Introduction
Background
Melanoma is a cutaneous malignancy of melanocytes, which are pigment-producing cells derived from the neural crest. Melanoma constitutes 3% of all cancers diagnosed in the United States. The incidence of melanoma is increasing faster than that of any other malignant neoplasm, except for lung cancer in women. For someone born in the United States in 2000, the projected lifetime risk of developing melanoma is 1 in 75. Melanoma is the most lethal form of skin cancer and the third most common malignancy causing CNS metastases, after lung and breast cancer. While early recognition and surgical excision of a cutaneous primary can be curative, treatment options for metastatic disease are limited and the prognosis becomes guarded.
Primary intracranial melanoma can arise from the leptomeninges or dura mater. Primary ocular melanoma is well recognized; however, orbital involvement usually is secondary to local invasion from an ocular, sinus, or CNS source or from hematogenous spread from a cutaneous or visceral site. Neurocutaneous melanosis is a congenital disorder in which infants with giant hairy melanocytic nevi have associated leptomeningeal melanocytosis involving the brain and/or spinal cord. This leptomeningeal invasion can cause severe neurological compromise or death.
Secondary CNS melanoma most often results from hematogenous spread from a known or unknown primary tumor. This chapter focuses on secondary CNS melanoma.
Pathophysiology
The 4 major histologic types of primary cutaneous melanoma are superficial spreading, nodular, acral lentiginous, and lentigo maligna melanoma. These tumors differ in their histologic and, possibly, biologic characteristics. Metastases reach the CNS via hematogenous spread of tumor cells. Tumor cells are released into the circulation, arrest in end arteries, penetrate the blood-brain barrier, enter the CNS, and establish growth in the new tissue. Neurotrophins can facilitate invasion by up-regulating enzymes such as heparanase, which destroy the extracellular matrix and basement membrane of the blood-brain barrier. Although initial metastatic foci involve the gray-white matter junction, any part of the brain can be involved, including the pituitary gland, cerebellum, and cerebral hemispheres. The tumors most often are multifocal and have a unique tendency to hemorrhage.
Other common sites of melanoma metastases are skin, subcutaneous tissue, spleen, liver, lymph nodes, lungs, gastrointestinal tract, and bone.
Frequency
United States
The prevalence of CNS metastases ranges from 10-40% in clinical series. Brain metastases are present in up to two thirds of patients with disseminated malignant melanoma.
Mortality/Morbidity
The brain is the initial site of metastasis in 12-20% of patients. The average time between first diagnosis of a cutaneous primary and discovery of CNS metastases is 45 months. Metastatic melanoma to the CNS is incurable. Treatment is aimed at tumor debulking, symptom relief, and palliation.
Race
Melanoma is 10 times more common in fair-skinned Caucasians than in dark-skinned individuals.
Sex
No sex predilection has been reported.
Clinical
History
- Individuals at highest risk for melanoma include the following:
- Individuals with fair skin, blue eyes, freckles, and red or blond hair
- People who tan poorly, burn easily, and have a history of blistering sunburn in the past
- People with a history of nonmelanoma skin cancer
- People with numerous melanocytic nevi
- People with atypical nevi
- Individuals with a family history of melanoma or atypical nevi
- Elicit history of previous melanoma.
- Date of diagnosis
- Location of melanoma on body
- Method of treatment (eg, type of excision, margin taken, whether reexcision was recommended and done)
- Details from the pathology report (eg, gross appearance, excisional margin, histological type, depth of tumor, growth phase, presence of ulceration, involvement of blood vessels or lymphatics)
- Stage of previous melanoma
- Ask patient about new or changing skin lesions.
- Does the patient have concerns about any skin lesions?
- Has the patient ever had any suspicious moles removed?
- Have any moles undergone changes in their shape, size, color, texture, and sensitivity (itching or burning)?
- Has the patient had any bleeding or ulceration from any skin lesions?
- Occasionally, patients may present with brain metastases and an unknown primary. This phenomenon may be secondary to spontaneous regression of a primary lesion or de novo melanoma within the lymph nodes, gastrointestinal tract, respiratory tract, or vagina. Approximately 10-20% of patients with an unknown primary have had a pigmented lesion removed in the past or have noted a pigmented cutaneous lesion that has involuted.
- Question all patients about symptoms suggestive of CNS metastases and other organ involvement.
- Headache
- Nausea and vomiting
- Visual changes
- Seizures
- Confusion or personality change
- Fatigue
- Fever, night sweats
- Cutaneous nodules near or distant to primary site
- Cough, chest pain, new respiratory symptoms
- Gastrointestinal bleeding
- Bone pain
Physical
- Cutaneous examination
- Document skin phototype and presence of actinic skin damage.
- Carefully examine entire cutaneous surface, including the scalp, mucous membranes, and perianal and genital regions.
- Identify any pigmented skin lesions that are asymmetric, have an irregular border, contain 2 or more colors, or are friable, bleeding, ulcerated, or polypoid.
- Check primary surgical site for evidence of subcutaneous nodules indicating local recurrence or in-transit disease.
- Reticuloendothelial examination
- Lymphadenopathy, particularly draining lymph nodes at the primary site
- Hepatosplenomegaly
- Neurologic examination
- Level of consciousness
- Mental status examination
- Cranial nerve abnormalities, including funduscopy for papilledema
- Upper motor neuron signs or sensory deficits
- Cerebellar ataxia
- Speech abnormalities
- Hyperreflexia
- Breast, rectal, renal, thyroid, and respiratory examination to search for other possible tumors in the differential diagnosis of CNS metastases
More on CNS Melanoma |
 Overview: CNS Melanoma |
| Differential Diagnoses & Workup: CNS Melanoma |
| Treatment & Medication: CNS Melanoma |
| Follow-up: CNS Melanoma |
| References |
| Next Page » |
References
Akslen LA, Heuch I, Hartveit F. Metastatic patterns in autopsy cases of cutaneous melanoma. Invasion Metastasis. 1988;8(4):193-204. [Medline].
Amer MH, Al-Sarraf M, Baker LH, Vaitkevicius VK. Malignant melanoma and central nervous system metastases: incidence, diagnosis, treatment and survival. Cancer. Aug 1978;42(2):660-8. [Medline].
Bafaloukos D, Gogas H. The treatment of brain metastases in melanoma patients. Cancer Treat Rev. Oct 2004;30(6):515-20. [Medline].
Brat DJ, Giannini C, Scheithauer BW, Burger PC. Primary melanocytic neoplasms of the central nervous systems. Am J Surg Pathol. Jul 1999;23(7):745-54. [Medline].
Canadian Pharmaceutical Association. Compendium of Pharmaceuticals and Specialties. 35th ed. Ottawa, Ontario: Canadian Pharmaceutical Association; 2000:. 500.
Cohn-Cedermark G, Mansson-Brahme E, Rutqvist LE, et al. Central nervous system metastases of cutaneous malignant melanoma--a population-based study. Acta Oncol. 1998;37(5):463-70. [Medline].
Dahnert W. Radiology Review Manual. 3rd ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 1996:. 225-6.
Douglas JD, Margolin K. The treatment of brain metastases from malignant melanoma. Seminars in Oncology. October 2002;29:518-524.
Finkelstein SE, Carrasquillo JA, Hoffman JM, et al. A prospective analysis of positron emission tomography and conventional imaging for detection of stage IV metastatic melanoma in patients undergoing metastasectomy. Ann Surg Oncol. Aug 2004;11(8):731-8. [Medline].
Friedman KP, Wahl RL. Clinical use of positron emission tomography in the management of cutaneous melanoma. Semin Nucl Med. Oct 2004;34(4):242-53. [Medline].
Homsi J, Kashani-Sabet M, Messina JL, Daud A. Cutaneous melanoma: prognostic factors. Cancer Control. Oct 2005;12(4):223-9. [Medline].
Hurwitz S. Clinical Pediatric Dermatology: A Textbook of Childhood and Adolescence. 2nd ed. Philadelphia, Pa: WB Saunders; 1993:. 204-5.
Johnson JD, Young B. Demographics of brain metastasis. Neurosurg Clin N Am. Jul 1996;7(3):337-44. [Medline].
Koeller KK. Fundamentals of Diagnostic Imaging. 2nd ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 1999:. 125-8.
Kumar R, Alavi A. Clinical applications of fluorodeoxyglucose--positron emission tomography in the management of malignant melanoma. Curr Opin Oncol. Mar 2005;17(2):154-9. [Medline].
Kumar R, Mavi A, Bural G, Alavi A. Fluorodeoxyglucose-PET in the management of malignant melanoma. Radiol Clin North Am. Jan 2005;43(1):23-33. [Medline].
Langley RG, Barnhill RL, Mihm MC, et al. Neoplasms: Cutaneous Melanoma. In: Freedberg IM, Eisen AZ, Wolff K, Austen KF, Goldsmith LA, Katz S, eds. Dermatology in General Medicine. 5th ed. New York, NY: McGraw-Hill; 1999:. 1080-116.
Le Chevalier T, Smith FP, Caille P, et al. Sites of primary malignancies in patients presenting with cerebral metastases. A review of 120 cases. Cancer. Aug 15 1985;56(4):880-2. [Medline].
Madajewicz S, Karakousis C, West CR, et al. Malignant melanoma brain metastases. Review of Roswell Park Memorial Institute experience. Cancer. Jun 1 1984;53(11):2550-2. [Medline].
Marchetti D, Denkins Y, Reiland J, et al. Brain-metastatic melanoma: a neurotrophic perspective. Pathol Oncol Res. 2003;9(3):147-58. [Medline].
Montone KT, Elder DE. Cutaneous Oncology - Pathophysiology, Diagnosis and Management. London, England: Blackwell Scientific; 1998:. 278-91.
Morton DL, Essner R, Kirkwood J, Parker RG. Malignant melanoma. In: Holland JF, Frei E, Bast RC Jr, Kufe DW, Morton DL, Weichselbaum RR, eds. Cancer Medicine. 4th ed. Baltimore, Md: Williams & Wilkins; 1997:. 2467-99.
Nguyen AT, Akhurst T, Larson SM, et al. PET Scanning with (18)F 2-Fluoro-2-Deoxy-D-Glucose (FDG) in Patients with Melanoma. Benefits and Limitations. Clin Positron Imaging. Mar 1999;2(2):93-98. [Medline].
Osborn AG, ed. Diagnostic Neuroradiology. St Louis, Mo: Mosby; 1994:. 657-65.
Rivers JK, Ho VC. Malignant melanoma. Who shall live and who shall die?. Arch Dermatol. Apr 1992;128(4):537-42. [Medline].
Rodriguez y Baena R, Gaetani P, Danova M, et al. Primary solitary intracranial melanoma: case report and review of the literature. Surg Neurol. Jul 1992;38(1):26-37. [Medline].
Sampson JH, Carter JH Jr, Friedman AH, Seigler HF. Demographics, prognosis, and therapy in 702 patients with brain metastases from malignant melanoma. J Neurosurg. Jan 1998;88(1):11-20. [Medline].
Swetter SM, Carroll LA, Johnson DL, Segall GM. Positron emission tomography is superior to computed tomography for metastatic detection in melanoma patients. Ann Surg Oncol. Aug 2002;9(7):646-53. [Medline].
Tarhini AA, Agarwala SS. Management of brain metastases in patients with melanoma. Curr Opin Oncol. Mar 2004;16(2):161-6. [Medline].
Tellada M, Specht CS, McLean IW, et al. Primary orbital melanomas. Ophthalmology. Jun 1996;103(6):929-32. [Medline].
Wong SL, Coit DG. Role of surgery in patients with stage IV melanoma. Curr Opin Oncol. Mar 2004;16(2):155-60. [Medline].
Zimm S, Wampler GL, Stablein D, et al. Intracerebral metastases in solid-tumor patients: natural history and results of treatment. Cancer. Jul 15 1981;48(2):384-94. [Medline].
de Gast GC, Batchelor D, Kersten MJ, et al. Temozolomide followed by combined immunotherapy with GM-CSF, low-dose IL2 and IFN alpha in patients with metastatic melanoma. Br J Cancer. Jan 27 2003;88(2):175-80. [Medline].
Further Reading
Keywords
intracerebral melanoma, intracerebral metastatic melanoma, metastatic melanoma, central nervous system melanoma, central nervous system cancer, CNS cancer, brain cancer, brain melanoma
