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Year : 2020  |  Volume : 2  |  Issue : 1  |  Page : 38

Orbital biopsy: Is it worth it? a 10-year review

Department of Ophthalmology, Centro Hospitalar Universitário Lisboa Norte; Ophthalmology University Clinic, Faculdade de Medicina de Lisboa, Portugal

Date of Submission14-Sep-2020
Date of Decision26-Oct-2020
Date of Acceptance16-Nov-2020
Date of Web Publication10-Dec-2020

Correspondence Address:
Dr. Patricia Jose
Department of Ophthalmology, Centro Hospitalar Universitário Lisboa Norte, Avenida Professor Egas Moniz, 1649-035 Lisboa
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/pajo.pajo_50_20

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Purpose: The purpose of the study was to evaluate the contribution of orbital biopsy for the management of patients with an orbital mass of unknown etiology using the Greenwich Grading System (GGS).
Methods: This was a retrospective case series conducted at a tertiary hospital over a period of 10 years (2007–2017). Case records of all patients with an orbital mass were reviewed. All relevant data collected from the medical records electronic database were analyzed. The GGS was used to assess the contribution of orbital biopsy for the diagnosis, investigation, and treatment of each patient.
Results: Ninety-two medical records were reviewed; 34 patients underwent orbital biopsy. The mean age was 53 ± 26 years and 58.7% were female. In the biopsied group, the most common histopathological diagnoses were lymphoma (44.1%), nonspecific orbital inflammation (14.4%), and squamous cell carcinoma (8.8%). After the biopsy, a new diagnosis was obtained in 41.2%, although in most patients (58.8%), the biopsy confirmed the suspected diagnosis. Regarding the therapeutic management, 32.4% started a new treatment, 29.4% did not change their treatment, 32.4% altered/stopped their treatment, and 5.9% allowed reassurance and explanation for the patients.
Conclusions: Orbital biopsy was considered a valuable investigation for the management of patients with an orbital mass of unknown etiology. In most cases (58.8%), the result of the biopsy confirmed the suspected diagnosis, and in around 41.2%, a new diagnosis was made. Most of the patients (64.8%) changed their treatment or started a new one based on the histopathological result.

Keywords: Greenwich Grading System, histopathological result, orbital biopsy

How to cite this article:
Jose P, Barão RC, Matos DB, Pinto F, Fonseca AC, Teixeira F. Orbital biopsy: Is it worth it? a 10-year review. Pan Am J Ophthalmol 2020;2:38

How to cite this URL:
Jose P, Barão RC, Matos DB, Pinto F, Fonseca AC, Teixeira F. Orbital biopsy: Is it worth it? a 10-year review. Pan Am J Ophthalmol [serial online] 2020 [cited 2021 Nov 27];2:38. Available from: https://www.thepajo.org/text.asp?2020/2/1/38/303004

  Introduction Top

Orbital diseases often present as serious ophthalmic emergencies. If the disease is not treated promptly, permanent sight-threatening complications, as the optic nerve compression and severe corneal exposure, may occur.[1],[2],[3]

Different types of neoplastic and nonneoplastic lesions can affect the orbit causing ocular damage. The reported frequencies of the different types of orbital lesions vary greatly in the literature.[4],[5],[6] Despite the differences, we learned from these major reviews that the differential diagnosis of an orbital mass should include lesions of vasculogenic, cystic, neurogenic, mesenchymal, lymphoproliferative, secondary orbital, or metastatic origin.[1],[4],[5],[6],[7],[8]

The heterogeneity of orbital diseases often poses great diagnostic difficulty to the ophthalmologists. In some cases, the diagnosis can be made on the ground of clinical and radiological findings.[3] When a diagnosis cannot be made confidently on these grounds, a histopathological analysis is needed and an orbital biopsy is required to achieve the definitive diagnosis.[7],[8] Even when a presentation strongly suggests a specific diagnosis, the result of a biopsy may reveal a surprising tissue diagnosis.[1]

Biopsy of a mass implies tissue sampling for histopathologic examination. Orbital biopsy techniques include excisional, incisional, core and aspiration. Anteriorly located and well-delineated tumors can be totally excised and provide ample tissue material for histopathological examination. Incisional biopsy material provides a moderate amount of tissue for pathological examination which is usually obtained from mid or posterior orbit. Infiltrating tumors can be sampled by multiple incisional biopsies. It is easier to reach the mid- and posterior orbit with core or fine-needle aspiration biopsy (FNAB) techniques, but these methods provide a limited amount of tissue.[7]

The Greenwich Grading System (GGS) was developed to quantify the contribution of an investigation to the overall management of a patient.[9] Previously, it has been used to assess the role of electrophysiology tests in adults[9]/children[10] and also to assess the role of temporal artery biopsy with suspected giant cell arteritis.[11]

The aim of this study was to evaluate the orbital biopsy contribution for the management of an orbital mass using the GGS.

  Methods Top

This was a retrospective single-center observational study. All patients with an orbital mass referred to the orbital section of ophthalmology department at a tertiary hospital between July 2007 and July 2017 were included in the study. Medical records were reviewed and collected patient's clinical details including age, sex, medical history, suspected diagnosis, imaging examinations (ophthalmic ultrasound [US], magnetic resonance imaging [MRI] and/or computed tomography [CT scan]), histopathological result, and orbital biopsy complications. Patient's selection for biopsy depended on age, past medical history, symptoms, and characteristics of the orbital mass like (1) rapidly progressive growth; (2) poorly defined/infiltrative margins; (3) compression of orbital structures with consequent visual functional deficit, diplopia, and severe pain; and (4) proptosis with corneal exposure. If patients were very elderly with poor performance status, a biopsy was not undertaken. In cases with a history of metastatic cancer in which imaging features were characteristic of orbital metastasis, the biopsy was also deferred.

Our study was conducted according to the Declaration of Helsinki. Written informed consent was obtained from all the patients prior to orbital biopsy.


The lesion location was defined by “anterior vs posterior” and “intraconal vs extraconal.” The orbit is divided into intraconal and extraconal spaces. The posterior limit of the globe was used as the cutoff point to distinguish between anterior and posterior lesions. The histopathological diagnoses were broadly divided into four groups: malignant tumors, benign tumors, cystic lesions, and inflammatory diseases.

The Greenwich Grading System

The GGS was used to quantify the contribution of orbital biopsy for the diagnosis, investigation, and treatment, as depicted in [Table 1]. From this, an overall value of orbital biopsy for the management of each patient was established by taking the highest score in the above three categories.
Table 1: Greenwich Grading System for assessing the value of an investigation in the management of a patient

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Concordance between the provisional diagnosis and/or clinical details on the referral and the histopathological result was assessed. A change in diagnosis meant a change from the provisional diagnosis to a postorbital biopsy diagnosis. A new diagnosis meant that a postorbital biopsy diagnosis was made when no initial provisional diagnosis had been made. Patients who repeated orbital biopsy were reviewed to identify the reason for repeat testing and whether subsequent biopsies resulted in a change to the initial diagnosis. The investigation was considered useful if a decision was made from the orbital biopsy (i.e., either Grade 3 – essential, Grade 2 – important, or Grade 1 – helpful).

Data description and statistical analysis were performed using statistical software, Statistical Package for the Social Sciences (SPSS, Inc., Chicago, IL, USA) version 23.0.

  Results Top

A total of 92 patients' medical records were reviewed. The mean age was 53 ± 26 years and 58.7% were female. Baseline characteristics are depicted in [Table 2].
Table 2: General demographics of patients with orbital lesions

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Provisional diagnoses were made on the ground of clinical presentation and imaging results in the nonbiopsied group. Patients who were selected for biopsy had a definite diagnosis made by the histopathological result. From the 92 patients, an orbital biopsy was performed in 34 (37.0%). About 11.8% repeated biopsy due to inconclusive histopathologic findings.

Clinical details of orbital biopsies are presented in [Table 3]. Nearly 79.4% were in the extraconal compartment of the orbit, 14.7% were intraconal, and 5.9% had both intra- and extraconal location. Most biopsies were excisional (67.6%); in 10 patients (29.4%), incisional biopsy was performed, and in 1 case (2.9%), we used FNAB. The anterior orbital biopsy was more frequent (82.4%) and the remaining patients had mid/posterior orbital biopsies.

The most common complaints in the biopsied group included proptosis (32.4%) and a palpable or visible mass (29.4%), as seen in [Table 4], and in the nonbiopsied group, complaints were proptosis (44.8%) and decreased visual acuity/visual field loss (29.3%).
Table 3: Clinical details of orbital biopsies

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Table 4: Symptoms of patients with an orbital mass

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The diagnosis comparison between both the groups is given in [Table 5]. The predominance of malignant tumors was noted in the biopsied group and of benign tumors in the nonbiopsied group. The provisional diagnosis of patients who were not biopsied is depected in [Table 5] and [Figure 1]a. The most common provisional diagnoses were benign tumors (60.3%), followed by inflammatory diseases (15.5%) and a small percentage of malignant tumors (10.3%). The most common histopathological diagnoses were optic nerve glioma (25.9%); sphenoid wing meningioma (18.9%); cavernous hemangioma (15.5%); and nonspecific orbital inflammation (NSOI) (15.5%).The distribution of histopathological diagnoses of all orbital biopsies is shown in [Table 5] and [Figure 1]b. Malignancies were predominant (64.7%), followed by inflammatory diseases (23.5%), a small percentage were benign tumors (5.9%) and dermoid cysts (5.9%). The most common histopathological diagnoses were malignant lymphoma (44.1%), NSOI (17.4%), and squamous cell carcinoma (SCC) (8.8%).
Table 5: Diagnoses of all orbital masses including histopathological results in the biopsied group and provisional diagnoses in the nonbiopsied group

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Figure 1: Breakdown of diagnoses (a) Nonbiopsied group provisional diagnoses. (b) Biopsied group histopathological diagnoses. NSOI: nonspecific orbital inflammation, ON: optic nerve, SCC: squamous cell carcinoma

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Only two complications (5.9%) were registered: orbital hemorrhage and diplopia. The retrobulbar hemorrhage occurred during an excisional biopsy of the lacrimal gland. Promptly lateral canthotomy with cantholysis was performed. The patient underwent orbital US in the operating room and emergent orbital computed tomography (CT) scan imaging after the biopsy that disclosed retrobulbar hemorrhage. One week later, the CT was repeated and most of the hemorrhage had disappeared. Previously to the biopsy, the patient had visual acuity of 6/10 due to myopic retinopathy and at 3-month postoperatively, visual acuity had decreased to 4/10, optic disc pallor was noted, and the optical coherence tomography revealed a decrease in the peripapillary nerve fiber layer, most probably due to acute compressive optic neuropathy. The postoperative diplopia was noted after excisional biopsy of a dermoid cyst located in the extraconal compartment in the anterior orbit. The patient complained of horizontal diplopia that was treated with lens sector occlusion with satisfactory results.

Greenwich Grading System scores

The benefit of orbital biopsy for patient's management was evaluated under the three GGS categories: effect on diagnosis, contribution to the investigation, and effect on treatment, as seen in [Figure 2].
Figure 2: The GGS classification of orbital biopsy. GGS: Greenwich Grading System

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After the orbital biopsy, in 58.8% of the patients, the suspected diagnosis was confirmed or excluded (Grade 1); in 11.8%, the diagnosis was changed (Grade 3); in 29.4%, a new diagnosis was provided (Grade 2), as seen in [Figure 2].

The diagnosis was changed (Grade 3) in 4 patients (11.8%): one patient was referred due to the suspicion of NSOI and the histopathology result revealed a neurofibroma; one patient had an orbital mass extending from the intra and extraconal compartment, in which the MRI was suspicious of meningioma or hemangioma and the biopsy disclosed small B-cell lymphoma; one patient had a CT-scan with enlarged lacrimal gland, suspicious of dacryoadenitis, and the histopathology result was a MALT lymphoma; and the other patient with an intraconal mass in which provisional diagnosis after MRI was orbital lymphoma and the biopsy result was IgG4-associated disease (IgG4-AD).

Most patients with a new diagnosis (Grade 2) were referred for orbital biopsy due to an orbital mass in which imaging did not provide enough information for a defined suspected diagnosis. The new final diagnoses included lymphoproliferative tumor (n = 5), NSOI (n = 4) and thyroid orbitopathy (n = 1).


The orbital biopsy was considered a useful contribution for the investigation of these patients, as it was the only test that could provide the required information as all patients had previously undergone inconclusive imaging examination of the orbit.


Regarding the benefit of orbital biopsy for patient's therapeutic management, in 32.4% of the patients (n = 11), a new treatment (Grade 3) was started, the results are shown in [Figure 2]. These cases included patients with lymphoproliferative tumors.

The treatment was modified or stopped after the result of the biopsy (Grade 2) in 32.4% (n = 11). Patients with orbital metastases were included in this category because they were the first manifestation of distant metastases and cranial radiotherapy was started. Three patients with orbital invasion due to SCC were initially proposed for surgery only, although after the confirmation of orbital invasion, treatment changed for radiotherapy. One patient with 93 years with a sebaceous carcinoma was initially proposed for surgery only; after the biopsy results, conjunctival invasion was detected, and the patient and treatment plan changed to topical mitomycin C.

In 5.9% of the patients (n = 2), histopathologic results allowed reassurance and explanation (Grade 1), these include one case of SCC and one of NSOI.

In 29.4% (n = 10), there was no change (Grade 0) in patient's treatment. Five cases of NSOI and the case of IgG4-AD were included in this category. These patients were previously under treatment with corticosteroids and maintained the same treatment after the result of the biopsy. The dermoid cysts (n = 2) were also included since the excisional biopsy was the treatment for these patients, so no further changes regarding treatment occurred. Two patients refused treatment after the biopsy (one had a meningioma and the other one had a sinonasal adenocarcinoma), so they were considered in this category.

  Discussion Top

Evaluation using the GGS had a useful contribution for the diagnosis, investigation, and treatment management of the most patients reviewed.

Overall, orbital biopsy was important in all patients (GGS overall category with Grade 3, 2, or 1). In most of the cases, the probable diagnosis made on clinical grounds was confirmed or excluded after the histopathological result. Besides, the orbital biopsy was even of the greatest value where a new diagnosis was established (29.4%) and in which changed the initial probable diagnosis (11.8%).

Large variation of orbital diseases has been reported in the literature.[1],[4],[5],[6],[7],[8] On the one hand, Bonavolontà et al.[4] observed that dermoid cyst and lymphoproliferative tumors are the most common orbital diseases. On the other hand, Shields et al.[5] reported NSOI and lymphoproliferative tumor as the two most common orbital diseases. Our study showed different diagnoses in the nonbiopsied and biopsied groups. In the nonbiopsied group, optic nerve glioma (25.9%) and sphenoid wing meningioma (18.9%) were the more common tumors, whereas in the biopsied group, lymphoproliferative tumors (44.1%) and NSOI (17.4%) were the two most common histopathological diagnoses. Since patients were selected for a biopsy if the orbital lesion had rapidly progressive growth or infiltrative margins with resulting functional deficits or entrapment of orbital structures, it is expected that most commonly malignant lesions have this kind of clinical presentation; therefore, these lesions were more common in the biopsied group (64.7%). Our results are in line with the Newcastle study by Ting et al.[3] that reported NOIS and lymphoproliferative tumors as the most common during a period of 10 years.

When analyzing the most frequent symptoms encountered in our patients, proptosis was the most common in both the groups. In the nonbiopsied group, proptosis reflects sphenoid wing meningioma, thyroid orbitopathy, and cavernous hemangioma which are frequently associated with painless proptosis.[1],[8] Still in this group, visual field/acuity loss was also frequent probably due to the large percentage of patients with optic nerve glioma and sphenoid wing meningioma, tumors in which this symptom is frequent.[1],[8] Lymphoproliferative tumors typically present with a palpable mass and proptosis,[1],[8] which may explain that in the biopsied group, both of these symptoms were the most common.

One case of IgG4-AD was reported in a patient with a suspected lymphoproliferative tumor due to the imaging characteristics on MRI. Two major series reviewed cases of ophthalmic IgG4-AD; in the Japanese study,[12] 21.4% of their presumed “lymphoproliferative disease” cases were IgG4-AD; and in the American study,[13] 3.6% were IgG4-AD, reflecting the geographical variation of this disease.

Our data demonstrated that in 11.8%, histopathological result was inconclusive and repeated biopsy was needed. After the second biopsy, a definite diagnosis was provided, suggesting that our approach and surgical technique yielded satisfactory results.

The study of Ting et al.[3] suggested that orbital biopsy was a safe diagnostic procedure in managing patients with orbital disease. The rate of postoperative blindness in orbital biopsy ranged between 0% and 0.87%.[14] The studies conducted by Purgason and Hornblass[15] and Salem and Qahtani[16] similarly reported a higher rate of complications following lateral orbitotomy as compared with anterior orbitotomy. They also observed that intraconal lesions carried a higher risk of complications in comparison with extraconal lesions. In addition, excisional biopsy involves more extensive removal of diseased tissues with a greater risk of postoperative diplopia. Our two complications (retrobulbar hemorrhage and diplopia) occurred after excisional biopsies of anterior extraconal masses. Therefore, careful counseling of the patient before undergoing orbital biopsy is of paramount importance.

The analysis of the benefit of orbital biopsy for treatment management of patients with an orbital mass, using the GGS, revealed that this examination is extremely helpful. In 32.4% of the patients, a new treatment was started, these included mostly lymphoproliferative tumors. The treatment was modified or stopped after the result of the biopsy in 32.4% of the patients, these included cases of orbital metastases, orbital invasion of SCC, and sebaceous carcinoma. No changes in treatment occurred in 29.4% of the patients, including cases of NSOI, IgG4-AD, dermoid cysts, meningioma and sino-nasal adenocarninoma (the last two refused treatment). Only in 5.9% of the biopsies, the histopathologic result allowed reassurance and explanation for the patients, these include one case of SCC and one of NSOI.

  Conclusions Top

Our study demonstrated that orbital biopsy seems to be an important and safe tool to diagnose and manage treatment of patients with an orbital mass, confirming the results of the Newcastle study by Ting et al.[3] However, not only we added the comparison between biopsied and nonbiopsied patients but also we highlighted the beneficial effect of orbital biopsy for the diagnosis, investigation, and treatment of an orbital mass using the GGS.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Perry JD, Singh A. Clinical Ophthalmic Oncology. 2nd ed. Berlin: Springer; 2014.  Back to cited text no. 1
Lima V, Burt B, Leibovitch I, Prabhakaran V, Goldberg RA, Selva D. Orbital compartment syndrome: The ophthalmic surgical emergency. Surv Ophthalmol 2009;54:441-9.  Back to cited text no. 2
Ting DS, Perez-Lopez M, Chew NJ, Clarke L, Dickinson AJ, Neoh C. A 10-year review of orbital biopsy: The Newcastle eye Centre study. Eye (Lond) 2015;29:1162-6.  Back to cited text no. 3
Karcioglu Z, Remus L. Orbital Tumors: Diagnosis and Treatment. 1st ed. New York: Springer; 2005.  Back to cited text no. 4
Tailor TD, Gupta D, Dalley RW, Keene CD, Anzai Y. Orbital neoplasms in adults: Clinical, radiologic, and pathologic review. Radiographics 2013;33:1739-58.  Back to cited text no. 5
Bonavola G, Strianese D, Grassi P, Comune C, Tranfa F, Uccello G, Iuliano A. An Analysis of 2480 space-occupying lesions of the orbit from 1976 to 2011. Ophthal Past Reconstr Surg. 2013;29:79-86.  Back to cited text no. 6
Shields JA, Bakewell B, Augsburger JJ, Flanagan JC. Classification and incidence of space-occupying lesions of the orbit. A survey of 645 biopsies. Arch Ophthalmol 1984;102:1606-11.  Back to cited text no. 7
Weerekoon L. Orbital space-occupying lesions. Four decades of Eye Hospital reports. Ann Ophthalmol 1971;3:299-305.  Back to cited text no. 8
Corbett MC, Shilling JS, Holder GE. The assessment of clinical investigations: The Greenwich Grading System and its application to electrodiagnostic testing in ophthalmology. Eye (Lond) 1995;9(Pt 6 Su):59-64.  Back to cited text no. 9
Woodruff SA, Fraser S, Burton LC, Holder GE, Sloper JJ. Evaluation of the electrodiagnostic investigation of children using the Greenwich Grading System. Eye (Lond) 2004;18:15-9.  Back to cited text no. 10
Varma D, O'Neill D. Quantification of the role of temporal artery biopsy in diagnosing clinically suspected giant cell arteritis. Eye (Lond) 2004;18:384-8.  Back to cited text no. 11
Japanese study group of IgG4-related ophthalmic disease. A prevalence study of IgG4-related ophthalmic disease in Japan. Jpn J Ophthalmol 2013;57:573-9.  Back to cited text no. 12
Karamchandani JR, Younes SF, Warnke RA, Natkunam Y. IgG4-related systemic sclerosing disease of the ocular adnexa: A potential mimic of ocular lymphoma. Am J Clin Pathol 2012;137:699-711.  Back to cited text no. 13
Jamison A, Gregory ME, Lyall DA, Kemp EG. Visual outcomes following orbital biopsy. Orbit 2013;32:304-8.  Back to cited text no. 14
Purgason PA, Hornblass A. Complications of surgery for orbital tumors. Ophthalmic Plast Reconstr Surg 1992;8:88-93.  Back to cited text no. 15
Salem M, Qahtani F. Risk factors associated with complications of orbital surgery in children. J Pediatr Ophthalmol Strabismus 2001;38:335-9.  Back to cited text no. 16


  [Figure 1], [Figure 2]

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]


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