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Year : 2014  |  Volume : 10  |  Issue : 2  |  Page : 294-298

Orbital alveolar soft-part sarcoma: Clinico-pathological profiles, management and outcomes

1 Ocular Pathology Service, L.V. Prasad Eye Institute, Hyderabad, Andhra Pradesh, India
2 Ocular Oncology Service, L.V. Prasad Eye Institute, Hyderabad, Andhra Pradesh, India

Date of Web Publication14-Jul-2014

Correspondence Address:
Santosh G Honavar
Ocular Oncology Service, L.V. Prasad Eye Institute, Road No 2, Banjara Hills, Hyderabad, Andhra Pradesh
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0973-1482.136570

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 > Abstract 

Aim: To study the clinico-radiological and clinic-pathological features of orbital alveolar soft-part sarcomas (ASPS).
Materials and Methods: We retrieved 9 cases of orbital ASPS. Histopathological and immunohistochemical features and clinico-radiological findings were evaluated.
Results: Age at presentation varied from 1 to 31 years. Both, children and adults were affected. Proptosis was the most common clinical presentation. PAS-positive diastase-resistant crystals and granules were found in all cases. All patients received adjuvant radiotherapy. Two cases had positive surgical margins and were treated with additional adjuvant chemotherapy. None of the patients had recurrence or metastases till the last follow up.
Conclusion: Early diagnosis with a multidisciplinary, multimodal approach of treatment is quintessential in achieving a long disease-free survival in patients with ASPS.

 > Abstract in Chinese 


Keywords: Adjuvant radiotherapy, alveolar soft-part sarcoma, orbits

How to cite this article:
Mulay K, Ali MJ, Honavar SG, Reddy VP. Orbital alveolar soft-part sarcoma: Clinico-pathological profiles, management and outcomes. J Can Res Ther 2014;10:294-8

How to cite this URL:
Mulay K, Ali MJ, Honavar SG, Reddy VP. Orbital alveolar soft-part sarcoma: Clinico-pathological profiles, management and outcomes. J Can Res Ther [serial online] 2014 [cited 2022 Jan 27];10:294-8. Available from: https://www.cancerjournal.net/text.asp?2014/10/2/294/136570

 > Introduction Top

Alveolar soft-part sarcoma (ASPS) is a rare but distinct soft-tissue tumor characterized by unique histopathological and electron microscopic features. It is a slow-growing malignant neoplasm with an uncertain histogenesis. ASPS has been described to occur mostly in the extremities of young adults, [1],[2] the head and neck region in children, [3] and other locations rarely and in isolation. [4],[5],[6],[7],[8] Orbital involvement is rare with only few reports published in literature. [9],[10],[11],[12],[13] Although it has an indolent clinical course, ASPS is known to metastasize. Awareness of its histopathological and immunohistochemical features would help in the early diagnosis and life salvage.

 > Materials and methods Top

Retrospective, interventional case series included nine cases of ASPS involving the orbit between the years 1995 and 2011. Patients were indentified from the hospital registry. Medical records were evaluated for demographic and clinico-radiological data. The hematoxylin-eosin stained sections from formalin-fixed paraffin-embedded tissues were studied for cytomorphology, presence of necrosis/lymphovascular invasion and status of surgical resected margin.

Immunohistochemical analysis reviewed included desmin, vimentin, S-100, pan-cytokeratin (CK), MyoD1, p53, neurone-specific enolase (NSE), smooth muscle actin (SMA), epithelial membrane antigen (EMA), chromogranin (CG), synaptophysin and Ki-67.

 > Results Top

Among the nine patients treated over the sixteen years period, the age at presentation ranged from 1 to 31 years (median 6 years) with 6 pediatric patients (66.6%). [Table 1] reflects the demographic and clinico-pathological profile of the patients.
Table 1: Clinico - pathological - radiological features of ASPS

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All patients presented with proptosis of the affected eye [Figure 1]. Other features at presentation were lid swelling (2/9, 22.2%), conjunctival congestion (3/9, 33.3%), pain (1/9, 11.1%) and diplopia (1/9, 11.1%). Restricted ocular motility was present in all cases. Visual acuity was normal except in one patient, whose best corrected visual acuity was 6/60. Computed tomography demonstrated a well-defined mass in close relation to extraocular muscles, rendering most of them indistinct from the mass [Figure 1]. One patient had an intraconal mass lesion in very close proximity to optic nerve.
Figure 1: (a) Clinical photograph of a 6-year-old girl presenting with right eye rapidly progressing proptosis, (b) CT-scan, saggital reconstruction of the same patient showing a right inferior orbital mass indistinguishable from the inferior rectus muscle, (c) CT-scan axial cut with contrast showing a diffusely enhancing fusiform mass in the left orbit in close proximity to the optic nerve, (d) Macroscopic examination of the cut section of an excised tumor, grayish white in color with occasional areas of necrosis

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Microscopic examination showed a mixed tumor pattern composed of a lobular, solid and hemangiopericytoma-like pattern in various proportions. The tumor cells were large, round to polygonal with distinct borders, abundant granular eosinophilic to clear cytoplasm and had large vesicular nuclei with prominent nucleoli [Figure 2]. Mitotic activity was low and ranged from 0 to 2 per 50 high-power fields (HPF). PAS-positive, diastase-resistant intracytoplasmic crystals and granules were seen in all cases [Figure 2]. Intracytoplasmic glycogen was seen in 77.7% (7/9) cases. Vascular tumor emboli were seen in 44.4% (4/9) cases, necrosis in 11.1% (1/9) and positive surgical margins in 22.2% (2/9) cases.
Figure 2: (a) Microphotograph showing alveolar pattern in an ASPS with delicate, intervening fibrovascular septae (H and E ×100), (b) Epithelioid tumor cells with abundant granular cytoplasm and nuclei having prominent nucleoli (H and E ×400), (c) Vascular tumor emboli (H and E ×400), (d) Intra-cytoplasmic PAS-positive, diastase-negative crystals (indicated by arrow) (PAS ×400)

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Immunoreactivity was variable with no specific pattern. Strong and diffuse cytoplasmic immunoreactivity was observed for myoD1, NSE (Neuron-specific enolase) and S-100 in 77.7% (7/9) cases. Focal but strong cytoplasmic immunoreactivity was observed for vimentin in 33.3% (3/9) cases [Figure 3]. The tumor cells lacked immunoreactivity for CK (cytokeratin), EMA (epithelial membrane antigen), SMA (smooth muscle actin), synaptophysin, CG (chromogranin) and desmin. p53 expression ranged from 10 to 21% and Ki-67 activity ranged from 1 to 4% indicating the low proliferative potential and indolent nature of ASPS.
Figure 3: (a) Microphotograph showing immunohistochemical staining showing diffuse cytoplasmic immunoreactivity for myoD1 (OM ×400), (b) NSE (OM ×400), (c) Alveolar pattern displayed by immunostaining with SMA (OM ×100, (d) Focal vimentin immunoreactivity seen in ASPS (OM ×400)

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Surgery was the primary treatment of choice in all the patients. Post-operative external beam radiotherapy (EBRT) was given to all the patients. Additionally, two patients with positive surgical margins were administered 3 cycles adjuvant chemotherapy composed of vincristine, Adriamycin and cyclophosphamide. Follow-up ranged from 6 to 126 months (median - 43 months). Local recurrence or distant metastases were not seen in any patient.

 > Discussion Top

ASPS is an uncommon but distinct entity that accounts for approximately 0.5-1% of all soft-tissue tumors. [14] Abrikossoff first published on tumors, which he named as "granular cell myoblastoma" and "malignant granular cell myoblastoma". [15],[16] Since then, several reports exist where these terminologies have been used to describe such tumors at various anatomical locations. [17],[18],[19],[20] Smetana and Scott's described a similar series of 14 cases with cells in an organoid arrangement and referred to them as "malignant non-chromaffin paraganglioma". [21] Christopherson in 1952, coined the term "alveolar soft-part sarcoma" when he published his study of 12 cases, which had cells similar to those in granular cell myoblastoma but were arranged in an alveolar pattern around a central space. [22] These tumors described under various names in different reports had distinct differences between them despite sharing certain features.

The histogenesis of ASPSs remains uncertain. Absence of neuroendocrine differentiation as shown by various ultrastructural, histochemical and immunohistochemical studies has ruled out the hypotheses of ASPS representing malignant tumors of nonchromaffin paraganglia. Negative studies for rennin have excluded a possibility of ASPS being malignant variety of angioreninomas. Similarity of ASPS crystals to actin filaments has suggested a possible myogenous line of differentiation. [23] The current concept is that ASPS displays a scrambled phenotype without a normal counterpart. [24] ASPS is characterized by the der (17) t (X; 17) p (11;25) translocation resulting in fusion of C-terminal of the transcription factor E3 (TFE3) located on Xp11.22 with the N-terminal of the alveolar soft-part sarcoma critical region 1(ASPSCR1) gene located on 17q25. Two alternative fusion junctions result in two distinct fusion transcripts, ASPL-TFE3 type 1 and type 2. [25] Further fundamental research is warranted before we can come to a conclusion.

Orbital involvement by ASPS is extremely rare. Orbital ASPS has been described to occur in both adults [11],[12],[16],[26] and children. [9],[10],[27],[28] No gender predilection has been described in orbital ASPS. The present study showed a predilection in the pediatric age group (6/9, 66.6%) as compared to adults (3/9, 33.3%). A female predilection was also observed in the pediatric population of this study. As described in literature and the present study, non-pulsatile and non-reducible proptosis is the commonest presenting feature. Restricted ocular motility is not a universal feature. [12],[28] Pain can also be a presenting feature. [16] Imaging studies display a circumscribed mass that indents or displaces the globe and is located in close approximation to the medial rectus muscle and the optic nerve. [12],[26] Compression of optic nerve might lead to decreased vision as was seen in one case of the present study. The circumscribed nature, orbital location and proximity to the rectus muscle or optic nerve prompts a clinical differential diagnosis of a schwannoma, neurofibroma or hemangioma. [10],[26] Neurofibromas are more common in the orbit as compared to schwannomas and present in middle ages. Both present with very slowly progressive proptosis secondary to a well-defied solitary mass in superior quadrants of the orbit. Occasionally, posterior indentation of globe and diplopia may be associated. CT scans would show a solid lesion isodense with brain with bony expansion and contrast enhancement.

Microscopic examination forms the mainstay of ASPS diagnosis. A pseudocapsule or a capsule is seen around the tumor. [12] The tumor usually has an organoid arrangement of epithelioid appearing tumor cells separated by delicate fibrovascular septae. A reticulin stain demonstrates the alveolar pattern well. [12] Sometimes, the organoid pattern might be less prominent or may be completely replaced by solid pattern. [29] A hemangiopericytoma-like pattern has also been described in ASPS. [30] The tumor cells are relatively similar having distinct cell borders, abundant eosinophilic granular to clear cytoplasm and large vesicular nuclei with prominent nucleoli. Mitotic activity is minimal. [31] Periodic acid-Schiff (PAS)-positive, diastase-resistant crystalline structures are characteristic of ASPS. [22],[32] They are usually rod-like but may be rhomboid, spiked or may even have a sheaf-like configuration. [29] These crystals may be seen in 80% of all ASPSs. Necrotic and hemorrhagic foci may be seen but have not been associated with prognosis in ASPS. Invasion into the resected margins, adjacent muscle and soft tissue and into the vascular channels is not uncommon. [33] Immunohistochemistry is not pathognomonic of ASPS as no specific pattern of staining has been established. ASPS are usually negative for epithelial markers EMA and CK, neuroendocrine markers synaptophysin and chromogranin A and melanocytic markers HMB45 and Melan A. Expression for vimentin, NSE, SMA, skeletal muscle actin and desmin has been documented in up to 50% of ASPS. [29] MyoD1 has been reported to be expressed strongly in ASPS. [34],[35] Certain studies have demonstrated convincing and consistent immunoreactivity for monocarboxylate transporter 1 (MCT1) and CD147 in ASPS. [36],[37]

Despite treatment, 11-50% of ASPS recur. [1] Surgery remains the primary treatment of choice followed by postoperative radiotherapy, which helps to achieve a good local control rate of up to 90%. [38],[39] Complete surgical resection is necessary for better survival. A recent study showed that preoperative radiotherapy increases the overall survival to some extent as compared to postoperative radiotherapy. However, it did not change the progression free survival, local and regional recurrence or metastasis. [40] Role of neoadjuvant chemotherapy has been uncertain with some studies reporting no benefit, [41] while others showing a prolonged 3-year disease specific survival. [42] Doxorubicin and ifosfamide are the most commonly used chemotherapy agents. [43],[44],[45],[46] Because of the relative lack of symptoms, there may be a diagnostic delay, and metastasis may be the first disease manifestation. [47] The most common metastatic sites are lung, bone, central nervous system and liver. [48] Metastasis has been reported as long as up to 15 years after initial resection of the tumor. Despite the occurrence of metastases in up to 79% of patients, 5-year overall survival rates ranged from 45 to 88%. [1],[38],[39] Treatment of metastases has not yielded any benefits. Molecular therapies targeting c-MET receptors look promising. [47],[48] Tyrosine kinase inhibitors like Nexavar (Sorafenib) are also being analyzed for their role by targeting platelet-derived growth factor receptor (PDGFR), epidermal growth factor receptor (EGFR) and MET family. [47],[48] A long-term follow-up is indicated for surveillance of metastases and therapy-related effects.

 > Conclusion Top

ASPS is an uncommon soft tissue tumor, which rarely involves the orbit. It has a propensity to recur or metastasize late in the follow-up period. Knowledge of its characteristic microscopic and ultrastructural features would facilitate an early diagnosis. With no validated treatment protocols available and targeted therapies under surveillance, a multidisciplinary treatment is quintessential in achieving a long disease-free survival.

 > References Top

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  [Figure 1], [Figure 2], [Figure 3]

  [Table 1]

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