Meningeal Melanocytosis Research Articles

Diffuse meningeal melanocytosis – a silent culprit

Abstract Introduction/Objective Diffuse meningeal melanocytosis is a rare melanocytic proliferation that poses significant risk of severe hydrocephalus and mortality among children and young adults. Although the clonal melanocytes do not typically exhibit malignant morphological features, their capability for extensive invasion and malignant-like behavior necessitates tissue biopsy alongside immunohistochemical and molecular testing for definitive diagnosis. Methods/Case Report A 17-year-old male presented with progressive headaches, photophobia, and nausea, initially attributed to migraines. Neuro-opthalmological assessment revealed papilledema, leading to a diagnosis of idiopathic intracranial hypertension. Serial imaging showed fluctuating leptomeningeal enhancement and moderate communicating hydrocephalus without parenchymal lesions. Therapeutic lumbar punctures provided modest symptom improvement; increased opening pressure was observed. Evaluation of seven CSF specimens showed low glucose levels, increased cellularity consisting of bland appearing epithelioid cells of unknown etiology, and increased lymphocytes. Infectious causes were excluded. Due to the indeterminate CSF findings, discussion between the cytopathologist and neuro-opthamologist was crucial to facilitate tissue biopsy to exclude a neoplastic process. Subsequent shunt placement and cerebral cortex biopsy revealed neoplastic cells with sheet-like architecture coating the dura without overt brain invasion. The tumor cells had eosinophilic cytoplasm without pigment and enlarged nuclei with irregular contours, vesicular chromatin, and prominent nucleoli. No high-grade features were seen. Immunohistochemical stains were positive for MART1, HMB45, and PRAME, consistent with a melanocytic lesion. FISH melanoma panel was negative. The final diagnosis was diffuse meningeal melanocytic neoplasm, most consistent with meningeal melanocytosis. The patient received chemotherapy with improved symptoms and stable disease. Results (if a Case Study enter NA) NA Conclusion Diffuse meningeal melanocytosis is a challenging cytologic diagnosis as melanocytes can morphologically mimic lymphocytes and monocytes, and the low cellularity of CSF specimens often results in insufficient cell blocks for ancillary tests. The direct communication of the pathologist with the clinical team to correlate pathology, radiology, and clinical symptoms was essential to ensure the proper management of this patient.

NIMG-77. EARLY DIAGNOSIS OF NEUROCUTANEOUS MELANOSIS MASQUERADING AS SUBARACHNOID HEMORRHAGE

Abstract A 50-year-old male presented to the emergency room with a sudden onset right upper limb facial numbness and dysphasia, soon followed by full-recovery. Brain computed tomography revealed hyperdense lesions within the left frontal sulcus, highly suspicious of subarachnoid hemorrhage. T1-weighted magnetic resonance imaging showed multiple leptomeningeal enhancement in the left frontal area.The digital subtraction angiography indicated an absence of vascular lesions. One-month after, the lesions progressed in the occipital area, when left sixth nerve palsy developed. Multiple giant nevus over the legs, trunk, and scalp had attracted attention. Owing to the suspicious symptomatic leptomeningeal lesions, open biopsy was performed. Surprisingly, diffuse, thick, black-colored tissue infiltration of the subarachnoid space, involving prominent cortical vessels, was noted. Pathology confirmed meningeal melanocytosis. Neurocutaneous melanosis is characterized by giant congenital or multiple satellite nevi and melanocytic tumors of the leptomeninges. Early disease diagnosis is crucial. Once the patient develops neurological symptoms, prognosis could quickly worsen.

Congenital Giant Melanocytic Nevus with Meningeal Melanocytosis in a Term Neonate- A Case Report

Congenital giant melanocytic nevus presenting in the neonatal period is a clinical diagnosis, but the extra dermatology manifestations require early recognition. Meningeal melanocytosis is one such association which increases the risk of epilepsy. We report a neonate with large congenital melanocytic nevus over the torso with satellite lesions presenting with meningeal melanocytotic in the right parietal and cerebellar region. We discuss the clinical course, management and review the literature on this condition.

Primary Melanocytic Tumors of the Central Nervous System in Children: Imaging Features with Pathologic Correlation

Primary melanocytic tumors of the central nervous system are rare neoplasms arising from proliferation of multipotent melanin-containing neural crest cells found in the leptomeninges. This review describes the imaging appearance of the entire spectrum of primary melanocytic tumors of the brain and spine in the pediatric population, in correlation with histopathology, clinical features, and prognosis, using sample cases from our institution. These tumors are subclassified by the World Health Organization on the basis of disease distribution and pathologic aggressiveness into the following 4 subtypes: meningeal melanocytoma, meningeal melanoma, meningeal melanocytosis, and meningeal melanomatosis. They can occur in any age group, though the diffuse form of the disease is more prevalent in children and has an association with giant cutaneous melanocytic nevi. Imaging is characterized by hyperattenuation on CT and intrinsic T1 hyperintensity on MR imaging from the presence of melanin and/or hemorrhage. The focal forms usually manifest as dural-based hemorrhagic masses, and the diffuse forms demonstrate dural thickening and enhancement, with or without hydrocephalus. There is a predilection for the medial temporal lobes, posterior fossa, and upper cervical spine. The prognosis is often poor, with a high incidence of malignant transformation of benign disease.Learning Objective: To describe the imaging appearance of the spectrum of primary melanocytic tumors of the brain and spine in the pediatric population and to review the histopathology, clinical, and prognostic data available

Case Report: Differential Genomics and Evolution of a Meningeal Melanoma Treated With Ipilimumab and Nivolumab

Primary melanocytic tumors of the CNS are extremely rare conditions, encompassing different disease processes including meningeal melanoma and meningeal melanocytosis. Its incidence range between 3-5%, with approximately 0.005 cases per 100,000 people. Tumor biological behavior is commonly aggressive, with poor prognosis and very low survivability, and a high recurrence rate, even after disease remission with multimodal treatments. Specific genetic alterations involving gene transcription, alternative splicing, RNA translation, and cell proliferation are usually seen, affecting genes like BRAF, TERT, GNAQ, SF3B1, and EIF1AX. Here we present an interesting case of a 59-year-old male presenting with neurologic symptoms and a further confirmed diagnosis of primary meningeal melanoma. Multiple therapy lines were used, including radiosurgery, immunotherapy, and chemotherapy. The patient developed two relapses and an evolving genetic makeup that confirmed the disease’s clonal origin. We also provide a review of the literature on the genetic basis of primary melanocytic tumors of the CNS.

Melanocytoma and meningeal melanocytosis, similar but different lesions

Abstract Background Meningeal melanomatosis is an extra-axial well-encapsulated malignant tumour with diffuse meningeal growth and dark colouration (due to high melanin contents), while meningeal melanocytoma is the focalised benign variant. Melanocytic lesions may be secondary to melanoma or be histologically benign, however, their diffuse nature makes them impossible to cure. Melanocytosis is a diffuse tumour that can form solitary extra-axial tumours, which invades the parenchyma and presents signs of malignancy with increased mitosis and Ki67, observed in 1 to 6% of immunopathological exams. Melanoma of the leptomeninges, presents signs of malignancy with anaplastic cells, which cluster in fascicles of melanin in the cytoplasm, with more than 3 atypical mitoses per field and Ki67 presenting in more than 6% of the immunopathological fields analysed. Clinical case We present the case of a patient with long-term meningeal melanomatosis, with progressive neurologic deficit and characteristic radiologic features, and another case of meningeal melanocytoma. Conclusions Benign melanocytic neoplasms of the central nervous system must be treated aggressively in the early phases with strict follow-up to avoid progression to advanced phases that do not respond to any treatment method. Unfortunately, the prognosis for malignant melanocytic lesions is very poor irrespective of the method of treatment given.

P08.19 * PRIMARY INTRATHECAL MELANOMA ARISING FROM MENINGEAL MELANOCYTOSIS: A CASE REPORT

INTRODUCTION: Primary melanocytic tumours of the leptomeninges are rare diseases. The WHO classification of 2007 described four entities: diffuse melanocytosis, melanocytoma, malignant melanoma and meningeal melanomatosis. Meningeal melanocytosis is a benign proliferation of melanocytes with a risk of malignant transformation and is often associated with neurocutaneos melanosis. CASE REPORT: A 65-year-old male patient presented with low back pain and disturbed micturition. Neurological examination revealed left sided S1- sensory radiculopathy. His medical history was unremarkable. MRI of the lumbar spine showed a contrast-enhancing intrathecal tumour of the conus medullaris and MRI of the brain was suspicious of neoplastic meningitis. Spinal surgery exhibited a brown tumour mass with diffuse spreading of pigmented lesions along the arachnoidea. Histological, immunohistochemical, and molecular analyses showed an intrathecal melanoma with a wild-type BRAF genotype. Dermatological examination was unremarkable. Lumbar stereotactic radiotherapy was applied. Subsequently, 3 cycles of temozolomide (150mg/m2 on 5 days out of 28) and bi-weekly intrathecal liposomal cytarabine were administered. Despite the poor prognosis of neoplastic meningitis in melanoma, the patient survived without clinical for more than one year. 15 months after the initial diagnosis spinal MRI showed a local relapse and a second surgery was performed. This time molecular analysis of the tumor revealed the presence of the BRAF V600E mutation. Due to the initially slow tumor progression treatment with B-Raf inhibitors was withheld and immunotherapy with the anti-CTLA-4 antibody ipilimumab was initiated together with stereotactic radiotherapy of the conus medullaris. Three months later, the patient complained about diplopia and dizziness. Neurological examination revealed oculomotor nerve palsy. MRI of the brain showed a meningeal contrast-enhancement in the brainstem area. The B-Raf inhibitor vemurafenib was initiated in combination with intrathecally administered liposomal cytarabine and whole brain radiotherapy. Despite this the patient's condition deteriorated and he died two weeks later. Considering the long progression-free interval and the diffuse intrathecal melanocytic spread, the initial diagnosis of neoplastic meningitis was re-evaluated. Differential diagnoses include neoplastic meningitis from an unknown primary melanoma and malignant transformation of leptomeningeal melanocytosis. Retrospectively, we speculate that the patient had a leptomeningeal melanocytosis and consecutive malignant transformation. Treatment options are palliative and include intrathecal and systemic chemotherapy, radiotherapy, immunotherapy, as well as kinase inhibitors. Since evidence based guidelines are lacking therapy has to be selected on an individual basis.

Primary Leptomeningeal Melanocytosis in a 10-Year-Old Girl

Primary leptomeningeal melanocytosis is rarely encountered in the pediatric population. Despite being considered a nonmalignant condition, it uniformly carries a poor prognosis given the ineluctable progression of meningeal infiltration. The case of a previously healthy 10-year-old girl who was first thought to suffer from recurrent hemiplegic migraine is reported. She later developed insidious subacute hydrocephalus. Meningeal biopsy performed during shunt insertion demonstrated an unexpectedly large number of melanocytes consistent with meningeal melanocytosis. Subsequently, the child developed recurrent shunt dysfunction and showed evidence of malignant transformation. The steps to reaching the proper diagnosis are discussed, and the current literature on this rare clinical entity as well as on related central nervous system melanocytic lesions that can occur in the pediatric population is reviewed.

Meningeal melanocytosis: a possibly useful treatment for a rare primary brain neoplasm

Meningeal melanocytosis (MM) is a rare primary leptomeningeal neoplasm of melanotic cells with a slow growing diffuse pattern [1]. It may occur as neurocutaneous melanosis associated with congenital cutaneous nevi, or as isolated MM. MM has a poor prognosis both due to melanocyte malignization and because of progressive meningeal thickening [2–4]. To date, no treatment has been reported for this neoplasm. A 46-year-old man experienced a secondary generalized partial motor seizure in 1999 (SGPS). Cranial T1-weighted MRI revealed a hyperintense cortical insular right lesion. Vascular study including arteriography was normal and a diagnosis of possible cavernoma with hemorrhagic suffusion was considered. In 2002, the patient was admitted to our hospital with SGPS. MRI revealed bilateral hyperintensity on T1-weighted and FLAIR sequences in frontal and temporal sulcus, suggesting leptomeningeal melanocytic infiltration. The patient remained asymptomatic and without changes on annual brain MRI until December 2006, when he was readmitted with daily headache and SGPS. MRI showed more extensive meningeal alteration in addition to new lesions, some with enhancement and underlying edema. Blood analysis, body scan, dermatologic and neurological examination, and cerebrospinal fluid study were evaluated for every admission from 2002, always with normal results. Pathologic examination by brain biopsy revealed thickened leptomeninges with an increased number of pigmented cells consistent with normally appearing melanocytes in the subarachnoidal space. The pigment stained intensely with the Masson-Fontana method and was negative for Perl’s stain. There was no accompanying hemorrhage or inflammation and no lesions or infiltration of the cerebral cortex were noted (Fig. 1d). Symptoms were controlled with antiepileptic drugs until 2007 when opercular epilepsia partialis continua appeared and MRI demonstrated disease progression. T1-weighted MRI images showed hyperintense areas on the cortical surface of the frontal and temporal lobes (Fig. 1a) that were hyperintense on FLAIR-weighted MRI images, and there was an area of edema in the left frontal lobe (Fig. 1e). The T1-weighted gadolinium-enhanced MRI image revealed contrast enhancement that involved the left frontal lobe Electronic supplementary material The online version of this article (doi:10.1007/s00415-010-5869-9) contains supplementary material, which is available to authorized users.