Journal of Pediatric Ophthalmology and Strabismus

Short Subjects 

Undifferentiated Sarcoma of the Orbit With Angiomyxoid Features

Jennifer E. De Niro, MD; Elaine M. Cham, MD; Rona Z. Silkiss, MD, FACS

Abstract

A 7-month-old female infant developed a grade 3 un-differentiated sarcoma with angiomyxoid features of the right orbit. The tumor expanded rapidly 2 months after an initial sub-total resection and extended posteriorly toward the right cavernous sinus. After treatment with ifosphamide, doxorubicin, and proton beam radiation, there was no discernible residual tumor 20 months after starting chemotherapy. [J Pediatr Ophthalmol Strabismus 2014;51:e4–e7.]

From the Department of Ophthalmology, California Pacific Medical Center, San Francisco, California (JED, RZS); and the Department of Pathology, Children’s Hospital and Research Center Oakland, Oakland, California (EMC).

The authors have no financial or proprietary interest in the materials presented herein.

Correspondence: Jennifer E. De Niro, MD, Department of Ophthalmology, California Pacific Medical Center, 2340 Clay Street, 5th Floor, San Francisco, CA 94115. E-mail: DeNiroEdie@gmail.com

Received: September 14, 2013
Accepted: January 06, 2014
Posted Online: February 25, 2014

Abstract

A 7-month-old female infant developed a grade 3 un-differentiated sarcoma with angiomyxoid features of the right orbit. The tumor expanded rapidly 2 months after an initial sub-total resection and extended posteriorly toward the right cavernous sinus. After treatment with ifosphamide, doxorubicin, and proton beam radiation, there was no discernible residual tumor 20 months after starting chemotherapy. [J Pediatr Ophthalmol Strabismus 2014;51:e4–e7.]

From the Department of Ophthalmology, California Pacific Medical Center, San Francisco, California (JED, RZS); and the Department of Pathology, Children’s Hospital and Research Center Oakland, Oakland, California (EMC).

The authors have no financial or proprietary interest in the materials presented herein.

Correspondence: Jennifer E. De Niro, MD, Department of Ophthalmology, California Pacific Medical Center, 2340 Clay Street, 5th Floor, San Francisco, CA 94115. E-mail: DeNiroEdie@gmail.com

Received: September 14, 2013
Accepted: January 06, 2014
Posted Online: February 25, 2014

Introduction

We report a rapidly growing intraorbital myxoid neoplasm in a female infant. The tumor was ultimately classified as a grade 3 undifferentiated sarcoma when it re-occurred after excision with increased atypia and mitotic figures. These types of tumors are rare and have been only seldomly described in the orbit.

Case Report

A 7-month-old female infant presented to her pediatrician with right upper eyelid swelling. She was referred to a pediatric ophthalmologist, who noted a spongy mass involving the right eyelid. He suspected a capillary hemangioma; however, the lesion did not respond to oral propanolol or a steroid injection. The patient was then referred to the oculoplastic service. Her medical history and family history were unremarkable. Initial examination revealed a non-tender 6 × 6 cm mass that filled the superior right orbit and caused significant hypoglobus (Figure 1). Vision was constant, steady, and maintained in both eyes. The ocular motility examination was notable for limited elevation of the right eye. Slit-lamp examination and retinal examination were normal.

The patient on initial presentation.

Figure 1.

The patient on initial presentation.

Magnetic resonance imaging demonstrated a T2-bright lobulated mass that extended anteriorly from the skin of the superior right orbit posteriorly to the orbital apex and edge of the cavernous sinus (Figure 2). The mass was predominantly extraconal with insinuation around the right superior oblique muscle. There was a minimal amount of patchy contrast enhancement. A biopsy of the mass was recommended.

(A) T2-weighted magnetic resonance imaging (MRI) showed a T2-bright mass. There was osseous remodeling of the right orbit, but no bone invasion. (B) Repeat MRI 5 months later (fat-saturated contrast-enhanced T1-weighted) demonstrated a 4.3 × 2.9 × 2.8 cm mass that occupied the intraconal and extraconal space of the right orbit. (C) T1-weighted MRI 20 months after the patient began chemotherapy with no apparent residual tumor.

Figure 2.

(A) T2-weighted magnetic resonance imaging (MRI) showed a T2-bright mass. There was osseous remodeling of the right orbit, but no bone invasion. (B) Repeat MRI 5 months later (fat-saturated contrast-enhanced T1-weighted) demonstrated a 4.3 × 2.9 × 2.8 cm mass that occupied the intraconal and extraconal space of the right orbit. (C) T1-weighted MRI 20 months after the patient began chemotherapy with no apparent residual tumor.

The tumor was accessed through an eyelid crease incision. Although most of the tumor was removed, complete excision was not possible due to its deep posterior extension. The mass was white, gelatinous, and semi-solid. Histologic sections showed a myxoid neoplasm (Figure 3) with a discrete nodule of moderately increased cellularity and mitotic activity (3 mitoses per 10 high power fields). The neoplastic cells condensed at the periphery of this nodule. There was a prominent arborizing capillary vasculature. Although most of the tumor cells outside the nodule were small and bland with few mitoses, the cells within the nodule appeared slightly larger and hyperchromatic, with one or more prominent nucleoli. Necrosis was absent. The cells did not show obvious features of differentiation, and immunostains were negative for smooth muscle actin, CD31, CD34, desmin, myogenin, S100, and estrogen and progesterone receptors. Although the tumor could not be definitely classified, overall it was believed to resemble a superficial angiomyxoma. Based on its expansile growth pattern radiologically, the fact that it was not locally destructive, and its resemblance histologically to a superficial angiomyxoma, it was classified as benign but was expected to have a high likelihood of recurrence.

(A) A well-circumscribed, nodular proliferation with arborizing capillaries is seen within the myxoid neoplasm. There is increased cellularity within the nodule compared to the surrounding tumor (hematoxylin–eosin stain). (B) Condensation of neoplastic cells at the periphery of the nodule (hematoxylin–eosin stain). (C) The neoplastic cells within the nodule show moderate cellular atypia (hematoxylin–eosin stain). (D) Cells on the outside of the nodule appear stellate-shaped (hematoxylin–eosin stain). Most are bland, but some are binucleated with mild to moderate atypia.

Figure 3.

(A) A well-circumscribed, nodular proliferation with arborizing capillaries is seen within the myxoid neoplasm. There is increased cellularity within the nodule compared to the surrounding tumor (hematoxylin–eosin stain). (B) Condensation of neoplastic cells at the periphery of the nodule (hematoxylin–eosin stain). (C) The neoplastic cells within the nodule show moderate cellular atypia (hematoxylin–eosin stain). (D) Cells on the outside of the nodule appear stellate-shaped (hematoxylin–eosin stain). Most are bland, but some are binucleated with mild to moderate atypia.

Two months after the initial surgery, the patient developed significant proptosis and recurrent hypoglobus of her right eye. Repeat magnetic resonance imaging demonstrated a large mass that occupied both the intraconal and extraconal space of the right orbit and extended posteriorly near the cavernous sinus (Figure 2). The mass demonstrated heterogeneous signal intensity on T1 and T2 sequences and enhanced more with contrast than the original tumor, especially at the margins. Due to rapid tumor recurrence, the patient underwent a debulking lateral orbitotomy. The lateral and superior intraconal tumor was removed. Overall, the histologic features of the recurrent tumor were largely similar to the initial tumor and most of it appeared bland with abundant myxoid stroma. However, there were focal areas of increased cellularity/atypia and increased mitotic activity (up to 5 mitoses per 10 high power fields). The neoplasm did not appear to fit well into any World Health Organization classification of a soft tissue tumor. Given the aggressive behavior following resection and the increase in atypia and mitotic figures, the tumor was classified as an undifferentiated soft tissue sarcoma, grade 3, which implied a high risk of malignant potential.

This diagnosis allowed the patient to be enrolled in a non-randomized phase 3 clinical trial for pathology-confirmed non-rhabdomyosarcoma soft tissue sarcomas. The trial compared observation with radiation therapy, combination chemotherapy, or surgery (clinicaltrials.gov identifier NCT00346164). Based on having an incompletely resected, high-grade tumor, our patient was treated with ifosphamide and doxorubicin lasting approximately 25 weeks. Additionally, the patient was treated with proton beam radiation (experimental group 2; regimen D). A computed tomography scan of the neck, abdomen, and pelvis, as well as a bone scan, showed no evidence of metastasis. Unfortunately, 1 month after beginning chemotherapy, the patient developed disseminated herpes zoster infection, which likely originated from a vaccine she had been given by her pediatrician several days prior to the administration of chemotherapy. She subsequently developed varicella zoster keratitis. Despite these setbacks, she completed the entire study protocol with only minimal delays. Magnetic resonance imaging of the brain and orbits 20 months after she had started chemotherapy showed no discernible residual right orbital mass (Figure 2).

Discussion

Although the tumor was ultimately classified as an undifferentiated sarcoma, it had myxomatous features and the differential diagnosis included myxoma and angiomxyoma. Myxomas are benign, mesenchymal neoplasms that usually arise in skeletal muscles, skin, subcutaneous tissue, the heart, and the genitourinary system.1 These tumors rarely arise in the orbit.2–4 They consist of modified mesenchymal cells that produce excessive amounts of glycosaminoglycans. Histologically, they are hypocellular and hypovascular. They contain spindle-shaped cells in an abundant myxoid stroma.1 Carney et al. described an autosomal dominant syndrome that included myxomas, spotty skin pigmentation, and endocrine overactivity.5 Although our patient did not appear to have this syndrome, it is important to recognize because these patients are at high risk for cardiac myxomas.6

Angiomyxomas, more similar to the tumor type of our patient, are more aggressive and contain more blood vessels than typical myxomas.2,7 Except for 1 case of an eyelid angiomyxoma8 and 7 cases of orbital angiomyxoma,2,9 these tumors are relatively unknown in the orbit. Although systemic metastasis has not been reported,1 the tumors have a high rate of local recurrence (30% to 70%) and therefore require long-term follow-up.1,2,7 Although a complete excision with a margin of healthy tissue has been recommended,2 this may be difficult due to the infiltrative nature of these tumors. Radiation therapy is probably not helpful because these neoplasms originate from fibroblastic cells and display low mitotic activity.

Our patient’s tumor was ultimately classified as a grade 3 undifferentiated sarcoma based on its aggressive behavior and increase in mitotic figures following resection. Soft tissue sarcomas represent a heterogenous group of tumors that may arise from a variety of mesenchymal tissues such as smooth muscle, connective tissue, vascular tissue, and the peripheral nervous system.10 Sarcomas that do not exhibit a known histologic pattern are classified as being an undifferentiated sarcoma. Undifferentiated sarcomas are among the more common non-rhabdomyosarcomatous soft tissue sarcomas encountered in children. The optimal treatment regimen for these tumors remains unclear.11 Our patient was enrolled in a phase 3 clinical trial and received ifosphamide, doxorubicin, and proton beam radiation. Twenty months after starting chemotherapy, magnetic resonance imaging showed no apparent residual tumor.

Although uncommon, these tumors should be included in the differential diagnosis of orbital neoplasms in childhood. More research is needed to better define and optimize treatment.

References

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10.3928/01913913-20140218-01

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