Metastasis to the skull base         go here for more

Malignant tumors that involve the skull base are less common than their benign counterparts. Their aggressive nature and tissue of origin, often adjacent to the intracranial vault, merit a unique approach to their surgical management. As the cranial nerves exit the bony foramina of the skull, they are vulnerable to entrapment and compression by osseous metastasis. Skull base metastases usually arise from a prostate, breast, lung, or head and neck primary lesion or from lymphoma. The cardinal sign of metastatic skull base invasion is cranial neuropathy, which is typically sudden in onset. Although skull base metastases are often painless, localized cranial or facial pain at the site of tumor invasion may be a symptom.


T1-weighted axial image of the brain at the level of skull base (Patient 3) demonstrates diffuse infiltration of bone marrow of the sphenoid secondary to tumor (solid white arrow) with extension into the left temporal bone (black arrow with white margin), resulting in left VIIth nerve deficit.
Cranial nerve deficits in patients with metastatic prostate carcinoma   Clinical features and treatment outcomes

Raymond S. McDermott, M.D., Ph.D. Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania


Cranial nerve lesions due to metastases from prostate carcinoma to the skull base are an uncommon yet clinically significant finding. The authors report the clinical features, treatment, and outcomes for 15 patients who presented with cranial nerve palsies complicating metastatic prostate carcinoma. Patient charts identified from a Fox Chase Cancer Center treatment data base were reviewed. A less common site of metastasis is to the base of the skull; however, expansive bone metastases in such strategic locations can cause cranial nerve compression. A number of cranial nerve dysfunction syndromes caused by metastatic prostate carcinoma have been described, including the Collet-Siccard syndrome, which is a palsy of the lower four cranial nerves; Villaret syndrome, which is a palsy of the lower four cranial nerves with ipsilateral Horner syndrome; occipital condyle syndrome, which consists of unilateral occipital pain with ipsilateral XIIth nerve paresis; trigeminal neuropathy due to mandibular metastasis; optic neuropathy causing blindness; jugular foramen syndrome with dysphagia and neck pain; parasellar syndrome with extraocular palsy; and isolated IIIrd, VIth, or VIIth nerve palsies. In addition, three small, descriptive case series have been published that outline the presentation and management of these patients.

RESULTS  All patients had hormone-refractory disease at the time of symptom onset. Twelve of 15 patients had received prior chemotherapy, and 13 of 15 patients had received prior radiation therapy to areas of bony pain. Symptoms varied from recognized clinical syndromes involving multiple cranial nerves to isolated cranial nerve lesions. All patients had lesions at the skull base that were visualized on computed tomography scans or magnetic resonance images. All patients were treated with palliative radiation therapy to either the whole brain or the skull base. Fourteen of 15 patients had a clinical (either partial or complete) response to radiation therapy. All responding patients subsequently died of prostate carcinoma without worsening of residual or development of new cranial nerve symptoms. Ten of 15 patients (67%) died within 3 months of developing symptoms, and the remaining 5 patients lived between 9 months and 31 months from onset of symptoms.

CONCLUSIONS  The authors concluded that palliative radiation therapy should be considered in this heterogeneous group of patients given the potential for significant symptom improvement.

Cranial nerve palsies secondary to skull base metastases represent an uncommon presentation of advanced prostate carcinoma. Nonetheless, these palsies usually have a significant impact on a patient's quality of life. Patients in this series presented both with recognized clinical syndromes, such as occipital condyle syndrome or parasellar syndrome, and with single cranial nerve deficits. Unsurprisingly, some patients had a variety of symptoms that were attributable to the diffuse nature of bony disease in advanced prostate carcinoma. Moreover, it is clear that many different cranial nerves can be affected whether alone or in combination, as manifest by the heterogeneity of presentations described both here and in prior series.

The differential diagnosis of patients who present with cranial nerve palsy in the context of prostate carcinoma includes leptomeningeal disease and paraneoplastic syndromes. The radiologic picture of skull base involvement along with the absence of other deficits or radiologic abnormalities usually is sufficient to distinguish these other potential etiologies. Moreover, meningeal involvement is very rare in patients with metastatic prostate carcinoma, whereas metastatic bone lesions are a hallmark of this disease. Nonetheless, the diagnosis of leptomeningeal disease is difficult to establish, and these patients were not assessed routinely with lumbar puncture and cerebrospinal fluid cytologic analysis, raising the potential that carcinomatous meningitis may have been a confounding variable in the presentation of some patients.

In this series, bone-directed CT and MRI studies were extremely effective in localizing lesions to the skull base. Due to its high-resolution bone algorithms, it is believed that CT scanning is superior to MRI studies for determining bone involvement and destruction at the skull base, whereas MRI studies are more sensitive in detecting leptomeningeal, dural, or cranial nerve involvement. Therefore, both CT and MRI appear to have a role in patients who present with cranial nerve deficits, because they may be used in a complementary fashion to demonstrate the full extent of disease.

Previous case series, from the pre-PSA era reported that the development of cranial nerve lesions was a grave prognostic sign, with most patients dying of their disease rapidly after the development of such symptoms. Similarly, 10 of 15 patients described in the current study died within 3 months of developing symptoms. The remaining 5 patients lived between 9 months and 31 months longer, indicating that there is a cohort of patients in which such symptoms do not represent a near terminal event. The patients in our series straddled the pre-PSA and post-PSA eras, and it is possible that, as patients are diagnosed earlier with their disease, hormone manipulation and chemotherapy may change the natural history of metastatic involvement. Therefore, it is possible that this clinical manifestation will become more common in the future as patients survive longer. Notably, all patients in this series had hormone-refractory disease, 11 patients also had failed 1 course of systemic chemotherapy, and 12 patients had received prior palliative radiation therapy to various fields, in addition to standard hormone manipulation.

With regard to treatment, in our hands, a brief course of external beam radiation therapy in association with corticosteroid administration was extremely effective in achieving palliative benefits. The dose schedules of 3000 cGy in 10 fractions or 2000 cGy in 5 fractions both are considered standard palliative treatment regimens that offer similar biologic equivalent doses. Shorter treatment courses sometimes are preferred if a patient is very debilitated or if convenience is a factor. Moreover, theoretically, there is a smaller late tissue toxicity effect with the 3000 cGy in 10 fractions regimen due to the smaller daily fraction sizes. Therefore, it may be reasonable to utilize this regimen in patients with maintained performance status and reasonable life expectancy. Using these regimens, 14 of 15 patients had evidence of clinical improvement in symptoms, including 10 patients who had complete resolution, as defined by symptom assessment and neurologic examination. The final patient died before any potential treatment benefit could be assessed. In addition, no patient had a recurrence of cranial nerve symptoms prior to their death. In each patient, the radiologic findings corresponded to the neurologic deficit described on clinical examination, and the deficits were apparent clinically, thereby rendering response to treatment easier to assess. Although it is possible that more subtle aspects of neurologic dysfunction were overlooked, we are confident that the lesions responsible for the patients' symptoms were captured on our neurologic examinations and imaging studies.

In conclusion, the diagnosis of metastases to the skull base should be considered strongly in patients who have cranial nerve palsies and prostate carcinoma. Although the presentation is heterogenous, it can be diagnosed readily with the use of modern imaging techniques. Given the superiority of MRI studies over CT scans in the evaluation of leptomeningeal disease, MRI is the preferred initial imaging modality for patients who present in this manner. Although the development of cranial nerve deficits is often a poor prognostic sign, there is a cohort of patients that will live for a significant time. Due to the potential for substantial symptomatic improvement in the majority of patients, a course of palliative radiation therapy should be considered, whether it is 2000 cGy in 5 fractions or 3000 cGy in 10 fractions, according to convenience and late toxicity concerns.


Skull-base metastases.

Laigle-Donadey F,. J Neurooncol. 2005 Oct;75(1):63-9

Paris Cedex 13, France.

Metastasis to the skull-base particularly affects patients with carcinoma of the breast and prostate. Clinically, the key feature is progressive ipsilateral involvement of cranial nerves. Five syndromes have been described according to the metastatic site including the orbital, parasellar, middle-fossa, jugular foramen and occipital condyle syndromes. Magnetic resonance imaging (MRI) is nowadays the most useful examination to establish the diagnosis but plain films, CT scans with bone windows and isotope bone scans remain helpful to demonstrate bone erosion. Normal imaging studies do not exclude the diagnosis. The treatment depends on the nature of the underlying tumor. Radiotherapy is generally the standard treatment, while some patients with chemosensitive or hormonosensitive lesions benefit from chemotherapy or hormonotherapy and selected patients from surgical removal. Gamma Knife radiosurgery is sometimes a useful alternative, particularly for previously irradiated skull-base regions, and for small tumors (diameter < 30 mm). The overall prognosis is poor, with an overall median survival of about 2.5 years, probably because skull-base metastases appear late in the course of the disease.

Metastasis to the base of the skull: clinical findings in 43 patients.

Greenberg HS Posner JB. Neurology. 1981 May;31(5):530-7.

We studied 43 patients with metastases to the base of the skull to determine whether clinical symptoms localized the lesions accurately. We identified five clinical syndromes: orbital, parasellar, middle fossa, jugular foramen, and occipital condyle. The orbital and parasellar syndromes were characterized by frontal headache, diplopia, and first-division trigeminal sensory loss. Proptosis occurred with the orbital but not the parasellar syndrome. The middle-fossa syndrome was characterized by facial pain or numbness. The jugular foramen syndrome was characterized by hoarseness and dysphagia, with paralysis of the ninth through eleventh cranial nerves. The occipital condyle syndrome was characterized by unilateral occipital pain and unilateral tongue paralysis.

Cranial nerve palsies in metastatic prostate cancer--results of base of skull radiotherapy.

O'Sullivan JM, .  Radiother Oncol. 2004 Jan;70(1):87-90.

Academic Unit of Radiotherapy and Clinical Oncology, Institute of Cancer Research/Royal Marsden Hospital, Sutton, Surrey SM2 5PT, UK.

We studied the rate of response to palliative external beam radiation therapy (20 Gy/5 or 30 Gy/10 fractions) to the base of skull in 32 prostate cancer patients with cranial nerve dysfunction. Sixteen patients (50%) had a useful response to therapy. The median survival post-therapy was 3 months.

Gamma Knife radiosurgery for skull base metastasis and invasion.

Iwai Y,.  Stereotact Funct Neurosurg. 1999;72 Suppl 1:81-

Department of Neurosurgery, Osaka City General Hospital, Osaka, Japan.

We treated 18 patients with skull base metastasis or invasion using Gamma Knife radiosurgery. Seven of these patients had invasive nasopharyngeal cancer and 11 had distant metastasis from other cancers. The mean diameter of tumors was 22-46 mm (median 32.1 mm) and the radiation dose to the tumor margin was 12-23 Gy (median 16.2 Gy). The median follow-up period was 10.5 months. Clinical symptoms were improved in 61% of the patients after treatment and tumor control was obtained in 67% of cases at their final followup. Radiation injury occurred in only one patient (6%) who had received previous radiotherapy to the same region. Gamma Knife radiosurgery is a useful therapeutic option for the treatment of skull base metastasis and invasion, either as a secondary treatment for recurrence after previous radiotherapy or as a primary treatment.