Metastasis to the extraocular muscles is a condition in which malignant tumors from other organs spread hematogenously to the extraocular muscles within the orbit. It is classified under ICD-10 code C69.6 (Malignant neoplasm of orbit).
Metastatic spread to the orbit itself is rare, accounting for only 2–4.7% of all cancer patients and 4–14.7% of all orbital tumors. In a study of 227 patients who died of cancer, orbital invasion was found in 28 (about 12%). Since there is no lymphoid tissue in the normal orbit, metastasis occurs hematogenously. About 90% of cases are unilateral.
Among orbital metastases, isolated spread to the extraocular muscles is even rarer, accounting for only 5–9% of all orbital metastasis cases. Extraocular muscle metastasis occurs in advanced systemic malignancies and is considered a poor prognostic indicator.
Orbital metastases are found in 2–4.7% of all cancer patients, and among these, isolated extraocular muscle metastasis accounts for only 5–9%. It is an extremely rare condition and is often discovered as a sign of advanced cancer.
Symptoms of extraocular muscle metastasis appear over days to weeks.
Examination of the anterior and posterior segments is usually normal, and intraocular pressure is within the normal range. Evaluation of the external ocular structures and eye movements is particularly important.
Proptosis and Displacement
Proptosis: Caused by an increase in orbital volume due to the tumor. One of the most common findings.
Enophthalmos: In scirrhous metastases from gastric or breast cancer, contraction and hardening of fibrous connective tissue may cause enophthalmos.
Lid retraction and ptosis: Either may occur depending on the location and size of the tumor.
Motility Disorders and Inflammatory Signs
Restricted eye movement: Due to dysfunction of the affected extraocular muscles. Causes diplopia.
Chemosis and conjunctival injection: Associated with the orbital mass effect or impaired venous drainage.
Eyelid swelling: Observed with anterior extension of the lesion.
In highly vascular tumors (e.g., renal cell carcinoma, thyroid carcinoma), a pulsation may be palpable.
In patients with unilateral or bilateral eye pain, diplopia, proptosis, and restricted eye movement over days to weeks, with normal anterior and posterior segment examinations, extraocular muscle metastasis should be suspected. A history of systemic malignancy should further raise clinical suspicion.
Primary tumors that metastasize to the extraocular muscles are diverse.
| Sex/Age | Main Primary Tumor | Frequency |
|---|---|---|
| Female | Breast cancer | Approximately 50% of all cases |
| Male | Lung cancer | Most common |
| Male | Gastrointestinal cancer, prostate cancer | Next most common |
| Children | Neuroblastoma | Most common at 89% |
The most commonly reported primary tumors for extraocular muscle metastasis are breast adenocarcinoma, cutaneous melanoma, gastrointestinal cancer, and lung cancer.
Other reported primary tumors are as follows:
Usually, the primary tumor is already diagnosed at the time of consultation. However, ocular symptoms related to extraocular muscle metastasis may be the first manifestation of an undiagnosed distant metastatic malignancy.
The most common are breast adenocarcinoma, cutaneous melanoma, gastrointestinal cancer, and lung cancer. In women, breast cancer accounts for about 50% of all cases, while in men, lung cancer is the most common. In children, neuroblastoma is overwhelmingly the most common, accounting for 89%.
CT or MRI of the orbit is the most frequently used imaging modality.
Fine-needle aspiration biopsy may be performed but is not essential for diagnosis. Histopathological features vary depending on the primary tumor, and the tissue findings of orbital metastasis may differ from those of the primary tumor.
It is important to differentiate from diseases that cause enlargement of the extraocular muscles.
| Disease | Key Points for Differentiation |
|---|---|
| Thyroid eye disease (TED) | Spindle-shaped thickening of the muscle belly, mild tendon thickening |
| Nonspecific orbital inflammation (NSOI) | Pain is the main symptom, responds to steroids |
| Sarcoidosis | Non-caseating granulomas, multi-organ involvement |
| Orbital lymphoma | Primary tumor, frequently involves extraocular muscles |
| Carotid-cavernous fistula | Pulsatile proptosis, vascular bruit |
In thyroid eye disease, the bellies of the extraocular muscles are spindle-shaped and thickened, while tendon thickening is mild, which is a characteristic imaging finding. In contrast, metastatic lesions may present as nodular masses. A history of systemic malignancy is also an important differentiating factor.
A standardized treatment approach for extraocular muscle metastasis has not been established. Since orbital metastasis occurs in advanced stages, the goal of treatment is palliative. The treatment plan is determined based on disease burden and the patient’s treatment goals.
Radiation Therapy
External beam radiation therapy: This is the preferred first-line treatment. Various primary tumors show high sensitivity to radiation.
Local effects: Effective in reducing orbital lesions and relieving symptoms.
Pharmacotherapy
Chemotherapy: Used as second-line treatment. Agents such as etoposide, methotrexate, actinomycin D, cyclophosphamide, docetaxel, and vincristine have been reported.
Hormone therapy: Hormone therapy is effective for breast cancer and prostate cancer.
Surgical Treatment
Tumor debulking: Rarely performed, but may improve symptoms.
Indications for complete resection: Complete resection of orbital metastases is rarely indicated.
PET or MRI of the extraocular muscles is used to monitor treatment response. Multidisciplinary treatment in collaboration with physicians managing the primary cancer is important. Maintaining the quality of life (QOL) of patients with orbital metastasis is also an important treatment goal.
Complete resection of the intraorbital metastatic lesion is rarely indicated. The goal of treatment is palliative, and external beam radiation therapy is the first choice. Drug therapy or hormone therapy effective for the primary cancer may also be used in combination.
Metastatic lesions to the extraocular muscles are thought to reach the orbit via hematogenous seeding from advanced systemic malignancies. Since there is no lymphoid tissue in the normal orbit, hematogenous metastasis, rather than lymphatic metastasis, is the main route.
Why the extraocular muscles are selected as the tumor microenvironment is not fully understood. However, the following features have been reported.
On imaging, isolated enlargement of the affected extraocular muscle is typical, but nodular lesions may also be seen.
The average age of patients with extraocular muscle metastasis is 53 years, which is younger than the average age for orbital metastasis in general (62–73 years). No gender predilection or laterality has been observed. The time to onset of ocular symptoms varies by primary tumor site, with an average of 2 years for cutaneous melanoma, 3 years for breast cancer, and 30 months for all tumors.
The exact pathogenesis of extraocular muscle metastasis remains unclear and is a subject for future research. At the case report level, radiotherapy has been used for extraocular muscle metastasis in patients including those with vulvar melanoma, carcinoid tumor, breast cancer, and rhabdomyosarcoma.
In recent years, molecular targeted drugs (immune checkpoint inhibitors) such as nivolumab (Opdivo) have been initiated for metastasis of ocular malignant melanoma, and their application to metastatic orbital tumors is expected.
The life prognosis of patients with orbital metastasis is generally very poor. Lesions within the extraocular muscles are considered an ominous sign of disease burden and are associated with poor clinical outcomes.
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