The role of ultrasonography in differential diagnosis of orbital lesions

Abstract

Aims

The aim of this study is to assess the value of ultrasound in the differential diagnosis of orbital lesions.

Methods

One hundred and thirty-eight patients with clinical features of an orbital mass were examined by orbital ultrasound prior to undergoing surgery, from January 2000 to January 2017. All patients underwent excisional or incisional orbital biopsy. The results of orbital ultrasonography were compared with the final histological diagnosis.

Results

Orbital lesions were localized by ultrasonography in 133/138 cases (96.4%); the false-negative rate of orbital echography was 3.6% (5/138). The nature of the orbital lesions was correctly determined by ultrasonography in 54.3% of the cases (75/138) preoperatively (true positives). In 58/138 (42%) patients, there was no correspondence between the ultrasound diagnosis and the histological diagnosis (false positives). The sensitivity of orbital ultrasonography for the detection of an orbital mass was 93.75% (CI 87.87–99.63%), while the specificity yielded no meaningful result (CI 0.00–60.24%). Moreover, the specificity of orbital ultrasonography to identify a malignant tumor falls within a CI of 0–62.72%.

Conclusions

Orbital ultrasonography is a rapid and noninvasive test that is highly sensitive in displaying an orbital mass; however, the specificity in the differential diagnosis of orbital lesions is not meaningful, particularly if malignancy is suspected. The assessment of orbital diseases requires multiple diagnostic approaches to balance the strengths and weaknesses of each method.

Introduction

Ultrasonography (US) is a relatively low cost, noninvasive, and well-tolerated first-line diagnostic technique, which provides highly informative images in real time [1]. It is an operator-dependent procedure requiring technical skills and expertise to achieve reliable results and avoid possible diagnostic pitfalls. US is widely used in ophthalmology for ocular and orbital pathology assessments [2]. Indeed, the “cystic-like” anatomy of the eye constitutes a favorable interface for US transduction and subsequent mechanical-to-electronic signal transformation, allowing for the evaluation of various orbital abnormalities, including tumor and tumor-like orbital masses [3].

Second- and third-line diagnostic techniques, such as computed tomography (CT) and magnetic resonance imaging (MRI), provide more information than US in characterizing expansive masses arising from the orbit, including precise lesion location and extension, shape of the mass, involvement of adjacent structures, and radiologic characterization of different tumor patterns [4]. Although MRI has greater specificity for orbital diseases, a CT scan is more frequently used, particularly for urgent evaluation and when MRI is contraindicated. These last two modalities are complementary to each other, whereas US is generally used as a quick noninvasive diagnostic tool to rule out the presence of an orbital lesion [5], with color Doppler US (CD-US) being used as an additional US tool for the evaluation of an orbital mass’s inner vascularization [6].

Against this background, we aimed to evaluate the role of US in the differential diagnosis of orbital diseases, retrospectively analyzing US results in a large cohort of patients who underwent surgery and subsequent confirmation of the nature of the pathological mass.

Materials and methods

A retrospective chart review was conducted on all the adult patients who were referred to the Orbital Unit of the University of Naples Federico II from January 2000 to January 2017 and who underwent US examination before orbital biopsy as part of their preoperative assessment. We included 164 patients with a unilateral orbital mass, who were examined by US as the only imaging prebiopsy modality. Patients were considered eligible when they had clinical data available, complete US photographic documentation, and pathological results. Patients with missing data/documentation and/or younger than 18 years were excluded from the study.

Data on best-corrected visual acuity, biomicroscopy of the anterior segment, fundus examination, and intraocular pressure, as well as clinical history, were collected for all patients.

Orbital US was performed using a Cinescan S Ophthalmic Ultrasound System (Cinescan S, Quantel Medical SA, Le Brezet, France) with an 8–10–20 MHz transducer in A- and B-scan modes. Two different experienced ultrasonographers performed A-mode and B-mode orbital US and CD-US. The examination was conducted with the patient placed in a supine position, with closed eyes covered with gel (sterile ophthalmic methylcellulose). The transducer was positioned directly on the eyelid. Grey-scale images of soft tissues were obtained in transverse, longitudinal, and anteroposterior planes. If abnormal traces were found during the basic examination, further quantitative, topographical, and kinetic criteria were subsequently applied [7, 12].

Quantitative US is based only on standardized A-scan ultrasound, providing information on the internal structure, reflectivity, and attenuation of orbital lesions. Different lesions have different quantitative US characteristics, ranging from regular and homogeneous lesions, such as lymphomas or carotid-cavernous fistulas, to less regular and heterogeneous masses, such as lymphangiomas or cavernous hemangiomas. The internal reflectivity of an orbital lesion can be correlated with its histological features (typically higher in cavernous hemangiomas and lower in lymphomas).

Topographic ultrasound is based on both A- and B-scan US. It provides information on the margins, shape, and location of the lesion. Margins are more clearly defined in capsulated lesions (for example, cavernous hemangiomas or orbital cysts) as well as in carotid-cavernous fistulas, in which it will be possible to highlight with extreme precision the walls of the dilated ophthalmic veins. Conversely, poorly defined margins are typical of malignant infiltrating lesions. The shape may be round, with an irregular or digitiform shape, such as the one observed in some arteriovenous malformations.

Finally, kinetic US provides information on vascularization and flow dynamics, with absent spontaneous movements in the case of cavernous hemangiomas (due to “stagnant” blood in internal vessels) or rapid movements and chaotic flow in the case of carotid-cavernous fistulas [8, 9].

Therefore, recorded US findings included quantitative, topographical, and kinetic examinations; a positive result was defined as the presence of an expansive mass within highly reflective orbital tissues.

Features of orbital US were then correlated with the final diagnosis of the orbital mass as determined by incisional or excisional biopsy.

Different orbital diseases were identified with each of those methods and classified into various categories: idiopathic orbital inflammation/lymphomas, vascular lesions, cavernous hemangiomas, cystic lesions, carotid-cavernous fistulas, lacrimal gland tumors, meningiomas, metastases, rhabdomyosarcomas, melanomas, frontoethmoidal mucoceles, and histiocytosis X.

Statistical analysis was performed with MedCalc 12 (MedCalc software bvba). Sensitivity and specificity were calculated to assess the ability of orbital US to discriminate orbital lesions based on the final diagnosis as ascertained by biopsy and were reported with a 95% confidence interval.

Results

Of the 164 patients who underwent US for the evaluation of orbital disease, 138 patients met the inclusion criteria and were enrolled in the study (mean age: 52 years; SD 13.8).

The orbital mass was localized with only US in 133/138 cases (96.4%). Five out of 138 patients (3.6%) were US false negatives, with mass presence further assessed with second-line techniques. The suspected diagnosis at US was confirmed by the pathological report in 75/138 cases (54.3%) preoperatively (true positives). In 58/138 (42%) patients, there was no correspondence between US diagnosis and histological diagnosis (false positives). US sensitivity in the detection of orbital masses was 93.75% (CI 87.87–99.63%), while the specificity was 0.00% (CI 0.00–60.24%) (Table 1).

Table 1.

Sensitivity and specificity of US in detecting orbital lesions in our patients cohort

	Sensitivity	Specificity
Idiopathic orbital inflammation/lymphoma	67.50% (CI 50.87–81.43%)	82.65% (CI 73.69–89.56%0
Vascular lesion	44.44% (CI 13.70–78.80%)	93.02% (CI 87.17–96.76%)
Cavernous haemangioma	50% (CI 18.71–81.29%)	94.53% (CI 89.06–97.77%)
Cystic lesion	59.09% (CI 36.35–79.29%)	95.69% (CI 90.23–98.59%)
Carotidcavernous fistula	100% (CI 66.37–100%)	93.35% (CI 90.15–98.27%)

Out of the 75 cases in which there was agreement between US and pathology, 17 (23%) patients were diagnosed as having idiopathic orbital inflammations, 11 (14%) lymphomas, 12 (16%) cystic lesions, 9 (12%) carotid-cavernous fistulas, 5 (7%) cavernous hemangiomas, 4 (5%) vascular lesions, 4 (5%) meningiomas, 3 (4%) metastases, 3 (4%) lacrimal gland tumors, 3 (4%) mucoceles, 2 (3%) melanomas, and 2 (3%) other lesions. An example of US-pathology correlation is shown in Fig. 1.

Fig. 1.

Example of US-pathologic correlation (cavernous angioma)

Out of the 58 patients in which US failed in raising the correct suspicion, 10 (17%) patients were misdiagnosed as having idiopathic orbital inflammations, 6 (10%) lymphomas, 9 (15.5%) vascular lesions, 7 (12%) cavernous hemangiomas, 6 (10.4%) carotid-cavernous fistulas, 6 (10.5%) cystic lesions, 4 (7%) lacrimal gland tumors, 3 (5.1%) meningiomas, 2 (3%) rhabdomyosarcomas, 1 (1.5%) metastases, 1 (15%) melanomas, and 4 (6.5%) other lesions. An example of misdiagnosis is shown in Fig. 2.

Fig. 2.

Example of misdiagnosis at US (orbital pseudotumor)

In analyzing US diagnostic accuracy, the sensitivity of orbital US in diagnosing idiopathic orbital inflammation/lymphomas was 67.50% (CI 50.87–81.43%), and the specificity was 82.65% (CI 73.69–89.56%). For vascular lesions, the sensitivity and specificity were 44.44% (CI 13.70–78.80%) and 93.02% (CI 87.17–96.76%), respectively; for cavernous hemangiomas, 50% (CI 18.71–81.29%) and 94.53% (CI 89.06–97.77%); for cystic lesions, 59.09% (CI 36.35–79.29%) and 95.69% (CI 90.23–98.59%); and for carotid-cavernous fistulas, 100% (CI 66.37–100%) and 93.35% (90.15–98.27%).

Among the true positives, 58 were benign lesions and 17 malignant orbital masses, while among the false positives, 48 were benign lesions and 10 malignant tumors. Therefore, the sensitivity of orbital US to recognize a benign lesion was 96.06% (CI 86.18–97.94%), and the specificity was 0.00% (CI 0.00–27.44%). The sensitivity to identify a malignant tumor was 77.27% (CI 59.63–94.91%), and the specificity was 0.00% (CI 0.00–62.72%).

Finally, idiopathic orbital inflammation/lymphomas incorrectly diagnosed by echography resulted in 5/16 (31%) cases from metastases in histology. In 3/16 cases a cavernous hemangioma was not diagnosed, in 2 cases an epithelial lacrimal gland tumor was not diagnosed, and in 6 cases a predominant histological diagnosis was not found. Patients with a US diagnosis of vascular lesions had in 4/9 (45%) cases histological results of idiopathic orbital inflammations/lymphomas, in 3/9 cases cystic lesions, and in 1 case a rhabdomyosarcoma. Cavernous hemangiomas were in 4/7 (57%) cases schwannomas and in 2/7 cases cystic lesions, while in one case there was an inconclusive pathological diagnosis. Carotid-cavernous fistulas were idiopathic orbital inflammations in 50% of the cases (3/6); in 1/6 cases a lacrimal gland tumor and in 2/6 patients histology was negative. Cystic lesions were in 33% of the cases (2/6) hemangiopericytomas.

Discussion

The orbit is a small anatomical region; however, it is composed of a wide variety of structures and different tissues, which may give rise to many types of benign and malignant lesions. Therefore, preoperative assessment by resorting to different imaging techniques is crucial for surgical planning [10].

CT and MRI are highly informative tools for the characterization of orbital lesions, providing information on the shape, margin, and volume of the lesions, as well as on the involvement of adjacent structures [4, 11]. Both CT and MRI, however, have some limitations, such as the need for sedation or general anesthesia, especially in the pediatric population; intravenous contrast injection; and relatively limited availability due to high cost. Conversely, US and CD-US are noninvasive techniques, normally well tolerated and easy to perform by specialized and trained personnel [12], with high diagnostic accuracy and good reproducibility. CD-US is also useful in discriminating between vascular and avascular tumors by quantitatively and qualitatively assessing the intralesional blood flow, and it can be further improved using contrast-enhanced techniques such as contrast-enhanced ultrasound (CEUS) [13, 14]. When suspicion of a malignant orbital mass with the invasion of adjacent structures and functional limitation is raised at clinical and instrumental examinations, US can be rapidly used as a first diagnostic approach to orienting the most appropriate instrumental work-up in guiding biopsy [15–17].

Our results suggest that the diagnostic accuracy of orbital US is only 54.3%, resulting in low reliability for this examination, particularly when a malignancy needs to be ruled out. Indeed, the sensitivity of orbital US to recognize a benign lesion was 96.06% (CI 86.18–97.94%), and the specificity was 0.00% (CI 0.00–27.44%); the sensitivity to identify a malignant tumor was 77.27% (CI 59.63–94.91%), and the specificity was 0.00% (CI 0.00–62.72%). These figures clearly show that US can well demonstrate and localize an orbital lesion but is not able to provide useful information on the nature of the lesion itself.

However, US proved to be a highly sensitive tool for localizing orbital masses, making it a useful tool for initial noninvasive assessment or, in an emergency setting, for ruling out the presence of an orbital mass, as in the differential diagnosis of thyroid disease [18, 19], orbital inflammations, and orbital tumors. In addition, it is a valid procedure to guide intraoperatively biopsy or fine-needle aspiration [20, 21].

Possible limitations of our study include the retrospective study design and the limited availability of second-line techniques for a comparison of the results. The main strength of this study is represented by the large number of patients who underwent US and by the histological examination of the lesions identified.

Although radiological imaging tools are improving [22], with each imaging pattern having its own differential diagnosis, orbital lesions often pose a diagnostic challenge [23]. To provide an accurate, specific, and sufficiently comprehensive diagnosis and to optimize clinical management and estimate prognosis, pathological examination of a tissue biopsy is essential [24]. Although tests capable of replacing the histological examination are lacking, our study shows that orbital US may serve as a noninvasive adjunct to clinical diagnosis to confirm and localize an orbital mass; however, it cannot provide a specific diagnosis.

The evaluation of orbital diseases requires multiple approaches. Enhancing the accuracy of US by resorting to CEUS [25], and combining these techniques with CT and MRI scans can highly contribute to the preoperative assessment for the biopsy of orbital lesions. Moreover, association with a good medical history will help us to establish the correct diagnosis, confirmed by biopsy [26].

Author contributions

All Authors make substantial contributions to conception and design, and/or acquisition of data, and/or analysis and interpretation of data according to ICMJE recommendations. All those who have made substantive contributions to the article have been named as Authors.

Funding

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Data availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.