Ординатура / Офтальмология / Английские материалы / Orbital Tumors Diagnosis and Treatment_Karcioglu_2005

FIGURE 26.3. Symptoms of rhabdomyosarcoma depend on the site and the growth rate of the tumor. This patient’s tumor involved the superior medial orbit, upper eyelid, and conjunctiva.

FIGURE 26.4. Large posterior tumor causing marked proptosis of the left eye with choroidal folds of the fundus.

be appreciable (Figure 26.5). On T1-weighted MR images the tumor may appear isoto hyperintense to the extraocular muscles and hypointense with respect to the orbital fat. On proton density and T2-weighted MR images, hypointensity, isointensity, and even hyperintensity with respect to both extraocular muscles and orbital fat may be appreciable (Figure 26.6). On T1weighted, contrast-enhanced MR images, rhab-

BOX 26.3. Differential Diagnosis of

Orbital RMS

Orbital cellulitis

Orbital abscess

Dermoid cyst

Lymphangioma

Eosinophilic granuloma

Capillary hemangioma

Burkitt’s lymphoma

Chloroma (myeloid sarcoma)

Metastatic neuroblastoma

FIGURE 26.5. Axial CT image shows a rather well-circumscribed homogeneous mass, isodense to the extraocular muscles in the superior portion of the right orbit.

TABLE 26.1. Staging by the Intergroup Rhabdomyosarcoma Study Group.

Group Description

ICompletely resected localized disease implying gross

domyosarcomas show moderate to marked enhancement, even though in some cases a highly vascular internal architecture mimicking a capillary hemangioma may be demonstrated.20

The staging of RMS proposed in the third Intergroup Rhabdomyosarcoma Study is summarized in Table 26.1.20 The simplification of this classification by Shields et al. can also be applied to cases of orbital RMS.21 Exenteration was the standard surgical treatment for orbital rhabdomyosarcoma up to the 1970s. Orbital exenteration is now confined to the treatment of patients with recurrent disease.21 The poor prognosis for children with orbital rhabdomyosarcoma following orbital exenteration suggested the use of radiotherapy. In fractionated doses, 4000 cGy offered satisfactory tumor control.22 Chemotherapy, introduced subsequently, also succeeded in reducing these lesions (Figure 26.7). Vincristine, actinomycin D, and,

FIGURE 26.6. Axial T1-weighted MR image of a rhabdomyosarcoma in a patient with neurofibromatosis type 1. The tumor shows isodensity with respect to the muscles and hypodensity with respect to the orbital fat. The belly of the lateral rectus muscle is involved with the tumor, which extends posteriorly into the superior orbital fissure. In this case, the greater wing of the sphenoid bone was absent because of neurofibromatosis.

recently, ifosfamide and etoposide following conservative surgery and combined with radiotherapy (5000 cGy) allow a survival rate of 90%.

The role of surgery in the management of orbital RMS is still controversial. Some centers perform extensive surgery while others prefer to do incisional biopsy only. The surgical approach should be planned according to the clinical and radiographic findings. When possible, a complete or near complete tumor excision is suggested without damaging vital structures (optic nerve and/or extraocular muscles) (Figures 26.8 and 26.9). If the suspected orbital RMS is located deep in the orbit, an incisional biopsy is appropriate. Fineneedle aspiration biopsy is usually unrepresentative and may be misleading.

Advances in chemotherapy and radiotherapy have significantly improved survival rates. The excellent survival rate has allowed following survivors for many years and observing the late effects of radiotherapy on both facial growth (bony hypoplasia of the orbit and facial asymmetry) and visual function (cataracts, keratopathy, retinopathy).23,24

The challenge for the future should be to identify the characteristics of patients who can safely be treated with primary chemotherapy alone to reserve radiotherapy for the remaining patients in an attempt to reduce late effects.25–27 Further reduction in radiation sequelae may derive from the use of threedimensional conformal radiation therapy techniques, by minimizing the inclusion of normal structures in the treated volume.28

Optic Nerve Glioma

Optic pathway gliomas account for 0.6 to 1.2% of all intracranial tumors (see Chapter 7).29 The incidence

A

B

C

FIGURE 26.8. Superior orbital rhabdomyosarcoma before (A) and after (C) treatment, which consisted of debulking (B), chemotherapy, and radiation treatment.

is 1 in 100,000 patients, with 90% presenting in the first two decades and 65% in the first 5 years of life. First reported by von Graefe in 1864, gliomas of the anterior visual pathways constitute about 1 to 5% of all childhood intracranial tumors.30 The majority of these tumors, including optic nerve gliomas, are lowgrade astrocytomas. Some astrocytes present spherical or cylindrical swollen cell processes called Rosenthal fibers, which stain eosinophilic (Figure 26.10). The astrocytic nature of the tumor can be confirmed using immunohistochemical techniques with antibodies against glial fibrillary acidic protein (GFAP, MW 15 kDa).31 Although this protein may also be present in some schwannomas, increased GFAP expression is typical for astrocytic tumors.32

Optic gliomas commonly occur in neurofibromatosis type 1 (NF1) and belong to the diagnostic criteria of NF1.33–35

The incidence of optic gliomas in children with NF1 is as high as to 15 to 20%, with symptomatic visual loss in approximately 20% of affected patients (Figure 26.11). Bilateral gliomas are most often seen in patients with NF1 (Figure 26.12). The optic nerve alone is involved in 24% of cases and the chiasm in 76% of cases; invasion of the midbrain is documented in 46% of patients.35,36

The most important prognostic factor is age at presentation. Early-onset optic gliomas ( 6 years) grow rapidly and must be followed closely.37,38 Primary symptoms include deterioration of visual acuity and progressive visual field defects. However, patients with NF1 seem to have a less aggressive variant of glioma. Neuro-ophthalmic aspects of optic nerve glioma are also covered in Chapter 7.39,40

The clinical course of optic pathway gliomas is related to the extent at diagnosis and histopathologic pattern (Figure 26.13). In pediatric patients with NF1 and optic pathway gliomas, the likelihood of visual

loss depends on the extent and location of the tumor as determined by MRI and is particularly associated with postchiasmal structure involvement.40

There is still controversy regarding the growth of optic gliomas and potential extension posteriorly to the chiasma. Hoyt and Baghdassarian suggested that optic gliomas represent congenital hamartomas with growth potential in the first years of life.41 Progression usually occurs in the first year of presentation.42 However, the variable and unpredictable course of these tumors makes standardization of treatment strategies difficult. Optic gliomas may undergo spontaneous regression. In a recent study, Parsa et al. documented spontaneous regression and tumor shrinkage in 12 patients with optic glioma. Regression was observed in patients with and without NF1.43 Accurate

follow-up of optic pathway gliomas to evaluate stability or progression should include a high-resolution MRI study. This is particularly helpful to evaluate the intracranial extent of optic nerve glioma.44,45

CT and MRI are important to establish the tumor extension, to plan treatment, and to allow radiologic

FIGURE 26.10. Histopathologic appearance of an optic nerve glioma that is composed of proliferating fibrillary astrocytes showing different degrees of pleomorphism.

FIGURE 26.11. (A) Patient with neurofibromatosis type 1 has cutaneous neurofibromas of the forehead and slight proptosis of the right eye secondary to a unilateral optic nerve glioma. (B) Note the missing greater wing of the sphenoid bone (arrow) on axial CT image.

FIGURE 26.12. Bilateral optic nerve gliomas in neurofibromatosis type I. Axial T2-weighted MR image shows enlargement of both optic nerves (arrows), which presents as isointense to the gray matter and as surrounded by hyperintense cerebrospinal fluid.

and clinical follow-up. The tumor causes fusiform enlargement of the optic nerve. On CT the tumor presents an enlarged, fusiform, not calcified optic nerve mass with frequent kinking and cystic areas.46 Uniform and marked enhancement after contrast administration is commonly observed. On T1weighted MR images, the tumor is usually isointense to the cerebral gray matter. On T2-weighted

MR-images fusiform lesions show high signal, while large lobulated tumors tend to have a more heterogeneous signal. A double-intensity “tubular thickening,” with kinked and elongated optic nerves, suggests but does not prove glioma in patients with NF1 (Figure 26.14). Enlargements of the chiasm and the optic tracts are signs of intracranial involvement. T1-weighted MR images after gadolinium administration usually show variable enhancement; when the tumor is large, the center of the mass shows a marked enhancement, but the periphery is not enhanced (consistent with ectactic or hyperplastic arachnoid around the nerve). Differential diagnosis of optic nerve glioma should include idiopathic optic neuritis, sarcoidosis, demyelinating disease, and optic nerve sheath meningioma.47,48

Treatment strategies include observation only, surgery, irradiation, chemotherapy, or a combination of these modalities. An “observation” policy may be applied in children with anterior tumors and absence of signs of progression.

Surgical resection is successful in tumors confined to an optic nerve. Radiotherapy is usually reserved for patients with progression after surgery and for opticohypothalamic gliomas. Chemotherapy is at an experimental stage. Chemotherapy of optic nerve glioma is further covered in Chapter 34.49,50

B

FIGURE 26.13. (A) A young child with mild proptosis of the left eye and a minimum pallor of the temporal disk (B) secondary to a unilateral optic nerve glioma.

FIGURE 26.14. (A) Axial and (B) sagittal T1-weighted MRI images show tubular thickening of the left optic nerve showing elongation and kinking at midorbit secondary to optic nerve glioma. The patient did not have neurofibromatosis.

SECONDARY AND

METASTATIC TUMORS

Neuroblastoma

Neuroblastoma is the most common extracranial solid tumor of childhood, accounting for 8 to 10% of all childhood cancers. It represents a malignant neoplasm of primitive neuroblast and is the most common metastatic orbital tumor, affecting children at a mean age of 2 years.51

Neuroblastoma arises in the abdomen, thoracic, cervical, and pelvic regions, and metastases occur by hematogenous spread. Ophthalmic manifestations are common, frequently resulting from periorbital soft tissue infiltration of the tumor.52,53 The most common sign of orbital metastic neuroblastoma is proptosis and periorbital ecchymosis (“panda bear eyes”), followed by unilateral Horner syndrome and opsoclonus (Figure 26.15). Proptosis and periorbital ecchy-

FIGURE 26.15. (A) Bilateral ecchymosis of the eyelids and periorbital skin of a patient with metastatic abdominal neuroblastoma of both orbits and brain. (B) Multiple metastatic nodules in orbits and brain are shown in T-1 weighted axial MRI image. (Courtesy of Dr. Robert A. Gordon of New Orleans, Louisiana.)

BOX 26.4. Orbital Neuroblastoma:

Clinical Presentation

Proptosis

Periorbital ecchymosis (“panda bear” eyes) Ptosis

Globe displacement Blindness (rare)

mosis are typical; ptosis and globe displacement are rather common. Symptoms are bilateral in 20 to 50% of cases (Box 26.4). Orbital involvement is almost exclusively associated with disseminated disease, while Horner syndrome and opsoclonus are frequently associated with localized neuroblastoma, particularly in the mediastinum.54 Horner syndrome, secondary to tumor in the cervical sympathetic chain, may be the presenting sign.

On a retrospective review of children, ophthalmic involvement in neuroblastoma was present in 80 of 405 cases (20%). The most common site of origin was the abdomen.51

At CT, a soft tissue mass inhomogeneously enhancing with associated lytic bony erosions is appreciable (typically involving the zygomatic bone adjacent temporal orbit). At MRI, the tumor often is isointense to the extraocular muscles, but intratumoral hemorrhages may lead to variable appearance both on T1and T2-weighted images, depending on the degree of hemoglobin catabolism. After gadolinium administration, variable degrees of enhancement are encountered. Histopathologically, neuroblastoma can be distinguished from most of the neurogenic tumors of the orbit by the presence of neurosecretory dense-core granules, detected by electron microscopy, and by positive neuron-specific enolase (NSE) activity, demonstrated by immunohistochemistry. Immunohistochemistry helps to differentiate a neuroblastoma from other small-cell tumors such as rhabdomyosarcoma, retinoblastoma, Ewing’s sarcoma, and lymphoma.55,56

The prognosis in neuroblastoma is influenced mainly by age, stage, and site of origin. In children diagnosed during the first year of life, the 2-year relapsefree survival rate is 75%; it drops to 12% after the age of 2 years.57 The survival rate in neuroblastoma has improved little in the past two decades; about 70% of the patients present with disseminated disease at the time of diagnosis. Early diagnosis is an important factor influencing the prognosis. The ophthalmologist may play a major role in the diagnosis of the disease, since 20% of the patients present with ophthalmologic involvement.51 The treatment consists of mul-

tiagent chemotherapy; combinations of cisplatin, teniposide, vincristine, and cyclophosphamide have been employed. Radiotherapy doses vary according to the age (1500–4000 cGy) Orbital metastasis has a poor prognosis; the 3-year survival rate is 11%.

Orbital Myeloid Sarcoma

(Granulocytic Sarcoma)

The orbit may be affected in all types of leukemia, but it has a greater propensity to be involved in acute myeloid leukemia (AML). Mass formation, however, is quite rare; diffuse infiltration is more common. The tumor may appear before, after, or concomitant with hematologic evidence of leukemia.58

The most frequent clinical manifestations include exophthalmos, ptosis, edema, and chemosis of the eyelids, with pain. Diagnosis is established by clinical and laboratory findings, imaging studies and biopsy. Gran-

FIGURE 26.16. Granulocytic sarcoma: two patients (A,C) with orbital mass lesions of granulocytic sarcoma. Cornea of the first patient (A) was exposed because of longstanding proptosis and developed corneal ulcer. (B) Biopsy sample from the second patient (C) shows clusters of myeloid cells infiltrating the orbicularis muscle. (Courtesy of Dr. A.O. Çavdar of Ankara, Turkey.)

ulocytic sarcoma (myeloblastoma or chloroma) is a very uncommon manifestation of acute myelocytic leukemia and presents as a focal soft tissue mass (Figure 26.16).

The term chloroma (green tumor) is derived from the greenish coloration of this lesion, which is due to the myeloperoxidase in cells of granulocytic lineage. On occasion, granulocytic sarcoma presents as an isolated soft tissue mass prior to the development of systemic disease. Correct diagnosis of the solitary lesion is important because it leads to early implementation of chemotherapy.59

While most childhood orbital tumors, such as lymphangioma, rhabdomyosarcoma, capillary hemangioma, dermoid cyst, and optic nerve glioma are unilateral, bilateral orbital involvement is observed in metastatic neuroblastoma and myeloid sarcoma.60

Orbital myeloid sarcoma occurs in young children and is quite rare among the orbital tumors of childhood, accounting for only 1 of 250 cases.3

On the basis of a review, Shields et al. calculated that about 88% of the patients with proptosis seen by an ophthalmologist have no history of leukemia at the time of presentation.60

Myeloid sarcomas are most common in certain subtypes of AML, in particular, M5a (monoblastic), M5b (monocytic), M4 (myelomonocytic), and M2 (myeloblastic with maturation).61 There appears to be a very strong association of orbital myeloid sarcoma with AML cases demonstrating a t(8;21) translocation, which is associated with a good prognosis.62,63 At T1-weighted MRI, granulocytic sarcoma is slighthy hyperintense to gray matter, muscle, and bone marrow. At T2-weighted imaging, it is isointense to white matter, muscle, and bone marrow.64 CT shows the mass to be isodense to muscle. This tumor trends to mold to contiguous structures and demonstrates relatively little bony destruction.65 Orbital myeloid sarcoma preferentially involves the lateral orbital wall. Imaging appearance, clinical history, and location can suggest the correct diagnosis, allowing prompt treatment before the development of systemic disease.66

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