mart-1-antigen and Meningeal-Neoplasms

Primary leptomeningeal melanoma is an extremely rare disease of the central nervous system. There are no standard treatment protocols with a poor prognosis in very few reported cases. Immunotherapy in primary brain melanoma has not been successfully applied so far.. We describe a female patient 72-year-old diagnosed in the Neurosurgery Department which presented with generalized seizures.. Histological examination confirmed atypical melanocytes immunohistochemically positive for melan A, HMB45 and S-100 protein in the meninges, BRAF V600E negative. Dermatological, ophthalmological examinations, and 18-FDG PET/CT were negative.. The patient was successfully treated with pembrolizumab 2 mg/kg every 3 weeks for 2 years.. The disease was stable for 2 years and the patient had no significant toxicity.. Our report describes durable intracranial tumor response suggesting the efficacy of PD-1 inhibitor pembrolizumab for central nervous system primary leptomeningeal melanoma.

Topics: Aged; Antibodies, Monoclonal, Humanized; Female; gp100 Melanoma Antigen; Humans; MART-1 Antigen; Melanoma; Melanoma-Specific Antigens; Meningeal Neoplasms; Programmed Cell Death 1 Receptor; S100 Proteins; Seizures; Treatment Outcome

Topics: Adult; Diagnosis, Differential; Humans; Magnetic Resonance Imaging; Male; MART-1 Antigen; Medulloblastoma; Melanocytes; Melanoma; Melanoma-Specific Antigens; Meningeal Neoplasms; Neoplasms, Multiple Primary; Neurilemmoma; Nevus of Ota; S100 Proteins; Skin Neoplasms; Vimentin

A 49-year-old patient with primary, recurrent melanoma on the lower extremity developed metastatic leptomeningeal melanoma that did not respond to treatment with radiation therapy or intrathecal interleukin 2 (IL-2). Disease was characterized by neurological symptoms, including loss of hearing, loss of short-term memory, and gait disturbance. CD8+ CTLs were generated in vitro using autologous dendritic cells pulsed with peptides from the melanoma-associated antigens tyrosinase (145-156), Melan-A/MART-1 (26-35), and gp100/Pmel 17 (209-217). The CTLs exhibited up to 74% specific lysis against peptide-pulsed autologous EBV-transformed B cells, with Melan-A-specific CTLs yielding the greatest lytic activity. CD8+ CTLs possessed a type 1 cytokine profile, expressing tumor necrosis factor alpha and IFNgamma but not IL-4. Infusions of CTLs were supported with systemic low-dose IL-2 administration. 111In labeling and computerized gamma imaging were used to monitor the distribution of CTLs up to 48 h after infusion. Intra-arterial delivery via the right carotid artery was followed by redistribution of the CTLs to the lungs, liver, and spleen within 16 h. In contrast, delivery via an indwelling Ommaya reservoir resulted in prolonged retention of CTLs within the brain for at least 48 h after infusion. Marked but transient elevations in tumor necrosis factor alpha, IFN-gamma, and IL-6 in the cerebrospinal fluid were observed within 4 h of CTL infusion. There was no evidence of tumor progression throughout the treatment period, and clinically the patient showed some resolution of neurological symptoms.

Topics: Antigens, Neoplasm; B-Lymphocytes; CD8-Positive T-Lymphocytes; Cytokines; Dendritic Cells; Enzyme-Linked Immunosorbent Assay; Female; Flow Cytometry; gp100 Melanoma Antigen; Humans; Immunotherapy; Immunotherapy, Adoptive; Indium; Interferon-gamma; Interleukin-2; Interleukin-4; Interleukin-6; MART-1 Antigen; Melanoma; Membrane Glycoproteins; Meningeal Neoplasms; Middle Aged; Monophenol Monooxygenase; Neoplasm Proteins; Proteins; Reverse Transcriptase Polymerase Chain Reaction; T-Lymphocytes, Cytotoxic; Time Factors; Tissue Distribution; Tumor Cells, Cultured; Tumor Necrosis Factor-alpha