Primary Malignant Skull Tumors

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[1]

• 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[2]

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.[3, 2, 4] 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), 19% 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.[5]

• 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

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• 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

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• 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

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• 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.[6]

• 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.

See the list below:

• 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.[7]

• Osteosarcomas and fibrosarcomas commonly are found in the mandible and maxilla.[4, 8]

• 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

See the list below:

• 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

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• 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.

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• 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.

See the list below:

• 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, depicted below, they are hyperdense, homogeneous enhancing lesions.

    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.

  • 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.

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• Bone marrow biopsy

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• Biopsy of the lesion is crucial for establishing the diagnosis and deciding on treatment options.

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• Osteosarcomas are composed of a malignant spindle cell stroma, which directly produces osteoid or immature bone (osteoblastic, chondroblastic, or fibroplastic form).[9]

• 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).[3]

• 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.[10]

• 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.

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• Analgesic medications can be used for painful lesions.

• Aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs) are used for osteoid osteoma.

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• 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.

See the list below:

• 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.

Class Summary

NSAIDs reduce pain and inflammation.

Ibuprofen (Motrin, Advil, Haltran, Nuprin)

Inhibits inflammatory reactions and pain by decreasing activity of enzyme cyclooxygenase, which in turn inhibits prostaglandin synthesis.

Class Summary

These agents provide abortive pain therapy.

Acetaminophen and codeine (Tylenol #3)

Significant abuse potential; may cause withdrawal headaches.

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• Postoperative

• Radiation therapy

• Chemotherapy

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• Postoperative

• Chemotherapy

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• Postoperative complications

  • Cranial nerve palsy

  • Meningitis

  • Paralysis

  • Cognitive dysfunction

• Carcinomatous meningitis

• Wound infection

• Immunosuppression due to chemotherapy and radiation therapy

• Recurrence

• Metastasis

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• 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).

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• The lesion should be identified and treated promptly.

• If required, patients should be referred for psychological counseling.