Orbital masses are a general term for tumors and mass lesions that develop inside the bony orbit housing the eyeball. They include a variety of conditions, from benign cysts and hemangiomas to life-threatening malignant tumors and infectious masses.
Orbital tumors account for approximately 1–5% of all new ophthalmic patients. In Japan, lymphoproliferative diseases (including malignant lymphoma, reactive lymphoid hyperplasia, IgG4-related ophthalmic disease, and idiopathic orbital inflammation) are the most common, comprising 50–60% of all orbital tumors, followed by hemangiomas, cystic lesions, and pleomorphic adenoma of the lacrimal gland.
The table below summarizes the frequency of major diseases.
| Disease | Number of Cases (Percentage) |
|---|---|
| Idiopathic orbital inflammation | 150 cases (20%) |
| Pleomorphic adenoma / Cavernous hemangioma | 98 cases each (13% each) |
| Dermoid cyst | 71 cases (10%) |
| Reactive lymphoid hyperplasia | 70 cases (10%) |
| Schwannoma | 38 cases (5%) |
Age-related characteristics are also significant. In adults, idiopathic orbital inflammation, cavernous hemangioma, lacrimal gland pleomorphic adenoma, and cysts are common, while in children, cysts, capillary hemangioma, lymphangioma, and optic nerve glioma are predominant. Among malignant tumors, malignant lymphoma is common in adults, while rhabdomyosarcoma and leukemia-related chloroma are important in children.
The location of the tumor also provides useful clues for diagnosis.
In Japan, lymphoproliferative diseases including malignant lymphoma, reactive lymphoid hyperplasia, IgG4-related ophthalmic disease, and idiopathic orbital inflammation account for 50–60% of all cases, making them the most common. Among benign tumors in adults, idiopathic orbital inflammation, cavernous hemangioma, and pleomorphic adenoma are frequent.
Symptoms vary greatly depending on the type and location of the tumor. The main symptoms are diplopia, decreased vision, eyelid swelling, and eye pain. Tumors at the orbital apex may additionally cause ocular motor palsy and ptosis. Metastatic carcinoma (especially scirrhous breast cancer) may present with enophthalmos.
Orbital tumors are broadly classified by cause and histological type into benign tumors, malignant tumors, infectious masses, inflammatory masses, and vascular lesions.
Malignant Lymphoma
Frequency: Up to 55% of malignant orbital tumors, 10–15% of all orbital tumors.
Features: Unilateral mild proptosis. Most common location is superolateral (extraconal).
Growth pattern: Molds around orbital structures without bone erosion.
Rhabdomyosarcoma
Frequency: Most common primary orbital malignancy in childhood. Accounts for 5–8% of childhood malignancies. Peak incidence before age 8.
Prognosis: 5-year survival rate 94% for embryonal type, 74% for alveolar type7).
Associated diseases: Known associations with Li-Fraumeni syndrome, NF1, and Noonan syndrome7).
Metastatic Tumors
Primary sites in adults: Breast cancer (53%), prostate cancer (12%), lung cancer (8%), melanoma (6%), renal cancer (5%) in descending order.
Children: Neuroblastoma is the most common. 11–56% of neuroblastomas metastasize to the orbit.
Characteristic findings: Eyelid ecchymosis is characteristic of neuroblastoma and leukemia.
Orbital invasion by sinonasal malignancies is also important. 90% of sinonasal tumors are malignant, and 80% are squamous cell carcinoma. Primary maxillary sinus origin accounts for 92.5%, and due to its invasive nature, functional impairment occurs early.
In children, common benign tumors include cysts, capillary hemangiomas, and lymphangiomas, many of which can spontaneously regress or be managed with observation. On the other hand, the most common primary malignant orbital tumor in childhood is rhabdomyosarcoma, which typically occurs before age 8. Rapidly progressive proptosis requires urgent specialist evaluation.
The time of onset, rate of growth, and history of other organ tumors are important clues. Palpation for consistency (compression test), direction of proptosis, and degree of ocular motility restriction are directly linked to diagnosis.
The classification of major tumors based on MRI T2 signal intensity is shown in the table below.
| T2 Signal | Representative Diseases |
|---|---|
| Low to intermediate signal (solid, rich in fibrous components) | Malignant lymphoma, reactive lymphoid hyperplasia, squamous cell carcinoma, pleomorphic adenoma of the lacrimal gland, rhabdomyosarcoma, metastatic tumors |
| High signal (watery, cystic) | Cavernous hemangioma, lymphangioma, hemorrhagic cyst, cystic schwannoma |
Definitive diagnosis is made by histopathological examination. All resected tumors must be submitted for pathological examination. Superficial lesions should be actively biopsied. Biopsy of deep tumors may be difficult due to visual function risks. For lacrimal gland pleomorphic adenoma, biopsy itself increases the risk of recurrence and malignant transformation, so the benefits and disadvantages of biopsy must be carefully considered.
PCR (AsperGenius kit) can detect Aspergillus fumigatus from paraffin-embedded tissue with high sensitivity and specificity, and can simultaneously detect azole resistance mutations 5).
Complete surgical resection is the basic treatment. Approaches such as anterior, lateral, lacrimal sac incision, transcranial, and transsinus approaches are selected according to the tumor location.
Because complete resection is difficult, radiation therapy and chemotherapy are initiated after definitive diagnosis by biopsy.
Complete resection is almost never indicated. Treatment effective for the primary cancer, such as chemotherapy and radiation therapy, is the mainstay. Hormone therapy is effective for breast and prostate cancers. In ER-positive ductal carcinoma (neuroendocrine differentiation, CK7 negative), there is a report of marked shrinkage and visual improvement with nab-paclitaxel induction followed by letrozole + abemaciclib (CDK4/6 inhibitor) combination6).
Combination of chemotherapy and radiation therapy is standard. VAC therapy (vincristine + actinomycin D + cyclophosphamide) is used for chemotherapy7).
Early complete resection can achieve cure. Advanced cases tend to invade intracranially, requiring aggressive treatment from an early stage. Carbon ion (heavy particle) radiation may be highly effective. If deemed unresectable, orbital exenteration should be actively considered.
It should not be judged as benign. Malignant lymphoma may temporarily shrink with steroids, but judging it as a benign disease based on shrinkage is dangerous. A biopsy for definitive diagnosis should always be performed.
The first-line drug differs depending on the pathogen. For mucormycosis, liposomal amphotericin B and isavuconazole are first-line (B recommendation), and prompt surgical debridement is critical for survival 2). For aspergillosis, voriconazole is first-line, and remission with conservative treatment has been reported even in immunocompetent patients 5).
Hyphae of zygomycetes such as Rhizopus oryzae invade orbital vessel walls, inducing a fibrin reaction and forming thrombi and aneurysms. This results in tissue ischemia and infarction, observed as black necrotic eschar. Vascular occlusion prevents antifungal drugs from penetrating the lesion, creating a vicious cycle of treatment resistance. Increased susceptibility in diabetic patients is thought to be due to elevated free iron in host serum promoting fungal growth 2).
Aspergillus fumigatus colonizes the upper respiratory tract and paranasal sinuses, then extends into the orbit. Progression into the intracranial space via the superior orbital fissure or optic canal can be fatal. Calcification on CT is highly suggestive of aspergillosis. Even if initial biopsy is histologically negative, PCR may be positive 5).
The three main features are lymphoplasmacytic infiltration rich in IgG4-positive plasma cells, storiform fibrosis, and obliterative phlebitis (less frequent in orbital lesions). In orbital lesions, the lacrimal gland is the most common site, accompanied by elevated serum IgG4 levels.
There is a characteristic molding pattern where the tumor grows by taking the shape of orbital structures (eyeball, extraocular muscles, bone walls) like a mold. The absence of bone erosion is useful for differentiating it from invasion by sinonasal carcinoma.
This is a disease caused by abnormal proliferation of lymphoid tissue. There are hyaline-vascular type (atrophic germinal centers with hyalinized blood vessels, “lollipop on a stick” appearance) and plasma cell type (sheets of plasma cells in the interfollicular area). In plasma cell type Castleman disease arising in the lacrimal gland, the IgG4/IgG ratio is often less than 40%, which is important for differentiation from IgG4-related disease 3).
Orbital myxoma is a benign tumor derived from primitive mesenchymal cells. CD34-positive spindle cells are scattered in a myxoid matrix, and due to its embryological relationship with neural crest cells, it commonly occurs in the heart (cardiac myxoma) and head and neck. An association with Carney complex has also been reported 1).
Lever et al. (2021) successfully identified Aspergillus fumigatus and simultaneously detected azole resistance mutations by applying PCR (AsperGenius kit) to paraffin-embedded tissue in a case of orbital aspergillosis in a 78-year-old immunocompetent woman 5). The initial biopsy histology was misdiagnosed as IOI, indicating that PCR can contribute to definitive diagnosis in histologically negative cases.
Ding et al. (2023) reported a case of ROCM in which Rhizopus oryzae was identified by metagenomics using next-generation sequencing (NGS) 2). Combining NGS with conventional fungal culture and pathological diagnosis may enable rapid determination of treatment strategy.
Zhang et al. (2025) reported a case of recurrent ameloblastoma that metastasized from the mandible to the orbit, treated with two surgical curettages while preserving visual function 4). Mandibular ameloblastoma is associated with BRAF mutations, while maxillary ameloblastoma is associated with SMO mutations. The efficacy of dual inhibition with BRAF/MEK inhibitors over an 8-year follow-up has been reported, and its application for preventing postoperative recurrence is attracting attention.
Togashi et al. (2021) reported a case of orbital metastasis of CK7-negative ductal carcinoma with neuroendocrine differentiation, in which administration of letrozole plus abemaciclib (CDK4/6 inhibitor) after three courses of nab-paclitaxel resulted in marked tumor shrinkage (Hertel value from 22 mm to 17 mm) and visual acuity improvement (logMAR 2.5 to normal range) 6). CDK4/6 inhibitors may become a treatment option for orbital metastases.
In a report of three cases of neonatal malignant orbital tumors by Zhang Y et al. (2021), a patient with peripheral PNET (Ki-67 70–80%, CD99-positive) died at 3 months despite orbital exenteration plus VACA/VAC-IE chemotherapy 7). In contrast, a patient with fetal-type rhabdomyosarcoma achieved 1-year recurrence-free survival after 7 cycles of VAC chemotherapy. The prognosis differs greatly between PNET and fetal-type RMS.
