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

The presentations and differential diagnoses of orbital tumefactions in children are quite different from those observed in adults. Even among children of different age groups, there is a marked variation in the frequency of different orbital tumors.

Children with orbital lesions should be evaluated in an urgent manner. While a number of series on pediatric orbital tumors have stressed that most lesions are not malignant, treatable primary orbital malignancies are not rare in childhood, and some histologically benign processes can produce profound ocular morbidity with visual loss, if not treated promptly.1–4

A list of the most frequent orbital tumors in childhood is shown in Table 16–1. The list is deliberately not all-inclusive; very rare tumors are not listed, and lesions that only involve older teenagers are discussed under adult orbital disease in other chapters.

As has been discussed by others, the frequency of orbital tumors is a function of the geographic location of the survey, the authors’ interest, and local referral patterns.3,5 As Moss pointed out in adult orbital tumefactions, depending on the series, the most frequent tumors had been described as mixed tumors of the lacrimal gland, meningiomas, hemangiomas, or as thyroid eye disease.5 Similarly, a recent histologic series by Shields and co-workers of 250 pediatric orbital biopsies seemed skewed toward cystic lesions, with 46 percent of biopsies being dermoid cysts, l6 percent inflammatory lesions, 7 percent vascular tumors (hemangioma or lymphangioma), 7 percent mainly adipose tissue (either orbital fat or dermolipomas), 4 percent rhabdomyosarcomas or secondary orbital malignancies, and lymphoid tumors and optic nerve tumors accounted for 2.4 percent of cases.4 In

a Turkish series, the most common pediatric orbital tumor was rhabdomyosarcoma, and dermoid cysts were the most common benign lesions.6 Kodsi and colleagues reviewed 340 childhood orbital lesions examined over a 60-year period at the Mayo Clinic.7 They noted the following frequencies of orbital tumefactions: cystic lesions 23 percent, vascular processes (hemangiomas and lymphangiomas) 18 percent, optic nerve and central nervous system (CNS) 16 percent, bone lesions 9 percent, and rhabdomyosarcoma 7 percent.7 Bullock and colleagues analyzed 141 cases of their own and reviewed 1,370 pediatric orbital tumors already in the literature.8 Overall, approximately 24 percent of the reported cases of orbital tumors were malignant.8 In the author’s experience in an ophthalmic oncology practice, I have managed a higher percentage of malignant pediatric orbital tumors. The author has arbitrarily divided pediatric orbital tumors into those that occur in infancy and those that occur in childhood. Teenagers are more prone to have the adult pattern of orbital disease, and those lesions are discussed under adult orbital tumors.

In infants, the most common causes of proptosis are hemangioma, metastatic neuroblastoma, superficial dermoids, and leukemia.9

NEUROBLASTOMA

Neuroblastoma is the most common tumor in early childhood and has an incidence of approximately 10 per 12 million live births.10 In a study of 9,308 systemic childhood malignancies, neuroblastoma accounted for approximately 7 percent of cases.11,12 These tumors are derived from sympathetic ganglion

tissue. Approximately 70 percent develop in the upper abdomen; however, they can rarely occur as a result of a cervical sympathetic ganglion chain tumor.12,13 Approximately 500 new cases of neurob-

Table 16–1. COMMON PEDIATRIC

ORBITAL TUMEFACTIONS

Primary orbital malignancies

Rhabdomyosarcoma

Alveolar soft part sarcoma

Fibrosarcoma

Malignant fibrous histiocytoma

Leiomyosarcoma

Osteosarcoma

Systemic malignancies with orbital involvement Burkitt’s lymphoma

Chloroma (myeloblastoma or myeloid sarcoma) Neuroblastoma

Ewing’s sarcoma Wilm’s tumor

Secondary orbital involvement from contigious malignancies Retinoblastoma

Esthesioneuroblastoma

Cystic lesions

Dermoid and epidermoid cysts

Hematic cysts

Aneurysmal bone cyst

Choristomatous cyst

Traumatic inclusion cyst

Microphthalmos with orbital cyst

Ecchinococcus cyst

Congenital teratoma

Vascular lesions

Hemangioendothelioma (hemangioma)

Lymphangioma

Orbital varix

Benign fibrous tumors

Fibrous dysplasia

Neurofibroma

Cartilaginous hamartoma

Juvenile ossifying fibroma

Inflammatory lesions

Pseudotumor

Histiocytosis syndromes

Pseudorheumatoid nodule

Thyroid orbital disease

Infectious processes

Contiguous orbital involvement from sinusitis

Orbital tuberculosis

Viral and bacterial lacrimal gland inflammation

Optic nerve tumors

Optic nerve glioma

Leukemic infiltrate

Pseudotumor

Meningioma

Sarcoid

Miscellaneous Brown tumor

Melanocytic neuroectodermal tumor of infancy (retinal anlage tumor)

lastoma are diagnosed in the United States each year.14 At the time of diagnosis, approximately 70 percent of neuroblastoma patients have metastatic disease.15

Molecular studies in neuroblastoma have demonstrated serial cumulative genomic alterations. Early changes may include loss of chromosome 1p (del-1p); probably, this represents the loss of a tumor suppressor gene at 1p36.16 Overexpression of the N-myc on 2p24 is associated with rapid disease progression, poor prognosis, and/or advanced disease. However, the exact prognostic relevance of different genomic changes has been subject to ultimate interpretation.20 Approximately 85 percent of patients have a deletion or rearrangement of chromosome 1p.21 N-myc has previously been shown to correlate with metastatic disease.22,23 A number of other genomic changes have also been noted in this tumor.24

Approximately 20 percent of children with neuroblastoma have evidence of ophthalmic involvement, either with proptosis, Horner’s syndrome, or opsoclonus.25 In a group of 648 children with metastatic neuroblastoma, 18 percent had either intracranial or orbital metastases.26 Patients with orbital metastases in this series had a decreased survival. In a retrospective study from St. Jude’s Hospital of 450 neuroblastoma patients, 47 had some physical abnormality of the eye.27 Often, ophthalmic signs are the first manifestation of neuroblastoma, and many of these patients present to the ophthalmologist with orbital metastases prior to the discovery of the primary neoplasm. Characteristic clinical findings of metastatic orbital neuroblastoma are the rapid onset of swelling and proptosis. Often, these signals are misdiagnosed as being of either inflammatory or traumatic origin, especially when children present with ecchymosis of the lower lids.28 Figure 16–1 demonstrates a child who presented with unilateral orbital proptosis after returning from a camping trip. Two days prior to presentation, he had had subtle ecchymosis of the lower lid.

A number of other presentations of neuroblastoma in the eye include squint, dilated or fixed pupils, edema or atrophy of the optic nerve, retinal edema, exudates and hemorrhages, or Horner’s syndrome. The latter presentation is most com-

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monly seen in patients under 2 years old who have mediastinal or cervical primary neuroblastomas.25 A unilateral Horner’s syndrome is often associated with localized cervical disease; it has a relatively favorable outcome. Eight of 11 cases had longterm survival. Similarly, opsoclonus was a feature of only localized disease, and these children also fared better.29

Almost all children with metastatic orbital neuroblastoma have bone involvement with diffuse orbital, bone, and brain metastases demonstrable on either computed tomography (CT) or magnetic resonance imaging (MRI). Figure 16–2A shows a plain skull radiograph of a child initially referred for a tripod fracture felt to be due to parental abuse. Figure 16–2B shows the extent of tumor involvement on CT with bony destruction and contiguous CNS disease. On fine-needle aspiration biopsy (FNAB), a small, malignant, round cell, nonlymphocytic tumor was diagnosed (Figure 16–2C). Rarely, as shown in Figure 16–3, the orbital bone changes associated with a metastatic neuroblastoma can be minimal.

We have found FNAB useful in establishing the correct diagnosis in many of these patients with orbital neuroblastoma. Unfortunately, it can sometimes be difficult to differentiate other small round cell neoplasms, such as Wilm’s tumor, rhabdomyosarcoma, lymphoma or Ewing’s sarcoma on the basis of FNAB.30,31 As discussed elsewhere in

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Figure 16–1. A and B, Clinical photographs of orbital neuroblastoma. Lid ecchymoses are often associated with this tumor and may mimic trauma.

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Figure 16–2. A, Plain skull radiograph, showing bone involvement from metastatic neuroblastoma that simulates trauma. B, Axial CT scan demonstrating neuroblastoma responsible for the bony lesion. C, Fine-needle biopsy shows a small round-cell malignant neoplasm consistent with neuroblastoma.

Figure 16–3. Direct coronal MRI of neuroblastoma with minimal bone involvement.

this book, modifications have allowed us to use FNAB samples to perform fluorescent in situ hybridization (FISH) and other molecular biologic techniques.

The evaluation of patients with possible metastatic orbital neuroblastoma involves multimodality examinations with pediatric and ocular oncologists. In patients < 2 years, destructive osseous lesions of the orbit are most likely due to neuroblastoma, although, rarely, one of the Langerhan’s histiocytosis syndromes can produce some similar features (see below). Often, on general physical examination, an abdominal mass can be palpated. Patients should have a careful physical and neurologic evaluations. Ancillary studies, in addition to orbital and brain CT or MRI, include bone marrow studies, complete skeletal survey, intravenous pyelogram, and urinary catecholamines. In one study of 145 metastatic neuroblastoma patients, single bone marrow aspirates underestimated the prevalence of marrow involvement by as much as 83 percent.32 In patients with widespread disease, elevation of the urinary catechol are found in over 80 percent of cases.33 Bone scan is useful, since approximately 15 percent of

patients with negative skeletal surveys will have a positive radionucleide study.10 The use of metaiodobenzylguanidine is another imaging study which appears to increase prognostic accuracy in metastatic disease.34

There is limited evidence to suggest that debulking of an orbital neuroblastoma metastasis improves prognosis. Generally, survival is best in children < 11 months of age. In one study, there was 72 percent survival for all stages of neuroblastoma in children < 11 months of age, versus 12 percent in children 2 years and older.37 Disseminated disease, including involvement of the orbit, has historically been almost uniformly fatal although newer combined multimodality regimens (surgery, chemotherapy, bone marrow transplantation) have increased the length of survival.35,38 In one series, 4 of 46 patients with metastases (stage IV disease) had survival of over 1 year.39 In contrast, infants with stage IV disease often do well; in another series, 10 of 11 were disease free between 2.5 and 13 years after diagnosis.40

Intensive chemotherapy with autologous bone marrow transplantation has increased the event-free 4-year survival to approximately 40 percent in some series. The therapeutic paramenters used in these trials are undergoing evolution.45,46 There have been some molecular pilot treatment studies, including a new agent reactive with topoisomerase.47,48

OTHER PRIMARY

ORBITAL MALIGNANCIES

Wilm’s tumor rarely metastasizes to the orbit in the same age group. It is much less frequent than orbital neuroblastoma but can be difficult to differentiate, either by clinical presentation or sometimes even on histologic examination.49

In a slightly older pediatric or an adult population, esthesioneuroblastoma, a tumor similar to neuroblastoma, occurs. This tumor was first recognized in 1924 and approximately 250 cases have now been reported.50 The peak incidence appears to be in the second and third decades of life. Often, these lesions can be difficult to diagnose. Most commonly, they involve the sinuses, but in approximately 10 percent of cases, ophthalmic symptoms

304 TUMORS OF THE EYE AND OCULAR ADNEXA

are the first sign of this tumor. More commonly, nasal blockage or a bloody nasal discharge are the initial presentation. Figure 16–4 demonstrates a CT scan of an esthesioneuroblastoma with secondary orbital involvement in a teenage boy. Often, these patients do quite well with a combination of resection, chemotherapy, and radiation.

Leukemic involvement of the orbit is another common cause of proptosis in infants (Figure 16–5). Most commonly, leukemic orbital involvement is observed in children from the Mediterranean basin or Africa. In the latter group of patients, it is the second most common cause of orbital proptosis after Burkitt’s lymphoma.9,51 Rarely, a neuroblastoma can be confused with a leukemic orbital lesion. In one report, this diagnostic uncertainty was resolved using special stains on a fine-needle aspirate.52 Occasionally, a combination of chromosomal and immunophenotypical analysis of tumor specimens can be helpful to differentiate these.53

ACUTE MYELOMONOCYTIC LEUKEMIA

Acute myelomonocytic leukemia (AMML) often produces a greenish orbital tumor which has been termed, because of the color, a chloroma. Other terms for this tumor are ocular granulocytic sarcoma, myeloblastoma, or myeloid sarcoma. In one Turkish series, 20 of 56 children with AMML had ocular involvement. Seventeen of these children were males, and bilateral involvement occurred in 9 patients.51,54 A more recent report noted that 33 of 121 such patients had ocular involvement.55 In that latter publication, the mean survival with ophthalmic manifestations was 8.7 months, compared with 28.6 months when the eye and adnexa were not involved.55 The hematologic diagnosis was made before the onset of ocular disease in only 1 of the 20 cases, and the orbital manifestations responded earlier to chemotherapy than the hematologic manifestations.54 A child with orbital and intraocular involvement from AMML is shown in Figure 16–6. Zimmerman and Font collected 33 cases of this tumor at the Armed Forces Institute of Pathology (AFIP), and the median age in that series was 7 years.56 Pui and colleagues noted that approximately 5 percent of children with AMML developed

granulocytic sarcomas. In orbital granulocytic sarcoma, there was homogenous gadolinium uptake MRI scans. In contrast, an intraorbital hemorrhage usually gives heterogeneous results, and an orbital

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Figure 16–4. A, Axial CT scan of an esthesioneuroblastoma with secondary orbital involvement in a teenage boy. Posterior orbital involvement is shown. B, The extent of sinus involvement of the lesion shown in Figure 16–4A.

abscess is usually either hypointense or isointense on T1-weighted images and hyperintense on T2- weighted scans.57 Overall, in a pediatric group, leukemias, including the more common acute lymphocyte type, account for 2 to 10 percent of orbital tumors.58–61 Clinically, we have noted two types of typical presentations with infants having leukemia in

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the orbit. Sometimes, these children present with only orbital disease, often in a preseptal location. An example of this pattern is shown in Figure 16–5. This child presented with a medial canthal mass. After orbital biopsy, a bone marrow biopsy confirmed systemic leukemia. Rarely, leukemia can present as an acute dacryocystitis.62 Figure 16–6 shows a child with AMML with panophthalmitis as a result of leukemic involvement. Figure 16–7 shows another acute leukemia patient with orbital involvement by this neoplasm. Some children have developed leukemic relapse in the orbit. As discussed above, the MRI pattern in leukemic children with orbital findings is quite useful, since the differential diagnosis includes neoplasm, infection, or hemorrhage, and often, these can be distinguished on the basis of MRI characteristics.57

The management of leukemia is outside the purview of this book. Better results have been obtained with more aggressive treatment, and this is being performed in several centers around the world.63–67 As discussed above with AMML, and acute leukemia in general, ophthalmic involvement is associated with a poorer prognosis. In one report, 27 of 28 patients with ophthalmic manifestations of acute leukemia died within 28 months.67 Rarely, in children, a lymphoma can involve the orbit.68

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Figure 16–5. A, Clinical view of preseptal orbital presentation of acute leukemia. B, Axial CT scan of preseptal orbital presentation of acute leukemia. C, Relapse of acute leukemia manifested as an orbital myositis.

Figure 16–6. Child with panophthalmitis and orbital mass secondary to acute myelomonocytic leukemia (AMML)

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Figure 16–7. Axial CT scan demonstrates orbital involvement in a 1-year-old child with acute leukemia.

Rhabdomyosarcoma can also present in the < 2-year age group, but it is more commonly seen in slightly older children, as discussed later.

BENIGN ORBITAL TUMORS OF INFANCY

Capillary Hemangiomas

The most common benign ocular tumor of infancy is capillary hemangioma; it may involve the lid, conjunctiva, orbit, or simultaneously more than one of these areas. Most commonly, capillary hemangiomas present in the first year of life, and orbital or lid hemangiomas are often noted at birth or within the first 2 months.69 As discussed in Chapter 1 on eyelid tumor diagnosis, hemangiomas have a 3:1 female-to-male ratio, and there have been a number of interesting animal models developed.70

Ninety-five percent of capillary hemangiomas are evident before 6 months of life. Figure 16–8 demonstrates a typical case of a lid-orbital capillary hemangioma, with progression over the first 9 months of life.70 Usually, these tumors grow rapidly for the first 6 to 12 months and then slowly regress. These lesions are almost always diffuse clinically, radiologically, or at surgery. There is usually a red or bluish hue to the mass, when seen either under the skin or through the conjunctiva. If the mass is palpable, it is relatively soft and can be compressed, but margins are poorly defined. As shown below, the CT or MRI patterns are characteristic, and usually they are in both the intraconal and extraconal areas of the

orbit. The orbit may be expanded, but bone invasion is rare; that latter finding mandates a biopsy to rule out a malignancy. As Henderson has pointed out, however, the course of hemangiomas can be unpredictable.71 Regression usually occurs between the ages of 5 and 7 years but may continue until age 18 years, and sometimes they spontaneously resolve during infancy.72

A number of previous series have demonstrated that there is up to an 80 percent incidence of serious ocular sequelae with capillary hemangiomas of the orbit and eyelids. Approximately 60 percent develop amblyopia and a significant number develop asymmetric refractive errors.73–75 Kushner and others (see pediatric lid tumors in Chapters 1 to 3) reviewed the rationale and results of intralesional steroid injection for infantile adnexal hemangiomas.76 He reported on 10 patients treated with intralesional steroids and found that reasonable shrinkage of the tumor was noted in 9. Others have noted similar responses.77 Significant complications have been reported with intralesional steroids.78 In the author’s personal experience, intralesional steroids are used and there has not been a major complication.

We do not intervene in infantile orbital or lid hemangiomas, unless they are causing visual problems. Children are evaluated clinically and, if the lesion is unusual or growing, with MRI (Figure 16–9). The MRI pattern of a capillary hemangioma usually shows an isodense lesion on T1-weighted images and a tumor that is hyperintense to brain on T2-weighted images (Figure 16–10).

Infantile capillary hemangiomas should be treated when definite growth has a possible effect on vision.

Figure 16–8. Orbital and lid capillary hemangioma. Presenting as a small lesion, this tumor showed growth on serial observation.

Our first mode of therapy is intralesional steroids. We inject 1 mL of methylprednisolone sodium succinate (SoluMedrol) (40 mg/mL) diffusely throughout the

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Figure 16–9. A, Axial CT scan of biopsy-proven capillary hemangioma. B, T1-weighted axial MRI scan of capillary hemangioma of the lid and anterior orbit. C, T2-weighted axial MRI scan. The T1 and T2 MRI patterns demonstrate the vascular nature of the lesion (see Table 15–2)

lesion with a 25-gauge needle. We do not use general anesthesia and have not seen complications with this approach, although they have been described (see Chapter 2).78 Usually, tumor regression begins in 2 to 3 days, and maximum effect is seen within 1 week. In the author’s experience, if two injections spaced 1 week apart yield no results, surgery is necessary.

Other authors have been more impressed with the use of oral steroids at 3 to 5 mg/kg of prednisone daily. In the author’s experience, injectable steroids are preferred, but there is a paucity of data that support one approach versus the other.79 The “clinical trade-off ” is between more likely systemic complications with oral agents, compared with local complications with rejection.

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Figure 16–10. A, T1-weighted axial MRI scan shows an isodense tumor. B, T2-weighted direct coronal scan shows that the capillary hemangioma is hyperintense with regard to brain.

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Although capillary hemangiomas are usually relatively diffuse, occasionally we and others have been able to remove most of the tumor with excellent cosmetic and visual results.80 Figures 16–11A and B demonstrate a growing capillary hemangioma producing amblyopia. The tumor was resected (Figure 16–11C); after aggressive patching, the patient had good return of vision (Figure 16–11D). Plager and Sneider reported three patients who had total resections of their hemangiomas with resolution of the astigmia. Others had noted that approximately 16 percent had marked reduction of astigmia after intralesional steroids.81

An intriguing report of treatment using interferon alpha-2b in a massive tumor that had not responded to oral steroids was published.82 This agent has been effective for hemangiomas in the respiratory system, but serious side effects have been reported.83 We would use it only if the above options were not effective.82 Very rarely, hemangiomas can involve the orbital bones; but only approximately a dozen cases have been reported.83

Cystic Infant Lesions

Cystic lesions of the orbit more commonly occur in slightly older children. We have seen 5 children who presented with neonatal hematic cysts.84 Figure 16–12 demonstrates such a cyst on a direct parasagittal MRI scan. In all the neonatal deep orbital cysts we have observed, there was a history of either birth trauma, poor Apgar scores, or a hematologic abnormality. In 4 of the 5 cases, simple aspiration with a needle resulted in complete resolution. One case recurred and eventually required removal of the cyst and its lining.

Colobomatous malformations with orbital cysts are not rare in children with microphthalmos.85 Occasionally, these lesions demonstrate growth and require removal because of concern about possible malignancy. Figure 16–13 shows the MRI and CT patterns of such a lesion in a child with microphthalmos with coloboma. While it is not always discernible whether or not an open connection exists between the microphthalmic eye and the contiguous

Figure 16–12. Direct sagittal MRI scan of a congenital neonatal orbital cyst.

cyst, we have been able to remove the cyst surgically and leave an intact eye (in terms of retaining space and not developing phthisis). Figure 16–14 shows an optic nerve coloboma, microphthalmos, and orbital cyst. Figure 16–15 shows an axial CT scan of a child thought to have the above clinical findings; however, both CT and histology demonstrated an enlarged cystic eye.

Orbital teratomas are relatively uncommon; only 60 cases have been reported.86–90 This group of conditions is reviewed well elsewhere.90,91 These teratomas are congenital tumors that consist of tissue derived from more than one layer. They usually present with sudden onset of proptosis in the neonatal or infant periods (Figure 16–16).85–89 Teratomas of the orbit are usually benign but should be removed surgically to decrease the likelihood of continued orbital expansion or malignant transformation (a rare occurrence).92 Even more rarely, ectopic brain tissue can occur in the orbit.

Encephaloceles can also present as orbital proptosis. However, on imaging, the direct connection with the CNS should be obvious.93 A child with a meningocele and typical downward displacement of the globe is shown in Figure 16–17.

In older children, orbital dermoids most commonly occur in the lacrimal fossa. In young chil-

dren, more often, there are anterior epidermoid cysts or superficial dermoids. An axial MRI scan shows such a lesion (Figure 16–18). These are almost always relatively hard, not fixed to bone, and not freely mobile (Figure 16–19). Most children with

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Figure 16–13. A, Parasagittal T1-weighted MRI scan demonstrating large orbital cyst in a microphthalmic eye with coloboma. B, Axial CT scan with parasagittal reconstruction demonstrates large colobomatous cyst with microphthalmos.