Melanoma is the most frequent solid tumor associated with leptomeningeal metastasis (LM). The usual diagnostic tools, that is, cytomorphological assessment of cerebro-spinal fluid (CSF) and gadolinium-enhanced MRI of the entire neuraxis both lack effectiveness. The CellSearch® Veridex technology for the detection of circulating tumor cells (CTC) in blood was designed for the follow-up and prognosis of breast, prostate, colorectal, and lung cancer, which express EpCAM markers. We have previously adapted this technology to detect malignant cells in the CSF of breast cancer LM. Our objective here was to check if this technology would also allow the detection and the enumeration of CTC in the CSF of melanoma patients presenting with LM although melanoma does not express EpCAM markers. On the occasion of the intrathecal treatment of LM in 2 melanoma patients, 5 mL of CSF and 7.5 mL of blood were collected on CellSave® Preservative Tubes and analyzed within 3 days after CSF sampling using a melanoma-dedicated kit. The CellSearch® Veridex technology was then adapted to direct enrichment, enumeration, and visualization of melanoma cells in the CSF. CD146+, HMW-MAA+, CD34−, and CD45− cells with typical morphology could be observed and enumerated sequentially with reproducible results, corresponding to CSF melanoma cells (CSFMC). In contrast to the current gold standard cytomorphological analysis, this new approach allowed a precise quantification of CSFMC in all samples concomitantly analyzed. This methodology, established on a limited volume of sample and allowing delayed processing, could prove of great interest in the diagnosis and follow-up of melanoma patients with LM.

Detection and quantification of CSF malignant cells by the CellSearch technology in patients with melanoma leptomeningeal metastasis.

Neoplastic meningitis due to the dissemination of systemic cancer or primary central nervous system tumors through the cerebrospinal fluid carries a very poor prognosis. Current treatments for this disease are ineffective, and new therapeutic modalities such as immunotoxins may be beneficial. We created an animal model of human carcinomatous meningitis with LOX melanoma-derived tissue-culture cells in athymic rats for testing the efficacy of intrathecal therapy with transferrin-Pseudomonas exotoxin A (Tfn-PE) immunotoxin. An injection of 5 x 10(5) LOX cells into the intrathecal space through an indwelling catheter resulted in the reproducible development of lower-extremity paraplegia at 9.24 +/- 1.77 days because of focal deposits of tumor growth adjacent to the thoracic and lumbar spinal cord. A dose of 2.5 or 5 micrograms of intrathecal Tfn-PE immunotoxin was neurotoxic and resulted in the deaths of 8 of 10 animals within 24 hours. Histological evidence of central nervous system damage was seen as hemorrhagic degeneration around the central canal or a pathological cleft at the level of the cervical spinal cord. Because no neurotoxicity was seen with 1 microgram of intrathecal Tfn-PE immunotoxin, this dose was administered in treatment experiments. Twenty-four hours after the intrathecal instillation of LOX cells, 10 animals received intrathecally either 1 microgram of Tfn-PE or phosphate-buffered saline with 0.1% human serum albumin (control group).(ABSTRACT TRUNCATED AT 250 WORDS)

In vivo efficacy of intrathecal transferrin-pseudomonas exotoxin a immunotoxin against lox melanoma

The intrathecal immune response in neoplastic meningitis (NM) was studied by quantitation of immune parameters such as immunoglobulin G (IgG); IgM; interleukins (IL) 1, 2, 4, and 6; soluble IL-2 receptors (sIL-2R); interferon gamma (IFNy); tumor necrosis factor-alpha (TNF alpha); and three tumor markers, carcinoembryonic antigen (CEA), alpha-fetoprotein (AFP), and fibronectin (FN), in 47 paired cerebrospinal fluid (CSF) and serum samples from patients with NM from different carcinomas, malignant melanoma, and lymphoma Elevated IgG and IgM indices, CSF oligoclonal Ig bands, and CSF IL-6 indicated an intrathecal immune activation in most patients with NM Results for IL-1, IL-2, and IL-4 were always negative sIL-2R and IFNy were detected occasionally but not associated with specific malignant neoplasms CSF TNF alpha was detected only in NM from cases of malignant melanoma None of the immune parameters proved useful for the differentiation of NM from autoimmune or inflammatory conditions Immune parameters were not correlated with tumor markers CEA, AFP, or FN Results for AFP were positive only in a case of glioblastoma CEA was a useful and specific diagnostic parameter in carcinomatous NM CSF FN levels frequently were elevated but are not specific for NM

Tumor cell dissemination triggers an intrathecal immune response in neoplastic meningitis.

Anatomy as a key to function of the spinal cord spinal modulation of noxious stimuli spasticity hazards of lumbar puncture neuropathology embryonic development of the spinal cord and associated disorders imaging of the spine and spinal cord neurophysiological investigation of the spinal cord radiculopathy due to diseases other than disc diseases disc and degenerative disease - stenosis, spondylosis and subluxation craniocervical anomalies and non-traumatic syringomyelia cervical myelopathy due to rheumatoid arthritis meningitic disorders and myelopathies anterior horn cell diseases three tropical spinal cord syndromes the conus medullaris and sphincter control spinal vascular disease decompression illnesses and the spinal cord hereditary and nutritional disorders of the spinal cord vertebral body collapse spinal epidural abscess spinal cord compression and spinal cord tumours trauma and paraplegia rehabilitation, walking aids, functional electrical stimulation and overcoming spasticity.

Diseases of the spinal cord

Craniopharyngioma, a common epithelial neoplasm of the sellar region, is the most frequent suprasellar neoplasm in children (1,2). However, neonatal or congenital tumors are very rare (3–5), as are tumors in the elderly (6).

Sellar Tumors Other Than Adenomas

Six patients with neoplastic melanomatous meningitis were studied. The diagnosis of this complication of malignant disease rests on the demonstration of malignant cells within the CSF. The addition of monoclonal antibody immunocytology to conventional techniques significantly improved the diagnostic sensitivity of CSF cytology, allowing for earlier and therefore more effective palliative treatment.

https://jnnp.bmj.com/content/jnnp/52/7/881.full.pdf

Neoplastic meningitis in malignant melanoma: diagnosis with monoclonal antibodies.

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Neoplastic meningitis in malignant melanoma: diagnosis with monoclonal antibodies.