Clinical and Imaging Characteristics of Metastatic Orbital Tumours in North China

Purpose This study was designed to review the primary sites, clinical manifestations, imaging features, treatments, and outcomes of 36 patients with orbital metastasis in North China. Methods This was a retrospective review of 36 patients with orbital metastasis at Tianjin Eye Hospital between January 2010 and December 2020 in North China as well as a review of the literature. Results Thirty-six patients were included in the study; 17 were male, and 19 were female, with an age range of 1–82 years (average 54.9 ± 19.8 years). All the tumours were unilateral. The mean duration from the onset of orbital signs to presentation at the hospital was 2.4 months (range 1–10 months). Breast carcinoma, gastrointestinal tract carcinoma, and lung carcinoma were the most common histological types. Proptosis, ocular pain, and diplopia were the most common clinical manifestations. The superior orbit was the most common quadrant involved. All patients received comprehensive therapy, including surgery, radiotherapy, or chemotherapy. The average follow-up time was 2.45 years (range 7 months to 5.5 years). Ten patients in this study died as a result of disseminated metastasis from the primary tumour. Conclusions In North China, the most common primary cancer that metastasizes to the orbit is breast cancer, followed by gastrointestinal tract carcinoma and lung cancer. The increasing trend of orbital gastrointestinal tract metastases in North China in recent years is noteworthy. The survival rate of patients with orbital metastasis of neuroblastoma is low.


Introduction
A number of tumours, infammatory lesions, and congenital lesions can afect the orbit.According to the site of occurrence, orbital lesions can be classifed as primary, secondary, or metastatic [1].Orbital metastases are rare, and previous studies have reported that orbital metastases represent approximately 3∼7% of all orbital space-occupying lesions [2,3].Ophthalmologists play an important role in the diagnosis of orbital metastasis; 19% to 25% of patients may have no history of systemic cancer when presenting with ophthalmic symptoms [4].Malignant tumours generally metastasize via the haematogenous route to the orbit [5].Orbital metastases are less common than uveal metastases because of their blood supply [6].Te primary site of orbital metastasis can vary widely.Previous reports have suggested that prostate and lung carcinomas are common primary sites in males, whereas in females, breast carcinoma tops the list [7].Te clinical manifestations of orbital metastases vary.According to a case series of orbital metastases by Ahmad et al., diplopia, proptosis, pain, decreased vision, ptosis, and a palpable orbital mass were among the most common symptoms [8].Most clinicians have little experience with orbital metastasis [6].In the past, ophthalmologists could provide little treatment for patients with metastases, particularly those with orbital metastasis, which often heralds multiple organ involvement [9].Owing to the lack of large sample size clinical studies from North China on orbital metastasis, we report 36 consecutive patients seen at Tianjin Eye Hospital between January 2010 and December 2020.In this study, we reviewed age, sex, symptoms, ophthalmic examinations, primary site and location, diagnosis, therapeutic methods, and prognosis.Te English literature regarding orbital metastasis was also reviewed for further comprehension of this rare type of cancer.

Methods
All procedures involving human participants were performed in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki Declaration and its later amendments.Te written informed consent form was signed by all patients after an explanation of the nature of the study.Te study was approved by the Foundation Institutional Review Board of Tianjin Eye Hospital.
Tis retrospective study included 36 patients who were diagnosed with orbital metastasis at Tianjin Eye Hospital between January 2010 and December 2020.All patients were of Chinese ethnicity.All patients underwent surgical resection of the lesion, obtaining a gross total resection, followed by postoperative radiotherapy or chemotherapy.
Patients were not included in the study if there was evidence of direct orbital invasion from adjacent structures, and patients with lymphoproliferative disorders, such as lymphoma, leukaemia, or multiple myeloma, were excluded.
Te main extracted data included sex, age, type of primary tumour, history of cancer, symptoms and duration, clinical manifestations, position, imaging fndings, survival time, treatment, follow-up, and prognosis.All patients underwent ophthalmology examinations, computed tomography (CT), and histopathological examination.Most of the patients underwent magnetic resonance imaging (MRI), and some patients underwent fuorodeoxyglucose positron emission tomography/computed tomography (PET-CT).Only patients with evidence of metastatic cancer to the orbit via the haematogenous route were included.

Results
Tirty-six consecutive patients with orbital metastasis were identifed and enrolled in this study.Te mean age was 54.9 ± 19.8 years (range: 1-82 years), and the median age was 59 years.Of the 36 patients, 17 were males and 19 were females.Tree patients (8.3%) were children.All patients were from the North provinces of China.All the tumours were unilateral (right: 17, left: 19) with no side predilection (p < 0.05), and no patients had bilateral involvement.Te mean duration from the onset of orbital signs to presentation at the hospital was 2.4 months (range 1-10 months).
Imaging data were available for all patients.Orbital CT scans were performed for all 36 patients.Twenty-three patients had a relatively high-density space-occupying soft tissue mass in the orbit involving the extraocular muscle without bony erosion (Figure 1).Tirteen patients had tumour invasion of the orbital wall, ethmoid sinus, maxillary sinus, or skull base (Figure 2).Twenty-one patients underwent MRI (Figure 3).Based on CT and MRI fndings, the site of metastasis in the orbit could be determined.Te most frequently invaded area was the superior orbit (19.4%), followed by the inferior orbit (13.9%), the central orbit (13.9%), the superolateral orbit (11.1%), and the apical orbit (11.1%) (Figure 4).Metastasis involved the extraocular muscle in 29 patients, the intraconal space in 15 patients, and the extraconal space in 21 patients.

Discussion
Orbital metastases are relatively uncommon.Te frst documented case of orbital metastasis was a case of lung cancer metastasis to the orbit reported by Horner in 1864 [10].Since then, several ophthalmologists have reported their experience with orbital metastases [11].Several studies have shown that the incidence of orbital metastasis has increased over the past two decades compared to what was previously reported in the literature [12].In the 21st century, the number of patients with systemic cancer with orbital metastasis has increased.Te prevalence of orbital metastasis difers among hospitals, countries, and races.Yan and Gao reported their experience with orbital metastasis in South China [13].However, there are no clinical studies on orbital metastasis in North China.Our hospital is a well-known tertiary ophthalmic centre in North China.According to previous reports, breast carcinoma, followed by lung carcinoma, is the most common source of orbital metastasis [14].However, our study difered from previous studies.Perhaps, the most interesting fnding in our study of orbital metastasis, which distinguishes it from others, is the much greater incidence of metastatic gastrointestinal tract carcinoma.According to the literature, China has the largest number of incident cancer patients and deaths from liver cancer, oesophageal cancer, and gastric cancer, comprising 1.21 million (two-thirds of the world's total) newly diagnosed cases in 2020 [15].Tese changes were mainly due to lifestyle changes in recent years.Terefore, the incidence of metastatic gastrointestinal tract carcinoma also increased with this trend.In contrast to a similar report in South China, there was no nasopharyngeal carcinoma in this cohort.Tis diference between North and South China is noteworthy.With the increasing incidence of gastrointestinal cancers in China, one must be vigilant for possible orbital metastasis in patients who present with diplopia, ptosis, eyelid swelling, and limited eye movement.In our study, there were slightly more females than males, but there were no signifcant sex-related diferences.According to previous foreign reports, due to the large proportion of breast metastases, more female patients than male patients were reported.Among our patients, only two more had breast metastases than gastrointestinal metastases.Moreover, among the 7 patients with metastatic carcinomas of the gastrointestinal tract, 5 patients were male.Orbital metastasis is uncommon in childhood and occurs more often in adults.Among our patients, only 3 had orbital metastasis of    neuroblastoma.Since our hospital is a specialized ophthalmic hospital, children with orbital metastasis of neuroblastoma were transferred to a children's hospital for comprehensive treatment after surgery.Blood fow to the eye accounts for 2-5% of the total blood circulation.Tus, blood fow to the eye is very low compared to that to other organs [16].Our study revealed that the most frequently invaded area was the superior orbit, followed by the inferior orbit, the central orbit, the superolateral orbit, and the apical orbit.Te distribution of orbital metastasis may be related to the distribution of blood vessels in the orbit.Orbital metastasis was characterized by proptosis (91.7%), ocular pain (86.1%), diplopia (83.3%), limited ocular movement (80.6%) and chemosis (72.2%).However, it should be noted that orbital metastases located at the orbital apex may present as orbital apex syndrome or supraorbital tissue syndrome.Before surgery, we did not observe unilateral acquired blepharoptosis, which was reported in a previous study [17].
Imaging is very important for the diagnosis and treatment of orbital metastasis.Te B-scan ultrasound and CT and MRI features of orbital metastases of diferent pathological types have been reported in previous literature.Orbital imaging via CT or MRI was helpful in guiding the biopsy to determine the appropriate surgical approach.Clinically, it is difcult to perform whole-body CTor MRI on patients, but PET-CT can provide more accurate information about orbital metastasis [18].In recent years, the application of PET-CT in orbital metastasis has received increased attention [19].PET-CT has been used as a new imaging method to improve the detection rate of orbital metastases [20].In our series, 24 patients underwent PET-CT imaging.New metastatic lesions were found on PET-CT in 5 of these patients.PET-CT can help doctors stage orbital metastases and provide a reference for the design of treatment.Terefore, attention should be given to PET-CT images of patients with orbital metastasis before and after treatment.
Our study has inherent biases and limitations.All of the patients included in this study were from specialized ophthalmic hospitals, which limit the generalization of our results, possibly due to selection bias.We only collected patient data whose diagnosis was defnitively confrmed through histopathological examination.Due to regional variability in our study and the fact that many patients were treated at other hospitals after surgery, these factors limit the accuracy of follow-up and the consistency of treatment protocols [21].Tis study, to some extent, investigated the pathogenesis of orbital metastasis in North China, and the results of this study are quite diferent from those of previous studies in other areas.
In conclusion, our study revealed that breast cancer, gastrointestinal tract carcinoma, and lung cancer were the most common orbital metastases in North China.Orbital gastrointestinal tract metastases showed an increasing trend.Orbital metastatic neuroblastoma is mainly observed in children and has a poor prognosis.Orbital metastasis can display a variety of clinical and imaging features, although there is still a lack of uniform treatment.

Figure 1 :
Figure 1: (a) Clinical photograph of a 49-year-old woman with orbital metastasis of breast cancer showed proptosis, ptosis, and chemosis of the right eye.(b) Te coronal computed tomography showed an irregular mass in the right orbit, surrounding the eyeball, exophthalmos, with extraocular muscle involvement.

Figure 2 :
Figure 2: (a) Clinical photograph of a 76-year-old man with orbital metastasis of lung cancer showed ptosis, eyelid swelling, and chemosis of the right eye.(b) Te coronal computed tomography showed a massive mass replacing the medial aspect of the orbit and ethmid sinus.(c) Te coronal computed tomography scan showed an irregular mass in the right orbit replacing the orbit, ethmid sinus, and maxillary sinus.

Figure 3 :
Figure 3: (a) Clinical photograph of a 49-year-old woman with orbital metastasis of gastrointestinal tract carcinoma showed proptosis, chemosis, and limited ocular movement of the right eye.(b) Te transverse T1WI section showed that the tumour was isointense to the extraocular muscle and cerebral gray matter.(c) Te transverse T2WI section showed minimal hyperintensity in the right orbit.

Table 1 :
Primary site, type of metastatic tumour, age, and sex in 36 patients.

Table 2 :
Te presenting symptoms and signs of 36 patients with orbital metastasis.