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Neurology > Neuro-oncology
Primary Malignant Skull Tumors
Article Last Updated: Jan 5, 2007
AUTHOR AND EDITOR INFORMATION
Section 1 of 11  
Author: Efstathios Papavassiliou, MD, Consulting Staff, Division of Neurosurgery, Beth Israel Deaconess Medical Center
Efstathios Papavassiliou is a member of the following medical societies: California Medical Association
Coauthor(s):
Draga Jichici, HBSc, MD, FRCP(C), FAHA, Assistant Professor, Department of Medicine, Division of Critical Care Medicine, McMaster University Medical School, Canada
Editors: Spiros Manolidis, MD, Associate Professor of Otolaryngology and Neurological Surgery, Columbia University; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Jorge Kattah, MD, Head, Program Director, Professor, Department of Neurology, University of Illinois College of Medicine at Peoria; Matthew J Baker, MD, Consulting Staff, Collier Neurologic Specialists, Naples Community Hospital; Nicholas Y Lorenzo, MD, Chief Editor, eMedicine Neurology; Consulting Staff, Neurology Specialists and Consultants
Author and Editor Disclosure
Synonyms and related keywords:
osteosarcoma, chondrosarcoma, fibrosarcoma, Ewing sarcoma, angiosarcoma, plasmocytoma, multiple myeloma, chordoma, metastatic neoplasm, giant cell tumor, bone-forming tumor, osteoblastoma
Background
Depending on the primary proliferating cell, both malignant and benign skull tumors can be any of the following:
- Bone forming
- Cartilage forming
- Of connective tissue origin
- Histiocytic
- Of blood or blood vessel origin
- Metastatic to bone
- Of neuroepithelial origin
- Of squamous cell origin
- Of apocrine gland (ie, major and minor salivary, lacrimal) origin
Pathophysiology
Salivary gland tumors, as well as other malignancies of the head and neck, such as squamous cell carcinoma and esthesioneuroblastoma, may invade the skull base by proximity or by perineural invasion. These tumors cause cranial nerve paralysis by invasion or direct extension; accompanying pain is due to erosion of the involved structures. Involvement of the periosteum or dura is the primary mechanism of direct tumor spread and the causative pathology.
Frequency
United States
One of the most comprehensive reported series of bone tumors came from the Mayo Clinic. Of the 7975 bone tumors in the series, 4% involved the skull (excluding the mandible, maxilla, and nasal cavity). Nineteen percent of these skull tumors were benign and 81% malignant. As the Mayo Clinic is a tertiary referral center, some degree of selection bias probably was in effect.
- Other studies estimate that skull tumors constitute 1% of bone tumors.
- Bone-forming tumors: Osteosarcoma is the second most frequent malignant skull tumor after multiple myeloma, accounting for 13% of this series.
- Cartilage-forming tumors: Chondrosarcoma is the third most common malignant bone tumor, with a frequency of 11-12.5%.
- Connective tissue tumors: Fibrosarcoma accounts for fewer than 5% of these tumors.
- Histiocytic tumors
- Ewing sarcomas account for about 5% of these tumors.
- Giant cell tumors (osteoclastomas) also account for about 5% of these tumors.
- Tumors of blood or blood vessel origin: Angiosarcomas are rare malignant tumors.
- Squamous cell carcinomas of the temporal bone occur with a frequency of 1 case per 25,000 patients with chronic otitis.
Mortality/Morbidity
- Recurrent sinusitis is a common complication of tumors affecting the sinuses.
- If the excision is incomplete, many tumors can recur.
- Cranial nerve compression can occur in skull-base tumors.
- Metastasis
- Death
- Persistence of disease after treatment is a serious problem, since it leads to persistent morbidity; patients have a significant decrease in the quality of life prior to dying from the disease. The aim of therapy is to control the disease locally.
Race
No racial predilection exists for any malignant skull tumor.
Sex
- Most malignant skull tumors have no sex predilection (except possibly metastatic disease).
- Fibrosarcoma, Ewing sarcoma, and chordomas occur more frequently in men than in women.
Age
- Bone-forming tumors and fibrosarcomas usually present in middle-aged adults.
- Cartilage-forming tumors may present at any age, with a peak during the second decade.
- Ewing sarcoma is a disease of childhood, whereas giant cell tumors are seen mainly between the second and fourth decades.
- Angiosarcoma can present at any age.
- Multiple myeloma is more common in older adults.
- Chordomas usually present in the third or fourth decade.
- Metastatic tumors follow the pattern of the primary tumor.
- Squamous cell carcinomas occur in the older adult, often in the sixth decade.
- Esthesioneuroblastomas occur in young adults in their 30s and 40s.
History
- Presentation may include any of the following:
- Rapidly growing mass with pain and swelling
- Mass without pain as in multiple myeloma and osteosarcoma
- Nonspecific headache
- Cranial nerve deficits: These are seen in giant cell tumors, angiosarcomas, and chordomas, as well as in tumors of the head and neck with propensity for perineural spread, such as tumors of salivary origin (eg, adenoid cystic carcinomas, adenocarcinomas, mucoepidermoid carcinomas).
- Fever and malaise
- Location of the tumor
- Although the location of the lesion is of little value in making the diagnosis, certain tumors prefer the convexity more than the skull base and vice versa; lesions of developmental origin have a propensity for the midline.
- Chondrosarcomas, giant cell tumors, angiosarcomas, and chordomas usually involve the skull base.
- Osteosarcomas and fibrosarcomas commonly are found in the mandible and maxilla.
- The remainder usually involve the calvaria.
- Patients may have a history of previous malignancy, fibrous dysplasia, or Paget disease.
- Multiple, small, nonmarginated lesions usually indicate metastatic disease.
- The absence of peripheral sclerosis strongly favors a malignant tumor.
- The differential diagnosis includes the following:
- Benign skull tumors
- Encephalocele, meningoencephalocele, venous lakes of the skull, pacchionian depression
- Fractures, surgical defects
- Osteomyelitis, tuberculosis, sarcoidosis, syphilis
- Hyperparathyroidism, osteoporosis, congenital hemolytic anemia
Physical
- Signs include the following:
- Soft or hard lesion
- Cranial nerve deficits: These may include diplopia from involvement of cranial nerves III, IV, or VI; facial paralysis; hearing loss; vertigo; and sensation loss along the distribution of the trigeminal nerve. Voice changes and swallowing disorders, with or without tongue fasciculations/paralysis, signify involvement of the cranial base at the jugular foramen with medial extension.
- Multiple findings related to the primary tumor
- Tender or nontender lesion
Causes
- Little information is available concerning the etiology of the malignant skull tumors (except in the case of metastatic disease).
- Chondrosarcomas often are associated with abnormalities of chromosomes 10 and 22.
Benign Skull Tumors
Brainstem Gliomas
Cerebral Aneurysms
Chronic Paroxysmal Hemicrania
Cluster Headache
Craniopharyngioma
Ependymoma
Glioblastoma Multiforme
Meningioma
Migraine Headache
Migraine Variants
Multiple Sclerosis
Neural Tube Defects
Oligodendroglioma
Subarachnoid Hemorrhage
Other Problems to be Considered
Angiosarcoma
Bone-forming tumor
Chondroma
Chondrosarcoma
Chordoma
Congenital hemolytic anemia
Connective tissue tumor
Dermoid
Eosinophilic granuloma
Encephalocele
Epidermoid
Fibrosarcoma
Fibrous dysplasia
Giant cell granuloma
Giant cell tumor
Hemangioma
Hyperparathyroidism
Lymphangioma
Meningoencephalocele
Multiple myeloma
Nonossifying fibroma
Ossifying fibroma
Osteoblastoma
Osteoid osteoma
Osteoma
Osteoporosis
Osteosarcoma
Osteomyelitis
Pacchionian depression
Paget disease
Syphilis
Tuberculosis
Venous lakes of the skull
Xanthoma
Lab Studies
- Anemia, an elevated white blood count (WBC), and reduced platelets are characteristic of malignancies involving the bone marrow.
- Immunoglobulins (eg, IgG, IgA, IgM, IgD) are elevated in multiple myeloma.
- Protein M can be found in the urine and serum in myeloma.
Imaging Studies
- Plain skull x-ray film and head CT scan
- Most of the malignant skull tumors appear as radiolucent lesions, single or multiple, with irregular borders and no periosteal reaction.
- Osteosarcomas appear as osteolytic soft-tissue extensions. They may have calcification within the lesion, no periosteal reaction, and poorly defined margins. The typical (but not frequent) appearance is the sun-ray picture.
- Chondrosarcomas have no reliable radiological features and are characterized by lytic and sclerotic changes within poorly defined margins.
- Fibrosarcomas are radiolucent lytic lesions with thinning and widening of the cortex, minimal periosteal involvement, and irregular margins.
- Ewing sarcoma has a typical onion skin appearance with laminated periosteal changes. On CT scan, it appears as an isodense mass surrounded by a hypodense area and hyperostosis. It is also contrast enhancing.
- Angiosarcomas are destructive lesions with cortical erosion and reactive ossification. On CT scan, they show heterogeneous enhancement with focal necrosis.
- Plasmocytomas/multiple myelomas usually present as multiple lytic lesions that involve both the inner and outer tables, as well as the diploë from which they arise. On CT scan, they are hyperdense, homogeneous enhancing lesions (see Image 1).
- Chordomas are soft-tissue masses usually seen in the nasopharyngeal area with various degrees of calcification. CT scan shows a soft-tissue mass with extensive bone destruction.
- Metastatic neoplasms can be either of the following:
- Osteoblastic, with sclerosis and thickening (eg, prostate, breast, bladder, hypernephroma)
- Osteoclastic, with bone destruction and lucency (eg, lung, uterus, GI tract, thyroid, melanoma, neuroblastoma)
- Giant cell tumors usually involve the sphenoid bone and commonly erode the sellar region. On brain CT scan, giant cell tumors are hyperdense, contrast-enhancing masses.
- MRI
- Most tumors are hypointense on T1-weighted images and hyperintense with heterogeneous signal on T2-weighted images.
- Enhancement is common.
- Bone scan: 99m technetium scan shows all malignant processes as hot areas.
- Arteriogram: Tumors of vessel origin or associated with multiple myeloma have a high degree of vascularity.
Other Tests
Procedures
- Biopsy of the lesion is crucial for establishing the diagnosis and deciding on treatment options.
Histologic Findings
- Osteosarcomas are composed of a malignant spindle cell stroma, which directly produces osteoid or immature bone (osteoblastic, chondroblastic, or fibroplastic form).
- Low-grade chondrosarcomas (myxochondrosarcoma) are characterized by chondroid and immature cartilage deposition in areas of myxomatous change and cystic degeneration. The high-grade type (mesenchymal chondrosarcoma) is characterized by the absence of cartilage lobules and the presence of fibrosarcomatous areas. Groups of chondromatous cells lose their usual lobulation and begin to spindle out. Both types are vimentin positive.
- Fibrosarcoma is characterized by varying amounts of collagen production and the absence of bone, osteoid, or cartilage. The medullary subtype has a better prognosis than the periosteal subtype.
- Giant cell tumor (osteoclastoma) consists of a well-vascularized tissue mass of plump, spindle, or ovoid stroma cells together with uniformly dispersed, numerous, large, multinucleated giant cells.
- Ewing sarcoma appears as uniform, densely packed small cells with indistinct cytoplasmic borders and many mitotic figures. They stain strongly with periodic acid-Schiff (PAS).
- Angiosarcomas (hemangiopericytoma or hemangioendothelioma) are characterized by the formation of irregular anastomosing vascular channels lined by one or more layers of atypical endothelial cells and pericytes, which have an anaplastic immature appearance.
- Multiple myeloma is characterized by widespread osteolytic bone destruction by dense tumor cells that look like plasma cells clustered in close aggregates.
- Chordomas consist of physaliphorous cells (large, vacuolated, mucus containing) with a lobular arrangement and abundant extracellular mucoid tissue.
- Metastatic tumors have the same or similar histologic features as their primary tumors.
Medical Care
- Analgesic medications can be used for painful lesions.
- Aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs) are used for osteoid osteoma.
Surgical Care
- Whenever possible, complete surgical excision is the treatment of choice for primary tumors (except multiple myeloma).
- Preoperative embolization is recommended for angiosarcomas to reduce intraoperative blood loss. If other means cannot control tumor expansion, surgery is still an option in metastatic disease.
Consultations
- Neurosurgeon
- Neurologist
- Radiation oncologist
- Hematologist/oncologist
- Radiation therapist
- Radiosurgery, including Gamma Knife and CyberKnife, can be useful for some tumors.
- Osteosarcomas - Primary form of treatment for secondary osteosarcoma, especially in elderly patients
- Ewing sarcoma
- Giant cell tumor
- Multiple myeloma, if chemotherapy fails
- Chordoma
- Radiosensitive metastatic tumors
- Not indicated for angiosarcoma and fibrosarcoma
- Use in chondrosarcoma controversial
- Chemotherapy also may be indicated. Chemotherapy should be administered under the direction of a hematologist and/or oncologist. Combinations of various drugs are used, including cisplatin, cyclophosphamide, carmustine (BCNU), and lomustine (CCNU).
- Osteosarcomas
- Fibrosarcomas
- Multiple myeloma (first choice of treatment)
- Efficacy in chondrosarcoma unknown
The goals of pharmacotherapy are to reduce morbidity and prevent complications.
Drug Category: Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs reduce pain and inflammation.
| Drug Name | Ibuprofen (Motrin, Advil, Haltran, Nuprin) |
|---|
| Description | Inhibits inflammatory reactions and pain by decreasing activity of enzyme cyclooxygenase, which in turn inhibits prostaglandin synthesis. |
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| Adult Dose | 200-800 mg PO q6-8h, while symptoms persist; not to exceed 3.2 g/d |
|---|
| Pediatric Dose | <6 months: Not established
6 months to 12 years: 30-70 mg/kg/d PO divided tid/qid; start at lower end of dosage range and titrate upwards; not to exceed 2.4 g/d
>12 years: Administer as in adults |
|---|
| Contraindications | Documented hypersensitivity; peptic ulcer disease; recent GI bleeding or perforation; renal insufficiency; high risk of bleeding |
|---|
| Interactions | May decrease effects of loop diuretics; may increase PT in patients taking anticoagulants (monitor and watch for signs of bleeding); may increase serum lithium levels; may increase risk of methotrexate toxicity (eg, stomatitis, bone marrow suppression, nephrotoxicity); probenecid may increase concentrations and probably toxicity |
|---|
| Pregnancy | B - Usually safe but benefits must outweigh the risks.
|
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| Precautions | Caution in congestive heart failure, hypertension, and decreased hepatic function; caution in coagulation abnormalities or during anticoagulant therapy; consider effects on platelet function and gastric mucosa; acute renal insufficiency, interstitial nephritis, hyperkalemia, hyponatremia, and renal papillary necrosis may occur; patients with preexisting renal disease or compromised renal perfusion are at greater risk of acute renal failure
Low WBC counts are rare and transient, usually returning to normal as therapy continues; persistent leukopenia, granulocytopenia, or thrombocytopenia warrants further evaluation and may require discontinuation of drug |
|---|
Drug Category: Analgesics
These agents provide abortive pain therapy.
| Drug Name | Acetaminophen and codeine (Tylenol #3) |
|---|
| Description | Significant abuse potential; may cause withdrawal headaches. |
|---|
| Adult Dose | 15-60 mg PO q4h prn pain |
|---|
| Pediatric Dose | 0.5-1 mg/kg/dose PO q4-6h prn pain |
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| Contraindications | Documented hypersensitivity |
|---|
| Interactions | CNS depressants or tricyclic antidepressants increase toxicity |
|---|
| Pregnancy | C - Safety for use during pregnancy has not been established.
|
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| Precautions | May result in acute opiate withdrawal symptoms in patients dependent on opiates; caution in severe renal or hepatic dysfunction; babies born to mothers using narcotics regularly may show signs of withdrawal |
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Further Inpatient Care
- Postoperative
- Chemotherapy
Further Outpatient Care
- Postoperative
- Radiation therapy
- Chemotherapy
Complications
- Postoperative complications
- Cranial nerve palsy
- Meningitis
- Paralysis
- Cognitive dysfunction
- Carcinomatous meningitis
- Wound infection
- Immunosuppression due to chemotherapy and radiation therapy
- Recurrence
- Metastasis
Prognosis
- Osteosarcoma has a 5-year survival rate between 20% and 50%.
- Chondrosarcoma has a 10-year survival rate of 30-80%, depending on the grade of the initial tumor.
- Fibrosarcomas metastasize in 50% of cases, and the 10-year survival rate is 40%.
- Ewing sarcoma has a 5-year survival rate of 40-65%.
- Giant cell tumor has a recurrence rate of 30% in 2 years, but otherwise its prognosis is relatively good.
- Angiosarcomas, if properly treated, have a cure rate of about 50%.
- Chordomas, although difficult to resect completely, are slow-growing tumors and have a 5-year survival rate of 40%.
- Myeloma survival rates vary depending on the grade. However, even in patients with widespread disease, complete remission can be achieved for up to 2-3 years (or longer).
Patient Education
- The lesion should be identified and treated promptly.
- If required, patients should be referred for psychological counseling.
Medical/Legal Pitfalls
- Failure to recognize signs and symptoms
- Failure to treat appropriately
| Media file 1:
Head CT scan of a 60-year-old man with a history of multiple myeloma for 2 years, showing multiple lytic lesions that involve both the inner and outer tables as well as the diploë. |
 |  View Full Size Image | |
Media type: CT
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| Media file 2:
This head CT scan shows multiple lytic lesions of the skull involving both the inner and outer tables. |
 | View Full Size Image | |
Media type: CT
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Primary Malignant Skull Tumors excerpt Article Last Updated: Jan 5, 2007
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