Soft tissue sarcomas comprise a large heterogeneous group of tumors that often exhibit aggressive behavior with high morbidity and mortality. Many sarcomas arise due to chromosomal aberrations or mutations in mesenchymal progenitor cells. However, the exact cellular origin of most of these tumors remains uncertain.²⁵ Genetic abnormalities in sarcomas are common and are divided into two types. The first includes tumors that are characterized by specific genetic mutations, simple karyotypes, and translocations that can result in the formation of fusion genes that can alter the regulatory proteins or transcription factors in tumor cells and contribute to tumorigenesis.²⁶ The second type includes sarcomas with no specific mutations or chromosomal aberrations, but instead involves complex karyotypes with copy number genetic losses of tumor suppressor genes and amplification of proto-oncogenes that favor oncogenesis.²⁷ Interestingly, a variety of translocations and gene fusions common in the pathogenesis of other sarcomas have not been found to play a role in the pathogenesis of UPS.²⁶,²⁸

A well-known etiologic factor for UPS is ionizing radiation, and this has been reported following radiotherapy for breast carcinoma, malignant lymphoma, cervical carcinoma, and brain tumors.²⁹ The most common radiation-induced sarcomas (RIS) are osteogenic sarcoma (36.4%) and UPS (33.3%).²⁹ The mechanisms resulting in the oncogenesis of RIS involve damage to DNA that results in genomic instability.³⁰ Radiotherapy has been used in the treatment of head and neck neoplasms, but radiation-induced secondary sarcomas in this region are uncommon, and the annual incidence has been estimated to be only 0.06% to 0.17%,³¹,³² compared to an incidence of 1.6% reported for the entire body.³³ Nevertheless, UPS of the head and neck has been described after irradiation for nasopharyngeal tumors and retinoblastoma.³⁴,³⁵,³⁶,³⁷,³⁸,³⁹,⁴⁰

The age at presentation for UPS can range from childhood to the ninth decade (range, 6-87 years), with a mean of about 67 years.⁴¹ For eyelid lesions, the few reported cases range in age from 70 to 90 years. The duration of symptoms is variable from 1 month to 20 years (mean = 31 months) for benign fibrous histiocytoma to 1 month to 5 months (mean = 3.4 months) for malignant UPS.⁷ Overall, UPS shows a high histologic grade, and 90% have deep invasion at the time of presentation.⁴² Eyelid and periorbital involvement are rare with less than a dozen cases reported.¹⁶,¹⁷,¹⁸,¹⁹,²⁰,²¹,²²,²³,²⁴,³⁴ Females are involved more frequently than males with a F:M ratio of 4:2.

Presentation is typically with a rapidly enlarging, painless soft tissue swelling and a palpable brownish indurated mass on the eyelid or conjunctiva (Figures 147.1 and 147.2), and that may rarely be ulcerated. There may be deep invasion of muscles, nerves, periosteum, and bone, or even extension into the orbit.

Clinically, UPS has been confused with inflamed pterygium, juvenile xanthogranuloma, nodular fasciitis, foreign body granuloma, solitary fibrous tumor, leiomyoma, keratoacanthoma, amelanotic melanoma, and squamous cell carcinoma.¹⁵,¹⁶,¹⁷,¹⁸,¹⁹,²⁰,²¹,²²,²³,²⁴ Pterygia are typically slowly enlarging vascular pink, triangular, or wing-shaped conjunctival lesions, more frequently on the nasal side that can extend onto the cornea. Juvenile xanthogranulomas are often multiple dome-shaped, pink to red papules or nodules that usually progress to a brown or yellowish color and may have telangiectasias or a scaly surface. Nodular fasciitis presents as rapidly growing, firm subcutaneous or submucosal lesions along fascia and occurs in younger patients in the 20 to- 40-year range.