Primary Orbital Liposarcoma
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Disease Entity
Disease
Liposarcoma is the most common soft-tissue sarcoma in adults, but the orbit is the least common primary site.[1] These masses are composed of adipocytes that have undergone malignant transformation. Different subtypes display varying levels of aggressive nature, and each will be described below. This article summarizes the current knowledge about primary orbital liposarcoma and addresses some of the challenges in managing this condition.
Etiology
The exact causes of liposarcoma are still under investigation.
Risk Factors
The American Cancer Society lists risk factors for soft tissue sarcomas, including prior radiation, neurofibromatosis, Gardner syndrome, Li-Fraumeni syndrome, Retinoblastoma, Werner syndrome, Gorlin syndrome, tuberous sclerosis, lymphedema, and possibly chemical exposure. There are reports of patients with primary orbital liposarcoma in the setting of comorbid Li-Fraumeni syndrome,[2] and retinoblastoma.[3]
General Pathology
The most common histologic subtype is myxoid, followed by well-differentiated.[1][4] Pleomorphic and dedifferentiated subtypes are more rare and associated with higher disease-specific mortality.[1] Tissue may stain positive for Vimentin, CD34, S-100, and smooth muscle actin.[5]
Pathophysiology
Well-differentiated and dedifferentiated subtypes of liposarcoma are characterized by a supernumerary ring and/or giant rod chromosomes[6] with amplified segments from 12q13-15[7] containing oncogenes.[7][8][9][10] Myxoid liposarcoma is characterized by FUS-CHOP gene fusion from recurrent translocation in 95 percent of cases and thought to be the primary oncogenic event.[11][12] Several growth factor pathways have also been implicated in the pathogenesis.[13][14][15] Pleomorphic adenoma is associated with complex rearrangments,[16][17][18][19] and 60 percent of cases show a deletion in a region containing the tumor suppressor RB1.[17] Deletions of regions containing p53 and NF1 tumor suppressor genes have also been reported.[20]
Primary Prevention
Given the unclear etiology, there is no specific guidance on primary prevention.
Diagnosis
History
Most patients present in the fifth decade,[1][4] but cases in adolescents and seniors have been reported.[4] There is a female predominance.[1][4]
Physical examination
Patients most commonly present with painless unilateral exophthalmos, but the presentation varies and may also include vision loss, epiphora, diplopia, and eyelid palpable mass.[4][5]
Diagnostic procedures
MRI and CT typically show an orbital mass arising from an extraocular muscle and irregular, ill-defined adipose tissue.[4] Due to the adipose component, lesions have low density on CT, and calcifications and bone destruction are infrequent. MRI is typically characterized by hyperintensity on T1 and T2-weighted images and hypointensity on fat-suppressed images.[4] The subtype may affect the morphology and appearance on imaging, with more well-differentiated masses displaying signs of adiposity compared with myxoid masses.[4]
Differential diagnosis
The differential diagnosis includes other primary orbital masses of infectious, inflammatory, vascular, and neoplastic etiologies. Inflammatory causes include IgG4 disease and nonspecific orbital inflammation. Vascular lesions include capillary hemangioma, cavernous venous malformation, lymphangioma, orbital venous varix, arteriovenous malformation, cavernous sinus thrombosis, and carotid-cavernous fistula. Benign tumors include optic nerve sheath meningioma, schwannoma, and neurofibroma. Malignant tumors include metastasis, lymphoma, rhabdomyosarcoma, and glioma.
For more information on orbital masses, please see Orbital Masses.
Management
General treatment
Primary orbital liposarcoma is rare and difficult to manage, with a high rate of recurrence.
Medical therapy
Chemotherapy for liposarcoma is still considered experimental, but radiation may be a valuable adjunct to surgery.[21]
Surgery
Management is typically surgical, and adjuvant radiotherapy has shown benefit in some patients.[4] Most masses are ill-defined without a capsule, making total excision difficult. Subtotal excision was associated with 100 percent recurrence in one study of 33 patients and 10 subtotal excisions.[4] Marginal and wide excisions exhibited 64 and 50 percent recurrence, respectively, and no recurrence in the few patients who also underwent radiotherapy.[4] The one patient who underwent subtotal excision and radiotherapy had recurrence.[4] Patients with optic nerve involvement may require orbital exenteration.[5]
Complications
Globe-sparing surgical approaches may be tried initially, but patients with recurrence and optic nerve involvement may require exenteration. Patients also should be monitored for distant metastasis. Mass effect and/or postsurgical changes may lead to strabismus, diplopia, exophthalmos/enophthalmos, and exposure keratopathy.
Prognosis
Histologic subtype, grade, and status of surgical margins all affect survival. In general, well-differentiated liposarcoma of any location has a 50 percent recurrence rate without risk of distant metastasis and excellent five-year survival rate.[21] Myxoid and pleomorphic liposarcoma has a recurrence rate up to 80 percent and a survival rate from 4 to 107 months.[21] Undifferentiated liposarcoma carries a greater risk of distant metastasis, increased by positive surgical resection margin.[21]
References
- ↑ Jump up to: 1.0 1.1 1.2 1.3 1.4 Chen T, Roelofs KA, Baugh S, Esfandiari M, Rootman DB. Orbital Liposarcoma: A Surveillance, Epidemiology and End Results Database Study. Ophthalmic Plast Reconstr Surg. 2024 Jan-Feb 01;40(1):93-98. doi: 10.1097/IOP.0000000000002516. Epub 2023 Sep 11. PMID: 37695202.
- ↑ Poli T, Laganà F, Caradonna L, et al. Primary orbital liposarcoma in Li-Fraumeni cancer family syndrome: a case report. Tumori 2005;91(1):96-100.
- ↑ Peck T, Gervasio KA, Zhang PJL, et al. Atypical Lipomatous Tumor/Well-Differentiated Liposarcoma with Myxoid Stroma in a Hereditary Retinoblastoma Survivor. Ocul Oncol Pathol 2020;6(2):79-86.
- ↑ Jump up to: 4.00 4.01 4.02 4.03 4.04 4.05 4.06 4.07 4.08 4.09 4.10 4.11 Wu W, Kang X, Fang W, Li Y, Ma R, Ma M, Hei Y, Wang Q, Wang X, Mu X, Zhao S, Yang X. Clinical, Diagnostic, and Treatment Characteristics of Orbital Liposarcoma. Am J Ophthalmol. 2024 Jun;262:134-140. doi: 10.1016/j.ajo.2024.01.014. Epub 2024 Jan 17. Erratum in: Am J Ophthalmol. 2024 Aug;264:248. doi: 10.1016/j.ajo.2024.03.020. PMID: 38237748.
- ↑ Jump up to: 5.0 5.1 5.2 Gao N, Ge X, Pei C, Ma JM, Hu YG. Orbital liposarcoma: a retrospective, single-center study of thirteen patients. Int J Ophthalmol. 2023 Aug 18;16(8):1293-1298. doi: 10.18240/ijo.2023.08.16. PMID: 37602347; PMCID: PMC10398515.
- ↑ Rosai J, Akerman M, Dal Cin P, et al. Combined morphologic and karyotypic study of 59 atypical lipomatous tumors: evaluation of their relationship and differential diagnosis with other adipose tissue tumors. (A report of the CHAMP Study Group) American Journal of Surgical Pathology. 1996;20(10):1182–1189. doi: 10.1097/00000478-199610000-00002.
- ↑ Jump up to: 7.0 7.1 Pedeutour F, Forus A, Coindre J-M, et al. Structure of the supernumerary ring and giant rod chromosomes in adipose tissue tumors. Genes Chromosomes and Cancer. 1999;24(1):30–41.
- ↑ Rieker RJ, Weitz J, Lehner B, et al. Genomic profiling reveals subsets of dedifferentiated liposarcoma to follow separate molecular pathways. Virchows Archiv. 2010;456(3):277–285. doi: 10.1007/s00428-009-0869-9.
- ↑ Szymanska J, Virolainen M, Tarkkanen M, et al. Overrepresentation of 1q21-23 and 12q13-21 in lipoma-like liposarcomas but not in benign lipomas: a comparative genomic hybridization study. Cancer Genetics and Cytogenetics. 1997;99(1):14–18. doi: 10.1016/s0165-4608(96)00436-0.
- ↑ Forus A, Weghuis DO, Smeets D, Fodstad O, Myklebost O, Van Kessel AG. Comparative genomic hybridization analysis of human sarcomas: I. Occurrence of genomic imbalances and identification of a novel major amplicon at 1q21-q22 in soft tissue sarcomas. Genes Chromosomes and Cancer. 1995;14(1):8–14. doi: 10.1002/gcc.2870140103.
- ↑ Antonescu CR, Tschernyavsky SJ, Decuseara R, et al. Prognostic impact of P53 status, TLS-CHOP fusion transcript structure, and histological grade in myxoid liposarcoma: a molecular and clinicopathologic study of 82 cases. Clinical Cancer Research. 2001;7(12):3977–3987.
- ↑ Crozat A, Aman P, Mandahl N, Ron D. Fusion of CHOP to a novel RNA-binding protein in human myxoid liposarcoma. Nature. 1993;363(6430):640–644. doi: 10.1038/363640a0.
- ↑ Thelin-Järnum S, Lassen C, Panagopoulos I, Mandahl N, Åman P. Identification of genes differentially expressed in TLS-CHOP carrying myxoid liposarcomas. International Journal of Cancer. 1999;83(1):30–33. doi: 10.1002/(sici)1097-0215(19990924)83:1<30::aid-ijc6>3.0.co;2-4.
- ↑ Tao Y, Pinzi V, Bourhis J, Deutsch E. Mechanisms of disease: signaling of the insulin-like growth factor 1 receptor pathway—therapeutic perspectives in cancer. Nature Clinical Practice Oncology. 2007;4(10):591–602. doi: 10.1038/ncponc0934.
- ↑ Cheng H, Dodge J, Mehl E, et al. Validation of immature adipogenic status and identification of prognostic biomarkers in myxoid liposarcoma using tissue microarrays. Human Pathology. 2009;40(9):1244–1251. doi: 10.1016/j.humpath.2009.01.011.
- ↑ Guillou L, Wadden C, Coindre J-M, Krausz T, Fletcher CDM. ’Proximal-type’ epithelioid sarcoma, a distinctive aggressive neoplasm showing rhabdoid features: clinicopathologic, immunohistochemical, and ultrastructural study of a series. American Journal of Surgical Pathology. 1997;21(2):130–146. doi: 10.1097/00000478-199702000-00002.
- ↑ Jump up to: 17.0 17.1 Taylor BS, Barretina J, Socci ND, et al. Functional copy-number alterations in cancer. PLoS ONE. 2008;3(9) doi: 10.1371/journal.pone.0003179. Article ID e3179.
- ↑ Idbaih A, Coindre J-M, Derré J, et al. Myxoid malignant fibrous histiocytoma and pleomorphic liposarcoma share very similar genomic imbalances. Laboratory Investigation. 2005;85(2):176–181. doi: 10.1038/labinvest.3700202.
- ↑ Schmidt H, Bartel F, Kappler M, et al. Gains of 13q are correlated with a poor prognosis in liposarcoma. Modern Pathology. 2005;18(5):638–644. doi: 10.1038/modpathol.3800326.
- ↑ Barretina J, Taylor BS, Banerji S, et al. Subtype-specific genomic alterations define new targets for soft-tissue sarcoma therapy. Nature Genetics. 2010;42(8):715–721. doi: 10.1038/ng.619.
- ↑ Jump up to: 21.0 21.1 21.2 21.3 Zafar R, Wheeler Y. Liposarcoma. 2023 Mar 20. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan–. PMID: 30855853.
