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Neurocutaneous melanocytosis (NCM) is a disorder characterized by multiple or large congenital nevi and excessive proliferation of melanocytes in the leptomeninges and brain parenchyma. The majority of NCM is a result of somatic mosaicism due to a single postzygotic mutation in codon 61 of NRAS. Patients with NCM are at high risk of developing leptomeningeal melanoma. The prognosis for leptomeningeal melanoma is poor with no known effective treatment options. We describe the clinical features, treatment, and outcome of 4 children with NCM and leptomeningeal melanoma and discuss the latest molecular findings and treatment options for this rare condition.

Background Primary leptomeningeal melanocytic tumors of the central nervous system are rare and, especially in the spine, less frequent compared with other entities. There is no consensus regarding the best care of these tumors. Case Description We report 2 cases of primary leptomeningeal melanocytic tumors, 1 primary leptomeningeal melanoma (PLM) and 1 primary leptomeningeal melanocytoma (PLMC) of the upper cervical spine, and emphasize different surgical findings and clinical courses of these patients. A review of the literature according to primary leptomeningeal melanocytic tumors of the spine was done, especially to compare different treatment modalities in the younger history. Conclusions Primary melanocytic tumors of the spine are exceedingly rare. Before surgery it is difficult to make a correct diagnosis. Usually an unexpected intraoperative finding with consecutive histopathologic analyses leads to the final diagnosis. An accurate search for melanocytic tumors outside the central nervous system as a primary source is mandatory. PLMC has a better prognosis than PLM. There is no consensus regarding the adjuvant therapy, but patients with PLM should be given radiotherapy, chemotherapy, and immunotherapeutic approaches as immune checkpoint blockade after surgery. Communicating hydrocephalus is highly associated with PLM, but may occur in PLMC as well.

Primary melanocytic tumors of the central nervous system (CNS) arise from leptomeningeal melanocytes and possess a variable degree of aggressiveness. They have been classified into melanomatosis, melanocytoma, malignant melanoma, and diffuse melanocytosis. Melanocytic lesions of the CNS include both benign (leptomeningeal melanocytosis, melanocytoma) and malignant (leptomeningeal melanomatosis, melanoma) pathologies and the extent of anatomical site involvement dictates their clinical features. Primary CNS melanoma accounts for approximately 1% of all melanoma cases with a peak incidence in the fourth decade. Though the most common location of occurrence is in the lumbar region, our patient presented with a thoracolumbar lesion. We present a case of a 66-year-old white Caucasian male who presented with complaints of headache for six months and was thoroughly evaluated leading to a rare diagnosis of primary leptomeningeal melanoma.

Importance: Few data are available on patients with leptomeningeal disease (LM) from melanoma treated with new systemic therapies. Objective: To gain a better understanding of patients, disease characteristics, and therapeutic interventions in melanoma patients with LM in the era of new systemic treatment. Design: Clinical characteristics, treatments, and survival of melanoma patients diagnosed with LM, isolated or associated with brain metastases, were collected. The Cox regression model assessed the influence of patient and melanoma characteristics on survival. Setting: Monocentric, retrospective, real-life cohort of patients with LM from melanoma. Participants: All patients followed up at Saint-Louis University Hospital and diagnosed with LM between December 2013 and February 2020 were included. For each patient identified, a central review by dermato-oncologist and neuro-oncologist experts was performed to confirm the diagnosis of LM. Exposure: Impact of new systemic therapies and radiotherapy. Results: Among the 452 advanced melanoma patients followed at St Louis Hospital between 2013 and 2020, 41 patients with LM from melanoma were identified. Among them, 29 patients with a diagnosis of LM &ldquo, confirmed&rdquo, or &ldquo, probable&rdquo, after central neuro-oncologists reviewing were included. Nineteen patients had known melanoma brain metastases at LM diagnosis. Among the 27 patients treated with systemic therapy, 17 patients were treated with immunotherapy, 5 patients received targeted therapy, 1 was treated with chemotherapy, and 4 patients were treated with anti-PD-1 in combination with BRAF inhibitor. The median overall survival (OS) from LM diagnosis was 5.1 months. Median OS was 7.1 months for the 9 patients receiving systemic therapy combined with radiotherapy, and 3.2 months for the 20 patients not receiving combined radiotherapy. Elevated serum lactate dehydrogenase (LDH) (HR 1.44, 95% CI 1.09&ndash, 1.90, p &lt, 0.01) and presence of neurological symptoms at LM diagnosis (HR 2.96, 95% CI 1.25&ndash, 6.99, p = 0.01) were associated with poor survival. At the time of data analysis, five patients were still alive with a median follow-up of 47.4 months and had persistent complete response. Conclusion: Targeted therapy and immunotherapy are promising new treatment options in LM from melanoma that can increase overall survival, and may induce long lasting remission in some patients.

Background: Melanocytic nevi present at birth, or within the first few months of life, are defined as congenital melanocytic nevi (CMN). Neurocutaneous melanosis (NCM) is a rare disorder, represents pigment cell tumors of the leptomeninges, and occurs in association with large or multiple CMN. NCM carries an extremely poor prognosis. NRAS and BRAFV600E genetic mutations were reported in CMN. Our aim was to report 2 rare cases of NCM associated with large-sized CMN. Materials and Methods: Two cases were enrolled, a 19-month-old boy with multiple satellite and giant CMN (GCMN); and a 57-month-old girl with large CMN (LCMN). Both patients had central nervous system (CNS) symptoms, and therefore, were studied from clinical, radiological, and immunohistopathological aspects. Cytogenetic study was done for one of them. Results: Both patients had CMN located in the head/neck, with no cutaneous melanoma. MRI was the most reliable method for early detection of NCM. NCM was proved in the 2 studied cases by immunohistopathology performed after surgery. The boy with GCMN carried NRAS mutation at codon 61, in addition to the characteristic facial features relevant to RASopathies. Both patients died despite surgical intervention. Conclusion: Our report highlights the need for pediatricians to be alert to the risk of NCM in association with CMN, especially when a CMN lesion is large, or there are multiple satellite lesions, or the nevus location is at the head or neck. Moreover, in the setting of CMN, the absence of skin melanoma does not exclude the presence of NCM.

Neurocutaneous melanoma is a rare congenital syndrome associated with congenital melanocytic nevi with meningeal melanosis or melanoma. The disease is aggressive and has a high propensity for leptomeningeal metastases. We present the case history of a man with neurocutaneous melanoma managed with radical excision followed by hypofractionated adjuvant radiotherapy. One year, eight months later, he had a recurrence of the condition with leptomeningeal spread and was managed with re-excision of the recurrent lesion. Although our patient was disease-free for 20 months after the initial surgery, he survived only approximately five months after the second surgery, which reflects the associated poor prognosis of the disease.

Aim Neurocutaneous melanocytosis is a rare neurocutaneous syndrome defined by the presence of large and/or multiple congenital cutaneous nevi and melanocytic deposits in the central nervous system. We sought to define the spectrum of central nervous system abnormalities in children with neurocutaneous melanocytosis. Method We retrospectively reviewed cases of neurocutaneous melanocytosis referred to the pediatric neuro-oncology service at our center from 2003 to 2010. Results Of 14 patients (11 males, 3 females) identified, eight were living. Median age of survivors was 31 months (range 12mo–6y 10mo) while median age of death was 81 months (19mo–28y). Of the six patients who died, all had diffuse leptomeningeal melanocytic deposits and four had leptomeningeal melanoma. All patients had neuroimaging: six had findings suggestive of diffuse leptomeningeal melanocytosis; seven had multifocal melanocytic deposits; and one patient had normal neuroimaging but focal seizures. Spinal abnormalities were common: three patients had extensive dorsal spinal arachnoid cysts and one had a benign cervical spindle cell tumor. Seven patients had epilepsy. Three patients had profound developmental delay; the other 11 patients had no or mild delay. Interpretation Children with neurocutaneous melanocytosis exhibit a wide range of intracranial and intraspinal abnormalities and variable clinical outcomes.

We report an unusual occurrence of a primary dural-based malignant melanoma in a 13-year-old boy with neurocutaneous melanosis. The lesion presented with rapid-onset symptoms characterized by raised intracranial pressure and seizures, had an aggressive clinical course, and proved to be fatal despite two surgeries and adjuvant therapy. There should be a high index of suspicion for the occurrence of such a malignant leptomeningeal tumor in patients with congenital melanocytic nevi presenting with neurological symptoms of recent onset.

Leptomeningeal spread of cancer can have protean presentations, increasing the difficulty of making this diagnosis. We present the case of a 77-year-old man with prior metastatic melanoma who presented with spontaneous headache that worsened over several days, and was found to have both intraventricular and cortical subarachnoid hemorrhage on CT head. His neurological exam was unremarkable. MRI of the brain with contrast confirmed the CT findings and did not reveal any evidence of parenchymal or leptomeningeal metastases. MR angiogram followed by a conventional angiogram did not demonstrate any vascular abnormalities. Cerebrospinal fluid examination revealed 110 white blood cells, 34000 red blood cells, and protein of 160. Cytology returned positive for malignant melanoma cells. No additional sites of disease were found on further evaluation with MRI spine and CT of the chest, abdomen and pelvis. In retrospect, the patient had endorsed some fluctuating nausea and fatigue three months prior to presentation, as well as positional vertigo two weeks prior to presentation. His oncologic history was notable for prior immunotherapy with ipilimumab, as well as diagnosis of dural-based brain metastases two years earlier, for which he underwent surgical resection and radiation therapy. He had no evidence of disease for one year prior to this new diagnosis of leptomeningeal involvement. This case highlights an unusual presentation of leptomeningeal metastasis and underscores the importance of maintaining heightened suspicion for this diagnosis when evaluating subarachnoid hemorrhage in a cancer patient, especially in the case of melanoma. It raises the question of whether this particular cancer type or the patient’s prior immunotherapy contributed to his presentation, and emphasizes the need for further elucidation of the biology of leptomeningeal metastasis.

To develop new treatment strategies for patients with leptomeningeal metastases (LM), potential therapeutic agents have to be tested in murine models first. In vivo magnetic resonance imaging has an additive value in non-invasive monitoring of the effects of therapeutic agents on LM. Previously, we described a reproducible mouse model for B16F-10 melanoma LM. In this paper, we visualize leptomeningeal melanoma metastases in mice on both T2 weighted MR images and gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) enhanced T1 weighted MR images, using a 4.7T MR spectrometer. We conclude that both MR sequences can be used to detect and monitor LM of melanoma cells in mice. Our data further suggest that LM are more clearly visualized using T1 weighted Gd-DTPA enhanced subtraction imaging than T2 weighted imaging.

Primary melanoma of the central nervous system is a rare melanocytic tumor typically located in the leptomeninges. We report a 57-year-old woman with an intracranial leptomeningeal melanoma who presented with myoclonic seizures. Brain CT scan and MRI revealed a hemorrhagic intracranial tumor. The tumor was completely removed and leptomeningeal melanoma was proven pathologically. Follow-up imaging studies up to 19 months showed no recurrence of the disease. Here we present radiological, gross, and pathological images of leptomeningeal melanoma, discuss its characteristics, and review the relevant literature.

Out of 16 patients, spinal leptomeningeal neoplastic disease was diagnosed by MRI in 4 patients, myelography in 14 patients and CT myelography in 12 cases. MR was superior to myelography in 2 patients

Diseases derived from leptomeningeal melanocytes have intrigued physicians for generations. Their original descriptions were contributed by among the most prominent pathologists. Diffuse leptomeningeal melanoma was first reported by Virchow (1859). Not much later, in 1861, Rokitansky (1861) detailed the rare phakomatosis, neurocutaneous melanosis, in a 14-year-old girl.

A case of leptomeningeal melanoma metastases with a confusing clinical picture is presented. Despite repeated cytological examinations of the cerebrospinal fluid proving negative, the diagnosis was eventually made by magnetic resonance imaging with gadolinium DTPA enhancement.

A case of primary leptomeningeal melanoma is presented in which the diagnosis was made by ultrastructural demonstration of melanoma cells from the cerebrospinal fluid (CSF) at a time when cranial computed tomography (CT) still gave negative results. Later CT examinations documented the emergence of a tumor mass of the left temporoparietal lobe. This case clearly illustrates the complementary role of these investigational procedures for the diagnosis of cerebrospinal melanoma: leptomeningeal involvement, characterized by two-dimensional diffuse spread of melanoma tissue ("leptomeningeal melanomatosis"), is invisible with CT, but easily recognisable by CSF cytology; in contrast, nodular parenchymal tumor deposits can be readily detected by CT. Identification of pigmented cells recovered from the CSF requires ultrastructural confirmation.

This study reviews the literature pertaining to primary meningeal melanoma and reports the clinical and ultrastructural findings in a case where the tumor appeared to be of pachymeningeal (dural) origin. This is clearly a departure from all previously described cases, in which a leptomeningeal (pial-arachnoidal) origin was either defined or assumed. Clinically. this case was remarkable in its rarity. its presentation as a cerebellopontine angle syndrome, and its occurrence in a Negro. a race in which melanomas are uncommon. Ultrastructurally. the tumor did demonstrate the presence of basement membrane abnormalities and numerous endothelial fenestrations. However, it was found to be made up of a homogenous cell population, consisting only of electron-lucent, melanin-laden cells. The mixed cell population noted previously in a primary leptomeningeal melanoma was not found in this tumor. In view of the fact that this patient continues to do well 1/12; years after operation, with no evidence of tumor recurrence, it is suggested that a homogenous cell population noted on electron microscopy could indicate a better prognosis. In addition, it may also indicate a pachymeningeal rather than a leptomeningeal origin for the tumor. A plea is made for greater specificity in terminology when describing primary meningeal melanomas and for a concerted effort to distinguish between those of dural and those of leptomeningeal origin.

A primary leptomeningeal melanoma in a 19-year-old white women has been shown by electron microscopy to contain light and dark cells. The light cells fill the subarachnoid space, contain mature melanosomes and exhibit intracytoplasmic fine fibrils. The dark cells are found within the collagen network of pia-arachnoid. They possess a small rim of ribosomal-rich cytoplasms, occasional premelanosomes and no intracytoplasmic fibrils. The tumor cells appear to arise from these dark activated melanoblasts in the pia-arachnoid and proliferate into more differentiated light cells. A similar pattern of two types of cells has not been described in primary CNS melanomas. The possibility of differentiation from cutaneous melanoma is discussed.

A case of primary leptomeningeal melanoma in a child is presented. The patient was studied with multiple neuroradiological methods, however computed tomography (CT) provided the most important information. The CT findings with leptomeningeal tumor, although not completely specific, do suggest the diagnosis, thus providing important information to explain the acute onset of symptoms in a previously healthy child. This case also differs from previously reported cases in terms of the type of hydrocephalus associated with the tumor.

A case of leptomeningeal melanoma in an African child of 7 years is presented together with a survey of pigmentation in the normal African brain. There is a direct relationship between the depth of pigment of the leptomeninges and the skin in Ugandan Africans, suggesting that similar factors operate in the control of melanocytes in these two sites.

A case of neurocutaneous melanosis developing a leptomeningeal melanoma is described in a ten year old girl in whom an intraspinal lipoma had been resected seven years earlier. Standard and CT myelographic findings are described and the complementary role of Gadolinium-enhanced MRI is discussed. The literature is reviewed and the association of a lipoma and neurocutaneous melanosis has not been encountered.

Background Leptomeningeal metastasis of melanoma is a devastating complication with a grave prognosis, and there are no known effective standard treatments. Although selective BRAF inhibitors have demonstrated a significant clinical activity in patients with metastatic melanoma harboring a BRAF mutation, the clinical benefit of BRAF inhibitor-based therapy in leptomeningeal disease is not clear. Case presentation We present a case of prolonged survival of a patient with BRAF V600E-mutant leptomeningeal disease who was treated with vemurafenib followed by whole brain radiation and a combination of dabrafenib and trametinib. Both vemurafenib and the sequential treatment of radiation and dabrafenib/trametinib led to regression of the leptomeningeal disease, and the patient survived for 19 months after the diagnosis of the leptomeningeal disease. Conclusion This case suggests a possible clinically meaningful benefit of BRAF inhibitor-based therapy and a need for close investigation of this therapeutic approach in patients with this devastating disease.

• A case of neurocutaneous melanosis with malignant leptomeningeal melanoma was seen in a black man. The presence of extracranial metastases was noted, and evidence is presented favoring the central nervous system as the primary source.

A previously healthy 16-year-old male patient came to the emergency department with a six-week history of left posterior hip pain following a head-on ATV collision. After failing conservative therapy, he was found to have weakness and atrophy of the left lower extremity on exam. MRI demonstrated an epidural mass that was hyperintense on T1 and hypointense on T2. Biopsy of the mass revealed a melanocytic lesion; further lesions were identified in the lungs, which biopsy proved to be malignant melanoma. Dermoscopy of the entire body, anoscopy, and retinal exam were negative for melanoma; a whole-body PET scan did not reveal any further lesions or evidence of a primary lesion. Given the lack of a primary lesion, this was thought to be a primary leptomeningeal melanoma. Primary melanomatous tumors of the spine are rare entities, with fewer than 40 cases described in the literature. This case was unique due to the patient's very young age and the presence of metastases on presentation.