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Metastatic Melanoma to the Central Nervous System: Case Report and Review of the Literature
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Metastatic Melanoma to the Central Nervous System: Case Report and Review of the Literature Michael J. Schneck,*,† Alkesh Patel,* Adriana Rodriguez-Quinonez,* Henry G. Brown,‡ Joseph I. Clark,§ Vikram Prabhu,† Rima Dafer,* and José Biller*,† An elderly man with multiple hemorrhagic, presumed neoplastic lesions of the brain is described who could not undergo magnetic resonance imaging because of a pacemaker. On autopsy, metastatic melanoma was identified. In this report, we discuss the differential diagnosis of hemorrhagic metastases, the incidence and prognosis of metastatic melanoma to the brain, and the limited therapeutic options for metastatic melanoma. Semin Cerebrovasc Dis Stroke 5:217-220 © 2005 Elsevier Inc. All rights reserved. KEYWORDS hemorrhage, brain neoplasm, melanoma
Case Report A 73-year-old right-handed man was admitted to an outside hospital for painless hematuria. He had cystoscopy and was found to have a low-grade papillary transitional cell carcinoma with no involvement of either the lamina or the muscularis propria. After the procedure, he developed postprocedural mental status changes. A computed tomography (CT) of the head without contrast showed multiple intracranial hemorrhages. He was transferred to a subacute care facility at the family’s request and then readmitted to that outside hospital because of worsening dysarthria and confusion. The family then requested transfer to our institution in an attempt to ascertain the underlying pathology for the multiple intracranial hemorrhages. The medical history was noteworthy for a history of mild memory difficulties of 6 months duration and removal of a basal cell carcinoma from the cheek several years before the admission. Other pertinent medical history included arterial *Department of Neurology, Loyola University Chicago, Stritch School of Medicine, Maywood, IL. †Department of Neurosurgery, Loyola University Chicago, Stritch School of Medicine, Maywood, IL. ‡Department of Pathology, Loyola University Chicago, Stritch School of Medicine, Maywood, IL. §Department of Medicine, Division of Hematology/Oncology, Loyola University Chicago, Stritch School of Medicine, Maywood, IL. Address reprint requests to: Michael J. Schneck, MD, Associate Professor of Neurology and Neurosurgery, Loyola University Chicago, Stritch School of Medicine, Maguire Building, Suite 2700, 2160 South First Avenue, Maywood, Illinois 60153. E-mail: [email protected].
1528-9931/05/$-see front matter © 2005 Elsevier Inc. All rights reserved. doi:10.1053/j.scds.2006.03.001
hypertension, non-insulin-dependent diabetes mellitus, prior myocardial infarction, gout, and benign prostatic hypertrophy. He also had a pacemaker for sick-sinus syndrome. Family history was noteworthy in that his mother had a history of skin “precancerous cells.” Medications on admission included dexamethasone, insulin, glipizide, pantoprazole, metoprolol, tamsulosin hydrochloride, allopurinol, and pioglitazone hydrochloride. Vital signs on admission were as follows: temperature, 36.7°C; blood pressure, 170/90 mm Hg; pulse, 62 per minute; and respiratory rate, 18 per minute. The general examination was unremarkable except for a midline sternotomy scar and pacemaker under the left chest wall. The patient opened his eyes only to noxious stimuli. He was nonverbal and unable to follow commands. On cranial nerve examination, he blinked to visual threat bilaterally. Funduscopy was unremarkable. Pupils were approximately 3.5 mm in size bilaterally and reactive. There were normal oculocephalic responses. There was normal facial symmetry and corneal reflexes were intact. There was minimal withdrawal to pain in all four limbs and muscle stretch reflexes were diffusely hyperactive with no clonus but bilateral Babinski signs. Admission laboratory studies were unremarkable. CT scan of the brain without contrast showed numerous high-density lesions throughout both cerebral and cerebellar hemispheres measuring 5 mm to 2.3 cm in diameter, with adjacent edema and slight rightward shift of the septum pellucidum due to mass effect; these lesions were suspicious for diffuse hemorrhagic metastases (Fig. 1A-C). These findings were un217
M.J. Schneck et al
218
Figure 1 A: Noncontrast head CT at level of the fourth ventricle. Multiple bilateral lesions in cerebellum and brainstem; some are hypodense and some have associated hyperdensities. B: Noncontrast head CT at level of the third ventricle. Multiple bilateral lesions in both the cortical and the subcortical regions. Some lesions are hypodense and some have associated hyperdensities. C: Noncontrast head CT of the high cerebral hemispheres. The image shows multiple bilateral lesions of varying densities and there is associated cerebral edema.
changed as compared with the head CTs from the outside institution. Further diagnostic evaluation included CT of chest, abdomen, and pelvis that showed an enlarged multinodular thyroid gland, discrete tiny nodules in the right lung, and a small focal 2-cm low-density lesion in the posterior segment of the right lobe of the liver and multiple bilateral renal cysts. Renal ultrasound showed increased renal cortical echogenicity consistent with hypertension and multiple right renal cysts. Thyroid ultrasound showed discrete nodules in both thyroid lobes, some of which were partially cystic but too small for biopsy. Ultrasound of the abdomen again showed a 2-cm hypoechoic lesion of the right liver lobe and sludge in the gallbladder without evidence of cholecystitis. A Dermatology consult was requested and a shave biopsy of an atypical lesion of the mons pubis was done; this was not diagnostic and only revealed a benign-appearing compound melanocytic nevus with slight atypia. Ophthalmology was consulted but no abnormal lesions were noted on ophthalmic examination. Pulmonary and Radiology consultants did not feel that the lung and liver lesions were large enough for biopsy. The patient was discussed at the neuro-oncology tumor board and Medical, Neurosurgical, and Radiation Oncology were consulted. The consensus was that the patient’s morbid status precluded surgical biopsy or empiric treatment of the cerebral lesions.
Discussion with the family led to the patient’s being transferred to a hospice facility. He died 3 days following discharge from our institution. Autopsy demonstrated metastatic melanoma with multiple hemorrhagic lesions to the brain (Fig. 2A-B), metastases to the abdominal and thoracic lymph nodes, foci of melanoma in the cardiac tissue, the submucosa of the stomach, and the mucosal wall of the small intestines. Immunoperoxidase staining with HMB-45 did not show infiltration of the Virchow–Robin spaces by tumor and the lesion was therefore felt to be metastatic as opposed to primary CNS melanoma. As an aside, the external examination was negative for malignant skin lesions. Note was incidentally made of acute tubular necrosis, multinodular goiter of the thyroid, bilateral bacterial pneumonic infiltrates, and diverticulosis of the large bowel. No liver nodules were identified.
Discussion Intracranial neoplasms that present with hemorrhage may be primary or metastatic. Incidence of CNS metastases exceeds that of primary brain tumors by a ratio of 10:1.1,2 However, multiple focal lesions with hemorrhagic conversion more typically suggest metastatic disease, though occasionally pri-
Metastatic melanoma to the CNS
Figure 2 A: Gross pathologic specimen showing multiple metastases with hemorrhagic and melanotic components. B: Medium power photomicrograph of metastatic melanoma. Typical features include poorly formed clusters of large, eosinophilic epithelioid cells with prominent nucleoli. Immunoperoxidase staining for HMB-45 (not shown) was positive, confirming this neoplasm as a metastatic melanoma.
mary CNS lymphoma may be also associated with hemorrhagic lesions. While primary lung tumors account for 50% of all cases of CNS metastases and, by virtue of the sheer number of metastatic lung cancer cases seen, represent the most frequent focal metastatic tumor with hemorrhage, most lung metastases to the brain do not typically have a hemorrhagic component.1 Of the neoplasms that spread to the brain, melanoma, renal cell carcinoma, choriocarcinoma, and thyroid carcinomas are quite frequently associated with multiple intracerebral hemorrhages.1 Given the history of this patient and the appearance of multiple hemorrhagic lesions of different densities (suggesting some of the lesions had bled at varying times), melanoma and thyroid cancer were both reasonable considerations. Melanoma was the diagnosis at autopsy. Intracranial melanoma may arise directly from the leptomeninges as a “primary CNS tumor” or from hematogenous spread arising from an extracranial source. As compared with other systemic ma-
219 lignancies, melanoma has an increased incidence of brain metastasis, and melanoma is the third most common cause of intracranial metastases after breast and lung carcinoma.1-5 However, approximately 14% of patients with CNS melanoma have no identifiable extracranial source. Most primary CNS tumors would not however include both the hemispheres and the posterior fossa. Malignant melanoma is the most significant skin cancer, and the most rapidly increasing malignancy in the US. In 2005, there were approximately 59,580 cases and 7,770 deaths. Approximately 1 of every 53 American men, and 1 of every 78 American women, will be diagnosed with melanoma during their lifetime.6 If detected early, this disease is highly curable, but 5-year survival rates for stage IV melanoma, which includes intracranial metastases, is less than 5%, and the median survival for Stage IV Melanoma is 6 to 9 months.3,7 The clinical occurrence of metastases has been described in up to 46% of patients and up to 75% of autopsy series; intracranial metastases are frequently the cause of death in patients with melanoma.8-10 Without treatment, the median survival in patients with neurological symptoms is less than 1 month and, even with therapy, prognosis is poor. The risk of recurrence and death from melanoma is closely related to the stage at presentation.4,7,10 The three most critical determinants of prognosis are tumor thickness, ulceration, and extent of lymph node involvement. Fortunately, the majority of patients currently present with stage I-IIA disease for which surgery can be curative in 70 to 90% of cases. By comparison, stage IIB, IIC, and III disease (lymph node involvement) is associated with 40 to 80% risk of recurrence, for which adjuvant therapy trials are considered. Since patients with a history of any melanoma are at very high risk of developing another melanoma, follow-up with a dermatologist and a medical oncologist on an annual basis is critical, as the best chance for cure is early detection and surgery. Sentinel lymph node biopsy is indicated for intermediate depth melanoma (1.0 to 4.0 mm). Adjuvant radiation therapy is reserved for postoperative treatment of patients with lymph nodes removed from the neck or as palliative treatment, ie, brain metastases or painful metastases. Systemic chemotherapy or immunotherapy is appropriate for high-risk disease including lymph node positive disease, deeply invasive melanoma, and metastatic disease.3,7,11 Systemic treatments over the past three decades have included chemotherapy, such as dacarbazine and most recently temozolomide, nonspecific immune adjuvants, and hormonal agents. However, none of these agents have proved beneficial. At present, the most promising results have been reported with a variety of melanoma-specific vaccines, cytokines such as interferon-␣ and interleukin 2 (IL-2), and granulocyte-macrophage colony-stimulating factor. In particular, IL-2 has been used with some success in a very small minority of patients.3,7,11 In a surgical series from Memorial Sloan–Kettering Cancer Center, the median time to diagnosis of the intracranial melanoma from diagnosis of the primary extracranial lesion was 14.1 months.12 Following resection of the intracranial lesion, overall survival was 6.7 months, with cerebellar and multiple
220 metastases being associated with shorter durations of survival. There was no difference in survival or recurrence of brain metastases between patients who underwent or did not undergo postoperative whole brain radiation. Overall 1-, 2-, and 5-year survival was poor with rates of 36.3, 18.7, and 6.6%, respectively. Melanoma is a relatively radioresistant tumor but a small series of stereotactic surgery has suggested a reasonable short-term palliative benefit for isolated intracranial metastatic disease. In one series using Gamma Knife irradiation, 26 patients with intracranial metastases had whole brain radiotherapy and Gamma Knife focal radiation or immunotherapy/chemotherapy with Gamma Knife irradiation.13 Overall median survival was 6 months and the 1-year survival rate was 25%. Absence of neurological signs or symptoms, small tumor volume, good Karnofsky score, supratentorial lesions, and female gender were important in terms of prognosis. In a second series of 45 patients from the University of Southern California, the median survival time was 43 months from the time of diagnosis of primary melanoma, and 8 months from the time of Gamma Knife treatment.14 In summary, multiple treatments are available for patients with metastatic melanoma but new approaches to treatment are clearly necessary, as high-risk melanoma remains a challenging condition. Given only a modest benefit to current therapies at the cost of considerable toxicity and expense, there is clearly considerable room for improvement.
References 1. Johnson JD, Young B. Demographics of brain metastasis. Neurosurg Clin North Am 7:337-344, 1996
M.J. Schneck et al 2. Barnholtz-Sloan JS, Sloan AE, Davis FG, et al: Incidence proportions of brain metastases in patients diagnosed (1973 to 2001) in the metropolitan Detroit cancer surveillance system. J Clin Oncol 22:2865-2872, 2004 3. McWilliams RR, Brown PD, Buckner JC, et al: Treatment of brain metastases from melanoma. Mayo Clin Proc 78:1529-1536, 2003 4. Amer M, Al-Sarraf M, Bake LH, et al: Malignant melanoma and central nervous system metastases: incidence, diagnosis, treatment and survival. Cancer 42:660-668, 1978 5. Saha S, Meyer M, Krementz ET, et al: Prognostic evaluation of intracranial metastasis in malignant melanoma. Ann Surg Oncol 1:38-44, 1994 6. Jemal A, Taylor M, Ward E, et al: Cancer Statistics 2005. CA Cancer J Clin 55:10-30, 2005 7. Tarhini AA, Argawala SS: Management of brain metastases in patients with melanoma. Curr Opin Oncol 16:161-166, 2004 8. Gupta G, Robertson AG, MacKie RM: Cerebral metastases of cutaneous melanoma. Br J Cancer 76:256-259, 1997 9. Patel JK, Didokar MS, Pickren JW, et al: Metastatic pattern of malignant melanoma: a study of 216 autopsy cases. Am J Surg 135:807-810, 1978 10. Lee ML, Tomsu K, von Eschen KB: Duration of survival for disseminated malignant melanoma: results of a meta-analysis. Melanoma Res 10:81-90, 2000 11. Weber RW, O’Day S, Rose M, et al: Low dose outpatient chemobiotherapy with temozolomide, granulocyte-macrophage colony stimulating factor, interferon-alpha 2b, and recombinant interleukin-2 for the treatment of metastatic melanoma. J Clin Oncol 23:8992-9000, 2005 12. Wronski M, Arbit E: Surgical treatment of brain metastases from melanoma: a retrospective study of 91 patients. J Neurosurg 93:9-18, 2000 13. Koc M, McGregor J, Grecula J, et al: Gamma Knife radiosurgery for intracranial metastatic melanoma: an analysis of survival and prognostic factors. J Neuro-Oncol 71:307-313, 2005 14. Lavine S, Petrovich Z, Cohen Gadol A, et al: Gamma knife radiosurgery for metastatic melanoma: an analysis of survival, outcomes and complications. Neurosurgery 44:59-65, 1999
Metastatic Melanoma to the Central Nervous System: Case Report and Review of the Literature Michael J. Schneck,*,† Alkesh Patel,* Adriana Rodriguez-Quinonez,* Henry G. Brown,‡ Joseph I. Clark,§ Vikram Prabhu,† Rima Dafer,* and José Biller*,† An elderly man with multiple hemorrhagic, presumed neoplastic lesions of the brain is described who could not undergo magnetic resonance imaging because of a pacemaker. On autopsy, metastatic melanoma was identified. In this report, we discuss the differential diagnosis of hemorrhagic metastases, the incidence and prognosis of metastatic melanoma to the brain, and the limited therapeutic options for metastatic melanoma. Semin Cerebrovasc Dis Stroke 5:217-220 © 2005 Elsevier Inc. All rights reserved. KEYWORDS hemorrhage, brain neoplasm, melanoma
Case Report A 73-year-old right-handed man was admitted to an outside hospital for painless hematuria. He had cystoscopy and was found to have a low-grade papillary transitional cell carcinoma with no involvement of either the lamina or the muscularis propria. After the procedure, he developed postprocedural mental status changes. A computed tomography (CT) of the head without contrast showed multiple intracranial hemorrhages. He was transferred to a subacute care facility at the family’s request and then readmitted to that outside hospital because of worsening dysarthria and confusion. The family then requested transfer to our institution in an attempt to ascertain the underlying pathology for the multiple intracranial hemorrhages. The medical history was noteworthy for a history of mild memory difficulties of 6 months duration and removal of a basal cell carcinoma from the cheek several years before the admission. Other pertinent medical history included arterial *Department of Neurology, Loyola University Chicago, Stritch School of Medicine, Maywood, IL. †Department of Neurosurgery, Loyola University Chicago, Stritch School of Medicine, Maywood, IL. ‡Department of Pathology, Loyola University Chicago, Stritch School of Medicine, Maywood, IL. §Department of Medicine, Division of Hematology/Oncology, Loyola University Chicago, Stritch School of Medicine, Maywood, IL. Address reprint requests to: Michael J. Schneck, MD, Associate Professor of Neurology and Neurosurgery, Loyola University Chicago, Stritch School of Medicine, Maguire Building, Suite 2700, 2160 South First Avenue, Maywood, Illinois 60153. E-mail: [email protected].
1528-9931/05/$-see front matter © 2005 Elsevier Inc. All rights reserved. doi:10.1053/j.scds.2006.03.001
hypertension, non-insulin-dependent diabetes mellitus, prior myocardial infarction, gout, and benign prostatic hypertrophy. He also had a pacemaker for sick-sinus syndrome. Family history was noteworthy in that his mother had a history of skin “precancerous cells.” Medications on admission included dexamethasone, insulin, glipizide, pantoprazole, metoprolol, tamsulosin hydrochloride, allopurinol, and pioglitazone hydrochloride. Vital signs on admission were as follows: temperature, 36.7°C; blood pressure, 170/90 mm Hg; pulse, 62 per minute; and respiratory rate, 18 per minute. The general examination was unremarkable except for a midline sternotomy scar and pacemaker under the left chest wall. The patient opened his eyes only to noxious stimuli. He was nonverbal and unable to follow commands. On cranial nerve examination, he blinked to visual threat bilaterally. Funduscopy was unremarkable. Pupils were approximately 3.5 mm in size bilaterally and reactive. There were normal oculocephalic responses. There was normal facial symmetry and corneal reflexes were intact. There was minimal withdrawal to pain in all four limbs and muscle stretch reflexes were diffusely hyperactive with no clonus but bilateral Babinski signs. Admission laboratory studies were unremarkable. CT scan of the brain without contrast showed numerous high-density lesions throughout both cerebral and cerebellar hemispheres measuring 5 mm to 2.3 cm in diameter, with adjacent edema and slight rightward shift of the septum pellucidum due to mass effect; these lesions were suspicious for diffuse hemorrhagic metastases (Fig. 1A-C). These findings were un217
M.J. Schneck et al
218
Figure 1 A: Noncontrast head CT at level of the fourth ventricle. Multiple bilateral lesions in cerebellum and brainstem; some are hypodense and some have associated hyperdensities. B: Noncontrast head CT at level of the third ventricle. Multiple bilateral lesions in both the cortical and the subcortical regions. Some lesions are hypodense and some have associated hyperdensities. C: Noncontrast head CT of the high cerebral hemispheres. The image shows multiple bilateral lesions of varying densities and there is associated cerebral edema.
changed as compared with the head CTs from the outside institution. Further diagnostic evaluation included CT of chest, abdomen, and pelvis that showed an enlarged multinodular thyroid gland, discrete tiny nodules in the right lung, and a small focal 2-cm low-density lesion in the posterior segment of the right lobe of the liver and multiple bilateral renal cysts. Renal ultrasound showed increased renal cortical echogenicity consistent with hypertension and multiple right renal cysts. Thyroid ultrasound showed discrete nodules in both thyroid lobes, some of which were partially cystic but too small for biopsy. Ultrasound of the abdomen again showed a 2-cm hypoechoic lesion of the right liver lobe and sludge in the gallbladder without evidence of cholecystitis. A Dermatology consult was requested and a shave biopsy of an atypical lesion of the mons pubis was done; this was not diagnostic and only revealed a benign-appearing compound melanocytic nevus with slight atypia. Ophthalmology was consulted but no abnormal lesions were noted on ophthalmic examination. Pulmonary and Radiology consultants did not feel that the lung and liver lesions were large enough for biopsy. The patient was discussed at the neuro-oncology tumor board and Medical, Neurosurgical, and Radiation Oncology were consulted. The consensus was that the patient’s morbid status precluded surgical biopsy or empiric treatment of the cerebral lesions.
Discussion with the family led to the patient’s being transferred to a hospice facility. He died 3 days following discharge from our institution. Autopsy demonstrated metastatic melanoma with multiple hemorrhagic lesions to the brain (Fig. 2A-B), metastases to the abdominal and thoracic lymph nodes, foci of melanoma in the cardiac tissue, the submucosa of the stomach, and the mucosal wall of the small intestines. Immunoperoxidase staining with HMB-45 did not show infiltration of the Virchow–Robin spaces by tumor and the lesion was therefore felt to be metastatic as opposed to primary CNS melanoma. As an aside, the external examination was negative for malignant skin lesions. Note was incidentally made of acute tubular necrosis, multinodular goiter of the thyroid, bilateral bacterial pneumonic infiltrates, and diverticulosis of the large bowel. No liver nodules were identified.
Discussion Intracranial neoplasms that present with hemorrhage may be primary or metastatic. Incidence of CNS metastases exceeds that of primary brain tumors by a ratio of 10:1.1,2 However, multiple focal lesions with hemorrhagic conversion more typically suggest metastatic disease, though occasionally pri-
Metastatic melanoma to the CNS
Figure 2 A: Gross pathologic specimen showing multiple metastases with hemorrhagic and melanotic components. B: Medium power photomicrograph of metastatic melanoma. Typical features include poorly formed clusters of large, eosinophilic epithelioid cells with prominent nucleoli. Immunoperoxidase staining for HMB-45 (not shown) was positive, confirming this neoplasm as a metastatic melanoma.
mary CNS lymphoma may be also associated with hemorrhagic lesions. While primary lung tumors account for 50% of all cases of CNS metastases and, by virtue of the sheer number of metastatic lung cancer cases seen, represent the most frequent focal metastatic tumor with hemorrhage, most lung metastases to the brain do not typically have a hemorrhagic component.1 Of the neoplasms that spread to the brain, melanoma, renal cell carcinoma, choriocarcinoma, and thyroid carcinomas are quite frequently associated with multiple intracerebral hemorrhages.1 Given the history of this patient and the appearance of multiple hemorrhagic lesions of different densities (suggesting some of the lesions had bled at varying times), melanoma and thyroid cancer were both reasonable considerations. Melanoma was the diagnosis at autopsy. Intracranial melanoma may arise directly from the leptomeninges as a “primary CNS tumor” or from hematogenous spread arising from an extracranial source. As compared with other systemic ma-
219 lignancies, melanoma has an increased incidence of brain metastasis, and melanoma is the third most common cause of intracranial metastases after breast and lung carcinoma.1-5 However, approximately 14% of patients with CNS melanoma have no identifiable extracranial source. Most primary CNS tumors would not however include both the hemispheres and the posterior fossa. Malignant melanoma is the most significant skin cancer, and the most rapidly increasing malignancy in the US. In 2005, there were approximately 59,580 cases and 7,770 deaths. Approximately 1 of every 53 American men, and 1 of every 78 American women, will be diagnosed with melanoma during their lifetime.6 If detected early, this disease is highly curable, but 5-year survival rates for stage IV melanoma, which includes intracranial metastases, is less than 5%, and the median survival for Stage IV Melanoma is 6 to 9 months.3,7 The clinical occurrence of metastases has been described in up to 46% of patients and up to 75% of autopsy series; intracranial metastases are frequently the cause of death in patients with melanoma.8-10 Without treatment, the median survival in patients with neurological symptoms is less than 1 month and, even with therapy, prognosis is poor. The risk of recurrence and death from melanoma is closely related to the stage at presentation.4,7,10 The three most critical determinants of prognosis are tumor thickness, ulceration, and extent of lymph node involvement. Fortunately, the majority of patients currently present with stage I-IIA disease for which surgery can be curative in 70 to 90% of cases. By comparison, stage IIB, IIC, and III disease (lymph node involvement) is associated with 40 to 80% risk of recurrence, for which adjuvant therapy trials are considered. Since patients with a history of any melanoma are at very high risk of developing another melanoma, follow-up with a dermatologist and a medical oncologist on an annual basis is critical, as the best chance for cure is early detection and surgery. Sentinel lymph node biopsy is indicated for intermediate depth melanoma (1.0 to 4.0 mm). Adjuvant radiation therapy is reserved for postoperative treatment of patients with lymph nodes removed from the neck or as palliative treatment, ie, brain metastases or painful metastases. Systemic chemotherapy or immunotherapy is appropriate for high-risk disease including lymph node positive disease, deeply invasive melanoma, and metastatic disease.3,7,11 Systemic treatments over the past three decades have included chemotherapy, such as dacarbazine and most recently temozolomide, nonspecific immune adjuvants, and hormonal agents. However, none of these agents have proved beneficial. At present, the most promising results have been reported with a variety of melanoma-specific vaccines, cytokines such as interferon-␣ and interleukin 2 (IL-2), and granulocyte-macrophage colony-stimulating factor. In particular, IL-2 has been used with some success in a very small minority of patients.3,7,11 In a surgical series from Memorial Sloan–Kettering Cancer Center, the median time to diagnosis of the intracranial melanoma from diagnosis of the primary extracranial lesion was 14.1 months.12 Following resection of the intracranial lesion, overall survival was 6.7 months, with cerebellar and multiple
220 metastases being associated with shorter durations of survival. There was no difference in survival or recurrence of brain metastases between patients who underwent or did not undergo postoperative whole brain radiation. Overall 1-, 2-, and 5-year survival was poor with rates of 36.3, 18.7, and 6.6%, respectively. Melanoma is a relatively radioresistant tumor but a small series of stereotactic surgery has suggested a reasonable short-term palliative benefit for isolated intracranial metastatic disease. In one series using Gamma Knife irradiation, 26 patients with intracranial metastases had whole brain radiotherapy and Gamma Knife focal radiation or immunotherapy/chemotherapy with Gamma Knife irradiation.13 Overall median survival was 6 months and the 1-year survival rate was 25%. Absence of neurological signs or symptoms, small tumor volume, good Karnofsky score, supratentorial lesions, and female gender were important in terms of prognosis. In a second series of 45 patients from the University of Southern California, the median survival time was 43 months from the time of diagnosis of primary melanoma, and 8 months from the time of Gamma Knife treatment.14 In summary, multiple treatments are available for patients with metastatic melanoma but new approaches to treatment are clearly necessary, as high-risk melanoma remains a challenging condition. Given only a modest benefit to current therapies at the cost of considerable toxicity and expense, there is clearly considerable room for improvement.
References 1. Johnson JD, Young B. Demographics of brain metastasis. Neurosurg Clin North Am 7:337-344, 1996
M.J. Schneck et al 2. Barnholtz-Sloan JS, Sloan AE, Davis FG, et al: Incidence proportions of brain metastases in patients diagnosed (1973 to 2001) in the metropolitan Detroit cancer surveillance system. J Clin Oncol 22:2865-2872, 2004 3. McWilliams RR, Brown PD, Buckner JC, et al: Treatment of brain metastases from melanoma. Mayo Clin Proc 78:1529-1536, 2003 4. Amer M, Al-Sarraf M, Bake LH, et al: Malignant melanoma and central nervous system metastases: incidence, diagnosis, treatment and survival. Cancer 42:660-668, 1978 5. Saha S, Meyer M, Krementz ET, et al: Prognostic evaluation of intracranial metastasis in malignant melanoma. Ann Surg Oncol 1:38-44, 1994 6. Jemal A, Taylor M, Ward E, et al: Cancer Statistics 2005. CA Cancer J Clin 55:10-30, 2005 7. Tarhini AA, Argawala SS: Management of brain metastases in patients with melanoma. Curr Opin Oncol 16:161-166, 2004 8. Gupta G, Robertson AG, MacKie RM: Cerebral metastases of cutaneous melanoma. Br J Cancer 76:256-259, 1997 9. Patel JK, Didokar MS, Pickren JW, et al: Metastatic pattern of malignant melanoma: a study of 216 autopsy cases. Am J Surg 135:807-810, 1978 10. Lee ML, Tomsu K, von Eschen KB: Duration of survival for disseminated malignant melanoma: results of a meta-analysis. Melanoma Res 10:81-90, 2000 11. Weber RW, O’Day S, Rose M, et al: Low dose outpatient chemobiotherapy with temozolomide, granulocyte-macrophage colony stimulating factor, interferon-alpha 2b, and recombinant interleukin-2 for the treatment of metastatic melanoma. J Clin Oncol 23:8992-9000, 2005 12. Wronski M, Arbit E: Surgical treatment of brain metastases from melanoma: a retrospective study of 91 patients. J Neurosurg 93:9-18, 2000 13. Koc M, McGregor J, Grecula J, et al: Gamma Knife radiosurgery for intracranial metastatic melanoma: an analysis of survival and prognostic factors. J Neuro-Oncol 71:307-313, 2005 14. Lavine S, Petrovich Z, Cohen Gadol A, et al: Gamma knife radiosurgery for metastatic melanoma: an analysis of survival, outcomes and complications. Neurosurgery 44:59-65, 1999