Ординатура / Офтальмология / Английские материалы / Tumors of the Eye and Ocular Adnexa_Char_2001

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previously been termed Letterer-Siwe disease, has multisystem involvement, including skin, middle ear, lungs, or abdominal viscera, and often occurs in younger patients. We have seen orbital involvement in these children, and in patients < 2 years of age with Langerhans’ cell histiocytosis syndrome, diffuse systemic involvement is quite common. A typical skin and orbital lesion prior to and after 6 Gy of radiation is shown in Figure 16–43. Unlike patients with unifocal eosinophilic granuloma that involves only the orbit, patients with diffuse histiocytosis usually present because of systemic illness.184

A number of therapeutic options can be used to manage Langerhans’ cell histiocytosis that involves the orbit.191 If the child has diffuse systemic disease, these lesions respond to low-dose orbital radiation and chemotherapy. If only the orbit is involved, curettage, intralesional steroid injection, or low-dose radiation are all effective.182 Figures 16–44A and B show a 2-year-old child with a unifo-

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Figure 16–41. A, Plain skull film demonstrates smooth punchedout area with surrounding sclerosis, typical of unifocal eosinophilic granuloma. B, CT scan demonstrating bone destruction with lateral orbital swelling.

The CT pattern of a unifocal eosinophilic granuloma is shown in Figure 16–41B. Occasionally, the bone destruction is more widespread, as shown in Figure 16–42, in a patient with diffuse or multifocal eosinophilic granuloma. Rarely, these have expanded into the middle cranial fossa.190

Multifocal eosinophilic granuloma has bony involvement at more than one site, and many patients previously classified as having Hand-Schuller-Chris- tian disease can be placed in this category. Any patient with possible Langerhans’ cell histiocytosis needs evaluation by a pediatric hematologist with skeletal survey, bone marrow, body CT, and blood studies (complete blood count, liver function tests, sedimentation rate). Diffuse histiocytosis, which has

Figure 16–42. Axial CT scan with coronal reconstruction demonstrates diffuse bone destruction in multifocal eosinophilic granuloma with orbital involvement.

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Figure 16–43. A and B, Cutaneous and orbital involvement in a child with diffuse histiocytosis. C, After 6 Gy (600 rads) of photon irradiation.

cal histiocytosis lesion in the lacrimal fossa prior to and after FNAB, which documented diagnosis, and injection of steroid. Usually, there is a 6- to 12-week interval between injection and complete resolution. We and others have made the diagnosis with FNAB and then treated it with local steroid injection.195 The trend in patients with more advanced disease has been to use less radiation and more etoposide.194 The longterm sequelae after Langerhans’ cell treatment are not innocuous. In a series of 71 patients, some of whom the author managed, 10 died of multisystem disease, and late sequelae were noted in 64 percent.196

Orbital involvement in malignant histiocytosis is rare. We have seen 2 patients who developed this picture. As is typical with malignant histiocytosis, our patients first presented in their late teenage years with fever and weight loss.182,197,198

Contiguous orbital inflammation or infection from sinusitis is discussed elsewhere. It is a frequent

cause of acute proptosis in children, usually between the ages of 5 and 10 years.

OPTIC NERVE TUMORS

Orbital optic nerve tumors in children are most commonly due to glioma (pilocytic astrocytomas). Much less commonly, meningioma, sarcoidosis, metastases, idiopathic inflammation, or leukemia can involve the pediatric optic nerve. Optic nerve glioma was first described in 1816 by Scarpa, and there have been over 2,300 optic nerve gliomas described in the literature.199–206 Approximately 75 percent of cases have occurred in patients < 10 years of age; most present between the ages of 5 and 8 years. Optic nerve gliomas account for approximately 5 to 10 percent of pediatric orbital tumors.2 Optic nerve glioma occurs as an isolated finding or as part of neurofibromatosis (NF).

The NF1 gene spans 350 kb in the region of 17q 11.2.207,208 It encodes a protein, neurofibromin, which is part of the GTPase activating family, and downregulates ras activity. Loss of this tumor suppressor gene is probably important in disease.

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Figure 16–44. A, A unifocal histiocytosis of the lacrimal fossa. The diagnosis was made by FNAB. B, Approximately 12 weeks after steroid injection, the area appears normal.

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In NF, the incidence of optic nerve glioma is between 12 and 38 percent.209 Conversely, approximately 25 to 50 percent of patients with optic nerve gliomas have NF. In a review by Dutton, 29 percent of optic nerve glioma patients had stigmata of NF1.206

NF is an autosomal-dominant disease that occurs in approximately 1 of 3,000 people.209 Lisch nodules, which are iris hamartomas, are noted in 94 percent of patients > 6 years, but only 28 percent of younger patients.209 Lewis and co-workers studied 217 patients with NF and found that 15 percent had anterior pathway tumors.210,211 Often, optic gliomas are asymptomatic in neurofibromatosis. Less than one-third of optic nerve tumors were suspected either on clinical or histologic evaluation in these patients, although MRI detects a greater number of cases.212–215 In one interesting report of 2 cases with asymptomatic chiasmal and hypothalamic lesions, MRI demonstrated spontaneous partial regression.216 Gadolinium with MRI increases the detection of CNS extension.214 The MRI signs of optic nerve gliomas in NF type 1 (NF1) have been well described by Imes and Hoyt.215,217 Optic nerve gliomas that are found in association with NF1 are usually fusiform, with a high signal intensity surrounding a core of lower signal intensity due to the perineural arachnoidal gliomatosis (Figure 16–45). In addition, there is often the double intensity tubular thickening with the downward kinking of the nerve in the NF1 population (Figure 16–46). This is rarely seen in those who have the idiopathic form of optic nerve gliomas.211–215

Figure 16–46. A parasagittal T1-weighted MRI scan shows downward kinking of the optic nerve in NF1.

Most patients with optic nerve gliomas initially present with decreased vision and field loss.212,213 Proptosis is usually < 3 mm; protrusion of the globe is more common in the optic nerve than chiasmal gliomas (Figure 16–47). Rarely, patients can have other ophthalmic signs or symptoms, including strabismus, nystagmus, optic neuritis, optic atrophy, or hypothalamic syndromes. Rarely, these tumors can calcify and produce acute visual loss.218 Even more rarely, patients can develop other findings, including venous stasis retinopathy, neovascular glaucoma, intraocular invasion, or enlarged optic disc. Pain is rare. Optic nerve gliomas are distinctly uncommon in NF type 2 (NF2).221

The location and degree of optic nerve and anterior visual pathway involvement are often difficult to ascertain, on either clinical or imaging examinations. It is estimated that < 15 percent of optic nerve

gliomas involve only the orbital portion of the nerve, 60 percent involve the chiasm, and 25 percent involve the intracranial structures.206,222,223 Optic nerve gliomas confined to the orbit are more common in NF1 patients versus those who do not have that disease. When patients have involvement in the hypothalamic area, they usually present with a diencephalic syndrome that is manifested as changes in alertness, lethargy, or seizures.224

MRI evaluations are the radiologic methods of choice in patients with optic nerve gliomas.217 It is important to determine the intracanalicular, chiasmal and postchiasmal extension of the lesion.214,224 There is usually enlargement and asymmetry of the optic foramen, without erosion or hyperostosis. Images of these lesions will be enhanced with contrast. On CT, gliomas will present with uniform thickening of the entire nerve, a solitary fusiform enlargement, or irregular thickening (Figures 16–48 to 16–50).225,226 Occasionally, the glioma has a kink in its appearance, which is very typical. Some of these tumors will not been seen to grow on long-term follow-up.227,228 In

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Figure 16–48. A, A case of blurred vision caused by left fusiform optic nerve glioma in a 15-year-old girl. On axial CT scan, the posterior of the proptotic left globe is indented (arrows). B, On coronal CT scan, the nerve is enlarged. (From Char et al.,226 with permission)

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Figure 16–49. A, Neurofibroma ptosis and an optic nerve and chiasmal glioma in a 13-year-old girl. Axial CT scan showing a fusiform enlarged optic nerve that extends through the optic canal (arrows). B, Axial scan at a higher level showing the mass involving the chiasm (open arrows). (From Char et al.,226 with permission).

an atypical case, CT-directed FNAB can be diagnostic.229 Figure 16–51 shows the axial MRI scan of a 25-year-old male with recently decreased vision and an optic nerve mass. Cytopathology is shown in Figure 16–52, and it was diagnostic for a glioma. The patient’s vision improved after radiation.

The management of optic nerve gliomas is controversial. Some authors believe that many of these tumors confined to the optic nerve and chiasm are congenital hamartomas and should be merely watched.230 Other authors believe all optic nerve gliomas require aggressive intervention with either surgery or radiation.231–233 In reviewing a number of different series, it is obvious that the disease can run a full spectrum from benign proliferation to extremely aggressive and malignant behavior. Gliomas posterior to the chiasm have greater malignant potential than have anterior lesions, but this is not always the

Increased intracranial pressure is a poor

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Figure 16–50. A, This child had progressive proptosis with loss of vision. The scans were obtained shortly before a debulking procedure was done through a lateral orbitotomy. Axial CT scan demonstrates a fusiform enlargement of the optic nerve. B, On postcontrast axial CT scan, the tumor shows peripheral enhancement, and a central radiolucent zone secondary to necrosis. This pattern was histologically confirmed. (From Char et al.,226 with permission).

when no intervention was undertaken, 25 percent progressed, while in the 28 eyes which received radiation, a similar number appeared to progress. This series was updated in 1986.239 Sixteen of the 28 patients originally reviewed in 1969 are dead, 5 from chiasmal gliomas. The mortality in patients with or without NF were similar. Nine of the 16 deaths occurred in patients with NF; 2 were from chiasmal tumors, 2 died as a result of surgery, and 3 died of other causes. The 12 surviving patients have not had any visual deterioration since 1969. The overall death rate was 57 percent; most deaths occurred within 3 years of diagnosis. Similarly, Listernick and colleagues noted that many of these lesions should be watched, and in a large series only 3 patients developed loss of vision.240

The roles of surgery, chemotherapy, and radiation in gliomas of the optic nerve tumors are evolving. In almost all series, survival in all tumors isolated to the orbit is excellent.206,23,241 In these anterior optic nerve gliomas that do not involve the chiasm, observation is indicated if visual acuity is good and the tumor remains stable. If the neoplasm starts to grow or vision decreases, treatment is advocated. The choice of treatment is uncertain. Historically, irradiation or surgery was used; however, there was significant morbidity, especially in young irradi-

prognostic sign.237 In a small series from London of about 69 patients treated from 1977 to 1994, using multivariate analysis, relapse-free survival was shown to have improved with older age, NF1, and treatment with chemotherapy and radiation.238

Review of the natural history of this tumor is confusing. Spontaneous regressions occur, and many papers presenting strong opinions on management probably have an inadvertent referral bias, in that their cases may not represent the usual pattern of disease course for this tumor. In 1969, Hoyt and Baghdassarian reviewed 36 patients with optic glioma.230 Twenty-nine had chiasmal hypothalamic involvement, and only 6 patients died, 1 as a complication of intervention.230 In 41 eyes in 23 patients,

Figure 16–51. Axial MRI scan shows an optic nerve mass in a 25- year-old patient who presented with decreased vision.

ated patients.240,242–244 Several groups have treated these gliomas and more posterior tumors with chemotherapy, with retention of vision.243–246 While a high percentage of patients who received chemotherapy relapsed and required radiation salvage, several clinicians believe that by delaying radiation, neurotoxicity may be diminished.243,247 Surgical intervention in orbital cases is usually limited to blind eyes with marked proptosis (Figure 16–53A). In such cases, we have removed the bulk of the tumor through a lateral orbitotomy with retention of the eye (Figure 16–53B).229 While local recurrences can occur, they are uncommon.200,248–250

Lesions isolated to the chiasm or to the chiasm and optic nerve are usually serially observed, unless there is visual loss or growth is documented. Some authors have advocated surgery, radiation, or chemotherapy.206,232,233,247 We have limited the use of intracranial surgery, chemotherapy, or radiation to enlarging tumors with marked visual and CNS symptoms.251 Kuenzle studied 21 optic nerve pathway gliomas in association with NF. Ten remained stable. Significantly 11 of the 21 developed other nonpathway CNS tumors within 4 years.252

Other clinicians have advocated radiation therapy for all chiasmal gliomas.253,254 In a report from the

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Curie Institute, between 1970 and 1986, 57 patients with chiasmal tumors were irradiated.255 These were a slightly older population than usual with a mean age of 17 years at presentation. Forty percent of the patients had NF. In those cases where the tumors were confined to the anterior chiasm, the relapse-free survival rate was 100 percent at 5 years and 88 percent at 10 years. When the tumor involved the adjacent structures the 10-year survival rate was 72 percent. Longterm visual results were evaluable in approximately 35 patients, and 21 had improved visual acuity after radiation.236 Pierce and colleagues irradiated 24 optic nerve gliomas that involved the chiasm.256 Sixteen of 24 had decreased vision; after radiation, only 3 had tumor progression. Vision stabilized or improved in 21 patients.256 Jenken and co-workers noted that 5 of 28 irradiated patients died of second tumors versus none of the 49 who did not receive radiation.242

In contrast, in another series, 85 patients were treated after histologic confirmation; only 2 had visual acuities of better than 20/50.257 Six of 33 tumors confined to the optic nerve had recurrences after treatment versus 19 of 52 chiasmal tumors.257 Five of the 33 patients with optic nerve gliomas died, as did 29 of 52 of those with chiasmal tumors. Some authors believe that patients with NF may have had a better prognosis.258

Radiation treatment of optic nerve gliomas generally is most effective, if at least 50 Gy is given, but as discussed above, it is uncertain how many of these lesions would have remained stable without therapy.259,260 Radiation is probably the treatment of choice for hypothalamic involvement.261–263 There are, however, no definitive data showing improved survival with radiation.206,264–266

The prognosis in patients with optic nerve glioma is a function of the location of the tumor, the presence of hydrocephalus and the histologic tumor grade.247,267 Lower radiation complications were noted when the fraction size was < 200 cGy, and the total dose was < 54 Gy.268,269

Less commonly, other tumors can involve the optic nerve in children. Leukemic infiltrates are discussed in the chapter on intraocular lymphoma. While optic nerve sheath meningiomas are much more frequent in adults, they can occur in children, especially in those with NF.270 Two cases of non–optic nerve intraorbital

meningiomas have been reported in young males at ages 7 and 10 years.271 Malignant teratomas of the optic nerve have also been reported, as have diffuse hyperplasia of the optic nerve in association with NF.272, 273 Other rarer optic nerve tumefactions in childhood include ganglionomas, hemangioblastomas, and optic nerve sheath meningoceles.273–276 Similarly, there can be multiple focal neurofibromas in the orbit in patients with NF.277 Rarely, acute optic nerve gliomas can occur.278

FIBROUS AND BONY LESIONS

Dermoid cysts that involve the orbital bones are more frequent in adults (see chapter on lacrimal gland tumors). A number of uncommon bony lesions can involve the pediatric orbit, including aneurysmal bone cysts, giant cell granulomas, intraosseous hemangioma, and brown tumors.279–282 Brown tumors occur in hyperparathyroidism and result in lytic destruction of bone with local hemorrhage.283 Often, the skull has a salt-and-pepper appearance on imaging studies secondary to the hyperparathyroidism.1,284 Less than 20 of reported cases of aneurysmal bone cysts involved the orbit, and most occurred in the orbital roof.279,285,286 Occasionally, these lesions can cause optic nerve compression, with loss of central vision.287 Usually, these lesions are hyperintense on T2–weighted MRI scans.286 Differentiation between a giant cell reparative granuloma, brown tumor, and aneurysmal bone cyst is relatively straightforward. Brown tumor is part of the osteitis fibrosis of hyperparathyroidism. Aneurysmal bone cysts versus orbit giant cell granulomas are diagnosed on the basis of histologic examination. The latter lesion is less common.288

A number of fibrous processes can involve the orbit, either primarily or secondarily. As discussed in the chapter on orbital pseudotumors, an inflammatory process can eventually become fibrotic. Juvenile ossifying fibroma of the orbit is a misnomer, since it can also occur in the adult.280,281 This entity, first described in 1949 by Gogl, has had a number of different terms and has occasionally been lumped with fibrous dysplasia.289 Patients usually present with proptosis and occasional visual complaints in the second decade of life. Most commonly, juvenile

ossifying fibromas arise in either the ethmoid or frontal sinuses and produce inferior displacement of the eye.288

In contradistinction to fibrous dysplasia, ossifying fibromas usually have well-defined margins and ovoid expansion of overlying bone.290 Juvenile nasopharyngeal angiofibromas are most commonly found in the second decade of life in young Caucasian males.291 These can have aggressive local growth, and rarely either develop spontaneous regression or malignant transformation. In approximately 12 percent of cases, orbital extension can occur with decreased vision.291,292 Sinus tumors secondarily involving the orbit are discussed in the chapter on lacrimal sac tumors.

Figure 16–54 shows a child with congenital orbital fibrosis of undetermined etiology.

Katz and Nerad recently reviewed 20 patients with fibrous dysplasia of the orbit. Eleven were older than 18 years at the time of presentation. Multiple bones of the orbit are involved, and in some cases, multiple transformations have occurred.293

LACRIMAL GLAND TUMORS

Lacrimal fossa tumors, with the exception of dermoid cysts or unifocal eosinophilic granulomas, are unusual in children. As discussed in the adult section, we have seen 2 teenagers (and 1 preteenager) with adenoid cystic carcinomas, but these are distinctly uncommon.

We had one child who presented with an adenoid cystic carcinoma and rapidly developed widespread disease. The group from the AFIP presented 11 such cases under the age of 18 years. They noted that, in general, these younger patients fared better than did older patients with this disease, probably because of histologic variation.294 While benign epithelial lacrimal gland tumors are much more common in adults, we have managed one 5-year-old who presented with a pleomorphic adenoma of the lacrimal gland.295 More commonly, children and teenagers with lacrimal gland enlargement have a chronic or acute dacryadenitis secondary to viral infection. Figure 16–55A and B shows a young girl with an acute S-shaped lid swelling typical of lacrimal gland inflammation. The patient had a history of a viral upper respiratory tract infection approximately 1 week prior to the development of the lacrimal gland swelling, and the lesion resolved spontaneously over 2 weeks. Figure 16–55B shows an axial CT demonstrating chronic dacryadenitis, without bone involvement in this patient. Occasionally, a lipoma or lipo-

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dermoid can occur in the area of the palpebral portion of the lacrimal gland, as shown in Figure 16–56.

SINUSITIS WITH CONTIGUOUS

INVOLVEMENT OF THE ORBIT

A problem that requires rapid surgical intervention in children is the development of bacterial sinusitis with secondary involvement of the orbit. Most of these children are between 6 and 10 years of age. Development of sinusitis at age > 2 years is very uncommon, since the sinuses are not completely aerated. Figure 16–57 shows a case in a 1-year-old child who presented with orbital cellulitis due to contigous ethmoid infection. Figure 16–58A demonstrates an 8-year-old boy with the onset of an upper respiratory tract infection with high fever approximately 2 days prior to the sudden development of proptosis and decreased vision. On axial CT evaluation, opacification of the ethmoid sinus is present with contiguous extension in the orbit (Figure 16–58B). Bacterial sinusitis with secondary orbital involvement will often cause loss of vision; patients with these symptoms should be treated on an urgent basis.296 In patients with severe orbital proptosis, paresis of extraocular movement, and inflammatory orbital signs that are progressive despite high-dose intravenous antibiotics, surgical drainage of the sinuses and orbital abscess is usually required in addition to medical therapy.

Occasionally, sinusitis associated with contiguous orbital disease can be quite subtle, and the presentation may mimic a primary orbital tumor (Figure 16–59A). The axial CT scan shown in Figure 16–59B was initially thought most likely to repre-

sent an orbital rhabdomyosarcoma; the patient was a young afebrile girl, whose only symptoms and signs were related to her orbital problem. At surgery, orbital and sinus abscesses were found, and they responded nicely to drainage and antibiotics.

Other sinus diseases that can involve the orbit are discussed in the section on adult orbital tumors.

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Figure 16–58. A, Eight-year-old boy with bacterial sinusitis secondarily involving the orbit. B, CT scan demonstrating ethmoid sinusitis with contiguous involvement of the orbit.

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