| Abstract|| |
Alveolar soft-part sarcoma (ASPS) is a rare soft tissue tumour of uncertain cellular origin. It accounts for only 1% of all sarcomas, which themselves represent only a small proportion of human tumours. ASPS can arise in any soft tissue of the body, but there is an unexplained predilection for the right side. The most common site for paediatric ASPS is in the head and neck region, although involvement of the orbit is rare, with fewer than 30 reported cases. A case of a 5-year-old Kenyan boy with left-sided orbital ASPS is reported and the difficulties of diagnosing rare tumours are discussed.
Keywords: Alveolar soft-part sarcoma, orbital, tumour
|How to cite this article:|
Rose AM, Kabiru J, Rose GE. Alveolar soft-part sarcoma of the orbit. Afr J Paediatr Surg 2011;8:82-4
| Introduction|| |
Alveolar soft-part sarcoma (ASPS) is an extremely rare soft-tissue tumour, with unique histological features, uncertain line of differentiation and variable clinical behaviour.  It represents less than 1% of all sarcomas, which themselves account for only 1% of adult and 15% of paediatric malignancies. , The tumour generally presents as a painless, slow-growing mass during adolescence or early adulthood, although childhood cases have been reported, with the head and neck being the most affected region.  Orbital ASPS is a very rare presentation of this tumour, with only eight cases reported in the last 25 years. ,,,,, Eighteen further cases were reported prior to this. , ASPS has a female preponderance and a predilection for affecting the right side of the body; the latter being, as yet, an unexplained phenomenon.
Since the first description of ASPS almost 60 years ago,  there has been much debate surrounding the cellular origin of the tumour. It has been claimed that ASPS may represent a malignant variant of granular cell myoblastoma, a non-chromaffin cell paraganglioma or a malignant angioreninoma. ,, In more recent years, the predominant theory has been that ASPS is a muscle-derived tumour, this being based on cellular morphology and molecular markers. However, it is now generally accepted that this tumour is a translocation-associated sarcoma, therefore having no normal cellular counterpart.
ASPS has an unbalanced translocation between chromosomes 17q25 and Xp11.2, resulting in the expression of a novel fusion protein.  This translocation joins two genes: a transcription factor, TFE3, on the X chromosome, and ASPL, a gene of unknown function on chromosome 17. The mechanism by which this fusion process causes disease remains unknown, but it has been hypothesized that loss of the upstream regulatory elements of the TFE3 gene may play a role.  Translocations involving TFE3 have been reported in some paediatric papillary renal cell adenocarcinomas. ,,,,, Furthermore, very recent reports have shown an almost identical translocation to the one seen in ASPS in a case of adult-onset renal cell carcinoma. 
| Case Report|| |
A healthy 5-year-old Kenyan boy presented with a 2 year history of slowly progressive left proptosis and painless swelling of the left upper eyelid. There was no family history of neurofibromatosis.
Snellen visual acuity was 6/6 on the right, 6/60 on the left, with no relative afferent pupillary defect. There was left hypoglobus and moderate proptosis. Left hypotropia was associated with global restriction of ocular ductions and a complete absence of left upgaze. Upper eyelid position was normal, with good levator muscle excursion. There was no intraocular abnormality. A rubbery, vermiform mass was palpable above the globe, this lying in close apposition to the upper sclera, with very large episcleral vessels visible both around and on the mass.
Computed tomography (CT) scan demonstrated a large, well-defined mass in the upper part of the left orbit, with passive remodelling of the orbital roof and downward depression of the orbital floor [[Figure 1]a]. The superior rectus and levator muscle complex could not be discriminated from the abnormal tissues [[Figure 1]b]. Imaging was suggestive of a significant vascular supply at the posterior pole of the mass [[Figure 1]c].
|Figure 1: CT imaging of tumour. (a) Coronal section showing hypoglobus and passive remodelling of the orbital roof and fl oor; (b) coronal section demonstrating absence of discernable superior rectus/levator muscle complex; (c) axial section showing signifi cant vascular supply to tumour at posterior pole|
Click here to view
The tumour was resected through a trans-conjunctival superior orbitotomy, during which it was found to have replaced the left superior rectus muscle throughout its length. Large feeder vessels were evident both around and within the large, lobulated, grey-white tumour [Figure 2].
|Figure 2: Intraoperative view of tumour, demonstrating massive vascular supply|
Click here to view
Histology showed a partially encapsulated tumour, comprising cohesive sheets of cells with mildly pleomorphic nuclei. There were small, but prominent nucleoli and copious pale cytoplasm which was eosinophilic and somewhat flocculent. Although partial thick, fibrous septa were present, an alveolar pattern was not prominent. Immunohistochemistry was negative for S-100 and smooth muscle actin, but diastase periodic acid - Schiff (PAS) staining highlighted intracellular granules which showed focally elongated crystalline structure. These histological findings are consistent with the diagnosis of ASPS.
One month postoperatively, the child was well and both he and his mother were pleased with the cosmetic result [Figure 3]. Corrective strabismus surgery was planned for a future date. The child was referred to the oncology specialists for further advice on management of ASPS.
| Discussion|| |
ASPS of the orbit is an extremely rare malignancy, accounting for only a small proportion of orbital tumours. The clinical presentation of the case was suggestive of an arteriovenous malformation or a vascular tumour such as haemangioma, but at surgery, the lobulated, grey-white tumour was not consistent with this clinical diagnosis. The tumour appeared more like a granular cell tumour, although the massive vascular supply would be unusual with this type of malignancy. Histology showed that the tumour was most likely to be ASPS, despite the lack of classical alveolar morphology. This case demonstrates that clinical diagnosis of orbital tumours can be problematic even when good imaging is available, and that the histological diagnosis may also be difficult to reach when the classic histological pattern is absent. In such cases, greater reliance has to be placed on immunohistochemistry and the identification of tumour markers.
| References|| |
|1.||Folpe AL, Deyrup AT. Alveolar soft-part sarcoma: A review and update. J Clin Pathol 2006;59:1127-32. |
|2.||Enzinger FM, Weiss SW. Soft Tissue Tumors. 3 rd ed. St. Louis: Mosby; 1995. p. 1067-93. |
|3.||Antman KS, Golub T, Helman LJ. Report of the Sarcoma Progress Review Group: A roadmap for sarcoma research. Bethesda, MD: U.S. Department of Health and Human Services; 2004. p. 1. |
|4.||Simmons WB, Haggerty HS, Ngan B, Anonsen CK. Alveolar soft part sarcoma of the head and neck. A disease of children and young adults. Int J Pediatr Otorhinolaryngol 1989;17:139-53. |
|5.||Morris WR, Padgett DM, Osborn FD, Fleming JC. Pathologic quiz case: An orbital mass in a 45-year-old woman. Alveolar soft part sarcoma. Arch Pathol Lab Med 2005;129:534-6. |
|6.||Kashyap S, Sen S, Sharma MC, Betharia SM, Bajaj MS. Alveolar soft-part sarcoma of the orbit: Report of three cases. Can J Ophthalmol 2004;39:552-6. |
|7.||Khan AO, Burke MJ. Alveolar soft-part sarcoma of the orbit. J Pediatr Ophthalmol Strabismus 2004;41:245-6. |
|8.||Chan WM, Liu DT, Lai CK, Tse MW, Ng JS, Lam DS. Soft tissue sarcomas. Case 2. Orbital alveolar soft part sarcoma in a child. J Clin Oncol 2004;22:2027-9. |
|9.||Jordan DR, MacDonald H, Noel L, Carpenter B, Brownstein S, Munro S. Alveolar soft-part sarcoma of the orbit. Ophthalmic Surg 1995;26:269-70. |
|10.||Chodankar CM, Pandit SP, Joshi MG, Deodhar KP. Alveolar soft-part sarcoma of the orbit (a case report). Indian J Ophthalmol 1986;34:67-8. |
|11.||Font RL, Jurco S 3 rd , Zimmerman LE. Alveolar soft-part sarcoma of the orbit: A clinicopathologic analysis of seventeen cases and a review of the literature. Hum Pathol 1982;13:569-79. |
|12.||Bunt AH, Bensinger RE. Alveolar soft-part sarcoma of the orbit. Ophthalmology 1981;88:1339-46. |
|13.||Christopherson WM, Foote FW, Stewart FW. Alveolar soft-part sarcomas; structurally characteristic tumors of uncertain histiogenesis. Cancer 1952;5:100-11. |
|14.||Smetana HF, Scott WF. Malignant tumors of non-chromaffin paraganglia. Mil Surg 1951;109:330-49. |
|15.||Mukai M, Iri H, Nakajima T, Hirose S, Torikata C, Kageyama K, et al. Alveolar soft-part sarcoma. A review on its histiogenesis and further studies based on electron microscopy, immunohistochemistry, and biochemistry. Am J Surg Pathol 1983;7:679-89. |
|16.||Joyama S, Ueda T, Shimizu K, Kudawara I, Mano M, Funai H, et al. Chromosome rearrangement at 17q25 abd Xp11.2 in alveolar soft-part sarcoma: A case report and review of the literature. Cancer 1999;86:1246-50. |
|17.||Ladanyi M, Lui MY, Antonescu CR, Krause-Boehm A, Meindl A, Argani P, et al. The der(17)t(X;17)(p11;q25) of human alveolar soft part sarcoma fuses the TFE3 transcription factor gene to ASPL, a novel gene at 17q25. Oncogene 2001;20:48-57. |
|18.||Argani P, Ladanyi M. Recent advances in pediatric renal neoplasia. Adv Anat Pathol 2003;10:243-60. |
|19.||Argani P, Antonescu CR, Illei PB, Lui MY, Timmons CF, Newbury R, et al. Primary renal neoplasms with the ASPL-TFE3 gene fusion of alveolar soft part sarcoma; a distinctive tumor entity previously included among renal cell carcinomas of children and adolescents. Am J Pathol 2001;159:179-92. |
|20.||Argani P, Laé M, Hutchinson B, Reuter VE, Collins MH, Perentesis J, et al. Renal carcinomas with the t(6;11)(p21;q12): Clinicopathologic features and demonstration of the specific alpha-TFEB gene fusion by immunohistochemistry, RT-PCR, and DNA PCR. Am J Surg Pathol 2005;29:230-40. |
|21.||Davis IJ, Hsi BL, Arroyo JD, Vargas SO, Yeh YA, Motyckova G, et al. Cloning of an Alpha-TFEB fusion in renal tumors harboring the t(6;11)(p21;q13) chromosome translocation. Proc Natl Acad Sci U S A 2003;100:6051-6. |
|22.||Clark J, Lu YJ, Sidhar SK, Parker C, Gill S, Smedley D, et al. Fusion of splicing factor genes PSF and NonO (p54nrb) to the TFE3 gene in papillary renal cell carcinoma. Oncogene 1997;15:2233-9. |
|23.||Kuroda N, Tamura M, Tanaka Y, Hes O, Michal M, Inoue K, et al. Adult-onset renal cell carcinoma associated with Xp11.2 translocations/TFE3 gene fusion with smooth muscle stroma and abnormal vessels. Pathol Int 2009;59:486-91. |
Geoffrey E Rose
Moorfields Eye Hospital, City Road, London EC1V 2PD
[Figure 1], [Figure 2], [Figure 3]