AUTHOR AND EDITOR INFORMATION

Section 1 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

INTRODUCTION

Section 2 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Background

Tumors of the skull are uncommon lesions that are not reported systematically in the medical literature. Therefore, assessing their true incidence and consequences to the health of the general population is difficult. Recent diagnostic advances have made such lesions easier to recognize, and new skull-base surgery techniques have provided access to previously inoperable skull tumors. Skull tumors are estimated to account for approximately 1% of bone tumors.

Treatment for most tumors is not controversial. However, the differentiation and identification of the tumor type is the greatest clinical challenge. The usual presentation is an enlarging skull mass, with or without pain, or cranial nerve deficits if the tumor involves the base of the skull.

Plain skull radiography with special projections is an important diagnostic tool. The initial classification of a lesion into radiolucent (osteolytic) or radiopaque (osteoblastic) is of considerable significance. The presence of sharply defined or irregular margins, presence or absence of sclerotic borders, and calcifications in the lesion are also important. Head CT scanning, with and without contrast, is useful in determining the extent of intracranial extension and other tumor characteristics.

Most skull tumors share certain MRI characteristics, such as hypointensity on T1-weighted images, hyperintensity on T2-weighted images, and some degree of contrast enhancement. The capability of imaging in multiple planes and enhanced soft tissue discrimination has made MRI an important diagnostic tool. The classification of benign and malignant brain tumors is based on that by Wilkins and Rengachary (which is a modified version of the system outlined by Huvos).

Pathophysiology

The tumor type and behavior determine radiographic appearance (eg, radiolucent, radiopaque). Depending on the primary proliferating cell, benign skull tumors can be any of the following:

• Bone forming
• Cartilage forming
• Tumors of connective tissue
• Histiocytic tumors
• Tumors of blood or blood vessel origin
• Other types, including fibrous dysplasia, Paget disease, or epidermoid, dermoid, or aneurysmal bone cysts

Frequency

United States

One of the most comprehensive series of bone tumors with classification originated from the Mayo Clinic. Of the 7975 patients in the series, 4% had tumors involving the skull (excluding the mandible, maxilla, and nasal cavity). Of these tumors, 19% were benign and 81% were malignant. Because the Mayo Clinic is a tertiary referral center, this series probably reflects some degree of selection bias. Other studies estimate that skull tumors comprise 1% of bone tumors.

Bone-forming tumors: Osteomas are the most common primary brain tumors of the calvaria, affecting 0.4% of the general population. Osteoid osteomas and ossifying fibromas are rare. Osteoblastomas account for approximately 1% of bone tumors.

Cartilage-forming tumors: Chondromas and chondromyxoid fibromas are rare. Chondroblastoma, although rare in some studies, accounted for 10% of the benign skull tumors in the Mayo series.

Connective tissue tumors: Desmoplastic fibroma is very rare in the skull (in the literature, only case reports exist).

Histiocytic tumors: Giant cell granuloma, nonossifying fibroma, and xanthoma are very rare in the skull.

Tumors of blood or blood vessel origin: Eosinophilic granuloma commonly affects the skull. Hemangiomas account for 10% of benign skull tumors (70% in the Mayo series).

Lymphangiomas: These tumors are rare.

Miscellaneous conditions: Aneurysmal bone cysts, epidermoid and dermoid tumors, intraosseous meningiomas, and fibrous dysplasia are relatively rare conditions. The prevalence of Paget disease is believed to be 1-5% in those older than 40 years, with involvement of any bone in the body, but most individuals remain asymptomatic and the condition is undiagnosed.

Mortality/Morbidity

• Morbidity is due to recurrent sinusitis (tumors affecting sinuses), recurrence of tumor after excision, and cranial nerve compression at the skull base.
• Malignant transformation to osteosarcoma, fibrosarcoma, or chondrosarcoma is observed in 2% of patients with Paget disease and 0.5% of patients with fibrous dysplasia.

Sex

Most tumors demonstrate no sex predilection.

• Osteomas, ossifying fibromas, chondromas, and giant cell granulomas are observed more often in females than in males.
• Osteoid osteomas, osteoblastomas, eosinophilic granuloma, and Paget disease affect males more often than females.
• The female-to-male ratio of hemangiomas is 1:2.

Age

• Bone-forming tumors, connective tissue tumors, giant cell granulomas, and fibrous dysplasias usually manifest in young adults. Cartilage-forming tumors affect those aged 20-50 years.
• Eosinophilic granuloma, nonossifying fibroma, and xanthoma usually manifest in those younger than 20 years. Epidermoids, dermoids, and lymphangiomas are usually observed in children.
• The usual age of presentation for hemangiomas is in the fourth to sixth decade of life. Intraosseous meningioma and Paget disease affect those older than 50 years.

CLINICAL

Section 3 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

History

• The challenge is to differentiate the varying types of bone tumors. Imaging studies and the appearance of the lesion are the primary differentiating factors. The location of the lesion is of little differential diagnostic value, although lesions of developmental origin have a strong midline propensity.
• Single, small, grossly round and oval lesions are more likely to be benign. The presence of peripheral sclerosis strongly favors a benign tumor. The margin of a lesion is of no diagnostic value.
• Intralesional calcifications are more common in benign tumors. Peripheral bone vascularity also indicates a benign process.
• The differential diagnosis includes encephalocele, meningoencephalocele, venous lakes of the skull, pacchionian depression, fractures, surgical defects, osteomyelitis, tuberculosis, syphilis, osteoporosis, and congenital hemolytic anemia.
• The following tumors manifest as slow-growing painless masses: osteoma, ossifying fibroma, chondroma, nonossifying fibroma, xanthoma, hemangioma, epidermoid, dermoid, meningioma, and fibrous dysplasia.
• Other tumors include osteoid osteoma, osteoblastoma, chondroblastoma, chondromyxoid fibroma, desmoplastic fibroma, giant cell granuloma, eosinophilic granuloma, and aneurysmal bone cyst.
• Associated headache is nonspecific in nature.
• Lymphangioma manifests as a painless cystic defect.
• Osteoid osteoma manifests with nocturnal local tenderness that is relieved by aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs).
• Cranial nerve deficits are observed in chondroblastoma, giant cell granuloma, epidermoid, dermoid, fibrous dysplasia, and Paget disease.
• A rapidly growing mass is observed in desmoplastic fibroma and giant cell granuloma.
• Tumor location is unreliable for diagnosis. However, certain tumors appear at the convexity more than the skull base and vice versa.
• Osteomas usually involve the frontal bone.
• • Ossifying fibromas favor the frontotemporal region.
  • Cartilage tumors involve the skull base.
  • Giant cell granuloma affects the sphenoid, temporal, and ethmoid areas.
  • Eosinophilic granuloma affects the frontoparietal area.
  • The globular variety of hemangiomas affects the skull base, and the sessile type affects the frontotemporal region.
  • Epidermoids and dermoids usually involve the cerebellopontine angle, parapituitary region, and calvaria. Dermoids prefer the midline.
  • Ossifying meningiomas involve the frontal parietal area.
  • Paget disease usually involves the skull base.

Physical

• Physical findings vary according to tumor type.
• • The lesion may be tender or nontender.
  • It may be soft or hard.
  • Cranial nerve deficits (eg, diplopia, hearing loss, vertigo, sensation loss) may be seen.

Causes

Benign skull tumors are sporadic in occurrence. However, specific syndromes involving skull tumors have been described.

• Gardner syndrome is the triad of the following:
• • Multiple osteomas of the skull, sinus, and mandible
  • Soft tissue tumors of skin
  • Colon polyps
• McCune-Albright syndrome comprises the triad of the following:
• • Polyostotic fibrous dysplasia
  • Hyperpigmented skin macules
  • Precocious puberty
• Hand-Schüller-Christian disease consists of the following:
• • Diabetes insipidus
  • Exophthalmos
  • Bone lesions
• Multiple enchondromas is known as Ollier syndrome.
• Maffucci syndrome consists of the following:
• • Enchondromas
  • Dyschondroplasia
  • Cavernous hemangiomas of soft tissues or viscera

DIFFERENTIALS

Section 4 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Other Problems to be Considered

Aneurysmal bone cyst
Angiosarcoma
Bone-forming tumor
Brainstem syndromes
Chondroblastoma
Chondroma
Chondromyxoid fibroma
Chondrosarcoma
Chordoma
Congenital hemolytic anemia
Connective tissue tumor
Desmoplastic fibroma
Dermoid
Eosinophilic granuloma
Encephalocele
Epidermoid
Fibrosarcoma
Fibrous dysplasia
Gardner syndrome
Giant cell granuloma
Giant cell tumor
Hand-Schüller-Christian disease
Hemangioma
Hyperparathyroidism
Lymphangioma
Maffucci syndrome
McCune-Albright syndrome
Meningoencephalocele
Multiple myeloma
Neurocytoma
Nonossifying fibroma
Ollier syndrome
Ossifying fibroma
Osteoblastoma
Osteoid osteoma
Osteoma
Osteoporosis
Osteosarcoma
Osteomyelitis
Pacchionian depression
Paget disease
Syphilis
Tuberculosis
Venous lakes of the skull
Xanthoma

WORKUP

Section 5 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Lab Studies

• Laboratory studies are not helpful in making the diagnosis.

Imaging Studies

• Plain skull radiography and head CT scanning
• • Most of the benign skull tumors appear as radiolucent lesions with the exception of osteomas, ossifying meningiomas, the sclerotic form of fibrous dysplasia, and the later stages of Paget disease.
    • Osteomas appear as round sclerotic lesions arising from the outer table (less frequently inner table) of the skull without involvement of diploë. The spongy osteoma may be radiolucent. Osteoid osteomas consist of a radiolucent nidus with a surrounding zone of dense sclerosis.
    • In ossifying fibromas, the initial lesion is radiolucent, but it progressively becomes radiopaque, with sharp margins and dilated vascular channels (see Image 1).
  • Osteoblastomas appear as well-demarcated noncontrast-enhancing lytic lesions with smooth calcified margins.
  • Chondromas are well circumscribed, with distinct areas of lucency.
  • Chondroblastoma manifests as a well-demarcated osteolytic area with varying degrees of calcification.
  • Chondromyxoid fibroma is radiolucent with tissue calcification.
  • Desmoplastic fibromas are well-defined lytic and expansile lesions with a typical soap bubble appearance. They cause thinning of the overlying cortex without periosteal reaction.
  • Giant cell granulomas are radiolucent, well demarcated, and multiloculated, with expansion and thinning of the bone cortex. CT scanning shows an isodense lesion, which may erode the overlying cortical bone.
  • Nonossifying fibromas and xanthomas are radiolucent with sclerotic margins and bony trabeculae with a soap bubble appearance.
  • Eosinophilic granuloma is a radiolucent, oval, well-demarcated lesion without sclerosis. It has the appearance of a punched-out defect or a doughnut-shaped lesion that involves both the inner and outer table. On CT scan, it appears as a soft tissue mass within an area of bony destruction. A central density may also be present.
  • Hemangiomas are well-defined nonenhancing lytic lesions with a characteristic honeycomb appearance. One third show peripheral sclerosis. Intralesional calcifications are common (see Images 2-4).
  • Lymphangiomas manifest as cystic defects of the bone.
  • Aneurysmal bone cysts are well-demarcated lesions that arise from the diploë and expand both the inner and outer tables of the skull. On CT scanning, they are multiloculated expansile bone lesions with characteristic fluid levels.
  • Epidermoids and dermoids are round lytic lesions arising within the diploë and have dense sclerotic borders. CT scanning shows a hypodense nonenhancing lesion with irregular borders (see Image 5).
  • Intraosseous meningiomas appear as irregular bone deposition on the inner and outer tables, usually in the vicinity of the coronal suture.
  • Fibrous dysplasia has 3 different forms: the cystic form, which involves mainly the outer table; the sclerotic form, which is characterized by bone thickening; and the mixed form, which usually manifests after the third decade. All these manifest as skull lucency with patches of increased density (see Image 6). CT scanning shows a multilobulated intradiploic lesion.
  • Paget disease manifests as a lytic lesion that resembles cotton wool, with varying degrees of bone formation and no clear edges (see Image 7).
• Magnetic resonance imaging
• • Most tumors are hypointense on T1-weighted images and hyperintense on T2-weighted images.
  • Hemangiomas are isointense on T1-weighted images.
• Bone scanning: Bone scanning with technetium Tc-99m shows an area of increased radioisotope uptake in osteomas, ossifying fibromas, and osteoblastomas.
• Arteriography
• • Arteriography shows high vascularity in tumors of vascular origin.
  • It is not helpful in making the diagnosis of other benign tumors.

Procedures

• Biopsy of the lesion is of paramount importance for establishing the diagnosis and considering treatment options.

Histologic Findings

Osteomas are composed of mature lamellar bone. The typical appearance is a nidus of osteoid tissue in a background of osteoblastic connective tissue, which is enclosed completely by reactive bone. Ossifying fibroma consists of fibrous spindle cells with varying amounts of woven bone. The periphery of the tumor is composed of mature lamellar bone.

Osteoblastoma consists of a fibrous stroma with irregular osteoid deposition. Chondromas (enchondroma, juxtacortical chondroma, osteochondroma) are rare skull tumors consisting of mature hyaline cartilage. Chondroblastomas consist of immature cartilage cells.

Chondromyxoid fibroma is characterized by chondroid and myxoid differentiation with lobular growth. Desmoplastic fibroma is of fibrous connective tissue origin marked by the formation of collagen. Giant cell granuloma manifests with giant cells around hemorrhagic foci, numerous spindle-shaped fibroblastic cells, and new bone formation. The tumor cells are smaller than those of the giant cell tumor of the bone, whereas stromal cells and giant cells resemble each other.

Nonossifying fibroma and xanthoma consist of fibroblast proliferation with multinucleated giant cells and foamy xanthomatous cells. In eosinophilic granuloma, mononuclear histiocytes are mixed with eosinophils. Giant cells and areas of hemorrhage or necrosis may also be observed. The histiocytes stain positive for the protein S-100. On electron microscopy, the Birbeck granules that characterize the Langerhans or X cells are noted. Hemangiomas are visualized macroscopically as brownish red lesions under the skull periosteum. Microscopically, they consist of capillary, cavernous, or venous blood vessels.

Lymphangiomas consist of lymph vessels. Aneurysmal bone cysts consist of large vascular spaces separated by trabeculae of connective tissue and bone. The vascular spaces lack endothelial lining. Epidermoids consist of an epithelial capsule filled by desquamated epithelial cells and keratin.

Dermoids usually contain hair follicles and sebaceous and sweat glands. Fibrous dysplasia is a developmental anomaly in which the normal bone formation is arrested at the woven stage; thus, lamellar bone is not formed. This results in an overgrowth of the fibrous tissue among woven bone, which is the typical histologic feature of this lesion. Paget disease is initially characterized by increased osteoclastic activity, which results in bone resorption, followed by increased osteoblastic activity and bone formation.

TREATMENT

Section 6 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Medical Care

• Administer aspirin or NSAIDs for osteoid osteoma.
• Provide pain control symptomatically.
• No treatment is required for asymptomatic lesions unless diagnostic concerns exist.

Surgical Care

• Complete surgical excision is possible for symptomatic relief, cosmetic reasons, or cranial nerve decompression.
• En bloc resection is the preferred intervention.
• Curettage is also performed for lesions that cannot be resected completely. Careful removal of the cyst wall is critical in epidermoids and dermoids. Gamma Knife and CyberKnife are possible new ways of treating unresectable symptomatic lesions.

Consultations

• Neurosurgeon
• Plastic surgeon
• Neurologist
• Radiation oncologist: Radiation therapy is acceptable as a second form of treatment in some partially resected lesions such as ossifying fibroma, hemangioma, and aneurysmal bone cyst because of their high recurrence rate. In addition, the Gamma Knife and the CyberKnife are under investigation.
• Ophthalmologist

MEDICATION

Section 7 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

The goals of pharmacotherapy are to reduce morbidity and prevent complications.

Drug Category: Nonsteroidal anti-inflammatory drugs (NSAIDs)

Have analgesic, anti-inflammatory, and antipyretic activities. Their mechanism of action is not known but may inhibit cyclooxygenase activity and prostaglandin synthesis. Other mechanisms may exist as well, such as inhibition of leukotriene synthesis, lysosomal enzyme release, lipoxygenase activity, neutrophil aggregation, and various cell membrane functions.

Drug Category: Narcotics

Pain control is essential to quality patient care. These agents ensure patient comfort, promote pulmonary toilet, and have sedating properties, which are beneficial for patients who have moderate to severe pain.

Drug Category: Salicylates

Can reduce inflammation and pain symptoms.

FOLLOW-UP

Section 8 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Further Inpatient Care

• Inpatient care is not usually required unless skull-base surgery is needed for nerve decompression.

Further Outpatient Care

• Postoperative care
• Radiation therapy

Complications

• Cranial nerve palsy
• Recurrence
• • Desmoplastic fibroma - 20-30%
  • Giant cell granuloma - 12-16%
  • Aneurysmal bone cyst - 40-50%
• Wound infection
• Malignant transformation

Prognosis

• Prognosis is good if tumor is resected completely.
• In malignant transformation of fibrous dysplasia and Paget disease, the prognosis depends on the malignant tumor that is finally diagnosed.

Patient Education

• Reassure patients regarding the benign nature of the tumor.
• Educate patients with Paget disease and fibrous dysplasia about the malignant potential of their disease.

MISCELLANEOUS

Section 9 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Medical/Legal Pitfalls

• Failure to recognize signs and symptoms
• Failure to treat appropriately

MULTIMEDIA

Section 10 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Media file 1:  Composite CT scan, MRI, and angiogram of a symptomatic ossifying fibroma with extensive involvement of the skull base in a 12-year-old girl whose primary symptom was exophthalmos and loss of vision bilaterally.
	View Full Size Image
Media type:  CT

Media file 2:  Lateral skull radiograph of a 73-year-old patient with a slow-growing nontender skull lesion. Note the typical honeycomb appearance.
	View Full Size Image
Media type:  X-RAY

Media file 3:  Head CT scan of a 73-year-old patient with a slow-growing nontender skull lesion shows a well-defined nonenhancing lytic lesion with calcification and honeycomb appearance.
	View Full Size Image
Media type:  CT

Media file 4:  Sagittal magnetic resonance imaging (MRI) section of the brain of a 73-year-old patient with a slow-growing nontender skull lesion showing a nonenhancing soft tissue mass. This lesion proved to be a hemangioma.
	View Full Size Image
Media type:  MRI

Media file 5:  Lateral skull radiograph of a 17-year-old adolescent male with a painless slow-growing mass. The single round lytic lesion was found to be an epidermoid.
	View Full Size Image
Media type:  X-RAY

Media file 6:  Fibrous dysplasia involving the sphenoid sinus and pterygoid plates as well as the sella. This is an asymptomatic lesion; observation was recommended.
	View Full Size Image
Media type:  CT

Media file 7:  Head CT scan of a 78-year-old woman with Paget disease. Note the cotton wool appearance of the lesion, with varying degrees of bone formation and no clear edges. Observation was recommended.
	View Full Size Image
Media type:  CT

REFERENCES

Section 11 of 11

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

• Burger PC, Scheithauer BW, Vogel FS. Surgical Pathology of the Nervous System and its Coverings. 3rd ed. New York, NY:. Churchill Livingstone;1991:1-66.
• Huvos AG. Bone Tumors: Diagnosis, Treatment and Prognosis. Philadelphia, Pa:. WB Saunders Company;1979.
• Keyserling H, Peterson K, Camacho D, Castillo M. Giant cell angiofibroma of the orbit. AJNR Am J Neuroradiol. Aug 2004;25(7):1266-8. [Medline].
• Mirra JM. Bone Tumors: Clinical, Radiological and Pathological Correlations. Philadelphia, Pa:. Lea and Febiger;1989.
• Morris JM, Lane JI, Witte RJ, Thompson DM. Giant cell reparative granuloma of the nasal cavity. AJNR Am J Neuroradiol. Aug 2004;25(7):1263-5. [Medline].
• Thomas JE, Baker HL Jr. Assessment of roentgenographic lucencies of the skull: a systematic approach. Neurology. Feb 1975;25(2):99-106. [Medline].
• Unni KK. Dahlin's Bone Tumors: General Aspects and Data on 11,087 Cases. 5th ed. Philadelphia, Pa:. Lippincott Williams & Wilkins;1996.
• Wilkins RH, Rengachary SS. Neurosurgery. 2nd ed. New York, NY:. McGraw-Hill;1996:1503-1528.
• Youmans JR. Neurological Surgery. 2nd ed. Philadelphia, Pa:. WB Saunders Company;1982:3227-3268.

Article Last Updated: Jan 5, 2007