Introductory Chapter: Soft Tissue Tumors of the Eye

1. Introduction

Orbital soft tissue tumors of eye are a highly diverse group of neoplasms. They tend to manifest clinically as exophthalmos, with varying degrees of severity depending on the location and nature of each lesion, since the small anatomical space of the orbit is crowded with different structures, including muscles, nerves, blood vessels, and connective tissues (Figure 1).

Figure 1.

Schematic depicting a soft tissue tumor within the orbit.

Recent advancements in radiological diagnostic tools, such as ultrasound, computerized tomography (CT) scan, and magnetic resonance imaging (MRI), have significantly improved the detection and patient management of these tumors. This chapter provides a concise overview of some of these primary orbital tumors of mesenchymal origin with a special focus on sarcomas.

2. Rhabdomyosarcoma

Rhabdomyosarcoma (RMS) is one of the most common orbital tumor in children accounting for 5% of all pediatric cancers [1]. Although few children have it at the time of birth, most patients are diagnosed on average between 6 and 8 years of age [2, 3]. Orbital RMS leads to a rapidly progressing proptosis, which is the hallmark of orbital RMS. Additionally, patients may experience ocular motility restriction, globe displacement, and a tangible mass [4]. Orbital RMS is derived from undifferentiated mesenchymal cells with the potential to differentiate into striated muscle cells in the extraocular muscles as well as in the eyelids. Local extension to parameningeal structures, such as roof orbit osteolysis, optic nerve, maxillary sinuses, ethmoidal sinuses, and sphenoid, has been observed. Prognosis is variable depending on the site of the primary tumor regardless of the histopathological features [5] or the staging proposed by the Intergroup Rhabdomyosarcoma Study Group (Figure 2) [6]. The location of the primary tumor correlates significantly with the success of local therapy and sequelae [5]. Patients with localized orbital RMS have a 90% survival rate [7]. Historically, orbital RMS patients were treated with exclusive orbital exenteration with 5-year survival rate less than 30% [4]. However, the survival rate has improved significantly in recent decades, up to over 90% [8], due to early detection [9] and combination therapies of chemotherapeutic agents and local radiotherapy [8]. However, relapse and refractory (R/R) orbital RMS can still occur in some patients, which leads to a significant poor prognosis [10, 11, 12] since no standardized treatment guidelines exist for these patients. The current combination therapies for R/R orbital RMS consists of multidrug chemotherapy, brachytherapy, radiotherapy, and different surgical modalities [10, 11].

Figure 2.

IRSG surgical ± pathologic grouping system according to the Intergroup Rhabdomyosarcoma Study Group (IRSG).

3. Leimyosarcoma

Leiomyosarcomas are malignant tumors of mesenchymal origin that recapitulate smooth muscle differentiation [13]. These tumors are usually characterized by local recurrences and distant metastases. Thus, they are typically diagnosed at an advanced stage leading to poor prognosis. However, in primary conjunctival leiomyosarcomas, prognosis is usually good due to their early detection and small tumor size [14]. It is, however, challenging to distinguish leiomyosarcoma from other nonpigmented conjunctival lesions morphologically [15]. Therefore, the differential diagnosis should include leiomyosarcoma for any rapidly progressing subconjunctival tumor in the vicinity of the limbus that maintains intact conjunctival epithelium and displays prominent vascularization. Upon excisional biopsy, the presence of spindle cells can help differentiate leiomyosarcoma from amelanotic melanoma. Primary conjunctival leiomyosarcomas are rare, only 12 patients have been diagnosed with this tumor to date. These patients (eight male, four female) ranged in age from 20 to 81 years [14] with half initially misdiagnosed at pathological examination [16, 17]. While all the tumors were located within the palpebral fissure, several other locations were reported in some patients, including the temporal limbus, the nasal limbus, and the cornea [18]. A complete surgical excision with wide margins is the preferred method of treatment for primary conjunctival leiomyosarcomas. Surgical treatment options include exenteration, enucleation, evisceration, and a globe-sparing resection, which can be attempted when only the bulbar conjunctiva is involved [14].

4. Alveolar soft part sarcoma

Alveolar soft part sarcoma (ASPS) is a slow-growing, distinct, and rare soft tissue tumor with uncertain histogenesis and unique electron microscopic and histopathological characteristics [19, 20]. The name is derived from the alveolar arrangement of epithelioid tumor cells separated by delicate fibrous septa. The tumor is typically circumscribed [21, 22] and surrounded by a capsule or a pseudocapsule [21]. A hallmark morphological feature of ASPS that is found in a majority of cases is the presence of cytoplasmic crystals, which are diastase resistant and can be stained with periodic acid Schiff (PAS) [23]. These morphological features can be pivotal for the early detection of ASPS before it becomes metastatic and incurable. Orbital ASPS is rare and can occur in adults and children alike [21, 22, 24, 25] with no gender predilection. In a study that included nine patients, proptosis and ocular motility restriction were observed in all the patients, two of nine had lid swelling, three of nine had conjunctival congestion, one of nine had pain, eight of nine had normal visual acuity, and one of nine had diplopia. The most common feature was nonpulsatile and nonreducible proptosis [21, 26]. The tumor frequently indents or displaces the globe and can compress the optic nerve resulting in decreased visual acuity due to its proximity to the optic nerve and medial rectus muscle [21, 22, 27]. The differential diagnosis of ASPS includes neurofibroma, schwannoma, and hemangioma [22, 27]. Wide surgical excision is the first-line treatment option as complete surgical resection is required for increased survival. Studies have shown that supplemental preoperative radiotherapy is preferential to postoperative radiotherapy for improved overall survival, but it had no effect on local and regional recurrence, progression-free survival, or the presence of metastases [28].

5. Ewing sarcoma

Ewing sarcoma family of tumors (ESFT) comes from within bone or soft tissue and includes peripheral primitive neuroectodermal tumor (pPNET) of the bone, Ewing sarcoma of the bone (ESB), extraosseous Ewing sarcoma (EES) and Askin’s tumor of the chest wall [29]. Most Ewing sarcoma in the orbit is due to metastases, while primary orbital ESFT is very rare [30]. One retrospective study included 12 patients with primary orbital ESFTs that were verified by a pathological examination of the biopsies. The patients’ average age was 12 years, and all the patients had unilateral eye involvement with about 80% of the cases involving the left eye. Patients complained of superior eyelid swelling and proptosis with their symptoms lasting for 9 weeks on average. The majority of patients had predominant osseous lesion and extraorbital invasion, including intra cranial, nasal cavity, ethmoid sinus, maxillary sinus, and temporal fossa. At presentation, systemic metastases involving the retroperitoneal lymph nodes, bone marrow, and kidney were seen in about half the patients. Seven patients were diagnosed with ESB, two with EES, and three with pPNET based on radiological findings, histopathology, and immunohistochemistry. Since Ewing sarcoma is a systemic disease, all the patients in the study received systemic chemotherapy, and half of the patients died while on chemotherapy. The other half also received adjuvant external beam radiotherapy of 50 Gy to the orbit since this type of tumor is considered radiosensitive. Follow-up over 21 months showed that 11 patients have died with a mean survival time of 10 months. After the diagnosis of ESFT, four patients survived for less than 6 months, and these patients were all over the age of 5 years and had systemic metastasis and predominant osseous lesion with intracranial tumor extension at the time of presentation. One patient, with ESB tumor invasion into the maxillary sinus and no metastatic disease, responded well to the treatment and remained disease free at 12 years of follow-up [31].

6. Kaposi sarcoma

Kaposi sarcoma is a malignant neoplasm of vascular origin. It is composed of vascular spaces that are lined up by endothelial cells and surrounded by a clonal population of spindle cells [32]. Kaposi sarcoma is commonly associated with acquired immunodeficiency syndrome (AIDS) [33]. According to the Centers for Disease Control, about 24% of AIDS patients manifest with Kaposi sarcoma, which tends to be aggressive and resistant to treatments [33]. Ocular involvement of Kaposi sarcoma was very rare before the AIDS epidemic [34]. One in five AIDS patients may present with ocular involvement, including the conjunctiva, orbit, or eyelids [35, 36]. Conjunctival lesions are found in about 5–10% of Kaposi sarcoma patients [37]. These tumors can be misdiagnosed as cavernous hemangioma, foreign-body granuloma, or subconjunctival hemorrhage. Morphologically, the lesions are slow-progressing [38], and they appear raised or flat, have bright red coloration, and are often surrounded by dilated tortuous vessels [39]. Eyelid lesions can be similar in appearance to a hordeolum. In a study that included 100 homosexual males with AIDS-related Kaposi sarcoma, ophthalmic involvement was observed in 20 out of the 100 patients and was distributed between conjunctival and eyelid lesions. Importantly, the ophthalmic lesion was the sole initial clinical manifestation of Kaposi sarcoma in four patients [38]. Treatment modalities for Kaposi sarcoma of the conjunctiva and eyelids include surgical excision, radiation, chemotherapy, immunotherapy, and cryotherapy [40, 41, 42].

7. Conclusion

In conclusion, the radiological evaluation of orbital soft tissue tumors using MRI and CT scans can be complemented with histopathological examination utilizing incisional biopsies, excisional biopsies, fine-needle aspirates, and immunohistochemistry for accurate diagnoses and classification of these tumors. Due to recent advancements in surgical procedures, chemotherapeutic agents, radiation therapy, and cancer immunotherapy modalities, the clinical outcomes and prognoses have improved significantly for patients inflicted with soft tissue tumors of the orbit.