The purpose of this study is to collect and bank samples of blood and tissues (such as brain tissue or lymph nodes), as well as cerebrospinal fluid (CSF), which is the fluid that bathes and cushions the spinal cord. The investigator will analyze DNA biomarkers in the samples. The investigator hopes that by studying the biomarkers, he can develop tests in the future that can detect central nervous system (CNS) metastasis in blood samples before they show up on x-ray and develop medicines that can specifically target CNS metastasis.

Among the different sites to which melanoma can spread, the Central Nervous System (CNS) has the highest chance of developing metastases. Prognosis for metastatic melanoma involving the CNS is worse than that of CNS metastases from other cancers. Therefore, it is felt that early identification of this condition, even before it is found on x-ray (either MRI or CT scan), would be beneficial so that patients can undergo treatment earlier.

The investigator hypothesizes that the tumor cell genetics, expressed proteins, and/or signaling pathways of melanoma brain metastases may exhibit features that distinguish melanoma brain metastases. The investigator further hypothesizes that melanoma brain metastases may be associated with changes in the cerebrospinal fluid, where protein fragments expressed by melanoma brain metastases may be shed that cannot be found in normal CNS tissues, extracranial metastases (MEM) or at the same levels in the peripheral blood.

Inclusion Criteria:

• Subjects must have provided written Informed Consent prior to any study procedure.

• Regarding patients with distant metastatic melanoma and established melanoma CNS metastases who are scheduled for craniotomy:

  • Histologically confirmed, primary cutaneous melanoma, metastatic to the CNS (brain OR spinal cord OR carcinomatous meningitis) based on:
  • Pathologic confirmation (i.e. prior craniotomy) OR
  • Radiography (brain MRI or CT scan with intravenous contrast)
  • Patients must have no contraindications for lumbar puncture for CSF collection
  • Hemoglobin level of 8g/dL or higher within the prior 30 days
  • FFPE tissue block containing a biopsy from the primary site available for retrieval.

• Regarding patients with distant metastatic melanoma and established melanoma CNS metastases who are not having a craniotomy and before they undergo external beam irradiation or stereotactic radiosurgery (patient's and/or neurosurgeon's preference):

  • Histologically confirmed melanoma (unknown primary, mucosal, ocular are allowed), metastatic to the CNS (brain OR spinal cord OR carcinomatous meningitis) based on
  • Pathologic confirmation (i.e. prior craniotomy) and/or
  • Radiography (brain MRI or CT scan with intravenous contrast)
  • Patients without contraindications to undergo lumbar puncture for the component that relates to CSF collection as determined by the neurosurgeon. An external ventricular drain (EVD) may be utilized if clinically indicated and the source of CSF (LP or EVD) clearly recorded (this is not required for enrollment in the overall protocol if there are any contra-indications to performance of this procedure)
  • Hemoglobin level of 8g/dL or higher within the prior 30 days

Exclusion Criteria:

• For study subjects, patients with extradural lesions, i.e. those that originate from the bone (calvarium or vertebrae), will not be considered.
• Any significant psychiatric disease, medical intervention, or other conditions, which in the opinion of the Investigators, could impair proper discussion of the informed consent or compromise participation to the clinical trial.
• Active systemic treatment for metastatic melanoma within 2 days from the collection of specimens (brain tumor tissue, peripheral blood, CSF). Corticosteroids, other immunosuppressive anti-inflammatory and anti-epileptic medications are allowed.
• Patients who have undergone whole brain irradiation therapy within the last 30 days. Therefore neither CNS lesions nor CSF are considered suitable for collection.
• Patients with growing CNS lesions at an area that has previously undergone radiosurgery within 3 months prior to enrollment in this study. Therefore CNS tumors from previously irradiated areas using radiosurgery are not considered suitable for collection although CSF is allowed for collection.
• Brain abscess.
• Other conditions that at the opinion of the investigator are contraindicated.

Patients with biopsy-proven melanoma who present with melanoma CNS metastases, a condition that has been previously either biopsy-proven or there is strong suspicion based on the radiologic imaging (brain MRI or brain CT with intravenous contrast) will be considered for the study.