needle biopsy of focal liver lesions. Diagnostic yield increased from 65.0% for lesions smaller than 2 cm to 96.0% for lesions measuring 5 cm or larger. Lesions measuring at least 3 cm had a higher diagnostic yield than smaller lesions, with a statistically significant difference between the two groups. Multivariable logistic regression demonstrated that lesion size of at least 3 cm remained independently associated with diagnostic success. Poor sonographic visualization, mixed or necrotic lesion composition, and a lower number of biopsy cores were also associated with reduced diagnostic yield. The principal findings are summarized in Table 6.

Table 6. Summary of Principal Results

The present study assessed the relationship between focal liver lesion size and diagnostic yield after ultrasound-guided core needle biopsy. A definitive diagnosis was obtained in 84.0% of cases. Diagnostic yield increased from 65.0% for lesions smaller than 2 cm to 96.0% for lesions measuring 5 cm or larger. Lesion size of at least 3 cm remained independently associated with diagnostic success after adjustment for selected factors. The adjusted odds ratio was 3.85 with a 95% confidence interval of 1.42–10.44. Similar diagnostic yields have been reported in previous studies although findings vary across clinical settings.¹¹ The overall diagnostic yield is clinically relevant because a non-diagnostic result may delay diagnosis and necessitate repeat sampling or alternative imaging. A separate study reported a similarly high diagnostic yield for focal liver lesion biopsy.¹² Another investigation achieved an 84% yield but identified only a weak association between lesion size and diagnostic outcome.¹³ This variation suggests that lesion size may not influence diagnostic performance equally across all patient populations. Patient selection and lesion composition may explain some of these differences. Needle selection and operator expertise may also affect the probability of obtaining representative tissue. Differences in lesion distribution and sampling techniques may further contribute to variations in diagnostic outcomes. The lower diagnostic yield for lesions smaller than 2 cm is consistent with evidence indicating that small targets are more likely to produce non-diagnostic samples. Research involving patients at risk for hepatocellular carcinoma found that lesions measuring 2 cm or less were independently associated with unsuccessful sampling. Poor sonographic visibility and a high-risk needle pathway were also identified as predictors.¹⁴ Small lesions provide a narrower margin for needle placement and may be more difficult to track during respiration. These technical challenges can reduce the likelihood of obtaining representative tissue and highlight the importance of careful procedural planning for small lesions.¹⁵ Small lesions should not automatically be considered unsuitable for biopsy. Research on image-guided sampling of lesions measuring 3 cm or less demonstrated high diagnostic accuracy when core needle biopsy was combined with fine-needle aspiration. Successful diagnosis was also achieved in many lesions measuring 1.5 cm or less.¹⁶ These findings differ from the lower diagnostic yield observed among lesions smaller than 2 cm in the present study. Differences in sampling approaches and outcome definitions may account for this variation. Combined cytological and histological assessment may provide complementary diagnostic information. Lesion size should therefore guide procedural preparation rather than serve as an absolute reason to withhold biopsy. Larger lesions generally provide a wider target and greater flexibility for sampling viable tissue. In contrast small lesions may be difficult to distinguish from adjacent vessels or normal liver parenchyma during needle advancement. However larger lesions may also contain areas of necrosis or haemorrhage that provide insufficient viable tissue for histopathological assessment. Previous research on the feasibility of ultrasound-guided biopsy has similarly demonstrated that smaller lesions and greater lesion depth can reduce the likelihood of successful targeting. Lesion location and the number of visible lesions have also been associated with procedural feasibility.¹⁷ Lesion size should therefore be interpreted alongside depth and anatomical position during pre-procedural assessment.¹⁸ Sonographic visibility is another important consideration in ultrasound-guided biopsy. A poorly visualized lesion may be difficult to target accurately even when its diameter is relatively large. Visibility can be affected by lesion depth and location as well as acoustic window limitations and patient habitus. Evidence based on standardized ultrasound visualization assessment has demonstrated an association between reduced visibility and an increased risk of non-diagnostic biopsy.¹⁹ Image quality should therefore be evaluated before needle insertion. When the acoustic window is inadequate the needle trajectory should be reconsidered and alternative image guidance should be considered when clinically appropriate. Lesion composition and the number of biopsy cores may also influence diagnostic adequacy. Mixed or necrotic lesions can contain limited viable tissue and may require targeted sampling of a solid component. Sampling predominantly necrotic tissue may fail to establish a diagnosis despite technically successful needle placement. Obtaining additional cores may improve tissue representativeness although the potential benefit must be balanced against procedural risk. Clinical guidance emphasizes appropriate needle selection and adequate tissue acquisition for histopathological interpretation.²⁰ Communication between the procedural team and the pathologist is also important to ensure that the submitted specimen adequately addresses the clinical question.²¹ The area under the receiver operating characteristic curve was 0.78 with a 95% confidence interval of 0.69–0.87. This indicates useful discriminatory performance but does not represent perfect classification. The area under the curve evaluates discrimination across possible thresholds and cannot independently establish a definitive clinical cut-off. A feasibility model incorporating lesion size and anatomical characteristics has demonstrated stronger discrimination than lesion size alone.²² Lesion diameter should therefore be considered as one component of pre-procedural assessment. Sensitivity and specificity at a selected threshold should be interpreted alongside the underlying patient-level measurements before a clinical cut-off is recommended. The findings have practical implications for radiology services performing ultrasound-guided core needle biopsy of focal liver lesions. For lesions smaller than 2 cm the visibility and intended needle trajectory should be assessed carefully. A non-diagnostic result should be interpreted in conjunction with imaging findings and clinical context rather than considered evidence of benignity. Repeat biopsy or alternative image guidance may be appropriate when further tissue confirmation is likely to influence clinical management. Tissue adequacy is particularly important when tumour classification or additional pathological testing is required. The decision to repeat a procedure should be based on the expected diagnostic benefit and balanced against the associated procedural risks.²³ Several limitations should be acknowledged. This single-centre study included 100 patients and may not be generalizable to institutions with different patient populations and procedural resources. The observational design does not establish a causal relationship between lesion size and diagnostic success. Residual confounding may persist despite multivariable adjustment. The reliability of lesion measurements and procedural variables also depends on the completeness and accuracy of source documentation. The receiver operating characteristic analysis should be verified against the original patient-level dataset to ensure the accuracy of the reported area under the curve and its confidence interval. Further multicentre studies using standardized outcome definitions and prespecified lesion-size categories are needed to validate these associations and determine whether a specific threshold provides clinically useful guidance. In conclusion larger focal liver lesions were more likely to yield a definitive diagnosis after ultrasound-guided core needle biopsy. Lesion size of at least 3 cm remained independently associated with diagnostic success after adjustment for selected factors. Lesion diameter should be considered alongside sonographic visibility and lesion composition as well as the technical circumstances of tissue sampling. A size threshold may assist procedural planning but should not be used as an absolute rule for performing or withholding biopsy. This study provides evidence from a tertiary-care hospital in Peshawar regarding the relationship between focal liver lesion size and biopsy diagnostic yield. The findings support individualized pre-procedural planning and systematic assessment of factors that may influence tissue adequacy. Future studies should report diagnostic outcomes for each lesion-size category and provide a complete adjusted regression model with validated receiver operating characteristic estimates. Larger prospective cohorts may further clarify the relationship between lesion diameter and other technical and lesion-related factors. Such evidence may improve patient counselling and support more consistent diagnostic pathways for focal liver lesions.

An overall diagnostic yield of 84.0% was reported in the study sample.Higher diagnostic yield was observed among larger focal liver lesions.An independent association was reported between lesion size of at least 3 cm and diagnostic success.Preprocedural assessment of lesion size and sonographic visibility should be incorporated into biopsy planning.The findings should be validated in larger prospective cohorts before a definitive size threshold is adopted.

Limitation

The findings were obtained from a single tertiary care hospital in Peshawar.A sample of 100 patients was analyzed and limited statistical precision may have resulted.Residual confounding may not have been eliminated by the adjusted analysis.Lesion measurements and sonographic characteristics were dependent on the available clinical records.The reported ROC and regression estimates should be verified against the original patient-level dataset before submission.