Figure 1. Axial computed tomographic image demonstrating an intraconal mass lying lateral to the right optic nerve.
Figure 2. Tumor appearance. A, Gelatinous appearance of the tumor at the time of surgery. B, Myxoid tumor with lipoblasts and curved vessels (hematoxylin-eosin, original magnification ×10).
Salam T, Salvi SM, Thaung C, Rose GE. Orbital Sarcoma in a Young Patient With Li-Fraumeni Syndrome. Arch Ophthalmol. 2012;130(5):662-664. doi:10.1001/archophthalmol.2011.2432
Author Affiliations: Department of Ophthalmology, Moorfields Eye Hospital (Drs Salam, Salvi, and Rose) and Institute of Ophthalmology (Dr Thaung), London, England.
We describe the first reported case, to our knowledge, of a myxoid liposarcoma in a young man with a family history of a p53 gene abnormality.
A 32-year-old man had diplopia and slowly progressive right proptosis for 2 months. He had a family history of Li-Fraumeni syndrome (LFS),1 with tumor-related death of 2 first-degree and 1 second-degree relatives all before age 30 years.
Visual functions were normal (unaided visual acuity 6/5 OU). Mild right optic disc swelling and macular choroidal folds were evident. There was 5-mm right relative proptosis and a right esotropia. Computed tomography revealed a large, well-defined intraconal mass lying lateral to the right optic nerve and extending to the orbital apex (Figure 1).
Biopsy was performed through a lateral canthotomy; the tumor showed a gelatinous gross appearance during handling (Figure 2A). Histopathological analysis showed features of a myxoid liposarcoma (Figure 2B). There was focal nuclear immunoreactivity with S-100 protein, but other markers including AE1/AE3, glial fibrillary acidic protein, desmin, and CD34 were negative.
Given the family history of LFS, the use of either radiotherapy or alkylating chemotherapy was considered to carry an unacceptable risk of secondary tumor formation.2 The patient underwent skin-sparing orbital exenteration with multiple staging biopsies.
Histopathological analysis showed an extensively infiltrating sarcoma with vacuolated cells and lipoblasts. Analysis demonstrated cells with 3 to 5 paired CHOP and FUS signals, but no cells with a split signal were seen. The multiple signals support the presence of an abnormal clone, but the lack of a split signal is evidence against a translocation of CHOP or FUS, which would typically be seen in this type of tumor. The morphological appearance was interpreted as a diagnosis of myxoid liposarcoma.
Healing of the exenteration socket was uncomplicated. The patient is recurrence free at 18 months after surgery.
Liposarcomas compose 20% of all soft-tissue sarcomas, typically occurring at a subfascial location in the extremities or retroperitoneum of young adults.3 Initially, LFS was identified through an excess of unrelated malignant neoplasms in close relatives of patients with rhabdomyosarcoma.3 It is an autosomal dominant syndrome that predisposes to various cancers; 50% to 70% of families with LFS have a p53 gene abnormality, leading to an unstable genome, acquisition of mutations, and the subsequent promotion of malignant transformation.3 Three criteria are required to establish a diagnosis of LFS: (1) a first-degree relative with any cancer before age 45 years; (2) a first- or second-degree relative with any cancer before age 45 years or sarcoma at any age; and (3) a proband with sarcoma diagnosed before age 45 years.
Liposarcomas may be divided histologically into well-differentiated, dedifferentiated, pleomorphic, or myxoid/round-cell subtypes.4 The diagnosis is dependent on the presence of lipoblasts. Myxoid liposarcomas have a specific reciprocal translocation between chromosomes 12 and 16, which results in fusion of CHOP and FUS/TLS.4
The prognosis for liposarcoma is poor, with 2 previous reports describing locally destructive recurrence and eventual death.5 Studies looking at the TLS-CHOP fusion transcription structure and p53 status have shown that this type of structure does not have a significant bearing on the outcome of patients with liposarcoma; the presence of tumor necrosis and p53 overexpression are, however, predictive of an unfavorable outcome in patients with this tumor.5
Rhabdomyosarcoma is the commonest orbital malignant neoplasm associated with LFS,3 and LFS is present in 5% to 9% of patients with this tumor1; orbital myxoid/round-cell liposarcoma does not appear to have been previously reported in this familial tumor syndrome. Our case highlights that a malignant neoplasm should be suspected in any patient with LFS and, if in a child or young adult, a history of familial cancers should be sought. The therapeutic options are also significantly limited in patients with a genetic anomaly such as LFS.
Correspondence: Dr Rose, Department of Ophthalmology, Orbital Clinic, Moorfields Eye Hospital, City Road, London EC1V 2PD, England (firstname.lastname@example.org).
Financial Disclosure: None reported.