Rhabdomyosarcoma is the most common primary malignant orbital tumor of childhood (average age at onset is 5–8 years). The typical presentation is a child with rapid-onset, progressive unilateral proptosis. Due to the extremely rapid growth of the tumor, these patients require immediate attention with urgent imaging and biopsy. There is often reddish discoloration of the eyelids that is not accompanied by local heat or systemic fever, as it is in cellulitis. Orbital rhabdomyosarcoma has a better prognosis (overall 5-year survival rate of about 90%) than does rhabdomyosarcoma occurring in other body sites.
Rhabdomyosarcoma arises from primitive mesenchymal cells that differentiate toward skeletal muscle. There are 3 recognized histologic types of orbital rhabdomyosarcoma (Fig 14-15):
Figure 14-15 Rhabdomyosarcoma. A, Child with a large right orbital mass with apparent erythema of the eyelids. B, CT scan (axial view) shows a large, poorly circumscribed orbital tumor (asterisk) and proptosis. C, In this embryonal example, cross-striations (arrow) representing the Z bands of actin–myosin complexes within the cytoplasm of a tumor cell can be identified. D, Poorly cohesive rhabdomyoblasts separated by fibrous septa (arrows) into “alveoli” are low-magnification histologic features of the alveolar variant of rhabdomyosarcoma. This variant has a less favorable prognosis than the more common embryonal type.
(Parts A and B courtesy of Sander Dubovy, MD.)
Embryonal rhabdomyosarcoma may develop in the conjunctival stroma and may present as grapelike submucosal clusters (ie, botryoid variant). Histologically, spindle cells are arranged in a loose syncytium with occasional elongated cells demonstrating cytoplasmic cross-striations (strap cells). These cross-striations are found in approximately 60% of embryonal rhabdomyosarcomas. Well-differentiated rhabdomyosarcomas feature numerous cells with well-defined cross-striations. Immunohistochemically, rhabdomyosarcoma typically is positive for desmin, muscle-specific actin, vimentin, and myogenin. Electron microscopy is helpful for demonstrating the typical sarcomeric banding pattern, especially in cases of embryonal rhabdomyosarcoma that are not as well-differentiated. Cytogenetic studies are important for identifying genetic translocations that have prognostic significance and may drive selection of treatment; this testing is routinely performed on these tumors. Presence of the fusion protein PAX3-FOXO1 is found in the alveolar subtype of the tumor and is associated with unfavorable outcomes.
See BCSC Section 6, Pediatric Ophthalmology and Strabismus, for additional discussion of rhabdomyosarcoma.
Leiomyomas and leiomyosarcomas
Orbital tumors with smooth muscle differentiation are rare. Leiomyomas of the orbit are benign tumors that typically manifest with slowly progressive unilateral proptosis in patients in the fourth or fifth decade of life. Histologically, these spindle cell tumors show slender blunt-ended, cigar-shaped nuclei and trichrome-positive filamentous cytoplasm. IHC demonstrates smooth muscle differentiation. Leiomyosarcomas are malignant lesions that occur most commonly in patients in their seventh decade of life. Histologically, these tumors show more cellularity, necrosis, and nuclear pleomorphism than their benign counterparts. Mitotic figures appear in leiomyosarcomas but typically are absent in leiomyomas.
Excerpted from BCSC 2020-2021 series: Section 4 - Ophthalmic Pathology and Intraocular Tumors. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.