Ultrasound Techniques for Suspected Malignant Pleural Effusion and Nonexpandable Lung

Abstract

The diagnosis of exudative pleural effusions can be challenging; this is particularly true for malignant pleural effusion (MPE). Current diagnostic algorithms are inadequate. Because of the low sensitivity of pleural fluid cytology, individuals with suspected MPE often require further invasive procedures. This underscores the importance of noninvasive tools for the prompt workup of MPE. Advances in ultrasound technology have improved diagnostic capabilities for various malignancies, but its role in the workup of MPE is yet to be established. This review explores the potential of various ultrasound techniques as a noninvasive tool for the workup of suspected MPE.

Pleural effusion is a common clinical problem with a wide range of causes, the most frequent being cardiac failure and pulmonary infection.¹ Determining the underlying diagnosis can be challenging, and individuals often undergo multiple invasive investigations. Among the differential diagnoses, malignant pleural effusion (MPE) is a frequent cause,2, 3, 4 with > 150,000 new cases estimated annually in the US.³ MPE reflects advanced cancer and is associated with poor prognosis,^5,6 with a median survival from 4 to 9 months.^7,8

The diagnostic process of suspected MPE involves performing investigations to confirm or exclude the diagnosis, within the shortest possible timeframe. The current algorithm involves imaging with chest radiograph (CXR), CT scan, or thoracic ultrasound (TUS) followed by thoracocentesis and cytologic examination of pleural fluid. The low sensitivity of pleural fluid cytology, detecting malignancy in only about 60% of cases,⁹ represents a significant limitation to the current approach. Consequently, a large proportion of individuals with suspected MPE require further invasive procedures to obtain a diagnosis. In many centers, the next step is thoracoscopy, which is often a more invasive surgical intervention.^9,10 These procedures carry heightened risks, and access may be limited, therefore further delaying diagnosis and any potential treatment. Increasingly, molecular profiling and biomarker testing are required to guide oncologic therapy, further driving the need for adequate and representative tissue samples beyond what cytology alone is often able to provide.

Nonexpandable lung (NEL), encompassing both lung entrapment and trapped lung, refers to the inability of the lung to fully reexpand after pleural fluid drainage because of visceral pleural restriction or parenchymal/airway processes.^11,12 NEL is a common finding in MPE¹³ and has been associated with worse outcomes in this population; however, its presence alone does not always indicate malignancy.^14,15 NEL has important clinical implications because pleurodesis is unlikely to be successful in the presence of impaired pleural apposition, thereby limiting therapeutic options. The ability to identify the presence of NEL before the procedure may save the individual time and unnecessary procedures. However, current diagnostic approaches typically identify NEL after pleural drainage, highlighting the need for reliable, noninvasive methods for preprocedural assessment.

There have been significant advancements in ultrasound imaging technology over the past few decades. Ultrasound techniques using motion mode (M-mode), elastography, and contrast-enhanced ultrasound (CEUS) were initially introduced for other indications,16, 17, 18 but have more recently been investigated for their potential role in evaluating pleural effusions.

This narrative review examines the role of various ultrasound techniques in the diagnostic workup of MPE.

Literature Search

A structured literature search was conducted in Ovid Medline (1946 to August 2025), Embase (1947 to August 2025), and the Cochrane Library (1995 to August 2025) to identify studies relevant to the use of TUS in the diagnostic evaluation of suspected MPE. Search terms relating to ultrasound and MPE were combined using the Boolean operators, and the detailed search strategy is provided in Table 1. The search focused on human studies published in English, and prioritized studies evaluating the use of TUS in the differential diagnosis of MPE, including NEL, lung entrapment, or trapped lung in association with MPE. Studies in which TUS was used solely for procedural guidance as an adjunct for therapeutic purposes were not considered relevant to the primary focus of this review. Review articles, conference abstracts, and case reports/series were not included in the primary synthesis but were examined where relevant for contextual discussion.

Table 1.

Key Search Terms

Key Search Terms	Ultrasound	Differential Diagnosis	Malignant Pleural Effusion
Synonyms and related terms	Ultrasonography/ultrasound∗	Diagnosis, Diagnos∗	Pleural effusion, Malignant Malignant pleural effusion∗ Trapped lung∗ Non-expandable lung∗ Entrapped lung∗ Lung entrapment∗
Query string	exp ultrasonography/ OR ultrasound∗ AND diagnosis/ OR “diagnos∗ AND Pleural Effusion, Malignant/ OR “malignant pleural effusion∗” OR “trapped lung∗” OR “non-expandable lung∗” OR “entrapped lung∗” OR “lung entrapment∗”

The search identified 720 articles, of which 11 studies were considered most relevant to the focus of this review. The study selection process is illustrated in Figure 1.

Figure 1.

Flow diagram of the literature search and study selection.

Evidence Review

The included studies comprised prospective single-center or multicenter studies, observational studies, and a retrospective study. There were no randomized controlled trials identified. Where specified, MPEs were associated with a range of malignancies, including lung primaries (predominantly adenocarcinoma), mesothelioma, and metastatic malignancies such as breast cancer. Although several studies included nonmalignant pleural effusions (NMPEs) secondary to conditions such as heart failure, infection, or inflammatory conditions within their comparator groups, the underlying tumor type and alternative causes of effusion were not consistently reported or analyzed in relation to imaging findings across studies. The key findings and limitations of each study are summarized in Table 2, with additional relevant literature that informed the broader discussion summarized in Table 3.

Table 2.

Summary of Articles Included in the Final Analysis

Study	Study Design	Ultrasound Mode	Comparison	Cohort Size	Effusion Presentation	Key Findings	Limitations
Qureshi et al19	Prospective single-center study	B-mode	N/A	52	Unilateral	Pleural thickening > 1 cm, presence of pleural nodularity, and diaphragmatic thickening > 7 mm were strongly suggestive of malignancy. TUS had an overall sensitivity of 79% and a specificity of 100%, and a PPV of 100% and NPV of 73% for the differentiation of malignant from benign effusions.	Small sample size Single observer with limited TUS experience Potential observer bias
Bugalho et al20	Prospective observational study	B-mode	N/A	133	Unilateral or Bilateral	TUS had an overall sensitivity and specificity of 80.3% and 83.6%, respectively, and a PPV and NPV of 82.8% and 81.2%, respectively. In pleural effusions of unknown etiology, US morphologic characteristics such as pleural and diaphragmatic nodularity can aid in differentiating MPE from NMPE. No finding was pathognomonic of MPE.	Single-center study; findings require further confirmation in a multicenter trial.
Fjaellegaard et al21	Prospective observational pilot study	B-mode	Standard imaging (predominantly CT scan)	55	Unilateral	Supplementary results suggest that in setting without prior chest CT scans, positive swirling sign, pleural thickening, or nodules and lung consolidation most likely to be tumor and suspected hepatic metastasis have a high specificity for malignancy. However, in a setting where chest CT scans often are available at referral, additional upfront, systematic TUS had limited clinically relevant effect on the planned diagnostic workup in patients with unilateral pleural effusion.	Study was not powered to bear a subgroup analysis in patients without available chest CT scans. TUS operators were not blinded to imaging, blood tests, or other diagnostics performed before inclusion; potential for confirmation bias. Vague definition of trapped lung, based on subjective assessment of underlying lung and not on patient symptoms during drainage and postprocedural radiograph or movement of the compressed lung at breath-hold on M-mode.
Shehata et al22	Prospective single-center cohort study	B-mode	CT scan	54	Unspecified	TUS and CT scan showed no significant difference in detecting parietal pleural abnormalities, lung lesions, chest wall invasion, or liver metastasis. TUS significantly outperformed CT scan in detecting diaphragmatic pleural thickening ≥ 10 mm (33.3% vs 6.1%; P < .001) and diaphragmatic pleural nodularity (45.5% vs 3%; P < .001). CT scan was superior to US at detecting mediastinal pleural thickening (48.5% vs 15.2%; P= .002). Diaphragmatic nodularity on US has a sensitivity of 45.5% and specificity of 100%, and mediastinal thickening on CT scan had a sensitivity of 48.5% and specificity of 90.5% for MPE.	Small sample size—limits statistical power and generalizability. Effect of operator experience on diagnostic performance of TUS and CT scan was not assessed and could have influenced the results. Interobserver variability was not assessed; could affect reproducibility and reliability of results. Performance of TUS and CT scan in detecting septations and complex morphology within pleural effusions, which could have complementary roles in assessing effusion complexity and internal architecture, were not analyzed or compared.
Jiang et al23	Prospective single-center cohort study	Ultrasound Elastography, B-mode	N/A	244	Unilateral or Bilateral	Ultrasound elastography quantitatively assesses tissue stiffness by measuring distortion from shear waves. Because tumor tissue is stiffer than normal, it is a valuable tool for distinguishing malignant from benign disease. A mean elasticity index of 47.25 kPa had a sensitivity of 83.64%, a specificity of 90.67%, a PPV of 86.79%, an NPV of 88.31% for diagnosing MPE. The sensitivity of ultrasound elastography was significantly higher than that of TUS.	Single-center study with small sample size; may impact determination of elasticity cutoff indices.
Nielsen et al24	Prospective single-center cohort study	B-mode, SWE	N/A	34	Unilateral	B-mode TUS index test (inclusive of the following: diaphragmatic nodules, diaphragmatic thickening > 7 mm, pleural thickening > 1 cm, visible tumors, or consolidations suspicious of malignancy) yielded a sensitivity of 28.57% and a specificity of 90.62%. The SWE maximum of the intercostal space yielded a sensitivity of 100% and a specificity of 59.09%. Integration of TUS and SWE shows potential for identifying MPE in the emergency department and improving referrals for the diagnostic workup of underlying malignancy.	Small sample size because of inclusion process depending on emergency physicians to inform the investigator; limits statistical power. Only 13 of 33 patients yielded analyzable results for SWE because of equipment limitations, operator competence, breath-holding difficulties and unassessable tissues. No healthy control patients for regions of interest such as pleural effusion and lung consolidation because of pathology/inaccessible nature of tissue.
Taymour et al25	Prospective single-center cohort study	B-mode, SWE	N/A	36	Unilateral or bilateral	SWE can significantly predict a malignant pleural effusion, with a SWE cutoff of ≥ 54.2 kPa giving a sensitivity and specificity of 94.4%, a positive and negative predictive value of 94.4%, respectively, and a diagnostic accuracy of 94%. Quantitative and qualitative assessment of pleural and parenchymal lesions using a combination of both conventional TUS (B-mode) and SWE can result in high diagnostic accuracy.	Small sample size may have affected the determination of cutoff elasticity values for SWE. Not all metastatic lesions were included in the study because of the inherent condition of available cases.
Petersen et al26	Prospective single-center cohort study	M-mode, B-mode, 2-D SWE	N/A	49	Unspecified	M-mode measurements of lung movement demonstrated the best diagnostic performance, achieving a receiver operating characteristic curve result with an area under the curve of 0.81 with strong internal validity. M-mode measurement of lung movement shows potential in diagnosing NEL before thoracentesis in patients with known or suspected MPE.	Single-center, small sample size; not powered to explore the number of participants needed. Lack of operator reliability limits validity of the study. Further validation needed.
Salamonsen et al27	Prospective multicenter cohort study	M-mode, elastography/STI strain analysis	Pleural manometry	81	Unspecified	Entrapped lung shows significantly reduced motion and strain (deformation) compared with nonentrapped lung because of less readily transmitted cardiac impulse, and is identifiable with ultrasonography.	Identification of isolated lower lobe entrapment can be difficult, and some patients may have been misclassified. An out-of-plane motion of the atelectatic lung through the 2-D ultrasound image can cause incorrect analysis by the software as tissue deformation, resulting in false negatives. However, this problem can be overcome by 3-dimensional STI.
Bajad et al28	Prospective single-center cohort study	M-mode	Pleural manometry	30	Unspecified	Absent sinusoidal sign on lung ultrasound had a sensitivity of 78.6% and specificity of 100% in identifying entrapped lung. An absent sinusoidal sign on predrainage lung ultrasound and raised pleural elastance in pleural manometry during thoracentesis are accurate predictors of entrapped lung in MPE. Lung ultrasound may serve as a useful, noninvasive bedside tool for early identification of NEL.	Small sample size limits generalizability. Single observer for TUS—no assessment of interobserver variability. Broad inclusion criteria may reduce specificity.
Safai Zadeh et al29	Retrospective single-center study	CEUS	N/A	83	Unspecified	Markedly enhanced pleural thickening and inhomogeneous enhanced lung consolidation were significantly associated with malignancy and may differentiate MPE from NMPE. Subgroup analysis supported the use of CEUS and B-mode to cytology for evaluation of pleural effusions with unknown etiology.	Retrospective nature of study. Ultrasound operators and interpreters were not blinded, potentially resulting in selection bias.

2-D = 2-dimensional; B-mode = brightness mode; CEUS = contrast-enhanced ultrasound; M-mode = motion mode; MPE = malignant pleural effusion; N/A = not applicable; NEL = nonexpandable lung; NMPE = nonmalignant pleural effusion; NPV = negative predictive value; PPV = positive predictive value; STI = speckle imaging tracking; SWE = shear wave elastography; TUS = thoracic ultrasound; US = ultrasound.

Table 3.

Summary of Additional Articles Not Included in the Review

Study	Type of Study	Ultrasound Technique/Mode	Cohort Size	Presentation (eg, Unilateral/Bilateral Effusion)	Key Findings	Limitations
Shiroshita et al30	Systematic review of 7 studies	B-mode	N/A	N/A	The specific combination of pleural nodularity, including parietal, somatic pleural nodules, and diaphragmatic nodules had high specificity and moderate overall quality of evidence for MPE. The presence of pleural nodularity on ultrasound can increase the pretest probability of MPE, justifying repeat thoracocentesis or other invasive procedures. The morphologic findings of TUS were not useful as a ruling-out test. However, pleural nodularity on TUS could motivate us to proceed with repeat thoracentesis or other invasive procedures when MPE is suspected.	TUS is operator-dependent and a relatively new module. Physicians and ultrasonographers require further education and experience to popularize the use of TUS. There are concerns regarding the applicability of pleural nodularity in patients in endemic areas because pleural TB can be visualized as pleural nodules on CT scan. Publication bias could not be assessed.
Marcun et al31	Prospective case series	B-mode	40	Unspecified	TUS is a useful bedside tool for the differential diagnosis of pleural effusion with unknown origin. A complex septated pattern is most common in a specific nonmalignant etiology (ie, TB), whereas a complex fibrous pattern is more suggestive of malignant disease.	Single-center study, small sample size. TUS was performed by 1 investigator; there was a potential for operator bias.
Khatim et al32	Case report	M-mode	1	Unilateral effusion	In the presence of NEL, M-mode revealed decreased lung displacement from transmitted cardiac impulse, illustrating reduced cardiophasic variability.	Case report—results may not be reproducible, and limited possibility of generalizing the validity of the study.

B-mode = brightness mode; M-mode = motion mode; MPE = malignant pleural effusion; N/A = not applicable; NEL = nonexpandable lung; TUS = thoracic ultrasound.

Brightness Mode

Brightness mode (B-mode) imaging, or B-mode ultrasound, is the most fundamental and common imaging mode. In B-mode, a linear array of transducers scan a plane simultaneously through the body, translating the information into a 2-dimensional image.³³ Specifically, in thoracic imaging, B-mode ultrasound provides detailed images of the pleura, detects the presence of any pleural fluid, and can also visualize part of the underlying lung parenchyma (Fig 2).

Figure 2.

Brightness mode ultrasound image demonstrating a loculated and heavily septated malignant pleural effusion. The parietal pleura is abnormally thickened, and the collapsed lung is visible deep to the effusion. E = malignant pleural effusion; L = lung; P = parietal pleura.

Across 3 prospective cohort studies evaluating the use of B-mode TUS in the differential diagnosis of MPE,19, 20, 21 morphologic features such as pleural thickening, nodularity, and diaphragmatic involvement were consistently associated with malignancy, with reported sensitivities ranging from 79% to 80.3% and specificities up to 100% for distinguishing malignant from pleural effusions. Supporting literature from a systematic review by Shiroshita et al³⁰ suggests that although other individual morphologic characteristics reported in the review had low sensitivity and a wide range of specificity for MPE, pleural nodularity has high specificity with moderate overall quality evidence for MPE.

Only 1 study incorporated a comparator imaging modality. In a direct comparison study, Shehata et al²² found no significant difference between TUS and CT scan in detecting parietal pleural abnormalities, lung lesions, or chest wall invasion; however, each modality demonstrated differing strengths in identifying site-specific pleural involvement, with TUS being preferable for assessing diaphragmatic pleural involvement and CT scan being preferable for mediastinal involvement.

Included studies evaluated heterogenous patient populations, ranging from those with clinical suspicion of malignancy to patients with pleural effusions of unknown etiology. For example, Qureshi et al¹⁹ evaluated patients with suspected MPE, whereas Bugalho et al²⁰ and Fjaellegaard et al²¹ included patients with undiagnosed pleural effusions referred for diagnostic workup.

Overall, findings across the studies demonstrate consistent associations between specific B-mode morphologic characteristics and MPE which may support differentiation of MPEs from NMPEs within the diagnostic workup of pleural effusions of unknown etiology.

Elastography

Ultrasound elastography, or shear wave elastography (SWE), is a novel ultrasound technique that assesses tissue stiffness quantitatively by measuring distortions caused by the application of an external force (shear waves). Because tumor tissue is stiffer than normal tissue, SWE can be used to distinguish between malignant (Fig 3) and benign disease (Fig 4).

Figure 3.

Shear wave elastography performed on an area of abnormally thickened parietal pleura from the same individual in Figure 2, showing areas of high stiffness (dark red) consistent with malignant pleural infiltration.

Figure 4.

Shear wave elastography performed on parietal pleura of an individual with a benign cause of pleural effusion (congestive cardiac failure), showing low stiffness values (blue).

Across 3 prospective cohort studies23, 24, 25 evaluating the diagnostic abilities of SWE for MPE, reported sensitivities ranged from 83.6% to 100% and specificities ranged from 59.1% to 94.4%; however, elasticity cutoff values and ultrasound acquisition protocols varied between studies. Specifically, studies used differing regions of interest and reported stiffness using alternative parameters, including shear wave velocity (m/s) or tissue elasticity (kPa), reflecting variability in SWE measurement techniques across cohorts. Jiang et al²³ demonstrated that at the specified cutoff values, SWE demonstrated higher sensitivity for diagnosing MPE than B-mode findings of pleural thickening and nodules, because SWE overcomes the diagnostic limitations of morphologic features often being absent in patients, by assessing pleural stiffness instead. In the remaining studies, SWE findings were evaluated against either conventional TUS findings or final clinical diagnoses, with no direct comparison against alternative imaging modalities reported.

Although SWE has established diagnostic applications in breast,³⁴ thyroid,³⁵ and liver disease,^36,37 its role in pleural pathology remains investigational, with evidence derived from a small number of studies and variability in measurement approaches across cohorts.

M-Mode

M-mode is one of the earliest sonographic techniques, originally developed for cardiac imaging.³⁸ It records the motion of structures along a single ultrasound line over time, producing a trace that allows quantification of movement and displacement (Fig 5).³⁹ It is already established in pleural imaging, where a characteristic seashore sign confirms normal lung sliding, whereas a barcode/stratosphere sign indicates absent lung sliding, such as in the case of pneumothorax.⁴⁰

Figure 5.

A, B, Motion mode ultrasound. A, Seashore sign of normal lung sliding. B, Barcode sign indicating absence of lung sliding in an individual with prior pleurodesis.

Two prospective cohort studies evaluated the use of M-mode in identifying NEL in patients with suspected pleural effusions.^26,27 Salamonsen et al²⁷ reported that total movement and strain (deformation) were significantly reduced in NEL, with speckle imaging tracking (STI) strain analysis demonstrating a sensitivity of 71% and specificity of 85%, and M-mode demonstrating a sensitivity of 50% and specificity of 85%. These findings suggest that reduced transmission of cardiac impulse on M-mode and STI strain analysis may be indicative of NEL before an intervention.

Petersen et al²⁶ compared M-mode, B-mode, and 2-dimensional SWE in the diagnosis of NEL, and found that M-mode lung movement measurements demonstrated superior diagnostic performance for identifying NEL, achieving the best diagnostic receiver operating characteristic curve results (area under the curve, 0.81). Across both cohorts, ultrasound findings were evaluated against pleural elastance measured by pleural manometry, with no direct comparison made against alternative imaging modalities.

Notably, the studies differ significantly in study design and protocol. In Salamonsen et al,²⁷ measurements were obtained using specialized strain analysis techniques, performed by operators experienced in this method, which may limit wider applicability in routine clinical practice. In contrast, Petersen et al²⁶ used an M-mode protocol that was more readily implemented by operators with basic proficiency in B-mode and M-mode.

In the context of pleural effusion, the absence of a sinusoidal pattern from respiratory movement of an atelectatic lung within surrounding pleural fluid indicating expandable lung, referred to as the sinusoid sign was previously hypothesized by Wong et al⁴¹ as a marker of NEL. This was corroborated by Bajad et al,²⁸ who demonstrated that the absence of a sinusoidal sign may be predictive of NEL. Identifying NEL has significant clinical relevance because pleurodesis, which is a common management approach for MPE, may be contraindicated when significant NEL is present.⁴²

Pleural manometry during thoracentesis has frequently been used to aid the diagnosis of NEL43, 44, 45; however, this approach identifies the condition only after drainage of the effusion. However, findings from a randomized controlled trial by Lentz et al⁴⁶ suggested that routine use of pleural manometry may not confer additional clinical benefit. In this context, CXR and CT scan both play pivotal roles in identifying NEL findings. Although CXR is commonly used, its reliability is limited by interobserver variability,⁴⁷ and CT imaging is more reliable in this aspect for assessing pleural apposition because it can more clearly delineate pleural thickening, loculations, and residual pneumothorax.^11,48 However, CT scan is less practical for routine use because of cost, radiation, and access constraints. This highlights ongoing uncertainty regarding the optimal diagnostic approach for NEL, and underscores the need for further evaluation of adjunctive imaging modalities that may assist in identifying NEL.

Contrast-Enhanced Ultrasound

CEUS has an established role in lesion characterization by allowing visualization of blood vessels and perfusion through microbubble contrast agents that are administered to the patient intravenously.⁴⁹ Specifically, CEUS helps to visualize different vascularization patterns of pleural thickening and allows focal lesions in lung to be identified, assisting in differentiating between malignant and benign causes of pleural effusion of unknown etiology.

One study²⁹ investigated the use of CEUS in differentiating MPE and NMPE. The study demonstrated that enhanced pleural thickening and inhomogeneous enhanced consolidation of the lung visualized on CEUS were significantly associated with malignancy. In individuals who had initial negative cytology but reasonable clinical suspicion of MPE, CEUS resulted in an increase in sensitivity to 92.3% and specificity to 90% for MPE. However, the study was limited by its retrospective design, potential selection bias, and lack of operator blinding.

Although the role of CEUS is relatively established in differentiating benign and malignant focal liver lesions,^50,51 its diagnostic capabilities in pleural pathology remain investigational. The European Federation of Societies for Ultrasound in Medicine and Biology guidelines⁵² acknowledge the potential utility of CEUS in evaluating lung lesions, including differentiation of benign from malignant disease and assessment of embolic consolidations. However, the guidelines emphasize that published studies are few and involve small patient cohorts, and the overall diagnostic value of CEUS in this setting has yet to be established. Similarly, a systematic review by Jacobsen et al⁵³ suggests that although CEUS may aid in differentiating MPE from NMPE based on enhancement patterns, current evidence is derived from small, heterogeneous studies, and its diagnostic performance in routine clinical practice for thoracic applications, especially in noninterventional applications, remains uncertain. As such, CEUS is currently considered an investigational adjunct to standard diagnostic approaches pending further evaluation with prospective studies.

Limitations

Although TUS holds potential as a noninvasive diagnostic tool for MPE, several considerations limit its clinical utility. A main limitation of TUS is its highly operator-dependent nature. Across the studies discussed, the operators’ skill levels were not consistently defined or discussed. TUS performance and interpretation of results relies on the experience of the ultrasonographer,⁵⁴ which can lead to significant operator bias and interobserver variability, and consequently influence interpretability of results. This underscores the need for standardized training and a robust ultrasound protocol, particularly for novel ultrasound techniques (M-mode, elastography, and CEUS). Second, ultrasound techniques have a limited field of view. Therefore, imaging the entire hemithorax or field of interest can be significantly time-consuming.

Most of the studies discussed, except for the study by Salamonsen et al,²⁷ reported small sample sizes and were conducted at single centers, limiting generalizability and statistical power in assessing the clinical utility of TUS in the current diagnostic algorithm. Furthermore, the paucity of studies evaluating specialized ultrasound modalities reflects their emerging role and underscores the imperative for further research to clarify their clinical utility.

Diagnostic performance is influenced by the characteristics of the study population and the underlying prevalence of MPE, which determine the pretest probability of disease. For example, some studies evaluated patients with clinical suspicion of malignancy, whereas others included patients with undiagnosed pleural effusions referred for diagnostic workup. Studies conducted in selected populations with a higher pretest probability of malignancy may therefore overestimate the diagnostic accuracy of TUS-based modalities, limiting the applicability of these findings to broader clinical settings.

Although several studies have evaluated the diagnostic capabilities of individual TUS modalities, few have directly compared these modalities against reference standards. As shown in Table 2, most included studies assessed diagnostic performance of TUS techniques against a final clinical diagnosis rather than directly comparing TUS with a gold standard diagnostic modality. Only a minority of studies included direct comparators, such as CT scan in Shehata et al.²² Several studies explored multimodal ultrasound approaches (eg, elastography alongside B-mode, as in Jiang et al²³ and Taymour et al²⁵), with findings suggesting a potential complementary role of combining ultrasound techniques. However, these approaches were not evaluated against an established comparator within the same cohort. The lack of direct comparisons between ultrasound modalities and established imaging alternatives, together with the variability in study design, ultrasound protocols, and outcome definitions across studies limits meaningful interpretation of the relative diagnostic performance of TUS. Therefore, further prospective studies incorporating direct modality comparisons are required to clarify the relative diagnostic utility of TUS modalities for the evaluation of MPE.

Heterogeneity in the definition and classification of NEL across studies also presents a challenge in interpreting the results. NEL is often defined in the literature using differing radiographic, manometric, and procedural (postdrainage behavior) criteria.^47,55 Variability in diagnostic thresholds and reference standards across studies may therefore influence reported results and limit comparability between modalities.

Tumor biology and malignancy type determine the patterns of pleural involvement and likelihood of effusion formation,⁵⁶ which in turn influence the pretest probability of MPE and diagnostic performance of imaging modalities. Molecular characteristics, including driver mutations in lung adenocarcinoma for example, may also affect disease behavior and patterns of pleural spread,⁵⁷ and conditions such as lung adenocarcinoma often require adequate tissue acquisition for molecular profiling to guide oncologic management. Conversely, in NMPE, accurate identification of the underlying etiology such as heart failure, infection, or inflammatory conditions remains essential to guide appropriate management. These factors should be considered when interpreting ultrasound findings in the broader clinical context because TUS alone cannot reliably distinguish between malignant and benign causes of pleural effusion. Integration with cytologic, histologic, and molecular analyses therefore remains pivotal in establishing a definitive diagnosis.

Future Directions

Further studies are warranted to establish the reproducibility and validity of current findings and to better define the advantages of the various ultrasound techniques, particularly given the high cost of implementing some of these advanced modalities.

These studies should investigate the diagnostic capabilities of the respective TUS modes with a comparator (eg, contrast-enhanced computed tomography (CECT) scan) and establish standardized pleural ultrasound protocols for emerging ultrasound techniques (ie, ultrasound elastography, M-mode and STI strain analysis, CEUS) while identifying the most appropriate reporting parameters, and quantitative indices to enable reproducible and comparable results. Moreover, the potential to combine different ultrasound modes could be explored to increase the sensitivity and/or specificity for detecting MPE. Additional studies investigating other promising modalities (eg, ultrasound Doppler^58,59), which have demonstrated utility in diagnosing other malignancies, are also needed to establish their role in diagnostics for MPE. Correlating these techniques with improved clinical outcomes (eg, reduced time to diagnosis, fewer interventions, reduced hospital length of stay) would be a compelling reason for broader adoption and acceptance.

With further investigation, these techniques may be of enough clinical value to be implemented into international practice guidelines for pleural disease.^5,60,61 For instance, in a new pleural effusion with high likelihood of malignancy, assessment of the presence of NEL using M-mode may be performed to determine whether the individual may be suitable for upfront pleurodesis, or be more suitable for simple thoracentesis or indwelling pleural catheter. Similarly, elastography may assist in targeting upfront pleural biopsy at the time of initial drainage, in an effusion without classic B-mode characteristics of an MPE. CEUS is the least developed technique, and may be helpful in the workup of a peripheral pleural lesion where the probability of malignancy is equivocal, and may for instance support surveillance of a lesion where the risks of an invasive procedure are substantial.

Summary

Advanced TUS techniques may offer additional insights in the evaluation of MPE and NEL. However, the current evidence base remains limited by small, heterogenous studies, and their role within existing diagnostic pathways remains to be clearly defined. At present, TUS modalities are best considered adjuncts to standard diagnostic investigations, and further high-quality studies are required to clarify their clinical utility and whether incorporation into routine practice may improve diagnostic pathways or clinical outcomes.

Financial/Nonfinancial Disclosures

None declared.