Chapter 4

Multidisciplinary Management of Orbital

Rhabdomyosarcoma

Winston W. Huh and Anita Mahajan

Abstract Rhabdomyosarcoma (RMS) is the most common orbital malignancy in childhood. Embryonal RMS and alveolar RMS are the two most common histologic subtypes of RMS, and embryonal RMS is the most common subtype of orbital RMS. The clinical presentation of orbital RMS depends on the tumor location in the orbit. Diagnosis is chiefly made through open biopsy, and complete initial tumor resection is uncommon because of the risk of ocular morbidity. The treatment of orbital RMS requires a coordinated effort by the disciplines of ophthalmology, pathology, pediatric oncology, and radiation oncology. Because of advances in the planning and administration of chemotherapy and radiation therapy, the outcome for patients with orbital RMS has improved; the 3-year failure-free survival rate is greater than 90%, and the 3-year overall survival rate is 100%. Continued improvements in therapy are being investigated in an effort to decrease the risk of treatment-related late effects, such as cataracts and facial asymmetry.

4.1 Introduction

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma of childhood. The disease accounts for approximately 50% of soft tissue sarcomas in children and has an incidence of 4.6 cases per million children per year [1]. RMS is generally diagnosed in younger children; 60% of cases are diagnosed in children younger than 5 years of age. Approximately one-third of all RMS cases occur in the head and neck area [2], and approximately 10% of all RMS cases occur in the orbit. Orbital RMS is the most common malignant orbital tumor in children [3].

There are two major subtypes of RMS, alveolar (ARMS) and embryonal (ERMS), of which the embryonal subtype is more common. In 80% of ARMS

W.W. Huh (B)

Division of Pediatrics, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA

e-mail: whuh@mdanderson.org

Oncology Series 6, DOI 10.1007/978-1-4419-0374-7_4,

C Springer Science+Business Media, LLC 2011

common location, but tumors can appear anywhere in the orbit [8]. The symptoms depend on the tumor location in the orbit. Anterior tumors result in eyelid edema and sometimes chemosis, while posterior tumors may result in vision changes, especially if there is compression of the optic nerve.

The differential diagnosis includes a variety of malignant and benign disorders, including cystic lesions, orbital cellulitis, granulocytic sarcoma, lymphoma, inflammatory pseudotumor, Langerhans cell histiocytosis, lacrimal gland lesions, peripheral nerve sheath lesions, and metastatic infiltrate from other solid tumors of childhood, such as neuroblastoma [3].

On computed tomography scans, tumors tend to appear isodense to extraocular muscles but enhance with contrast [8, 9]. On magnetic resonance imaging scans, tumors tend to appear isodense to extraocular muscles and hypointense to orbital fat on T1-weighted images [10]. The tumors can be intraconal, extraconal, or both [8]. Bony involvement with erosion can be seen, but invasion of the globe or direct intracranial extension is very uncommon [8].

4.3 Staging

Imaging of the primary tumor site should be done with either computed tomography or magnetic resonance imaging; this imaging should also include the entire neck in order to fully assess nodal status. Although regional lymph node involvement is uncommon, it is encountered occasionally, particularly with the more aggressive histologic subtypes. The posterior orbit lacks lymphatic vessels, but the anterior orbit and eyelids contain lymphatic vessels, by which cancer cells can spread to form regional lymph node metastases. Any clinically or radiographically suspicious nodes should be removed and subjected to histopathologic evaluation since positive nodes would have an impact on the radiation treatment field and dose. The standard evaluation for metastatic disease includes a computed tomography scan of the chest, a bone scan, and bilateral bone marrow aspiration and core biopsies of the iliac crests. Because of the potential for intracranial extension, a lumbar puncture and cytologic analysis of cerebrospinal fluid is part of the standard evaluation. However, distant metastasis of orbital RMS is uncommon [11].

In the first IRSG study, IRS-I, tumors were grouped clinically on the basis of extent of surgical resection [12]. However, subsequent clinical trials demonstrated that other factors, such as histology, anatomic site, and tumor size, were also important [13, 14] Thus, the current staging system combines the classification system of the IRSG with the TNM staging system (Tables 4.1 and 4.2). Because it is difficult to achieve complete tumor resection at the time of presentation because of the risk of damage to surrounding vital ocular structures, orbital RMS is typically diagnosed through open biopsy. In an international review of 306 patients with orbital RMS, only 3% of the patients were able to undergo complete tumor resection at initial surgery, resulting in clinical group I status, whereas 72% of patients had biopsy without attempt at resection as initial surgery and 25% had partial excision as initial surgery [15]. Thus, most orbital RMS cases are classified as stage 1, clinical group III (Tables 4.1 and 4.2).

Definitions: T1, confined to site of origin; T2, extension and/or fixation to surrounding tissue; a, ≤5 cm in diameter; b, >5 cm in diameter; N0, regional nodes not clinically involved; N1, regional nodes clinically involved by neoplasm; Nx, clinical status of regional nodes unknown; M0, no distant metastasis present; M1, metastasis present

Table 4.2 Clinical grouping classification for rhabdomyosarcoma

Group Definition

IITotal gross resection with evidence of regional spread Grossly resected tumor with microscopic residual disease

Regional disease with involved nodes, completely resected with no microscopic residual disease

Regional disease with involved nodes, grossly resected but with evidence of microscopic residual disease and/or histologic involvement of the most distal

4.4 Surgery

Prior to the 1970s, orbital exenteration was a standard procedure for achieving local control of orbital RMS. However, now that it has been established that radiation therapy can also provide local control, exenteration is largely reserved for patients with progressive disease or recurrence within a previously irradiated field. It is often difficult to achieve complete surgical resection at the time of initial diagnosis because of the close proximity of the tumor to vital ocular structures and the high risk of unacceptable ocular morbidity or loss of function. However, in patients with ERMS, if complete surgical resection can be performed without undue morbidity and the patient does not have clinically suspicious lymph nodes, surgery is recommended since complete surgical local control obviates the need for radiation