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From the Archives of the AFIP

Pediatric Orbit Tumors and Tumorlike Lesions: Osseous Lesions of the Orbit¹

¹ From the Department of Radiology, F. Edward Hébert School of Medicine, Uniformed University of the Health Sciences, 4301 Jones Bridge Rd, Bethesda, MD 20814 (E.M.C., J.G.S.); Department of Radiologic Pathology (M.D.M.) and Ophthalmic Pathology Section, Department of Neuropathology (C.S.S.), Armed Forces Institute of Pathology, Washington, DC; and Department of Medical Education, Madigan Army Medical Center, Tacoma, Wash (R.C.). Received January 21, 2008; revision requested March 4 and received March 31; accepted April 3. All authors have no financial relationships to disclose. Address correspondence to E.M.C. (e-mail: echung{at}usuhs.mil).

	Abstract

Top Abstract LEARNING OBJECTIVES FOR TEST... Introduction Dermoid and Epidermoid Inclusion... Fibro-osseous Lesions Langerhans Cell Histiocytosis Granulocytic Sarcoma Neuroblastoma Metastases Primary Malignant Bone Tumors Conclusions References

 
Many extraocular masses involving the pediatric orbit have an osseous origin. The most common is the dermoid inclusion cyst; these cystic lesions may contain lipid and are most often found near the zygomaticofrontal suture, adjacent to an indolent-appearing erosion of bone. Some primary bone lesions may involve the orbit, producing a lytic or dense lesion with enlargement of the bone; these lesions include fibrous dysplasia, juvenile ossifying fibroma, and osteosarcoma. Fibrous dysplasia tends to produce a mass of ground-glass appearance with longitudinal osseous expansion, whereas juvenile ossifying fibroma is likely to produce a mixed lytic and sclerotic lesion and focal osseous enlargement. Osteosarcoma causes marked bone destruction and variable osteoid production. Langerhans cell histiocytosis, an idiopathic reticuloendothelial proliferative disorder, tends to involve the bones of the skull, especially the lateral orbital roof; it produces lytic destruction of bone with a sclerotic rim and a large intraorbital soft-tissue mass. Granulocytic sarcoma is a solid tumor that may occur in children with myelogenous leukemia. These tumors tend to arise in the subperiosteum of the lateral orbital wall, although they usually do not disrupt the bone. Finally, the orbit is a common site for bone metastases from neuroblastoma, which cause aggressive periosteal reaction in the orbital roof or lateral wall. The last three conditions are often bilateral. At imaging evaluation, osseous lesions may appear similar to each other and to nonosseous masses of the orbit. Knowledge of the pathologic features of these tumors and how these features are reflected in their imaging appearances may help radiologists differentiate them.

	LEARNING OBJECTIVES FOR TEST 6

Top Abstract LEARNING OBJECTIVES FOR TEST... Introduction Dermoid and Epidermoid Inclusion... Fibro-osseous Lesions Langerhans Cell Histiocytosis Granulocytic Sarcoma Neuroblastoma Metastases Primary Malignant Bone Tumors Conclusions References

 
After reading this article and taking the test, the reader will be able to:

• Describe the imaging features and pathologic basis of osseous, nonocular orbital masses in children.
  
• Recognize the features of osseous, nonocular orbital masses that may allow them to be differentiated from other orbital masses in children.
  
• Discuss the management of osseous, nonocular orbital masses in children.
  

	Introduction

Top Abstract LEARNING OBJECTIVES FOR TEST... Introduction Dermoid and Epidermoid Inclusion... Fibro-osseous Lesions Langerhans Cell Histiocytosis Granulocytic Sarcoma Neuroblastoma Metastases Primary Malignant Bone Tumors Conclusions References

 
Some extraocular masses that cause proptosis in children originate from the osseous orbit. These masses vary in histologic type and differ from those encountered in adults. They include congenital lesions associated with development of the osseous orbit (dermoid and epidermoid inclusion cysts), primary bone lesions that may involve the orbit (fibrous dysplasia, juvenile or psammomatoid ossifying fibroma, and Langerhans cell histiocytosis [LCH]), malignant tumors that involve multiple sites (granulocytic sarcoma), and hematogenous metastases. Most of these conditions also occur in adults, but they are more frequently found in children. Leukemia is much more likely than lymphoma to involve the orbit in children, whereas orbital lymphoma is common in adults. Ophthalmic metastases in children arise in the osseous or extraocular soft-tissue structures and virtually never involve the ocular structures; in contrast, metastases in adults often arise in the ocular choroid. Many common primary tumors in adults metastasize to the ocular structures, but the vast majority of orbital metastases in children arise from neuroblastoma.

At imaging evaluation, osseous orbital lesions may appear similar to each other and to nonosseous masses of the orbit. Knowledge of the pathologic features of these lesions and how these features are reflected in their imaging appearances may help radiologists differentiate them. Since the treatment and prognosis of osseous orbital lesions are widely varied, careful interpretation of the imaging studies may help in their diagnosis and management. In this article, the clinical, pathologic, and imaging features of these lesions are described and correlated, and the differential diagnoses are reviewed.

	Dermoid and Epidermoid Inclusion Cysts

Top Abstract LEARNING OBJECTIVES FOR TEST... Introduction Dermoid and Epidermoid Inclusion... Fibro-osseous Lesions Langerhans Cell Histiocytosis Granulocytic Sarcoma Neuroblastoma Metastases Primary Malignant Bone Tumors Conclusions References

 
Dermoid inclusion cysts are congenital and perhaps the most common orbital tumor of childhood, accounting for the majority of such lesions (either sampled in biopsy or excised) (1). Unlike teratomas, these lesions are not neoplasms, but rather represent closed sacs lined by an ectodermal epithelium (2–9). Both dermoid and epidermoid inclusion cysts probably arise from the same mechanism: a failure of the surface ectoderm to separate completely from the underlying cephalic mesenchyme. They may arise when the surface ectoderm fails to separate completely from the developing neural tube (neuroectoderm) or when surface ectoderm undergoes complex infolding, invagination, and fusion as the ears, eyes, and face begin to form. In the orbital region, these cysts most commonly arise near the developing sutures of the orbital bones (5,8). Epidermoid cysts are thought to develop later in embryonic life, after the ectodermal cells become committed to a single cell type. They are lined only by squamous epithelium. In contrast, dermoid inclusion cysts have a more complex histologic make-up, with several types of cells, a characteristic that suggests these cysts arise from an earlier embryologic event involving undifferentiated pluripotential cells.

Clinical Features
Although they are congenital, less than one-quarter of dermoid and epidermoid inclusion cysts are diagnosed at birth (10). They grow slowly and often become apparent in the first decade of life (1,11). Most manifest as painless, visible masses and are usually found along the lines of embryologic fusion: the zygomaticofrontal and the frontoethmoidal sutures (5,11). Dermoid inclusion cysts are overwhelmingly superficial, occurring in the supraorbital ridge, in the lateral third of the eyebrow (12). More than 80% of orbital dermoid inclusion cysts are in the upper outer quadrant or the lacrimal fossa (12). Deeper lesions are often identified as incidental masses, or they may occupy much of the orbit and manifest with proptosis in older children or adults. Dermoid inclusion cysts may rupture spontaneously or following trauma, and the leaked keratinous contents may incite an intense inflammatory response in the surrounding tissues, a finding that suggests orbital cellulitis (13,14).

Pathologic and Histologic Features
Dermoid and epidermoid inclusion cysts are characteristically unilocular lesions. They expand over years or decades, slowly enlarging by the accumulation of debris into their enclosed space. The thin squamous cell lining of the epidermoid cyst produces material by desquamation and fills the sac with dry waxy or flaky keratin (Fig 1d, 1e). Epidermoid cysts are often described as shiny or "pearly" tumors because of the whitish dry keratin material (Fig 1c, 1d). By definition, the lining of an epidermoid contains only squamous cells.

View larger version (100K): [in this window] [in a new window] [Download PPT slide]   Figure 1a.  Epidermoid inclusion cyst in a 2-year-old girl with a visible mass. (a) Coronal computed tomographic (CT) image obtained after intravenous administration of contrast material shows a well-circumscribed, fluid-attenuation mass with a thin rim of enhancement (arrowhead). (b) Intraoperative photograph depicts the mass in the medial orbit surrounded by an intact wall. (c) Photograph of a gross specimen of an epidermoid inclusion cyst from another patient demonstrates its "pearly" appearance. Scale is in centimeters. (d) Photograph of a cut section of an epidermoid inclusion cyst from a different patient demonstrates the iridescent appearance of the layers of keratin within the cyst (*). (e) Photomicrograph (original magnification x200; hematoxylin-eosin [H-E] stain) of a section from the specimen in c depicts squamous epithelium (arrowheads) and layers of keratin (*).

View larger version (107K): [in this window] [in a new window] [Download PPT slide]   Figure 1b.  Epidermoid inclusion cyst in a 2-year-old girl with a visible mass. (a) Coronal computed tomographic (CT) image obtained after intravenous administration of contrast material shows a well-circumscribed, fluid-attenuation mass with a thin rim of enhancement (arrowhead). (b) Intraoperative photograph depicts the mass in the medial orbit surrounded by an intact wall. (c) Photograph of a gross specimen of an epidermoid inclusion cyst from another patient demonstrates its "pearly" appearance. Scale is in centimeters. (d) Photograph of a cut section of an epidermoid inclusion cyst from a different patient demonstrates the iridescent appearance of the layers of keratin within the cyst (*). (e) Photomicrograph (original magnification x200; hematoxylin-eosin [H-E] stain) of a section from the specimen in c depicts squamous epithelium (arrowheads) and layers of keratin (*).

View larger version (114K): [in this window] [in a new window] [Download PPT slide]   Figure 1c.  Epidermoid inclusion cyst in a 2-year-old girl with a visible mass. (a) Coronal computed tomographic (CT) image obtained after intravenous administration of contrast material shows a well-circumscribed, fluid-attenuation mass with a thin rim of enhancement (arrowhead). (b) Intraoperative photograph depicts the mass in the medial orbit surrounded by an intact wall. (c) Photograph of a gross specimen of an epidermoid inclusion cyst from another patient demonstrates its "pearly" appearance. Scale is in centimeters. (d) Photograph of a cut section of an epidermoid inclusion cyst from a different patient demonstrates the iridescent appearance of the layers of keratin within the cyst (*). (e) Photomicrograph (original magnification x200; hematoxylin-eosin [H-E] stain) of a section from the specimen in c depicts squamous epithelium (arrowheads) and layers of keratin (*).

View larger version (122K): [in this window] [in a new window] [Download PPT slide]   Figure 1d.  Epidermoid inclusion cyst in a 2-year-old girl with a visible mass. (a) Coronal computed tomographic (CT) image obtained after intravenous administration of contrast material shows a well-circumscribed, fluid-attenuation mass with a thin rim of enhancement (arrowhead). (b) Intraoperative photograph depicts the mass in the medial orbit surrounded by an intact wall. (c) Photograph of a gross specimen of an epidermoid inclusion cyst from another patient demonstrates its "pearly" appearance. Scale is in centimeters. (d) Photograph of a cut section of an epidermoid inclusion cyst from a different patient demonstrates the iridescent appearance of the layers of keratin within the cyst (*). (e) Photomicrograph (original magnification x200; hematoxylin-eosin [H-E] stain) of a section from the specimen in c depicts squamous epithelium (arrowheads) and layers of keratin (*).

View larger version (130K): [in this window] [in a new window] [Download PPT slide]   Figure 1e.  Epidermoid inclusion cyst in a 2-year-old girl with a visible mass. (a) Coronal computed tomographic (CT) image obtained after intravenous administration of contrast material shows a well-circumscribed, fluid-attenuation mass with a thin rim of enhancement (arrowhead). (b) Intraoperative photograph depicts the mass in the medial orbit surrounded by an intact wall. (c) Photograph of a gross specimen of an epidermoid inclusion cyst from another patient demonstrates its "pearly" appearance. Scale is in centimeters. (d) Photograph of a cut section of an epidermoid inclusion cyst from a different patient demonstrates the iridescent appearance of the layers of keratin within the cyst (*). (e) Photomicrograph (original magnification x200; hematoxylin-eosin [H-E] stain) of a section from the specimen in c depicts squamous epithelium (arrowheads) and layers of keratin (*).

In comparison to the epidermoid, the dermoid inclusion cyst is more complex. Dermoid inclusion cysts have a thicker lining that requires some scant vascularity, and they may develop dystrophic calcifications over time. The lining is composed of stratified squamous epithelium identical to that of the epidermis (Fig 2h). By definition, the wall of a dermoid inclusion cyst contains additional ectodermal features, such as hair follicles or sebaceous glands, which are typically arranged in pilosebaceous units (Fig 2h). Although these features are complex structures, they are all derivatives of ectoderm. Thus, a dermoid inclusion cyst is monodermal—that is, derived from a single germ layer—and is distinguished from a teratoma, which contains additional tissues of mesodermal or endodermal origin. The presence of lipid material in a dermoid inclusion cyst represents the oily secretion of ectodermally derived sebaceous glands and should not be confused with lipid from mesodermal fat. The lipid material within the cyst is lighter than its proteinaceous keratin debris, and it may float on top of the latter, like oil on water.

View larger version (98K): [in this window] [in a new window] [Download PPT slide]   Figure 2a.  Dermoid inclusion cyst in a 21-year-old man with a 9-year history of facial asymmetry. (a) Nonenhanced coronal CT scan (bone window) shows a lucent tract through the right lateral frontal bone with a sclerotic margin (arrowhead) near the zygomaticofrontal suture. Note the scalloping of the adjacent superolateral orbit (arrow). (b) Coronal CT section slightly posterior to a shows the medial end of the lucent tract (arrowhead) leading to an intraorbital mass. Note the normal left zygomaticofrontal suture (arrow). (c) Coronal CT section (soft-tissue window) slightly posterior to b demonstrates the well-circumscribed mass adjacent to the scalloped portion of the orbital roof (arrowhead). Internal attenuation of the mass is less than that of the vitreous humor, a finding that suggests the presence of lipid. (d) Coronal spin-echo T2-weighted image demonstrates the well-circumscribed, predominantly high-signal-intensity mass in the right superolateral orbit (arrow), adjacent to the site of osseous scalloping seen in a and c. Pansinusitis is also apparent. (e) Coronal T1-weighted image depicts the well-defined mass with heterogeneous, predominantly high signal intensity, suggestive of fat (arrow). (f) Coronal fat-suppressed T1-weighted image obtained after intravenous administration of gadolinium at the same location as e shows suppression of the high signal within the mass, a finding that confirms its fat content (arrow). Enhancement is seen only in the rim and in adjacent, displaced extraocular muscles. (g) Intraoperative photograph shows the defect in the bone (arrowhead). (h) Photomicrograph (original magnification x100; H-E stain) of a specimen from a different patient demonstrates the cyst wall lined by keratinized squamous epithelium similar to epidermis (straight arrows) and deeper sebaceous gland lobules (arrowheads) and hair follicles and shafts (curved arrows). Note the keratin within the cyst lumen (*).

View larger version (99K): [in this window] [in a new window] [Download PPT slide]   Figure 2b.  Dermoid inclusion cyst in a 21-year-old man with a 9-year history of facial asymmetry. (a) Nonenhanced coronal CT scan (bone window) shows a lucent tract through the right lateral frontal bone with a sclerotic margin (arrowhead) near the zygomaticofrontal suture. Note the scalloping of the adjacent superolateral orbit (arrow). (b) Coronal CT section slightly posterior to a shows the medial end of the lucent tract (arrowhead) leading to an intraorbital mass. Note the normal left zygomaticofrontal suture (arrow). (c) Coronal CT section (soft-tissue window) slightly posterior to b demonstrates the well-circumscribed mass adjacent to the scalloped portion of the orbital roof (arrowhead). Internal attenuation of the mass is less than that of the vitreous humor, a finding that suggests the presence of lipid. (d) Coronal spin-echo T2-weighted image demonstrates the well-circumscribed, predominantly high-signal-intensity mass in the right superolateral orbit (arrow), adjacent to the site of osseous scalloping seen in a and c. Pansinusitis is also apparent. (e) Coronal T1-weighted image depicts the well-defined mass with heterogeneous, predominantly high signal intensity, suggestive of fat (arrow). (f) Coronal fat-suppressed T1-weighted image obtained after intravenous administration of gadolinium at the same location as e shows suppression of the high signal within the mass, a finding that confirms its fat content (arrow). Enhancement is seen only in the rim and in adjacent, displaced extraocular muscles. (g) Intraoperative photograph shows the defect in the bone (arrowhead). (h) Photomicrograph (original magnification x100; H-E stain) of a specimen from a different patient demonstrates the cyst wall lined by keratinized squamous epithelium similar to epidermis (straight arrows) and deeper sebaceous gland lobules (arrowheads) and hair follicles and shafts (curved arrows). Note the keratin within the cyst lumen (*).

View larger version (122K): [in this window] [in a new window] [Download PPT slide]   Figure 2c.  Dermoid inclusion cyst in a 21-year-old man with a 9-year history of facial asymmetry. (a) Nonenhanced coronal CT scan (bone window) shows a lucent tract through the right lateral frontal bone with a sclerotic margin (arrowhead) near the zygomaticofrontal suture. Note the scalloping of the adjacent superolateral orbit (arrow). (b) Coronal CT section slightly posterior to a shows the medial end of the lucent tract (arrowhead) leading to an intraorbital mass. Note the normal left zygomaticofrontal suture (arrow). (c) Coronal CT section (soft-tissue window) slightly posterior to b demonstrates the well-circumscribed mass adjacent to the scalloped portion of the orbital roof (arrowhead). Internal attenuation of the mass is less than that of the vitreous humor, a finding that suggests the presence of lipid. (d) Coronal spin-echo T2-weighted image demonstrates the well-circumscribed, predominantly high-signal-intensity mass in the right superolateral orbit (arrow), adjacent to the site of osseous scalloping seen in a and c. Pansinusitis is also apparent. (e) Coronal T1-weighted image depicts the well-defined mass with heterogeneous, predominantly high signal intensity, suggestive of fat (arrow). (f) Coronal fat-suppressed T1-weighted image obtained after intravenous administration of gadolinium at the same location as e shows suppression of the high signal within the mass, a finding that confirms its fat content (arrow). Enhancement is seen only in the rim and in adjacent, displaced extraocular muscles. (g) Intraoperative photograph shows the defect in the bone (arrowhead). (h) Photomicrograph (original magnification x100; H-E stain) of a specimen from a different patient demonstrates the cyst wall lined by keratinized squamous epithelium similar to epidermis (straight arrows) and deeper sebaceous gland lobules (arrowheads) and hair follicles and shafts (curved arrows). Note the keratin within the cyst lumen (*).

View larger version (122K): [in this window] [in a new window] [Download PPT slide]   Figure 2d.  Dermoid inclusion cyst in a 21-year-old man with a 9-year history of facial asymmetry. (a) Nonenhanced coronal CT scan (bone window) shows a lucent tract through the right lateral frontal bone with a sclerotic margin (arrowhead) near the zygomaticofrontal suture. Note the scalloping of the adjacent superolateral orbit (arrow). (b) Coronal CT section slightly posterior to a shows the medial end of the lucent tract (arrowhead) leading to an intraorbital mass. Note the normal left zygomaticofrontal suture (arrow). (c) Coronal CT section (soft-tissue window) slightly posterior to b demonstrates the well-circumscribed mass adjacent to the scalloped portion of the orbital roof (arrowhead). Internal attenuation of the mass is less than that of the vitreous humor, a finding that suggests the presence of lipid. (d) Coronal spin-echo T2-weighted image demonstrates the well-circumscribed, predominantly high-signal-intensity mass in the right superolateral orbit (arrow), adjacent to the site of osseous scalloping seen in a and c. Pansinusitis is also apparent. (e) Coronal T1-weighted image depicts the well-defined mass with heterogeneous, predominantly high signal intensity, suggestive of fat (arrow). (f) Coronal fat-suppressed T1-weighted image obtained after intravenous administration of gadolinium at the same location as e shows suppression of the high signal within the mass, a finding that confirms its fat content (arrow). Enhancement is seen only in the rim and in adjacent, displaced extraocular muscles. (g) Intraoperative photograph shows the defect in the bone (arrowhead). (h) Photomicrograph (original magnification x100; H-E stain) of a specimen from a different patient demonstrates the cyst wall lined by keratinized squamous epithelium similar to epidermis (straight arrows) and deeper sebaceous gland lobules (arrowheads) and hair follicles and shafts (curved arrows). Note the keratin within the cyst lumen (*).

View larger version (132K): [in this window] [in a new window] [Download PPT slide]   Figure 2e.  Dermoid inclusion cyst in a 21-year-old man with a 9-year history of facial asymmetry. (a) Nonenhanced coronal CT scan (bone window) shows a lucent tract through the right lateral frontal bone with a sclerotic margin (arrowhead) near the zygomaticofrontal suture. Note the scalloping of the adjacent superolateral orbit (arrow). (b) Coronal CT section slightly posterior to a shows the medial end of the lucent tract (arrowhead) leading to an intraorbital mass. Note the normal left zygomaticofrontal suture (arrow). (c) Coronal CT section (soft-tissue window) slightly posterior to b demonstrates the well-circumscribed mass adjacent to the scalloped portion of the orbital roof (arrowhead). Internal attenuation of the mass is less than that of the vitreous humor, a finding that suggests the presence of lipid. (d) Coronal spin-echo T2-weighted image demonstrates the well-circumscribed, predominantly high-signal-intensity mass in the right superolateral orbit (arrow), adjacent to the site of osseous scalloping seen in a and c. Pansinusitis is also apparent. (e) Coronal T1-weighted image depicts the well-defined mass with heterogeneous, predominantly high signal intensity, suggestive of fat (arrow). (f) Coronal fat-suppressed T1-weighted image obtained after intravenous administration of gadolinium at the same location as e shows suppression of the high signal within the mass, a finding that confirms its fat content (arrow). Enhancement is seen only in the rim and in adjacent, displaced extraocular muscles. (g) Intraoperative photograph shows the defect in the bone (arrowhead). (h) Photomicrograph (original magnification x100; H-E stain) of a specimen from a different patient demonstrates the cyst wall lined by keratinized squamous epithelium similar to epidermis (straight arrows) and deeper sebaceous gland lobules (arrowheads) and hair follicles and shafts (curved arrows). Note the keratin within the cyst lumen (*).

View larger version (128K): [in this window] [in a new window] [Download PPT slide]   Figure 2f.  Dermoid inclusion cyst in a 21-year-old man with a 9-year history of facial asymmetry. (a) Nonenhanced coronal CT scan (bone window) shows a lucent tract through the right lateral frontal bone with a sclerotic margin (arrowhead) near the zygomaticofrontal suture. Note the scalloping of the adjacent superolateral orbit (arrow). (b) Coronal CT section slightly posterior to a shows the medial end of the lucent tract (arrowhead) leading to an intraorbital mass. Note the normal left zygomaticofrontal suture (arrow). (c) Coronal CT section (soft-tissue window) slightly posterior to b demonstrates the well-circumscribed mass adjacent to the scalloped portion of the orbital roof (arrowhead). Internal attenuation of the mass is less than that of the vitreous humor, a finding that suggests the presence of lipid. (d) Coronal spin-echo T2-weighted image demonstrates the well-circumscribed, predominantly high-signal-intensity mass in the right superolateral orbit (arrow), adjacent to the site of osseous scalloping seen in a and c. Pansinusitis is also apparent. (e) Coronal T1-weighted image depicts the well-defined mass with heterogeneous, predominantly high signal intensity, suggestive of fat (arrow). (f) Coronal fat-suppressed T1-weighted image obtained after intravenous administration of gadolinium at the same location as e shows suppression of the high signal within the mass, a finding that confirms its fat content (arrow). Enhancement is seen only in the rim and in adjacent, displaced extraocular muscles. (g) Intraoperative photograph shows the defect in the bone (arrowhead). (h) Photomicrograph (original magnification x100; H-E stain) of a specimen from a different patient demonstrates the cyst wall lined by keratinized squamous epithelium similar to epidermis (straight arrows) and deeper sebaceous gland lobules (arrowheads) and hair follicles and shafts (curved arrows). Note the keratin within the cyst lumen (*).

View larger version (121K): [in this window] [in a new window] [Download PPT slide]   Figure 2g.  Dermoid inclusion cyst in a 21-year-old man with a 9-year history of facial asymmetry. (a) Nonenhanced coronal CT scan (bone window) shows a lucent tract through the right lateral frontal bone with a sclerotic margin (arrowhead) near the zygomaticofrontal suture. Note the scalloping of the adjacent superolateral orbit (arrow). (b) Coronal CT section slightly posterior to a shows the medial end of the lucent tract (arrowhead) leading to an intraorbital mass. Note the normal left zygomaticofrontal suture (arrow). (c) Coronal CT section (soft-tissue window) slightly posterior to b demonstrates the well-circumscribed mass adjacent to the scalloped portion of the orbital roof (arrowhead). Internal attenuation of the mass is less than that of the vitreous humor, a finding that suggests the presence of lipid. (d) Coronal spin-echo T2-weighted image demonstrates the well-circumscribed, predominantly high-signal-intensity mass in the right superolateral orbit (arrow), adjacent to the site of osseous scalloping seen in a and c. Pansinusitis is also apparent. (e) Coronal T1-weighted image depicts the well-defined mass with heterogeneous, predominantly high signal intensity, suggestive of fat (arrow). (f) Coronal fat-suppressed T1-weighted image obtained after intravenous administration of gadolinium at the same location as e shows suppression of the high signal within the mass, a finding that confirms its fat content (arrow). Enhancement is seen only in the rim and in adjacent, displaced extraocular muscles. (g) Intraoperative photograph shows the defect in the bone (arrowhead). (h) Photomicrograph (original magnification x100; H-E stain) of a specimen from a different patient demonstrates the cyst wall lined by keratinized squamous epithelium similar to epidermis (straight arrows) and deeper sebaceous gland lobules (arrowheads) and hair follicles and shafts (curved arrows). Note the keratin within the cyst lumen (*).

View larger version (159K): [in this window] [in a new window] [Download PPT slide]   Figure 2h.  Dermoid inclusion cyst in a 21-year-old man with a 9-year history of facial asymmetry. (a) Nonenhanced coronal CT scan (bone window) shows a lucent tract through the right lateral frontal bone with a sclerotic margin (arrowhead) near the zygomaticofrontal suture. Note the scalloping of the adjacent superolateral orbit (arrow). (b) Coronal CT section slightly posterior to a shows the medial end of the lucent tract (arrowhead) leading to an intraorbital mass. Note the normal left zygomaticofrontal suture (arrow). (c) Coronal CT section (soft-tissue window) slightly posterior to b demonstrates the well-circumscribed mass adjacent to the scalloped portion of the orbital roof (arrowhead). Internal attenuation of the mass is less than that of the vitreous humor, a finding that suggests the presence of lipid. (d) Coronal spin-echo T2-weighted image demonstrates the well-circumscribed, predominantly high-signal-intensity mass in the right superolateral orbit (arrow), adjacent to the site of osseous scalloping seen in a and c. Pansinusitis is also apparent. (e) Coronal T1-weighted image depicts the well-defined mass with heterogeneous, predominantly high signal intensity, suggestive of fat (arrow). (f) Coronal fat-suppressed T1-weighted image obtained after intravenous administration of gadolinium at the same location as e shows suppression of the high signal within the mass, a finding that confirms its fat content (arrow). Enhancement is seen only in the rim and in adjacent, displaced extraocular muscles. (g) Intraoperative photograph shows the defect in the bone (arrowhead). (h) Photomicrograph (original magnification x100; H-E stain) of a specimen from a different patient demonstrates the cyst wall lined by keratinized squamous epithelium similar to epidermis (straight arrows) and deeper sebaceous gland lobules (arrowheads) and hair follicles and shafts (curved arrows). Note the keratin within the cyst lumen (*).

Imaging Appearance
Dermoid and epidermoid inclusion cysts slowly expand because of the accumulation of debris produced by the cutaneous lining. The increasing diameter and pressure of the cyst produce indolent periosteal and intradiploic remodeling of bone, usually with a reactive sclerotic margin or shell of dense bone. Because of these features, the cyst typically appears on radiographs and CT images as a sharply delimited, lucent lesion with a dense, surrounding rim of bone (Fig 2a) (14). Orbital dermoid and epidermoid inclusion cysts typically appear as encapsulated, well-circumscribed, unilocular cystic masses, and the appearance of the cyst contents varies depending on its composition.

Epidermoid inclusion cysts, probably because of their proteinaceous contents, are usually very similar in appearance to water or cerebral spinal fluid on both magnetic resonance (MR) and CT images (Fig 1); however, careful measurement of attenuation on CT scans may show that an epidermoid has a slightly higher attenuation coefficient compared with that of cerebral spinal fluid. Use of MR images obtained with fluid-attenuated inversion recovery (FLAIR), diffusion-weighted, and apparent diffusion coefficient (ADC) sequences allows epidermoid cysts to be clearly distinguished from water. The internal signal of an epidermoid is not suppressed on FLAIR images, and epidermoid cysts have high signal intensity on diffusion-weighted images. Although this appearance is mostly caused by T2 shine through, epidermoid cysts do actually have reduced diffusion on ADC maps (3,15,16). Diffusion-weighted pulse sequences may be superior for delineating the margin or boundaries of these cysts (15).

Most dermoid inclusion cysts, in contrast to epidermoids and most other orbital masses, have the attenuation and signal intensity characteristics of lipid material because of their sebaceous secretions (Fig 2). Dermoid inclusion cysts may have CT attenuation coefficient values below zero, in the range of –60 HU to –90 HU. On MR images, their lipid components cause T1 shortening, and dermoid inclusion cysts often appear as bright as the subcutaneous fat. The lipid signal in a dermoid inclusion cyst also becomes dark on fat-suppressed images. Although the cyst contents do not enhance (Fig 2f), these lesions often have a discernable wall that may enhance on both CT and MR images. The wall may also contain high-attenuation foci of calcification on CT images.

Differential Diagnosis
Cephaloceles may also occur in the fronto-orbital region near the midline, often contain cerebral spinal fluid, and generally have adjacent osseous abnormalities, but these abnormalities are in the form of tracts that lead to the midline anterior cranial fossa. In addition, unlike dermoid inclusion cysts, cephaloceles do not contain lipid.

Treatment and Prognosis
Small, asymptomatic dermoid and epidermoid inclusion cysts that remain stable for years do not require treatment. Treatment is indicated when they continue to grow or to prevent complications of rupture and infection. Inclusion cysts are completely surgically excised, preferably with the wall intact. Recurrence is unusual after complete excision (1,13,17).

	Fibro-osseous Lesions

Top Abstract LEARNING OBJECTIVES FOR TEST... Introduction Dermoid and Epidermoid Inclusion... Fibro-osseous Lesions Langerhans Cell Histiocytosis Granulocytic Sarcoma Neuroblastoma Metastases Primary Malignant Bone Tumors Conclusions References

 
Fibrous dysplasia and juvenile ossifying fibroma are variants in a spectrum of histologically similar but biologically diverse fibro-osseous lesions that affect the craniofacial bones (the group also includes cementifying fibroma). These lesions vary in location (gnathic vs sinonasal), clinical behavior (aggressive vs indolent), and composition of mineralized component (cementum vs osteoid); however, there is a great deal of overlap in their histologic features, and clinical and radiologic correlation is often necessary to render a precise pathologic diagnosis (19). Differentiation of fibrous dysplasia from juvenile ossifying fibroma, both of which affect a similar age group, has important clinical implications, because the former condition is self limited and rarely requires surgery, whereas the latter behaves aggressively and requires complete surgical resection.

Fibrous Dysplasia
Fibrous dysplasia represents a benign developmental anomaly in which the osteoblast fails to undergo normal differentiation and maturation. This process leads to replacement of the normal bone marrow by immature fibro-osseous tissue. Fibrous dysplasia is a slowly progressive disease centered in the medullary canal and may involve one or multiple bones, including the facial bones and orbit (19–21).

Clinical Features.— Fibrous dysplasia most frequently affects children (older than 2 years of age), adolescents, and young adults, although it has a wider age distribution. Fibrous dysplasia is monostotic in 70%–80% of cases (19–21). Polyostotic disease occurs in 20%–30% of cases, with a variable extent of involvement, from only a few osseous sites to most of the skeleton (19–21). The sex distribution of fibrous dysplasia has been variably reported, from a mild female predilection (1.2:1 ratio) to a male predominance (almost 2:1 male-to-female ratio) (19–23). Craniofacial involvement is common, with the craniofacial region being affected in 10%–27% of cases of monostotic disease and 50% of cases of polyostotic disease (22,24–28). Frequently affected craniofacial sites include the frontal, sphenoid, ethmoid maxilla, zygoma, parietal, occipital, and temporal areas (in decreasing order of frequency) (22,24–28). The orbit is affected in 20%–39% of patients with craniofacial involvement (22,24–28).

Clinical symptoms of ocular involvement of fibrous dysplasia have been divided into primary and secondary processes (29). Primary complications result from osseous orbital involvement and include facial asymmetry, hypertelorism, proptosis, exophthalmos, diplopia, extraocular muscle palsies, and visual impairment (29,30). Visual symptoms may result from osseous expansion and compression of the optic nerve or chiasm. Secondary ocular complications of fibrous dysplasia include development of a mucocele or rare malignant transformation (20).

Additional clinical findings may include café-au-lait spots whose configuration resembles the coast of Maine and multiple endocrinopathies related to hypothalamic dysfunction, including the McCune-Albright syndrome of precocious puberty in girls with polyostotic fibrous dysplasia and cutaneous pigmentation.

Pathologic Features.— Lesions of fibrous dysplasia are composed of mixtures of fibrous and osseous components in varying proportions. The osseous component consists of woven bone and varies from solid round areas to curved, serpentine, or curlicue shapes (Fig 3d, 3e). The irregular shapes of these trabeculae usually predominate, leading to a histologic appearance described as "Chinese characters" or alphabet soup (20,29). Osteoblastic rimming about the trabeculae is usually absent (20,29). The fibrous component or stroma surrounding the osseous trabeculae is typically of low cellularity and mitotic rate, and it has a variable degree of collagen and myxoid component (Fig 3e). Hemorrhage and cystic change may be apparent.

View larger version (135K): [in this window] [in a new window] [Download PPT slide]   Figure 3a.  Polyostotic fibrous dysplasia with orbital involvement in a 15-year-old boy. (a) Coronal CT scan shows marked, expansile osseous remodeling with a ground-glass appearance (*) in the frontal bone, superior orbit, and nasal regions. The tissue encroaches on the left orbit and displaces the globe inferiorly. (b) Sagittal T1-weighted MR image reveals marrow replacement with expansion of the diploic space by extensive tissue with low to intermediate signal intensity (*). (c) Axial T2-weighted MR image demonstrates low signal intensity and mild heterogeneity of the fibrous dysplasia tissue (*). (d, e) Photograph of a sectioned whole-mount specimen (H-E stain) (d) and a photomicrograph (original magnification x100; H-E stain) (e) show the diploic space marrow replacement by the fibrous dysplasia tissue (* in d), with the fibrous component (F in e) and trabecular bone (arrows in e) creating an alphabet-soup appearance.

View larger version (133K): [in this window] [in a new window] [Download PPT slide]   Figure 3b.  Polyostotic fibrous dysplasia with orbital involvement in a 15-year-old boy. (a) Coronal CT scan shows marked, expansile osseous remodeling with a ground-glass appearance (*) in the frontal bone, superior orbit, and nasal regions. The tissue encroaches on the left orbit and displaces the globe inferiorly. (b) Sagittal T1-weighted MR image reveals marrow replacement with expansion of the diploic space by extensive tissue with low to intermediate signal intensity (*). (c) Axial T2-weighted MR image demonstrates low signal intensity and mild heterogeneity of the fibrous dysplasia tissue (*). (d, e) Photograph of a sectioned whole-mount specimen (H-E stain) (d) and a photomicrograph (original magnification x100; H-E stain) (e) show the diploic space marrow replacement by the fibrous dysplasia tissue (* in d), with the fibrous component (F in e) and trabecular bone (arrows in e) creating an alphabet-soup appearance.

View larger version (127K): [in this window] [in a new window] [Download PPT slide]   Figure 3c.  Polyostotic fibrous dysplasia with orbital involvement in a 15-year-old boy. (a) Coronal CT scan shows marked, expansile osseous remodeling with a ground-glass appearance (*) in the frontal bone, superior orbit, and nasal regions. The tissue encroaches on the left orbit and displaces the globe inferiorly. (b) Sagittal T1-weighted MR image reveals marrow replacement with expansion of the diploic space by extensive tissue with low to intermediate signal intensity (*). (c) Axial T2-weighted MR image demonstrates low signal intensity and mild heterogeneity of the fibrous dysplasia tissue (*). (d, e) Photograph of a sectioned whole-mount specimen (H-E stain) (d) and a photomicrograph (original magnification x100; H-E stain) (e) show the diploic space marrow replacement by the fibrous dysplasia tissue (* in d), with the fibrous component (F in e) and trabecular bone (arrows in e) creating an alphabet-soup appearance.

View larger version (149K): [in this window] [in a new window] [Download PPT slide]   Figure 3d.  Polyostotic fibrous dysplasia with orbital involvement in a 15-year-old boy. (a) Coronal CT scan shows marked, expansile osseous remodeling with a ground-glass appearance (*) in the frontal bone, superior orbit, and nasal regions. The tissue encroaches on the left orbit and displaces the globe inferiorly. (b) Sagittal T1-weighted MR image reveals marrow replacement with expansion of the diploic space by extensive tissue with low to intermediate signal intensity (*). (c) Axial T2-weighted MR image demonstrates low signal intensity and mild heterogeneity of the fibrous dysplasia tissue (*). (d, e) Photograph of a sectioned whole-mount specimen (H-E stain) (d) and a photomicrograph (original magnification x100; H-E stain) (e) show the diploic space marrow replacement by the fibrous dysplasia tissue (* in d), with the fibrous component (F in e) and trabecular bone (arrows in e) creating an alphabet-soup appearance.

View larger version (151K): [in this window] [in a new window] [Download PPT slide]   Figure 3e.  Polyostotic fibrous dysplasia with orbital involvement in a 15-year-old boy. (a) Coronal CT scan shows marked, expansile osseous remodeling with a ground-glass appearance (*) in the frontal bone, superior orbit, and nasal regions. The tissue encroaches on the left orbit and displaces the globe inferiorly. (b) Sagittal T1-weighted MR image reveals marrow replacement with expansion of the diploic space by extensive tissue with low to intermediate signal intensity (*). (c) Axial T2-weighted MR image demonstrates low signal intensity and mild heterogeneity of the fibrous dysplasia tissue (*). (d, e) Photograph of a sectioned whole-mount specimen (H-E stain) (d) and a photomicrograph (original magnification x100; H-E stain) (e) show the diploic space marrow replacement by the fibrous dysplasia tissue (* in d), with the fibrous component (F in e) and trabecular bone (arrows in e) creating an alphabet-soup appearance.

Imaging Appearance.— Radiographs of fibrous dysplasia typically demonstrate a medullary-based lesion with expansile osseous remodeling. In the calvaria, the outer table is usually more prominently affected, compared with the inner table. A characteristic "ground-glass" appearance is created by the mixture of woven bone and fibrous components that replace the medullary space (Fig 3a). The overall density of bone is determined by the amount of woven bone present and the degree to which it is mineralized (20,23,31,32). Areas of sclerosis are particularly common in craniofacial lesions, particularly those in the skull base and in the orbit. This sclerosis may be diffuse and obscure the ground-glass appearance of craniofacial lesions.

CT reveals features similar to those seen on radiographs, but it provides better anatomic delineation of the extent of involvement. Typical attenuation values of fibrous dysplasia are 70–130 HU, with areas of sclerosis demonstrating higher values (33–35). Intermixed areas of sclerosis and characteristic ground-glass appearing regions are more easily appreciated with the superior contrast resolution of CT (Fig 3a).

At MR imaging, fibrous dysplasia has a variable appearance. The predominant signal intensity is low to intermediate on T1-weighted images. On T2-weighted images, the signal intensity may be low (18%–38% of cases), intermediate (18%), or high (62%–64%) (20,23,36,37). In our experience, craniofacial lesions are more likely to have low signal intensity on T2-weighted MR images, a finding that likely corresponds to the increased sclerosis seen with other imaging modalities (Fig 3). Lesions are often relatively homogeneous on T1-weighted images, with more heterogeneity seen on long repetition time images. MR imaging performed after intravenous administration of contrast material demonstrated two patterns, as described by Jee and coworkers (36). In the majority of cases (73%), central enhancement was seen, whereas 27% revealed a peripheral rim pattern (36).

Bone scintigraphy of fibrous dysplasia typically reveals intense radionuclide uptake (20,38). The increased radionuclide activity is seen on blood flow and blood pool images, but it is most intense on static delayed images. Recently, positron emission tomographic (PET) images of fibrous dysplasia have demonstrated its marked radiotracer avidity (standardized uptake value, 3–19), a finding that simulates the appearance of malignant disease (39).

Differential Diagnosis.— The radiologic differential diagnosis of craniofacial fibrous dysplasia in children includes ossifying fibroma, cherubism, and renal osteodystrophy.

Juvenile ossifying fibroma, which is discussed in the next section, is a round to oval mass that causes focal expansile remodeling at a single osseous site. In contradistinction, fibrous dysplasia is often polyostotic, with more extensive and elongated bone involvement, characteristics that reflect its developmental rather than neoplastic etiology. Ossifying fibroma also may reveal multiple focal punctate areas of calcification within the fibrous tissue without a ground-glass appearance, whereas fibrous dysplasia typically contains some ground-glass density without punctate areas of sclerosis.

Cherubism is a benign disease of childhood with a pathologic appearance similar to that of fibrous dysplasia (40). The radiologic appearances of fibrous dysplasia and cherubism are similar; however, cherubism is limited to involvement of the jaw (40).

Renal osteodystrophy may cause expansion and sclerosis in the medullary space of the craniofacial bones, characteristics that simulate those of polyostotic fibrous dysplasia (41). This involvement can become extensive and may be referred to as leontiasis ossea (41). Additional manifestations of renal osteodystrophy and hyperparathyroidism and a clinical history of chronic renal failure help to distinguish renal osteodystrophy from fibrous dysplasia.

Treatment and Prognosis.— Treatment of fibrous dysplasia is typically supportive, with surgical intervention used in cases with complications (21,42,43). Orbital involvement with optic nerve impingement is often treated with decompressive surgery to prevent and limit progression of visual loss (29).

Juvenile Ossifying Fibroma
Juvenile (psammomatoid) ossifying fibroma is a nonmetastasizing, benign tumor that arises in the sinonasal region of young patients and often involves the orbit. The condition is distinguished clinically by its tendency for locally aggressive behavior and histologically by a substantial component of small, round, psammomatoid ossicles.

Clinical Features.— Juvenile ossifying fibroma most commonly affects children and adolescents, but it occurs in patients with a wide range of ages (44,45). It has no gender predilection (46). Facial bones are involved in 85% of cases, with the paranasal sinuses being affected in the vast majority of these (47) and more than one sinus being involved in half of them (47,48). Juvenile ossifying fibromas that involve the orbit usually arise in the ethmoid region or superior orbital plate of the frontal bone and enlarge to invade the orbit (45,48).

The most common symptom is proptosis (45). Less frequent presenting symptoms include facial swelling, nasal obstruction, visual or ocular motility disturbance, headache, and sinusitis (45,47,49). Intracranial extension is not uncommon, but it develops so slowly that neurologic symptoms are usually absent, even with very large tumors (47). Juvenile ossifying fibromas are usually slow growing (45,47), but a subset of these tumors demonstrates very infiltrative, rapid growth in young children.

Pathologic Features.— At gross inspection, juvenile ossifying fibroma is a yellow-white or pink mass, which may appear gritty or cheesy (Fig 4f). Cystic spaces may be filled with serous or hemorrhagic fluid (45).

View larger version (130K): [in this window] [in a new window] [Download PPT slide]   Figure 4a.  Juvenile ossifying fibroma involving the orbit in a 17-year-old girl. (a) Frontal radiograph shows a mixed lytic and sclerotic lesion involving the left nasal and orbital region (arrows). (b) Axial CT scan reveals the expansile lesion with a partial thin sclerotic rim (arrows); the lesion contains small, focal punctate areas of mineralization (arrowheads). (c, d) Sagittal (c) and coronal (d) T1-weighted MR images demonstrate the oval configuration and intermediate signal intensity (*) of the lesion, which displaces and effaces the orbit. (e) Axial T2-weighted MR image shows predominantly high signal intensity within the mass, with small lower-signal-intensity regions (arrowheads) that correspond to areas of focal calcification better seen in b. (f) Photograph of a sectioned gross specimen reveals the mass, which contains small focal regions of punctate calcification (arrowheads) that correspond to the imaging appearance. (g) Photomicrograph (original magnification x200; H-E stain) demonstrates multiple ovoid and irregular osteoid spicules within a background of densely cellular stroma consisting of round to spindle-shaped cells with prominent nuclei. Also shown are multiple, lamellated, psammoma-like bodies dispersed within the stroma but also within the spicules (arrowheads). (h) Higher-power photomicrograph (original magnification x400; H-E stain) shows small, flat osteoblasts that rim a spicule (arrows). A few osteoclasts are also seen at the edge of the spicule (arrowhead).

View larger version (97K): [in this window] [in a new window] [Download PPT slide]   Figure 4b.  Juvenile ossifying fibroma involving the orbit in a 17-year-old girl. (a) Frontal radiograph shows a mixed lytic and sclerotic lesion involving the left nasal and orbital region (arrows). (b) Axial CT scan reveals the expansile lesion with a partial thin sclerotic rim (arrows); the lesion contains small, focal punctate areas of mineralization (arrowheads). (c, d) Sagittal (c) and coronal (d) T1-weighted MR images demonstrate the oval configuration and intermediate signal intensity (*) of the lesion, which displaces and effaces the orbit. (e) Axial T2-weighted MR image shows predominantly high signal intensity within the mass, with small lower-signal-intensity regions (arrowheads) that correspond to areas of focal calcification better seen in b. (f) Photograph of a sectioned gross specimen reveals the mass, which contains small focal regions of punctate calcification (arrowheads) that correspond to the imaging appearance. (g) Photomicrograph (original magnification x200; H-E stain) demonstrates multiple ovoid and irregular osteoid spicules within a background of densely cellular stroma consisting of round to spindle-shaped cells with prominent nuclei. Also shown are multiple, lamellated, psammoma-like bodies dispersed within the stroma but also within the spicules (arrowheads). (h) Higher-power photomicrograph (original magnification x400; H-E stain) shows small, flat osteoblasts that rim a spicule (arrows). A few osteoclasts are also seen at the edge of the spicule (arrowhead).

View larger version (133K): [in this window] [in a new window] [Download PPT slide]   Figure 4c.  Juvenile ossifying fibroma involving the orbit in a 17-year-old girl. (a) Frontal radiograph shows a mixed lytic and sclerotic lesion involving the left nasal and orbital region (arrows). (b) Axial CT scan reveals the expansile lesion with a partial thin sclerotic rim (arrows); the lesion contains small, focal punctate areas of mineralization (arrowheads). (c, d) Sagittal (c) and coronal (d) T1-weighted MR images demonstrate the oval configuration and intermediate signal intensity (*) of the lesion, which displaces and effaces the orbit. (e) Axial T2-weighted MR image shows predominantly high signal intensity within the mass, with small lower-signal-intensity regions (arrowheads) that correspond to areas of focal calcification better seen in b. (f) Photograph of a sectioned gross specimen reveals the mass, which contains small focal regions of punctate calcification (arrowheads) that correspond to the imaging appearance. (g) Photomicrograph (original magnification x200; H-E stain) demonstrates multiple ovoid and irregular osteoid spicules within a background of densely cellular stroma consisting of round to spindle-shaped cells with prominent nuclei. Also shown are multiple, lamellated, psammoma-like bodies dispersed within the stroma but also within the spicules (arrowheads). (h) Higher-power photomicrograph (original magnification x400; H-E stain) shows small, flat osteoblasts that rim a spicule (arrows). A few osteoclasts are also seen at the edge of the spicule (arrowhead).

View larger version (140K): [in this window] [in a new window] [Download PPT slide]   Figure 4d.  Juvenile ossifying fibroma involving the orbit in a 17-year-old girl. (a) Frontal radiograph shows a mixed lytic and sclerotic lesion involving the left nasal and orbital region (arrows). (b) Axial CT scan reveals the expansile lesion with a partial thin sclerotic rim (arrows); the lesion contains small, focal punctate areas of mineralization (arrowheads). (c, d) Sagittal (c) and coronal (d) T1-weighted MR images demonstrate the oval configuration and intermediate signal intensity (*) of the lesion, which displaces and effaces the orbit. (e) Axial T2-weighted MR image shows predominantly high signal intensity within the mass, with small lower-signal-intensity regions (arrowheads) that correspond to areas of focal calcification better seen in b. (f) Photograph of a sectioned gross specimen reveals the mass, which contains small focal regions of punctate calcification (arrowheads) that correspond to the imaging appearance. (g) Photomicrograph (original magnification x200; H-E stain) demonstrates multiple ovoid and irregular osteoid spicules within a background of densely cellular stroma consisting of round to spindle-shaped cells with prominent nuclei. Also shown are multiple, lamellated, psammoma-like bodies dispersed within the stroma but also within the spicules (arrowheads). (h) Higher-power photomicrograph (original magnification x400; H-E stain) shows small, flat osteoblasts that rim a spicule (arrows). A few osteoclasts are also seen at the edge of the spicule (arrowhead).

View larger version (93K): [in this window] [in a new window] [Download PPT slide]   Figure 4e.  Juvenile ossifying fibroma involving the orbit in a 17-year-old girl. (a) Frontal radiograph shows a mixed lytic and sclerotic lesion involving the left nasal and orbital region (arrows). (b) Axial CT scan reveals the expansile lesion with a partial thin sclerotic rim (arrows); the lesion contains small, focal punctate areas of mineralization (arrowheads). (c, d) Sagittal (c) and coronal (d) T1-weighted MR images demonstrate the oval configuration and intermediate signal intensity (*) of the lesion, which displaces and effaces the orbit. (e) Axial T2-weighted MR image shows predominantly high signal intensity within the mass, with small lower-signal-intensity regions (arrowheads) that correspond to areas of focal calcification better seen in b. (f) Photograph of a sectioned gross specimen reveals the mass, which contains small focal regions of punctate calcification (arrowheads) that correspond to the imaging appearance. (g) Photomicrograph (original magnification x200; H-E stain) demonstrates multiple ovoid and irregular osteoid spicules within a background of densely cellular stroma consisting of round to spindle-shaped cells with prominent nuclei. Also shown are multiple, lamellated, psammoma-like bodies dispersed within the stroma but also within the spicules (arrowheads). (h) Higher-power photomicrograph (original magnification x400; H-E stain) shows small, flat osteoblasts that rim a spicule (arrows). A few osteoclasts are also seen at the edge of the spicule (arrowhead).

View larger version (87K): [in this window] [in a new window] [Download PPT slide]   Figure 4f.  Juvenile ossifying fibroma involving the orbit in a 17-year-old girl. (a) Frontal radiograph shows a mixed lytic and sclerotic lesion involving the left nasal and orbital region (arrows). (b) Axial CT scan reveals the expansile lesion with a partial thin sclerotic rim (arrows); the lesion contains small, focal punctate areas of mineralization (arrowheads). (c, d) Sagittal (c) and coronal (d) T1-weighted MR images demonstrate the oval configuration and intermediate signal intensity (*) of the lesion, which displaces and effaces the orbit. (e) Axial T2-weighted MR image shows predominantly high signal intensity within the mass, with small lower-signal-intensity regions (arrowheads) that correspond to areas of focal calcification better seen in b. (f) Photograph of a sectioned gross specimen reveals the mass, which contains small focal regions of punctate calcification (arrowheads) that correspond to the imaging appearance. (g) Photomicrograph (original magnification x200; H-E stain) demonstrates multiple ovoid and irregular osteoid spicules within a background of densely cellular stroma consisting of round to spindle-shaped cells with prominent nuclei. Also shown are multiple, lamellated, psammoma-like bodies dispersed within the stroma but also within the spicules (arrowheads). (h) Higher-power photomicrograph (original magnification x400; H-E stain) shows small, flat osteoblasts that rim a spicule (arrows). A few osteoclasts are also seen at the edge of the spicule (arrowhead).

View larger version (164K): [in this window] [in a new window] [Download PPT slide]   Figure 4g.  Juvenile ossifying fibroma involving the orbit in a 17-year-old girl. (a) Frontal radiograph shows a mixed lytic and sclerotic lesion involving the left nasal and orbital region (arrows). (b) Axial CT scan reveals the expansile lesion with a partial thin sclerotic rim (arrows); the lesion contains small, focal punctate areas of mineralization (arrowheads). (c, d) Sagittal (c) and coronal (d) T1-weighted MR images demonstrate the oval configuration and intermediate signal intensity (*) of the lesion, which displaces and effaces the orbit. (e) Axial T2-weighted MR image shows predominantly high signal intensity within the mass, with small lower-signal-intensity regions (arrowheads) that correspond to areas of focal calcification better seen in b. (f) Photograph of a sectioned gross specimen reveals the mass, which contains small focal regions of punctate calcification (arrowheads) that correspond to the imaging appearance. (g) Photomicrograph (original magnification x200; H-E stain) demonstrates multiple ovoid and irregular osteoid spicules within a background of densely cellular stroma consisting of round to spindle-shaped cells with prominent nuclei. Also shown are multiple, lamellated, psammoma-like bodies dispersed within the stroma but also within the spicules (arrowheads). (h) Higher-power photomicrograph (original magnification x400; H-E stain) shows small, flat osteoblasts that rim a spicule (arrows). A few osteoclasts are also seen at the edge of the spicule (arrowhead).

View larger version (142K): [in this window] [in a new window] [Download PPT slide]   Figure 4h.  Juvenile ossifying fibroma involving the orbit in a 17-year-old girl. (a) Frontal radiograph shows a mixed lytic and sclerotic lesion involving the left nasal and orbital region (arrows). (b) Axial CT scan reveals the expansile lesion with a partial thin sclerotic rim (arrows); the lesion contains small, focal punctate areas of mineralization (arrowheads). (c, d) Sagittal (c) and coronal (d) T1-weighted MR images demonstrate the oval configuration and intermediate signal intensity (*) of the lesion, which displaces and effaces the orbit. (e) Axial T2-weighted MR image shows predominantly high signal intensity within the mass, with small lower-signal-intensity regions (arrowheads) that correspond to areas of focal calcification better seen in b. (f) Photograph of a sectioned gross specimen reveals the mass, which contains small focal regions of punctate calcification (arrowheads) that correspond to the imaging appearance. (g) Photomicrograph (original magnification x200; H-E stain) demonstrates multiple ovoid and irregular osteoid spicules within a background of densely cellular stroma consisting of round to spindle-shaped cells with prominent nuclei. Also shown are multiple, lamellated, psammoma-like bodies dispersed within the stroma but also within the spicules (arrowheads). (h) Higher-power photomicrograph (original magnification x400; H-E stain) shows small, flat osteoblasts that rim a spicule (arrows). A few osteoclasts are also seen at the edge of the spicule (arrowhead).

At histologic analysis, the mass consists of mineralized bodies formed from osteoid within a cellular fibrous stroma. The most conspicuous osteoid component is the uniform, small, round, lamellated, "psammoma-like" ossicles (Fig 4g). With H-E staining, the psammomatoid ossicles appear blue-black, surrounded by a pinkish osteoid rim. The population of these ossicles ranges from sparse to quite dense. Another common osteoid component is the irregular spicules or trabeculae of lamellar bone that are surrounded or rimmed by osteoblasts (Fig 4g, 4h). Osteoclasts may be seen within these spicules (Fig 4h).

The fibrous component of juvenile ossifying fibroma consists of a densely cellular stroma, which is predominantly nuclear with inapparent cytoplasmic borders and little production of collagen (Fig 4g). The cells vary from round to spindle shaped. Focal, cystic degeneration may be identified, particularly in tumors larger than 5 cm (50). A few mitoses may be seen within the cellular stroma, but no atypical mitoses or anaplasia is observed (13,47,48,50,51).

At the interface of the tumor with adjacent normal bone, osteoblastic activity is observed on the convex outer margin of the bone, whereas osteoclastic activity is seen on the concave inner margin. These findings account for the ballooned or bowed appearance of the sclerotic margin seen at radiography (50).

Imaging Appearance.— On radiographs, juvenile ossifying fibroma appears as a monostotic, round or ovoid, well-demarcated, expansile lesion of mixed lytic and sclerotic density (Fig 4). The internal density varies depending on the relative content of the mass, the type of cystic changes, and the osteoid components (45,48).

On CT scans, the lesions usually have predominantly soft-tissue attenuation with multiple foci of calcification (Fig 4b). Lower-attenuation areas represent areas of cystic change (50,51). The internal composition may appear multiloculated, with sclerotic septa or enhancing soft-tissue attenuation septa (52). Juvenile ossifying fibroma frequently involves multiple anatomic spaces, often with bowing and ballooning of the osseous margins; however, the tumor is usually surrounded by a sclerotic rim or shell that may be partially disrupted (Fig 4b) (50). This shell and the solid portions of the tumor enhance with intravenously administered contrast material (48–52).

On T1-weighted MR images, juvenile ossifying fibroma is generally isointense relative to muscle (Fig 4c, 4d). On T2-weighted images, the tumor appears hypointense relative to muscle, and foci of high signal intensity representing fluid-filled cystic spaces may be seen (Fig 4e). Solid portions enhance with gadolinium (18,51,53,54).

Differential Diagnosis.— As previously discussed, the most prominent lesion in the differential diagnosis of juvenile ossifying fibroma is fibrous dysplasia. Other lesions include cementifying fibroma and aneurysmal bone cyst. Cementifying fibroma is a histologically similar lesion that arises from the periodontal ligament; thus, it is intimately associated with the molar teeth in the mandible or maxilla.

Aneurysmal bone cyst only infrequently involves the sinonasal region. When it does, it causes ballooning of osseous margins, similar to the manifestations of juvenile ossifying fibroma. Although it is predominantly cystic and relatively radiolucent compared with bone, aneurysmal bone cyst may occur secondary to another lesion such as giant cell tumor, which may contain radiopaque components. MR images of these lesions reveal fluid levels throughout the cystic component, a finding that is uncommon in juvenile ossifying fibroma (45).

Treatment and Prognosis.— Most authors agree that the treatment of choice for juvenile ossifying fibroma is complete local excision, preferably by means of an open procedure, because the tumor tends to recur after incomplete resection (13,50,52,53). There have been no reports of metastases.

	Langerhans Cell Histiocytosis

Top Abstract LEARNING OBJECTIVES FOR TEST... Introduction Dermoid and Epidermoid Inclusion... Fibro-osseous Lesions Langerhans Cell Histiocytosis Granulocytic Sarcoma Neuroblastoma Metastases Primary Malignant Bone Tumors Conclusions References

 
The three clinical syndromes included within the designation Langerhans cell histiocytosis (formerly called histiocytosis X) are part of a spectrum of disorders with a common underlying etiology: the proliferation of the Langerhans cell, an immature dendritic cell of bone marrow origin (55). It is useful to classify the possible patterns of disease of each of these entities, even though these syndromes often clinically overlap. Letterer-Siwe disease is the acute disseminated form of LCH that affects infants and involves vital organs, often with fatal consequences. Hand-Schüller-Christian disease is a disorder found in young children and is characterized by a classic triad of diabetes insipidus (due to involvement of the posterior pituitary stalk), osteolytic calvarial defects, and exophthalmos. Eosinophilic granuloma may manifest as an indolent disease limited to bone in older children or adults (56,57). Orbital LCH most commonly manifests as eosinophilic granuloma (58). This form of LCH may include substantial juxtaneural or intracranial extension; however, this pattern of disease spread follows a relatively benign course (59).

Clinical Features
Histiocytic lesions of the orbit are rare (60), but among patients with LCH, orbital involvement is fairly common. LCH may occur at any age, but it most frequently develops in children less than 4 years of age (58,61).

The most common presenting sign of orbital LCH is unilateral or bilateral proptosis (58). Other typical clinical manifestations include ptosis, palpebral and periocular erythema, and enlargement of the associated palpebral fissure (58,61).

LCH involvement of the orbit most frequently occurs in the supratemporal frontal bone (13). Stem cell precursors of Langerhans cells are located in hematopoetic bone marrow, which is found in the frontal bone. As the frontal sinus develops, the marrow space is crowded into the lateral orbital roof (62). The finding of orbital LCH in children should prompt a full work-up for more generalized disease (59).

Pathologic Features
At gross inspection, LCH appears as a soft, friable, hemorrhagic, tan-yellow mass (58,61). The histiocytic proliferation manifests with sheets of large mononuclear histiocytes, with abundant eosinophilic cytoplasm and grooved, indented, coffee bean– or kidney-shaped nuclei with bland, stippled chromatin and inconspicuous nucleoli (Fig 5c) (61). Lymphocytes, plasma cells, multinucleated giant cells, and eosinophils are often scattered within the proliferation (Figs 5c, 6d) (13,61).

View larger version (111K): [in this window] [in a new window] [Download PPT slide]   Figure 5a.  Langerhans cell histiocytosis in a 13-year-old boy. (a) Axial CT image (bone window) shows a small soft-tissue mass and beveled erosion of the adjacent greater wing of the sphenoid bone (arrowhead). (b) Axial proton density–weighted MR image, obtained after intravenous administration of gadolinium, shows the well-circumscribed, hyperintense mass, which replaces the bone and extends into the orbit and middle cranial fossa (arrowhead). (c) Photomicrograph (original magnification x400; H-E stain) of a specimen from another patient shows multiple cells with indented or reniform nuclei (arrowheads) and multinucleated giant cells (straight arrows), as well as a few eosinophils (curved arrows).

View larger version (125K): [in this window] [in a new window] [Download PPT slide]   Figure 5b.  Langerhans cell histiocytosis in a 13-year-old boy. (a) Axial CT image (bone window) shows a small soft-tissue mass and beveled erosion of the adjacent greater wing of the sphenoid bone (arrowhead). (b) Axial proton density–weighted MR image, obtained after intravenous administration of gadolinium, shows the well-circumscribed, hyperintense mass, which replaces the bone and extends into the orbit and middle cranial fossa (arrowhead). (c) Photomicrograph (original magnification x400; H-E stain) of a specimen from another patient shows multiple cells with indented or reniform nuclei (arrowheads) and multinucleated giant cells (straight arrows), as well as a few eosinophils (curved arrows).

View larger version (159K): [in this window] [in a new window] [Download PPT slide]   Figure 5c.  Langerhans cell histiocytosis in a 13-year-old boy. (a) Axial CT image (bone window) shows a small soft-tissue mass and beveled erosion of the adjacent greater wing of the sphenoid bone (arrowhead). (b) Axial proton density–weighted MR image, obtained after intravenous administration of gadolinium, shows the well-circumscribed, hyperintense mass, which replaces the bone and extends into the orbit and middle cranial fossa (arrowhead). (c) Photomicrograph (original magnification x400; H-E stain) of a specimen from another patient shows multiple cells with indented or reniform nuclei (arrowheads) and multinucleated giant cells (straight arrows), as well as a few eosinophils (curved arrows).

View larger version (128K): [in this window] [in a new window] [Download PPT slide]   Figure 6a.  Langerhans cell histiocytosis in a 10-year-old child. (a) Coronal T1-weighted image shows a mass that is isointense relative to normal brain tissue and that replaces lateral frontal and zygomatic bones and extends into the orbit, temporal region, and anterior cranial fossa (arrowhead). (b) On a coronal T2-weighted image, the mass (arrowhead) is heterogeneously hyperintense relative to the brain. (c) Coronal fat-saturated T1-weighted image, obtained after intravenous administration of gadolinium, shows marked enhancement of the mass and the adjacent dura mater (arrowheads). (d) Photomicrograph (original magnification x400; H-E stain) shows multiple cells with indented nuclei (arrows) and multiple eosinophils (arrowheads).

View larger version (122K): [in this window] [in a new window] [Download PPT slide]   Figure 6b.  Langerhans cell histiocytosis in a 10-year-old child. (a) Coronal T1-weighted image shows a mass that is isointense relative to normal brain tissue and that replaces lateral frontal and zygomatic bones and extends into the orbit, temporal region, and anterior cranial fossa (arrowhead). (b) On a coronal T2-weighted image, the mass (arrowhead) is heterogeneously hyperintense relative to the brain. (c) Coronal fat-saturated T1-weighted image, obtained after intravenous administration of gadolinium, shows marked enhancement of the mass and the adjacent dura mater (arrowheads). (d) Photomicrograph (original magnification x400; H-E stain) shows multiple cells with indented nuclei (arrows) and multiple eosinophils (arrowheads).

View larger version (107K): [in this window] [in a new window] [Download PPT slide]   Figure 6c.  Langerhans cell histiocytosis in a 10-year-old child. (a) Coronal T1-weighted image shows a mass that is isointense relative to normal brain tissue and that replaces lateral frontal and zygomatic bones and extends into the orbit, temporal region, and anterior cranial fossa (arrowhead). (b) On a coronal T2-weighted image, the mass (arrowhead) is heterogeneously hyperintense relative to the brain. (c) Coronal fat-saturated T1-weighted image, obtained after intravenous administration of gadolinium, shows marked enhancement of the mass and the adjacent dura mater (arrowheads). (d) Photomicrograph (original magnification x400; H-E stain) shows multiple cells with indented nuclei (arrows) and multiple eosinophils (arrowheads).

View larger version (135K): [in this window] [in a new window] [Download PPT slide]   Figure 6d.  Langerhans cell histiocytosis in a 10-year-old child. (a) Coronal T1-weighted image shows a mass that is isointense relative to normal brain tissue and that replaces lateral frontal and zygomatic bones and extends into the orbit, temporal region, and anterior cranial fossa (arrowhead). (b) On a coronal T2-weighted image, the mass (arrowhead) is heterogeneously hyperintense relative to the brain. (c) Coronal fat-saturated T1-weighted image, obtained after intravenous administration of gadolinium, shows marked enhancement of the mass and the adjacent dura mater (arrowheads). (d) Photomicrograph (original magnification x400; H-E stain) shows multiple cells with indented nuclei (arrows) and multiple eosinophils (arrowheads).

Imaging Appearance
At radiography, LCH appears as osteolytic lesions with beveled or irregular margins, with or without sclerosis (Fig 5) (61). At ultrasonography (US), the proliferation of LCH is seen as a well-defined, heteroechoic mass in the supratemporal orbit (10).

On CT scans, LCH appears as soft-tissue masses that replace and destroy the osseous structures; these masses are well-defined (Fig 5a) or diffuse with a somewhat homogeneous appearance. The lesions exhibit moderate to marked enhancement following intravenous injection of contrast material (61). Common sites of osteolytic lesions include the superior or superolateral orbital region (Fig 6), although similar osseous defects may be seen in other cranial bones (59,61). In addition to its osseous destruction, an LCH soft-tissue mass may extend into the orbit and possibly the temporal fossa, forehead, face, and epidural space as well (Fig 6).

MR imaging is particularly suited to the evaluation of the intracranial extension of LCH. The LCH proliferation is seen as a mass of heterogeneous signal intensity that replaces the bone (Fig 6). On T1-weighted images, the intermediate-signal-intensity mass replaces the relatively high-signal-intensity fat of the bone marrow (Fig 6a). On T2-weighted images, the mass often shows hyperintense components (Fig 6b), but it may also appear hypointense relative to fat (57,63). Gadolinium-enhanced T1-weighted images with fat suppression are useful for evaluating the extent of LCH, and they demonstrate enhancement of the osteolytic lesion that replaces bone (Fig 6c) (61). Additional findings in patients with diabetes insipidus may include absence of the posterior pituitary "bright spot" or enhancement of the hypothalamus or pituitary stalk (64).

Scintigraphic evaluation of patients with suspected LCH includes technetium 99m (^99mTc) diphosphonate skeletal scintigraphy. Radiographic skeletal survey may also be helpful. These methods yield complementary information. Fluorine 18 (¹⁸F) fluorodeoxyglucose PET/CT can localize lesions not detected with the routine evaluation. LCH may have a standardized uptake value greater than 2, a finding suggestive of a malignant lesion (65–67).

Treatment and Prognosis
The prognosis of LCH depends on multiple factors. Negative prognostic indicators include diffuse, multisystem disease with the presence of organ dysfunction and an onset during infancy (58,59). Orbital histiocytosis most commonly manifests in the form of eosinophilic granuloma; thus, its course is relatively benign, although morbidity may be increased if either juxtaneural involvement of the central nervous system or intracranial extension is present.

For unifocal orbital histiocytosis, the initial management after incisional biopsy is often observation, as these lesions frequently heal spontaneously (59,61). Rapid-onset, single-system disease often warrants active intervention (59,61). Systemic chemotherapy and corticosteroid therapy effects a rapid response in children with multifocal disease (59).

	Granulocytic Sarcoma

Top Abstract LEARNING OBJECTIVES FOR TEST... Introduction Dermoid and Epidermoid Inclusion... Fibro-osseous Lesions Langerhans Cell Histiocytosis Granulocytic Sarcoma Neuroblastoma Metastases Primary Malignant Bone Tumors Conclusions References

 
Leukemia is the most common malignancy of childhood, and 15%–20% of cases of leukemia are myelogenetic. Patients with myelogenous leukemia may develop uncommon solid tumors of primitive granulocyte precursor cells called granulocytic sarcomas or myeloid sarcomas . These tumors were previously termed chloromas, in reference to the greenish color imparted by the pigmented enzyme myeloperoxidase in most of these tumors. Granulocytic sarcomas are more common in children than in adults; are often multifocal; and most frequently arise in bones, especially the skull and orbit (68–70).

The temporal relationship between the manifestation of granulocytic sarcoma and the onset of systemic disease evident in the peripheral blood or bone marrow is variable. Granulocytic sarcoma may occur in a patient with a known diagnosis of myelogenous leukemia, possibly heralding relapse; may be the presenting sign of coincident systemic disease; or may antedate the development of systemic disease by months or even years (71–74).

Clinical Features
The peak prevalence for orbital granulocytic sarcoma occurs in patients aged 7–8 years (68,69,71); three-quarters of the patients in a large series were younger than 10 years of age (68). Some authors report that the tumor has no gender predilection (69,70), whereas others have observed a slight male predominance (68,71,75). Orbital granulocytic sarcoma has a higher prevalence among African, East Asian, Latin American, and Middle Eastern populations (68,71,74). The most common presenting symptom of orbital disease is proptosis (68,70). Other presenting symptoms include periorbital cellulitis or swelling and a mass in the lacrimal gland or eyelid. Orbital involvement may be bilateral (68,74).

Granulocytic sarcoma of the orbit usually arises in the subperiosteal region of the osseous wall of the orbit (68,70), but it may involve the extraocular muscles, intra- or extraconal spaces, or the lacrimal gland.

Pathologic Features
Granulocytic sarcoma is composed of immature myelocytic precursor cells, supporting connective tissue, and vascular stroma. Most tumors are predominantly composed of uniform, undifferentiated cells with little cytoplasm and round to ovoid nuclei. The finding of histologic features of myeloid differentiation, such as eosinophilic cytoplasmic granules and indented nuclei (Fig 7c), in some of the cells facilitates making the diagnosis, but the precursor cells are frequently poorly differentiated and these features are often absent (68,71,75).

View larger version (115K): [in this window] [in a new window] [Download PPT slide]   Figure 7a.  Granulocytic sarcoma in a 3-year-old boy. (a) Contrast material–enhanced axial CT image shows bilateral masses centered on the lateral orbital walls without bone erosion; they extend into the extraconal orbits and temporal fossae (arrowheads). (b) On an image superior to a, the masses extend superiorly (arrowheads) and invade the eyelid anteriorly and retrobulbar fat posteriorly (arrows). (c) Photomicrograph (original magnification x200; H-E stain) of a specimen from another patient shows infiltration of the lacrimal gland, represented by acini (straight arrows), by sheets of cells with round to ovoid nuclei. Some cells contain eosinophilic granules (arrowheads) and indented nuclei (curved arrows), characteristics suggestive of myeloid differentiation.

View larger version (108K): [in this window] [in a new window] [Download PPT slide]   Figure 7b.  Granulocytic sarcoma in a 3-year-old boy. (a) Contrast material–enhanced axial CT image shows bilateral masses centered on the lateral orbital walls without bone erosion; they extend into the extraconal orbits and temporal fossae (arrowheads). (b) On an image superior to a, the masses extend superiorly (arrowheads) and invade the eyelid anteriorly and retrobulbar fat posteriorly (arrows). (c) Photomicrograph (original magnification x200; H-E stain) of a specimen from another patient shows infiltration of the lacrimal gland, represented by acini (straight arrows), by sheets of cells with round to ovoid nuclei. Some cells contain eosinophilic granules (arrowheads) and indented nuclei (curved arrows), characteristics suggestive of myeloid differentiation.

View larger version (167K): [in this window] [in a new window] [Download PPT slide]   Figure 7c.  Granulocytic sarcoma in a 3-year-old boy. (a) Contrast material–enhanced axial CT image shows bilateral masses centered on the lateral orbital walls without bone erosion; they extend into the extraconal orbits and temporal fossae (arrowheads). (b) On an image superior to a, the masses extend superiorly (arrowheads) and invade the eyelid anteriorly and retrobulbar fat posteriorly (arrows). (c) Photomicrograph (original magnification x200; H-E stain) of a specimen from another patient shows infiltration of the lacrimal gland, represented by acini (straight arrows), by sheets of cells with round to ovoid nuclei. Some cells contain eosinophilic granules (arrowheads) and indented nuclei (curved arrows), characteristics suggestive of myeloid differentiation.

Imaging Appearance
Granulocytic sarcomas of the orbit usually arise from the lateral orbital wall (Fig 7) (73,74). They tend to encase, rather than invade, normal structures, including bone and sclera (Figs 7, 8). They usually do not disrupt the bone, although the lamina paprycea may be breached by a mass arising in the ethmoid air cells or nasal cavity and secondarily invading the orbit (Fig 8) (74,76).

View larger version (116K): [in this window] [in a new window] [Download PPT slide]   Figure 8a.  Granulocytic sarcoma in a 4-year-old boy. (a) Sagittal T1-weighted MR image shows an inferior extraconal mass that is isointense relative to gray matter (arrowhead). Arrow = optic nerve. (b) Axial T2-weighted image shows that the mass (arrowheads) involves the right retrobulbar space and ethmoid air cells. It is hyperintense relative to the dark signal of the highly collagenized sclera (arrow). (c) Axial proton density–weighted MR image, obtained slightly superior to b, reveals that the mass (arrowheads) surrounds the optic nerve (straight arrow) and medial rectus muscle (curved arrow).

View larger version (153K): [in this window] [in a new window] [Download PPT slide]   Figure 8b.  Granulocytic sarcoma in a 4-year-old boy. (a) Sagittal T1-weighted MR image shows an inferior extraconal mass that is isointense relative to gray matter (arrowhead). Arrow = optic nerve. (b) Axial T2-weighted image shows that the mass (arrowheads) involves the right retrobulbar space and ethmoid air cells. It is hyperintense relative to the dark signal of the highly collagenized sclera (arrow). (c) Axial proton density–weighted MR image, obtained slightly superior to b, reveals that the mass (arrowheads) surrounds the optic nerve (straight arrow) and medial rectus muscle (curved arrow).

View larger version (144K): [in this window] [in a new window] [Download PPT slide]   Figure 8c.  Granulocytic sarcoma in a 4-year-old boy. (a) Sagittal T1-weighted MR image shows an inferior extraconal mass that is isointense relative to gray matter (arrowhead). Arrow = optic nerve. (b) Axial T2-weighted image shows that the mass (arrowheads) involves the right retrobulbar space and ethmoid air cells. It is hyperintense relative to the dark signal of the highly collagenized sclera (arrow). (c) Axial proton density–weighted MR image, obtained slightly superior to b, reveals that the mass (arrowheads) surrounds the optic nerve (straight arrow) and medial rectus muscle (curved arrow).

At radiography, granulocytic sarcoma usually appears as a soft-tissue mass. Less commonly, bone erosion or demineralization or periosteal reaction may be seen (69). At US, a nonspecific, homogeneous, hypoechoic or echogenic solid mass is seen. The borders may appear infiltrative (10,69).

On unenhanced CT scans, granulocytic sarcomas are generally homogeneously isoattenuating to slightly hyperattenuating relative to muscle or brain and less attenuating than the sclera. Invasion of the orbital fat and extension to the eyelid are commonly observed (Fig 7b). No calcification is detected. Uniform enhancement is seen after intravenous administration of iodinated contrast media (Fig 7) (63,69,74,76).

On T1-weighted MR images, granulocytic sarcomas are iso- to hypointense relative to gray matter or muscle (Fig 8a), and they replace the high signal intensity in the yellow bone marrow. They are heterogeneously iso- to slightly hyperintense on T2-weighted images. The signal intensity of the tumor, which contains little fibrous stroma, is quite different from the very dark signal of the highly collagenized sclera (Fig 8b) (76). Homogeneous enhancement is seen after intravenous administration of gadolinium (64,69,74,76).

Differential Diagnosis
In patients with a known diagnosis of leukemia, differential diagnosis of a solid mass includes several complications of the disease: abscess, hematoma, or secondary malignancy. The diffuse enhancement seen in granulocytic sarcomas distinguishes them from abscesses, which enhance only in the wall, and hematomas, which do not enhance at all. Differentiation of granulocytic sarcoma from another malignancy is more challenging. When a uniformly enhancing orbital mass develops in this patient group, it is reasonable to presume a diagnosis of granulocytic sarcoma and to treat it with chemotherapy. If the tumor does not respond, biopsy should be pursued.

In patients with no history of leukemia, the differential diagnosis of a retrobulbar orbital mass that causes rapidly progressive proptosis includes malignant and inflammatory processes. Rhabdomyosarcoma is the most common extraocular malignancy of the orbit in children. Rhabdomyosarcoma is much more likely than granulocytic sarcoma to cause bone erosion. In contrast to granulocytic sarcoma, which usually involves the lateral orbit, rhabdomyosarcoma usually arises in the superior orbit.

Patients with granulocytic sarcoma may present with inflammatory signs including redness and swelling of the orbit, infiltration of the conal fat, and diffuse enhancement at imaging. These findings suggest the much more common condition of orbital cellulitis. Symptoms of systemic disease in patients with synchronous onset of leukemia, such as paleness, lethargy, or epistaxis, or the finding of well-defined masses with central enhancement may suggest the proper diagnosis.

Orbital granulocytic sarcomas may be bilateral, which suggests another differential diagnosis, including LCH and metastatic neuroblastoma. LCH may involve both orbits. However, LCH is associated with bone erosions with beveled edges in the skull, concomitant lytic lesions of other bones, or the syndrome of diabetes insipidus related to involvement of the infundibulum. Metastatic neuroblastoma also has a predilection for the orbits, is frequently bilateral, and also originates in the osseous walls of the orbits. But this tumor contains calcifications and may be accompanied by aggressive periosteal reaction, lytic lesions elsewhere in the skeleton, abdominal masses, and excess urinary levels of catecholamines.

Treatment and Prognosis
Early diagnosis and induction chemotherapy are critical for achieving complete remission in cases of leukemia. In patients with no hematologic evidence of leukemia, the finding of granulocytic sarcoma portends its development, and some authors support initiation of chemotherapy upon diagnosis of isolated granulocytic sarcoma to abort the leukemic process (13,68).

	Neuroblastoma Metastases

Top Abstract LEARNING OBJECTIVES FOR TEST... Introduction Dermoid and Epidermoid Inclusion... Fibro-osseous Lesions Langerhans Cell Histiocytosis Granulocytic Sarcoma Neuroblastoma Metastases Primary Malignant Bone Tumors Conclusions References

 
Neuroblastoma, the most frequent extracranial solid tumor of childhood, often metastasizes to bone, and it is the most common primary tumor to involve the orbit. Other primary tumors of childhood, including Ewing sarcoma and Wilms tumor, only rarely metastasize to the orbit (77,78).

Clinical Features
Ophthalmic manifestations occur in 19.8–54.7% (78–80) of patients with neuroblastoma and include signs and symptoms of orbital metastasis, Horner syndrome due to local mass effect of the primary tumor, and opsoclonus/myoclonus (a paraneoplastic syndrome of "dancing eyes" and cerebellar ataxia). Ophthalmic findings are often bilateral and occasionally are the first presenting sign of the tumor (77–80).

The most common ophthalmic findings in neuroblastoma are proptosis and periorbital ecchymosis ("raccoon eyes"). These manifestations of metastatic disease are bilateral in about half of cases (78–80). Less frequent clinical features include periorbital swelling, subconjunctival hemorrhage, ocular mobility disturbance, strabismus, and atrophy of the optic head (57,79,80).

Most patients are less than 2 years old; they are rarely over 8 years of age (80). There is no definite gender bias. Most patients with orbital metastatic neuroblastoma have abdominal primary tumors (78,79). In three-quarters of patients, excessive amounts of catecholamine metabolites are found in the urine (79).

Pathologic Features
Generally, neuroblastoma metastases arise in the marrow of the bony orbit, especially in the roof and lateral wall (81,82). The tumor, which may be circumscribed or infiltrative, is usually extraconal and may be contained by the periosteum of the orbital bone. The pathologic appearance of neuroblastoma metastases is similar to that of the primary tumor. The cut surface varies from gray-tan and mucoid to deep red and grossly hemorrhagic. The internal content may be solid, lobular, hemorrhagic, necrotic, or gritty due to small, coarse calcifications (83,84).

At histologic examination, the tumor contains neuroblasts, which are small round cells, supported by stroma composed of Schwann cells and a framework of fibrovascular tissue (Fig 9c). Most of the tumor is composed of primitive, small, round cells with scant cytoplasm and round to ovoid, hyperchromatic or densely speckled nuclei. Scattered among these primitive cells may be a variable number of cells differentiating toward ganglion cells, which are larger round cells with abundant eosinophilic cytoplasm and prominent distinct nucleoli (Fig 9d).

View larger version (110K): [in this window] [in a new window] [Download PPT slide]   Figure 9a.  Neuroblastoma metastasis in a 6-year-old girl. (a) Axial CT image obtained after intravenous administration of iodinated contrast material demonstrates a mass centered on the lateral wall of the orbit and extending into extraconal space with an associated aggressive-appearing periosteal reaction (arrowhead). (b) Same image as a, but displayed with a bone window, better shows the sunburst-pattern periosteal reaction (arrowhead). (c) Photomicrograph (original magnification x400; H-E stain) shows nests of uniform, small, round blue cells separated by thin pink fibrous septa. (d) Photomicrograph (original magnification x400; H-E stain) of a specimen from a more differentiated neuroblastoma in another patient demonstrates larger cells with abundant cytoplasm and prominent nucleoli (arrowheads).

View larger version (92K): [in this window] [in a new window] [Download PPT slide]   Figure 9b.  Neuroblastoma metastasis in a 6-year-old girl. (a) Axial CT image obtained after intravenous administration of iodinated contrast material demonstrates a mass centered on the lateral wall of the orbit and extending into extraconal space with an associated aggressive-appearing periosteal reaction (arrowhead). (b) Same image as a, but displayed with a bone window, better shows the sunburst-pattern periosteal reaction (arrowhead). (c) Photomicrograph (original magnification x400; H-E stain) shows nests of uniform, small, round blue cells separated by thin pink fibrous septa. (d) Photomicrograph (original magnification x400; H-E stain) of a specimen from a more differentiated neuroblastoma in another patient demonstrates larger cells with abundant cytoplasm and prominent nucleoli (arrowheads).

View larger version (181K): [in this window] [in a new window] [Download PPT slide]   Figure 9c.  Neuroblastoma metastasis in a 6-year-old girl. (a) Axial CT image obtained after intravenous administration of iodinated contrast material demonstrates a mass centered on the lateral wall of the orbit and extending into extraconal space with an associated aggressive-appearing periosteal reaction (arrowhead). (b) Same image as a, but displayed with a bone window, better shows the sunburst-pattern periosteal reaction (arrowhead). (c) Photomicrograph (original magnification x400; H-E stain) shows nests of uniform, small, round blue cells separated by thin pink fibrous septa. (d) Photomicrograph (original magnification x400; H-E stain) of a specimen from a more differentiated neuroblastoma in another patient demonstrates larger cells with abundant cytoplasm and prominent nucleoli (arrowheads).

View larger version (166K): [in this window] [in a new window] [Download PPT slide]   Figure 9d.  Neuroblastoma metastasis in a 6-year-old girl. (a) Axial CT image obtained after intravenous administration of iodinated contrast material demonstrates a mass centered on the lateral wall of the orbit and extending into extraconal space with an associated aggressive-appearing periosteal reaction (arrowhead). (b) Same image as a, but displayed with a bone window, better shows the sunburst-pattern periosteal reaction (arrowhead). (c) Photomicrograph (original magnification x400; H-E stain) shows nests of uniform, small, round blue cells separated by thin pink fibrous septa. (d) Photomicrograph (original magnification x400; H-E stain) of a specimen from a more differentiated neuroblastoma in another patient demonstrates larger cells with abundant cytoplasm and prominent nucleoli (arrowheads).

A highly characteristic feature of neuroblasts is the formation of fine eosinophilic, cellular processes that create the appearance of a fibrillary extracellular network called neuropil. Homer-Wright rosettes are a highly characteristic arrangement of these cells; they consist of round or ovoid clusters of cells surrounding a central core of light pink neuropil. In addition to the neuropil, groups of neuroblasts are also surrounded by a stroma of fusiform cells with elongated nuclei that represent Schwann cells and are supported by incomplete fibrovascular septa that confer a lobular appearance to the tumor as a whole. The relative composition of these cellular components of the tumor determines its gross appearance: Abundant stroma or neuropil is seen in tumors with a gray to tan mucoid appearance, whereas abundant neuroblasts are seen in grossly hemorrhagic tumors (80,83,84).

Imaging Appearance
Radiographic findings of orbital neuroblastoma metastases include destruction or spiculated thickening of the orbital roof or lateral orbital wall, a soft-tissue mass, or orbital calcification (Fig 9) (80,85). At US, these masses have a nonspecific appearance of variable echogenicity and infiltrative margins (10).

At CT and MR imaging, neuroblastoma metastases appear as circumscribed or poorly defined, extraconal masses that usually arise from the lateral wall of the orbit (Figs 9, 10). Frequently, these masses are bilateral. Adjacent permeative bone destruction is commonly seen on CT scans (Fig 9b). On unenhanced CT scans, the mass may show high attenuation relative to that of muscle, and small calcific foci may be noted (82). The tumor may infiltrate adjacent structures, including the infratemporal fossa, the face, and the intracranial contents, but preseptal extension is uncommon.

View larger version (124K): [in this window] [in a new window] [Download PPT slide]   Figure 10a.  Neuroblastoma metastases in a 10- month-old boy with right proptosis. (a) Axial T1-weighted MR image shows a homogeneous mass that is isointense relative to gray matter and that arises from the right sphenoid bone. It extends into the lateral extraconal space, temporal fossa, and middle cranial fossa (arrowheads). (b) Axial T2-weighted image shows that the mass causes right proptosis (arrowheads). The tumor is slightly heterogeneous and mostly hyperintense relative to the medial rectus muscle (arrow). (c) Axial T2-weighted image obtained inferior to b shows bilateral masses of the lower sphenoid bones (arrowheads). The left mass extends into the inferior orbit. (d) Contrast-enhanced axial T1-weighted image reveals diffuse enhancement of the mass (arrowheads). (e) Anterior image of the upper body from a bone scintigraphic study shows a mask of increased radiotracer uptake around both orbits (arrowhead) and radiotracer accumulation in the left adrenal primary tumor (arrow).

View larger version (137K): [in this window] [in a new window] [Download PPT slide]   Figure 10b.  Neuroblastoma metastases in a 10- month-old boy with right proptosis. (a) Axial T1-weighted MR image shows a homogeneous mass that is isointense relative to gray matter and that arises from the right sphenoid bone. It extends into the lateral extraconal space, temporal fossa, and middle cranial fossa (arrowheads). (b) Axial T2-weighted image shows that the mass causes right proptosis (arrowheads). The tumor is slightly heterogeneous and mostly hyperintense relative to the medial rectus muscle (arrow). (c) Axial T2-weighted image obtained inferior to b shows bilateral masses of the lower sphenoid bones (arrowheads). The left mass extends into the inferior orbit. (d) Contrast-enhanced axial T1-weighted image reveals diffuse enhancement of the mass (arrowheads). (e) Anterior image of the upper body from a bone scintigraphic study shows a mask of increased radiotracer uptake around both orbits (arrowhead) and radiotracer accumulation in the left adrenal primary tumor (arrow).

View larger version (163K): [in this window] [in a new window] [Download PPT slide]   Figure 10c.  Neuroblastoma metastases in a 10- month-old boy with right proptosis. (a) Axial T1-weighted MR image shows a homogeneous mass that is isointense relative to gray matter and that arises from the right sphenoid bone. It extends into the lateral extraconal space, temporal fossa, and middle cranial fossa (arrowheads). (b) Axial T2-weighted image shows that the mass causes right proptosis (arrowheads). The tumor is slightly heterogeneous and mostly hyperintense relative to the medial rectus muscle (arrow). (c) Axial T2-weighted image obtained inferior to b shows bilateral masses of the lower sphenoid bones (arrowheads). The left mass extends into the inferior orbit. (d) Contrast-enhanced axial T1-weighted image reveals diffuse enhancement of the mass (arrowheads). (e) Anterior image of the upper body from a bone scintigraphic study shows a mask of increased radiotracer uptake around both orbits (arrowhead) and radiotracer accumulation in the left adrenal primary tumor (arrow).

View larger version (121K): [in this window] [in a new window] [Download PPT slide]   Figure 10d.  Neuroblastoma metastases in a 10- month-old boy with right proptosis. (a) Axial T1-weighted MR image shows a homogeneous mass that is isointense relative to gray matter and that arises from the right sphenoid bone. It extends into the lateral extraconal space, temporal fossa, and middle cranial fossa (arrowheads). (b) Axial T2-weighted image shows that the mass causes right proptosis (arrowheads). The tumor is slightly heterogeneous and mostly hyperintense relative to the medial rectus muscle (arrow). (c) Axial T2-weighted image obtained inferior to b shows bilateral masses of the lower sphenoid bones (arrowheads). The left mass extends into the inferior orbit. (d) Contrast-enhanced axial T1-weighted image reveals diffuse enhancement of the mass (arrowheads). (e) Anterior image of the upper body from a bone scintigraphic study shows a mask of increased radiotracer uptake around both orbits (arrowhead) and radiotracer accumulation in the left adrenal primary tumor (arrow).

View larger version (108K): [in this window] [in a new window] [Download PPT slide]   Figure 10e.  Neuroblastoma metastases in a 10- month-old boy with right proptosis. (a) Axial T1-weighted MR image shows a homogeneous mass that is isointense relative to gray matter and that arises from the right sphenoid bone. It extends into the lateral extraconal space, temporal fossa, and middle cranial fossa (arrowheads). (b) Axial T2-weighted image shows that the mass causes right proptosis (arrowheads). The tumor is slightly heterogeneous and mostly hyperintense relative to the medial rectus muscle (arrow). (c) Axial T2-weighted image obtained inferior to b shows bilateral masses of the lower sphenoid bones (arrowheads). The left mass extends into the inferior orbit. (d) Contrast-enhanced axial T1-weighted image reveals diffuse enhancement of the mass (arrowheads). (e) Anterior image of the upper body from a bone scintigraphic study shows a mask of increased radiotracer uptake around both orbits (arrowhead) and radiotracer accumulation in the left adrenal primary tumor (arrow).

On T1-weighted MR images, orbital neuroblastoma typically has low signal intensity compared with that of muscle; it appears slightly hyperintense relative to muscle on T2-weighted images (Fig 10). The mass may appear heterogeneous because of necrosis or hemorrhage. Heterogeneous enhancement is typical following intravenous administration of contrast material (Fig 10d) (63,81,82,85,86).

Several scintigraphic studies are used to evaluate patients with orbital neuroblastoma. Bone metastases show increased radiotracer uptake on ^99mTc diphosphonate bone scintigrams (Fig 10e). This study is a sensitive screen for bone metastases, but it does not allow cortical involvement to be differentiated from medullary involvement. Iodine 123 metaiodobenzylguanidine (MIBG) is a radiolabeled catecholamine analog that is highly sensitive and specific for the primary tumor and its metastases and is routinely used in staging and follow-up. Somatostatin receptor scintigraphy with indium 111 pentetreotide shows radiotracer accumulation in the primary tumor and its metastases, but it is not as sensitive nor as specific as ¹²³I MIBG. ¹⁸F-fluorodeoxyglucose PET/CT and immunoscintigraphy are also sensitive and specific for neuroblastoma and its metastases (83,87).

Additional findings that may be observed in patients with orbital neuroblastoma include dural metastases, which may cause sutural widening; permeative lesions of other bones, including the metaphyseal region of long bones; and an adrenal or sympathetic chain mass representing the primary tumor.

Differential Diagnosis
Rhabdomyosarcoma, which also manifests with rapidly progressive proptosis, is the most common tumor of the extraocular soft tissues in children and often erodes the osseous orbit, causing an appearance similar to that of neuroblastoma metastases. Rhabdomyosarcoma is the more likely diagnosis if the mass involves the anterior orbit, because neuroblastoma typically does not extend into the preseptal soft tissues. On the other hand, hyperattenuation of the mass compared with that of muscle on CT scans or bilateral findings are suggestive of neuroblastoma rather than rhabdomyosarcoma (82).

Treatment and Prognosis
The prognosis for patients with neuroblastoma depends on many factors, but particularly age and stage at presentation. Patients who, at presentation, are less than 1 year old; have surgically resectable disease (stage I or II); or have metastases limited to the liver, skin, and bone marrow (stage IVS) have a good prognosis with therapy. Metastatic orbital involvement is stage IV disease, which is considered high risk (79) and is treated with polychemotherapy at high doses.

	Primary Malignant Bone Tumors

Top Abstract LEARNING OBJECTIVES FOR TEST... Introduction Dermoid and Epidermoid Inclusion... Fibro-osseous Lesions Langerhans Cell Histiocytosis Granulocytic Sarcoma Neuroblastoma Metastases Primary Malignant Bone Tumors Conclusions References

 
Primary malignant bone tumors arising in or near the orbit are rare, but the most common of these is osteosarcoma. About 10% of orbital osteosarcomas arise in the craniofacial region, most frequently from the gnathic bones (18). They may also arise from the paranasal sinuses and extend to involve the orbit. In young children, osteosarcomas generally occur in normal bone, but they may also develop in bone affected by such conditions as fibrous dysplasia or osteogenesis imperfecta. Children with hereditary retinoblastoma have a mutation of the RB1 gene, which also places them at risk for developing osteosarcoma and other mesenchymal tumors. This risk is increased if the retinoblastoma was treated with radiation, in which case the second primary tumor usually, but not always, arises within the radiation port, in or near the orbit.

Osteosarcomas are mainly formed of two components, matrix and sarcomatous stroma. Depending on the amount and degree of mineralization of its matrix component, the tumor may be grossly firm and sclerotic or soft and fleshy (18,88). Craniofacial osteosarcomas may be osteoblastic or chondroblastic. At histologic analysis, osteoblastic osteosarcomas are formed from irregular foci of pinkish hyaline osteoid material surrounded by spindled to polygonal stromal cells. Chondroblastic osteosarcomas contain lobules of cartilage with malignant cells within the lacunae.

On radiographs and CT scans, osteosarcomas appear as destructive, expansile lesions of bone, which may be sclerotic, lytic, or both. Dense mineralized matrix may be prominent or minimal. On MR images, especially those obtained with T2-weighted pulse sequences, these tumors appear heterogeneous. Fluid levels may be seen (89). On T1-weighted images, osteosarcomas have intermediate signal intensity and they enhance heterogeneously after administration of gadolinium (18,89).

	Conclusions

Top Abstract LEARNING OBJECTIVES FOR TEST... Introduction Dermoid and Epidermoid Inclusion... Fibro-osseous Lesions Langerhans Cell Histiocytosis Granulocytic Sarcoma Neuroblastoma Metastases Primary Malignant Bone Tumors Conclusions References

 
Orbital lesions of osseous origin represent a wide histologic spectrum, from developmental anomalies to neoplastic and proliferative disorders. These conditions share imaging features with each other and with nonosseous lesions of the orbit, but their pathologic features often influence their radiologic appearances and may allow them to be distinguished at imaging.

	Footnotes

 

Abbreviations: H-E = hematoxylin-eosin, LCH = Langerhans cell histiocytosis

The opinions and assertions contained herein are the private views of the authors and are not to be construed as official nor as representing the views of the Departments of the Army or Defense.

	References

Top Abstract LEARNING OBJECTIVES FOR TEST... Introduction Dermoid and Epidermoid Inclusion... Fibro-osseous Lesions Langerhans Cell Histiocytosis Granulocytic Sarcoma Neuroblastoma Metastases Primary Malignant Bone Tumors Conclusions References

 

1. Shields JA, Shields CL. Orbital cysts of childhood: classification, clinical features, and management. Surv Ophthalmol 2004;49:281–299.[CrossRef][Medline]
2. Rubinstein LJ. Tumors of the central nervous system. In: Hartmann WH, Cowan WR, eds. Anonymous tumors of the central nervous system. Washington, DC: Armed Forces Institute of Pathology, 1982;288–292.
3. Chen S, Ikawa F, Kurisu K, Arita K, Takaba J, Kanou Y. Quantitative MR evaluation of intracranial epidermoid tumors by fast fluid-attenuated inversion recovery imaging and echo-planar diffusion-weighted imaging. AJNR Am J Neuroradiol 2001;22:1089–1096.[Abstract/Free Full Text]
4. Russell DS, Rubinstein LJ. Tumours and tumour-like lesions of maldevelopmental origin. In: Rubinstein LJ, ed. Pathology of tumours of the nervous system. 5th ed. Baltimore, Md: Williams & Wilkins, 1989;664–765.
5. Pear BL. Epidermoid and dermoid sequestration cysts. Am J Roentgenol Radium Ther Nucl Med 1970;110:148–155.[Medline]
6. Lee SH, Delgado TE, Buchheit WA. Intracranial dermoid tumor: diagnosis by computed tomography—a case report. Neurosurgery 1977;1:281–283.[Medline]
7. Kountakis SE, Minotti AM, Maillard A, Stiernberg CM. Teratomas of the head and neck. Am J Otolaryngol 1994;15:292–296.[CrossRef][Medline]
8. Brownstein MH, Helwig EB. Subcutaneous dermoid cysts. Arch Dermatol 1973;107:237–239.[Abstract/Free Full Text]
9. Batsakis JG. Pathology consultation. Nomenclature of developmental tumors. Ann Otol Rhinol Laryngol 1984;93:98–99.[Medline]
10. Berrocal T, de Orbe A, Prieto C, et al. US and color Doppler imaging of ocular and orbital disease in the pediatric age group. RadioGraphics 1996;16: 251–272.[Abstract]
11. Bilaniuk LT, Farber M. Imaging of developmental anomalies of the eye and the orbit. AJNR Am J Neuroradiol 1992;13:793–803.[Medline]
12. New GB, Drich JB. Dermoid cysts of the head and neck. Surg Gynecol Obstet 1937;65:48–55.
13. Font R, Croxatto J, Rao N. Tumors of the orbit. In: Silverberg S, Sobin L, eds. AFIP atlas of tumor pathology: tumors of the eye and ocular adnexa. Washington, DC: American Registry of Pathology, 2006;265–319.
14. Chawda SJ, Moseley IF. Computed tomography of orbital dermoids: a 20-year review. Clin Radiol 1999;54:821–825.[CrossRef][Medline]
15. Hakyemez B, Aksoy U, Yildiz H, Ergin N. Intracranial epidermoid cysts: diffusion-weighted, FLAIR and conventional MR findings. Eur J Radiol 2005; 54:214–220.[CrossRef][Medline]
16. Aikele P, Kittner T, Offergeld C, Kaftan H, Huttenbrink KB, Laniado M. Diffusion-weighted MR imaging of cholesteatoma in pediatric and adult patients who have undergone middle ear surgery. AJR Am J Roentgenol 2003;181:261–265.[Abstract/Free Full Text]
17. Pryor SG, Lewis JE, Weaver AL, Orvidas LJ. Pediatric dermoid cysts of the head and neck. Otolaryngol Head Neck Surg 2005;132:938–942.[CrossRef][Medline]
18. Wenig BM, Mafee MF, Ghosh L. Fibro-osseous, osseous, and cartilaginous lesions of the orbit and paraorbital region: correlative clinicopathologic and radiographic features, including the diagnostic role of CT and MR imaging. Radiol Clin North Am 1998;36:1241–1259, xii.[CrossRef][Medline]
19. Liakos GM, Walker CB, Carruth JA. Ocular complications in craniofacial fibrous dysplasia. Br J Ophthalmol 1979;63:611–616.[Abstract/Free Full Text]
20. Kransdorf MJ, Moser RP Jr, Gilkey FW. Fibrous dysplasia. RadioGraphics 1990;10:519–537.[Abstract]
21. Edgerton MT, Persing JA, Jane JA. The surgical treatment of fibrous dysplasia with emphasis on recent contributions from cranio-maxillo-facial surgery. Ann Surg 1985;202:459–479.[Medline]
22. Bibby K, McFadzean R. Fibrous dysplasia of the orbit. Br J Ophthalmol 1994;78:266–270.[Abstract/Free Full Text]
23. Utz JA, Kransdorf MJ, Jelinek JS, Moser RP Jr, Berrey BH. MR appearance of fibrous dysplasia. J Comput Assist Tomogr 1989;13:845–851.[Medline]
24. Ricalde P, Horswell BB. Craniofacial fibrous dysplasia of the fronto-orbital region: a case series and literature review. J Oral Maxillofac Surg 2001; 59:157–167.[CrossRef][Medline]
25. Ramsey HE, Strong EW, Frazell EL. Fibrous dysplasia of the craniofacial bones. Am J Surg 1968; 116:542–547.[CrossRef][Medline]
26. Mohammadi-Araghi H, Haery C. Fibro-osseous lesions of craniofacial bones: the role of imaging. Radiol Clin North Am 1993;31:121–134.[Medline]
27. Lello GE, Sparrow OC. Craniofacial polyostotic fibrous dysplasia. J Maxillofac Surg 1985;13: 267–272.[CrossRef][Medline]
28. Jan M, Dweik A, Destrieux C, Djebbari Y. Fronto-orbital sphenoidal fibrous dysplasia. Neurosurgery 1994;34:544–547.[Medline]
29. Chen YR, Breidahl A, Chang CN. Optic nerve decompression in fibrous dysplasia: indications, efficacy, and safety. Plast Reconstr Surg 1997;99: 22–30.[Medline]
30. Horgan MA, Delashaw JB, Dailey RA. Bilateral proptosis: an unusual presentation of fibrous dysplasia. Br J Neurosurg 1999;13:335–337.[CrossRef][Medline]
31. Obisesan AA, Lagundoye SB, Daramola JO, Ajagbe HA, Oluwasanmi JO. The radiologic features of fibrous dysplasia of the craniofacial bones. Oral Surg Oral Med Oral Pathol 1977;44:949–959.[CrossRef][Medline]
32. Fitzpatrick KA, Taljanovic MS, Speer DP, et al. Imaging findings of fibrous dysplasia with histopathologic and intraoperative correlation. AJR Am J Roentgenol 2004;182:1389–1398.[Free Full Text]
33. Tehranzadeh J, Fung Y, Donohue M, Anavim A, Pribram HW. Computed tomography of Paget disease of the skull versus fibrous dysplasia. Skeletal Radiol 1998;27:664–672.[CrossRef][Medline]
34. Mendelsohn DB, Hertzanu Y, Cohen M, Lello G. Computed tomography of craniofacial fibrous dysplasia. J Comput Assist Tomogr 1984;8:1062–1065.[Medline]
35. Chong VF, Khoo JB, Fan YF. Fibrous dysplasia involving the base of the skull. AJR Am J Roentgenol 2002;178:717–720.[Free Full Text]
36. Jee WH, Choi KH, Choe BY, Park JM, Shinn KS. Fibrous dysplasia: MR imaging characteristics with radiopathologic correlation. AJR Am J Roentgenol 1996;167:1523–1527.[Abstract/Free Full Text]
37. Casselman JW, Jonge I, Neyt L, Clercq C, D’Hont G. MRI in craniofacial fibrous dysplasia. Neuroradiology 1993;35:234–237.[CrossRef][Medline]
38. Johns WD, Gupta SM, Kayani N. Scintigraphic evaluation of polyostotic fibrous dysplasia. Clin Nucl Med 1987;12:627–631.[CrossRef][Medline]
39. Singnurkar A, Rush C. The "pirate sign" in fibrous dysplasia. Clin Nucl Med 2006;31:727–728.[CrossRef][Medline]
40. Beaman FD, Bancroft LW, Peterson JJ, Kransdorf MJ, Murphey MD, Menke DM. Imaging characteristics of cherubism. AJR Am J Roentgenol 2004; 182:1051–1054.[Abstract/Free Full Text]
41. Robbin MR, Murphey MD, Temple HT, Kransdorf MJ, Choi JJ. Imaging of musculoskeletal fibromatosis. RadioGraphics 2001;21:585–600.[Abstract/Free Full Text]
42. Tharanon W, Sinn DP, Hobar PC, Sklar FH, Salomon J. Surgical outcomes using bioabsorbable plating systems in pediatric craniofacial surgery. J Craniofac Surg 1998;9:441–444.[Medline]
43. Munro IR, Chen YR. Radical treatment for fronto-orbital fibrous dysplasia: the chain-link fence. Plast Reconstr Surg 1981;67:719–730.[Medline]
44. Slootweg PJ, Muller H. Juvenile ossifying fibroma: report of four cases. J Craniomaxillofac Surg 1990; 18:125–129.[Medline]
45. Margo CE, Ragsdale BD, Perman KI, Zimmerman LE, Sweet DE. Psammomatoid (juvenile) ossifying fibroma of the orbit. Ophthalmology 1985;92: 150–159.[Medline]
46. Slootweg PJ, Panders AK, Koopmans R, Nikkels PG. Juvenile ossifying fibroma: an analysis of 33 cases with emphasis on histopathological aspects. J Oral Pathol Med 1994;23:385–388.[CrossRef][Medline]
47. Johnson LC, Yousefi M, Vinh TN, Heffner DK, Hyams VJ, Hartman KS. Juvenile active ossifying fibroma: its nature, dynamics and origin. Acta Otolaryngol Suppl 1991;488:1–40.[Medline]
48. Wenig BM, Vinh TN, Smirniotopoulos JG, Fowler CB, Houston GD, Heffner DK. Aggressive psammomatoid ossifying fibromas of the sinonasal region: a clinicopathologic study of a distinct group of fibro-osseous lesions. Cancer 1995;76: 1155–1165.[Medline]
49. Bendet E, Bakon M, Talmi YP, Tadmor R, Kronenberg J. Juvenile cemento-ossifying fibroma of the maxilla. Ann Otol Rhinol Laryngol 1997;106: 75–78.[Medline]
50. Margo CE, Weiss A, Habal MB. Psammomatoid ossifying fibroma. Arch Ophthalmol 1986;104: 1347–1351.[Abstract/Free Full Text]
51. Khoury NJ, Naffaa LN, Shabb NS, Haddad MC. Juvenile ossifying fibroma: CT and MR findings. Eur Radiol 2002;12(suppl 3):S109–S113.[CrossRef][Medline]
52. Han MH, Chang KH, Lee CH, Seo JW, Han MC, Kim CW. Sinonasal psammomatoid ossifying fibromas: CT and MR manifestations. AJNR Am J Neuroradiol 1991;12:25–30.[Abstract]
53. Lawton MT, Heiserman JE, Coons SW, Ragsdale BD, Spetzler RF. Juvenile active ossifying fibroma: report of four cases. J Neurosurg 1997;86: 279–285.[Medline]
54. Kuta AJ, Worley CM, Kaugars GE. Central cemento-ossifying fibroma of the maxillary sinus: a review of six cases. AJNR Am J Neuroradiol 1995;16: 1282–1286.[Abstract]
55. Writing Group of the Histiocyte Society. Histiocytosis syndromes in children. Lancet 1987;1:208–209.[CrossRef][Medline]
56. Lichtenstein L. Histiocytosis X (eosinophilic granuloma of bone, Letterer-Siwe disease, and Schueller-Christian disease): further observations of pathological and clinical importance. J Bone Joint Surg Am 1964;46:76–90.[Abstract/Free Full Text]
57. Atlas SW. Magnetic resonance imaging of the brain and spine. New York, NY: Raven, 1996.
58. Luu QC, Lasky JL, Moore TB, Nelson S, Wang MB. Treatment of embryonal rhabdomyosarcoma of the sinus and orbit with chemotherapy, radiation, and endoscopic surgery. J Pediatr Surg 2006; 41:e15–e17.[Medline]
59. Kramer TR, Noecker RJ, Miller JM, Clark LC. Langerhans cell histiocytosis with orbital involvement. Am J Ophthalmol 1997;124:814–824.[Medline]
60. Shields JA, Shields CL, Scartozzi R. Survey of 1264 patients with orbital tumors and simulating lesions: the 2002 Montgomery lecture, part 1. Ophthalmology 2004;111:997–1008.[CrossRef][Medline]
61. Hidayat AA, Mafee MF, Laver NV, Noujaim S. Langerhans’ cell histiocytosis and juvenile xanthogranuloma of the orbit: clinicopathologic, CT, and MR imaging features. Radiol Clin North Am 1998;36:1229–1240, xii.[CrossRef][Medline]
62. Harris GJ. Langerhans cell histiocytosis of the orbit: a need for interdisciplinary dialogue. Am J Ophthalmol 2006;141:374–378.[CrossRef][Medline]
63. Gorospe L, Royo A, Berrocal T, Garcia-Raya P, Moreno P, Abelairas J. Imaging of orbital disorders in pediatric patients. Eur Radiol 2003;13: 2012–2026.[CrossRef][Medline]
64. Barnes PD, Robson CD, Robertson RL, Poussaint TY. Pediatric orbital and visual pathway lesions. Neuroimaging Clin North Am 1996;6:179–198.
65. Kaste SC, Rodriguez-Galindo C, McCarville ME, Shulkin BL. PET-CT in pediatric Langerhans cell histiocytosis. Pediatr Radiol 2007;37:615–622.[CrossRef][Medline]
66. Daldrup-Link HE, Franzius C, Link TM, et al. Whole-body MR imaging for detection of bone metastases in children and young adults: comparison with skeletal scintigraphy and FDG PET. AJR Am J Roentgenol 2001;177:229–236.[Abstract/Free Full Text]
67. Aoki J, Watanabe H, Shinozaki T, et al. FDG PET of primary benign and malignant bone tumors: standardized uptake value in 52 lesions. Radiology 2001;219:774–777.[Abstract/Free Full Text]
68. Zimmerman LE, Font RL. Ophthalmologic manifestations of granulocytic sarcoma (myeloid sarcoma or chloroma): the third Pan American Association of Ophthalmology and American Journal of Ophthalmology Lecture. Am J Ophthalmol 1975; 80:975–990.[Medline]
69. Pui MH, Fletcher BD, Langston JW. Granulocytic sarcoma in childhood leukemia: imaging features. Radiology 1994;190:698–702.[Abstract/Free Full Text]
70. Liu PI, Ishimaru T, McGregor DH, Okada H, Steer A. Autopsy study of granulocytic sarcoma (chloroma) in patients with myelogenous leukemia, Hiroshima-Nagasaki 1949–1969. Cancer 1973;31: 948–955.[CrossRef][Medline]
71. Stockl FA, Dolmetsch AM, Saornil MA, Font RL, Burnier MN Jr. Orbital granulocytic sarcoma. Br J Ophthalmol 1997;81:1084–1088.[Abstract/Free Full Text]
72. Pomeranz SJ, Hawkins HH, Towbin R, Lisberg WN, Clark RA. Granulocytic sarcoma (chloroma): CT manifestations. Radiology 1985;155:167–170.[Abstract/Free Full Text]
73. Jakobiec FA. Granulocytic sarcoma. AJNR Am J Neuroradiol 1991;12:263–264.[Medline]
74. Banna M, Aur R, Akkad S. Orbital granulocytic sarcoma. AJNR Am J Neuroradiol 1991;12:255–258.[Medline]
75. Neiman RS, Barcos M, Berard C, et al. Granulocytic sarcoma: a clinicopathologic study of 61 biopsied cases. Cancer 1981;48:1426–1437.[CrossRef][Medline]
76. Vazquez E, Lucaya J, Castellote A, et al. Neuroimaging in pediatric leukemia and lymphoma: differential diagnosis. RadioGraphics 2002;22: 1411–1428.[Abstract/Free Full Text]
77. Gunalp I, Gunduz K. Metastatic orbital tumors. Jpn J Ophthalmol 1995;39:65–70.[Medline]
78. Albert DM, Rubenstein RA, Scheie HG. Tumor metastasis to the eye. II. Clinical study in infants and children. Am J Ophthalmol 1967;63:727–732.[Medline]
79. Musarella MA, Chan HS, DeBoer G, Gallie BL. Ocular involvement in neuroblastoma: prognostic implications. Ophthalmology 1984;91:936–940.[Medline]
80. Alfano JE. Ophthalmological aspects of neuroblastomatosis: a study of 53 verified cases. Trans Am Acad Ophthalmol Otolaryngol 1968;72:830–848.[Medline]
81. Wells RG, Sty JR, Gonnering RS. Imaging of the pediatric eye and orbit. RadioGraphics 1989;9: 1023–1044.[Abstract]
82. Lallemand DP, Brasch RC, Char DH, Norman D. Orbital tumors in children: characterization by computed tomography. Radiology 1984;151: 85–88.[Abstract/Free Full Text]
83. Lonergan GJ, Schwab CM, Suarez ES, Carlson CL. Neuroblastoma, ganglioneuroblastoma, and ganglioneuroma: radiologic-pathologic correlation. RadioGraphics 2002;22:911–934.[Abstract/Free Full Text]
84. Conran RM, Askin FB, Dehner LP. The pineal, pituitary, parathyroid, thyroid and adrenal glands. In: Stocker JT, Dehner LP, eds. Pediatric pathology. 2nd ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2002; 1051–1071.
85. Hopper KD, Sherman JL, Boal DK, Eggli KD. CT and MR imaging of the pediatric orbit. RadioGraphics 1992;12:485–503.[Abstract]
86. Belgaumi AF, Kauffman WM, Jenkins JJ, et al. Blindness in children with neuroblastoma. Cancer 1997;80:1997–2004.[CrossRef][Medline]
87. Boubaker A, Bischof Delaloye A. Nuclear medicine procedures and neuroblastoma in childhood: their value in the diagnosis, staging and assessment of response to therapy. Q J Nucl Med 2003;47:31–40.[Medline]
88. Unni KK, Inwards CY, Bridge JA, Kindblom LG, Wold LE. Bone-forming lesions. In: Silverberg S, Sobin L, eds. AFIP atlas of tumor pathology: tumors of the bones and joints. Washington, DC: American Registry of Pathology, 2005; 135–160.
89. Tateishi U, Hasegawa T, Miyakawa K, Sumi M, Moriyama N. CT and MRI features of recurrent tumors and second primary neoplasms in pediatric patients with retinoblastoma. AJR Am J Roentgenol 2003;181:879–884.[Abstract/Free Full Text]

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