Meningeal Melanoma Research Articles

Teaching NeuroImage: Meningeal Melanoma Associated With Blue Nevi and Nevi of Ota.

Teaching NeuroImage: Meningeal Melanoma Associated With Blue Nevi and Nevi of Ota.

PATH-43. MALIGNANT TRANSFORMATION OF MENINGEAL MELANOCYTOMA - GENETIC ALTERATIONS AND RESPONSE TO CHECKPOINT BLOCKADE IMMUNOTHERAPY

Abstract INTRODUCTION Meningeal melanocytomas are uncommon tumors that develop from leptomeningeal melanocytes. These tumors can exhibit aggressive behavior, leading to symptoms due to compression and potential invasion of nearby central nervous tissue. Case: In this report, we discuss the case of a 45-year-old man who was diagnosed 18 years ago with a meningeal melanocytoma in the right temporal region. He underwent complete resection with each recurrence and received focal intensity-modulated radiation therapy after a third recurrence in 2013. In May 2022, he developed progressive headaches and diplopia secondary to tumor recurrence on the right temporal region. Resection revealed that the tumor had progressed to malignant meningeal melanoma with 34 mitoses per 10 high-power fields. Next-generation sequencing (NGS) showed GNAQ mutation confirming tumor of central nervous system (CNS) origin, and also showed an SF3B1 mutation, indicating aggressive behavior. Several chromosomal abnormalities were also detected. Systemic workup revealed liver, lung, and bone metastasis. Liver biopsy confirmed meningeal melanoma of central origin. The patient received radiosurgery with a total of 30Gy over five fractions to intracranial surgical cavity, followed by three cycles of nivolumab and relatlimab. Unfortunately, the patient experienced severe intracranial and systemic progression, leading to his death six months after the malignant transformation. DISCUSSION Meningeal melanocytomas are rare however these tumors have a high recurrence rate with potential malignant transformation over time. NGS is a valuable tool for confirming the CNS origin of the tumor and predicting its aggressive behavior. Despite microscopic similarity with cutaneous melanomas, meningeal melanocytomas have different pathogenesis and do not seem to respond to immunotherapy, as observed in this case.

Clinical characteristics, prognosis, and immunotherapy outcome in pediatric melanoma: Analysis from a large Chinese cohort.

10050 Background: Malignant melanoma in children and adolescents is rare, with limited data on Chinese populations.To assess the clinical characteristics, survival, prognostic factors, and the efficacy of immunotherapy in a real-world cohort of Chinese pediatric patients with melanoma. Methods: This is a retrospective, cohort study included pediatric melanoma patients between February, 2005 and May, 2021, with a median follow-up time of 76.7 months. Data analyses were conducted in May, 2023. This study enrolled patients from Sun Yat-sen University Cancer Center, the biggest cancer institution in South China for cancer prevention, diagnosis and treatment. Inclusion criteria for this study were as follows: 1) histopathologically confirmed diagnosis of melanoma; 2) Age ≤18 year; 3) with complete clinical data on sex, age, histopathological features, etc. The exclusion criteria was secondary malignant melanoma. Main outcomes and measures were patient’s OS and EFS. Results: 43 patients were enrolled, with median age of 138.9 (range 13.1-215.0) months, including 30 cutaneous melanoma, 7 meningeal melanoma, 5 mucosal melanoma, and 1 uveal melanoma. The frequency of BRAF V600E mutation was 16.7% (4/24). Mismatch repair proteins were normally expressed (7/7), and the positive rate of programmed cell death ligand 1 expression was 55.6% (5/9). The event-free survival and overall survival of cutaneous, mucosal and meningeal melanoma were 46.7±9.1% vs 75.0±21.7% vs 16.7±15.2% ( P = 0.010), 65.5±8.9% vs 75.0±21.7% vs 16.7±15.2% (P< 0.001), respectively. Survival of cutaneous melanoma were associated with pathological type, ulceration, Clark level, disease spread, sentinel lymph node status, tumor stage and Ki-67 expression. 5 of 9 patients who were treated with PD-1 inhibitors (5 with PD-1 inhibitors alone, 3 with PD-1 inhibitors plus angiogenesis inhibitors, 1 with combination of anti-PD1, anti-angiogenic inhibitors plus chemotherapy) were evaluable with the overall response rate of 20%. The most common immune-related adverse event was hypothyroidism. Conclusions: This is the largest real-world study in pediatric melanoma patients in Asia. The prognosis of mucosal melanoma was favorable, followed by cutaneous melanoma, and meningeal melanoma had the worst prognosis. PD-1 antibody combined with angiogenesis inhibitors maybe a promising choice in pediatric melanoma.

Construction of hematoxylin-eosin, immunohistochemistry, and EBER-ISH methodology after trichloroisocyanuric acid treatment in melanin-containing tissues.

This study investigated the effects of trichloroisocyanuric acid (TCCA) on the bleaching and morphology of melanin-containing pathological sections. The pathological sections of 27 patients with high melanin content were bleached with 0.5% potassium permanganate, 10% hydrogen peroxide, and different concentrations of TCCA. Significant differences were found among the blank control group, 1% TCCA group (P < 0.0001). The hematoxylin–eosin (HE) score of the "recovery pH" HE staining group after treatment with 1% TCCA was similar to that of the "Conventional HE" scheme group (P > 0.05). The morphological diagnostic scores of 50 cases of pathological sections with different melanin content before and after TCCA bleaching were compared. The results showed a significant difference in the diagnostic score between the middle- and high-melanin content groups before and after 1% TCCA bleaching (P < 0.05). Immunohistochemical staining was performed on meningeal melanoma tissue. For this, 8% TCCA solution was used to remove melanin after Ki67, S100, and β-catenin immunohistochemical staining. After bleaching with TCCA, the staining and positioning of each marker with different localization were accurate and the background was clear. The same results were also shown with EBER-ISH. This study concluded that 1% TCCA could be used for HE staining of pathological sections containing melanin, and "restore pH" HE scheme as the staining method after TCCA melanin removal. Further, 8% TCCA was used for bleaching after immunohistochemical DAB staining. Melanin can be completely removed, and sections can meet diagnostic needs.

P.141 Primary intracranial melanoma complicated by cerebral venous sinus thrombosis: a case report and literature review

Background: Melanocytic tumors of the central nervous system (CNS) such as meningeal melanoma are exceedingly rare tumours derived from leptomeningeal melanocytes. Primary meningeal melanomas account for 0.1% of intracranial neoplasms with an incidence of approximately 0.5 per 10 million. Methods: We report the case of a previously healthy 47 year old male who presented with bilateral tonic-clonic seizure. Magnetic resonance imaging (MRI) demonstrated a homogenously-enhancing right temporal extra-axial lesion. The patient was stabilized on anti-epileptic medications and dexamethasone prior to proceeding with complete surgical resection of the lesion. Review of the current literature was conducted. Results: Macroscopically, the extra-axial lesion was heavily pigmented with invasion of the surrounding dura and skull. Histopathology revealed a poorly differentiated neoplasm with nuclear atypia and melanin-containing cells with strong SOX10 positivity and variable S100 positivity. Systemic workup was negative including absent ocular or cutaneous melanomas. Oncopanel was negative including absent BRAF mutation. He began checkpoint inhibitor therapy and subsequently developed cerebral venous sinus thrombosis (CVST) managed with anticoagulation. At 6 month follow-up, he was neurologically intact, working full-time, and had resumed immunotherapy. Conclusions: Primary intracranial melanoma is a rare tumour that can appear radiographically similar to meningioma. Surgical resection remains the mainstay of therapy for best long-term prognosis.

Neurocutaneous melanosis with an intracranial cystic-solid meningeal melanoma in an adult: A case report and review of literature

BACKGROUNDNeurocutaneous melanosis (NCM) is a rare congenital, nonhereditary neurocutaneous syndrome that mainly occurs in children; adult NCM is very rare. Due to its rarity, the clinical features and treatment strategies for NCM remain unclear. The purpose of this study was to explore the clinical features, diagnosis, treatment and prognosis of NCM in adults. Most intracranial meningeal melanomas are solid masses, and cystic-solid malignant melanomas are very rare. Due to the lack of data, the cause of cystic changes and the effect on prognosis are unknown.CASE SUMMARYA 41-year-old woman was admitted to the hospital with intermittent headache for 1 mo. Magnetic resonance imaging (MRI) showed a 4.7 cm × 3.6 cm cystic-solid mass in the left temporal lobe with peritumoral edema. The entire mass was removed, and postoperative pathology indicated malignant melanoma.CONCLUSIONMRI is the first-choice imaging approach for diagnosing central nervous system diseases in NCM patients, although cerebrospinal fluid may also be used. At present, there is no optimal treatment plan; gross total resection combined with BRAF inhibitors and MEK inhibitors might be the most beneficial treatment.

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.

Magnetic Resonance Imaging (MRI) Differential Diagnosis of Meningiomas Using ANOVA.

This work explored the diagnostic value of different subtypes of meningiomas under T2WI low signal based on analysis of variance (ANOVA), and the expression differences of Ki67, VEGF, and P73 in different subtypes were analyzed. 67 patients with meningioma confirmed surgically and pathologically in hospital were selected as the research subjects, whose pathological classification occurs with obvious low signal on T2WI. First, the age distribution of the subjects and the distribution of different subtypes were counted. Then, ANOVA was adopted to analyze the MRI imaging signs of patients with different subtypes of meningioma. Finally, the differences of Ki67, VEGF, and P73 proteins and mRNA expression levels in different subtypes were detected via immunohistochemical assay and qPCR. The results showed that the proportion of patients with transitional meningioma was the most, which was 43.28%, while the proportion of patients with meningeal melanoma was the least, which was 7.46%. In patients with transitional meningioma, the MRI images showed mixed signals in different layers. Fibrous MRI images showed hyalinosis and calcification of collagen fibers in the tumor, with low T2WI signal. Sand-shape MRI images showed double low signals. MRI images of meningeal melanoma showed high signal on T1-weighted Imaging (T1WI) and low signal on T2WI. The protein expression and mRNA levels of Ki67 and P73 in transitional meningioma were evidently higher in contrast to those in fibrous meningioma (P < 0.05). The expression level of VEGF protein and mRNA in meningeal melanoma were notably higher in contrast to those in fibro meningioma (P < 0.05). It was revealed that the MRI images of the four subtypes of meningiomas under ANOVA-based T2WI low signal were quite different, and the expressions of Ki67, P73, and VEGF in different subtypes had significant differences. This work provided a reference basis for the preoperative diagnosis, treatment, and prognosis of meningiomas.

A case of intracranial primary meningeal melanoma misdiagnosed as cortical venous infarction with hemorrhage.

Intracranial primary melanoma is a rare and highly differentiated borderline or malignant tumor. The prognosis of tumors varies significantly depending on their location and resection range. Therefore, accurate diagnosis before surgery together with complete resection of the tumor as much as possible and adjuvant chemoradiotherapy is the key to improve the prognosis of patients. Imaging is important for preoperative diagnosis. The tumor in the patients was dominated by pial meningeal lesions. It was obviously uneven after MRI enhancement, and there was no obvious low T2WI signal. It is not easy to distinguish it from cortical venous infarction with hemorrhage. Moreover, the tumor often shows different imaging manifestations due to the different melanin contents, and it is easy to be misdiagnosed before operation. The final diagnosis depends on pathological and immunohistochemical examination.

Congenital intradural melanoma surrounding the spinal cord of a nine-day-old Saanen goat

A nine-day-old Saanen kid presented for progressive hind limb paresis since birth. Euthanasia was elected, and on postmortem examination a large, pigmented mass was present in the vertebral canal surrounding...

Bevacizumab treatment of meningeal melanoma metastases

BackgroundMelanoma patients with metastatic growth in the meninges have poor prognosis and few treatment options. Although treatment with BRAF inhibitors or immune checkpoint inhibitors has provided promising results, most patients with advanced melanoma are resistant to these treatments and develop severe side effects. Novel treatment strategies are needed for patients with meningeal melanoma metastases, and the potential of antiangiogenic therapy was investigated in this preclinical study.MethodsTwo GFP-transfected melanoma models (A-07 and D-12) differing substantially in VEGF-A expression were included in the study, and the anti-VEGF-A antibody bevacizumab was used as therapeutic agent. Meningeal metastases were initiated in BALB/c nu/nu mice by intracranial inoculation of melanoma cells, and bevacizumab treatment was given twice a week in i.p. doses of 10 mg/kg until the mice became moribund. Therapeutic effects were evaluated by determining tumor host survival time, assessing tumor growth and angiogenic activity by quantitative analyses of histological preparations, and measuring the expression of angiogenesis-related genes by quantitative PCR.ResultsMeningeal A-07 melanomas showed higher expression of VEGF-A than meningeal D-12 melanomas, whereas the expression of ANGPT2 and IL8, two important angiogenesis drivers in melanoma, was much higher in D-12 than in A-07 tumors. Bevacizumab treatment inhibited tumor angiogenesis and prolonged host survival in mice with A-07 tumors but not in mice with D-12 tumors. Meningeal A-07 tumors in bevacizumab-treated mice compensated for the reduced VEGF-A activity by up-regulating a large number of angiogenesis-related genes, including ANGPT2 and its receptors TIE1 and TIE2. Melanoma cells migrated from meningeal tumors into the cerebrum, where they initiated metastatic growth by vessel co-option. In the A-07 model, the density of cerebral micrometastases was higher in bevacizumab-treated than in untreated mice, either because bevacizumab treatment increased mouse survival or induced increased tumor gene expression.ConclusionsThe development of antiangiogenic strategies for the treatment of meningeal melanoma metastases is a challenging task because the outcome of treatment will depend on the angiogenic signature of the tumor tissue, treatment-induced alterations of the angiogenic signature, and the treatment sensitivity of metastatic lesions in other intracranial sites.

Profiling Gαq Cancer Mutations Using a Novel BRET‐based Biosensor

Heterotrimeric G proteins are critical signal transducers and dysregulation of their activity causes many diseases, including cancer. For instance, activating mutations in the Gα subunit Gαq are frequently found in uveal and meningeal melanomas. A current challenge in the field of cancer in general and oncogenic G protein signaling in particular is that the rate of discovery of cancer‐associated mutations clearly outpaces our ability to analyze their functional consequences. This limits our ability to discern driver mutations from passenger mutations, and to elucidate possible mechanisms by which they favor cancer progression. Here, we set out to develop and implement a novel approach to rapidly profile cancer‐associated mutations that impact Gq‐dependent signaling. We envisioned the design of a Gq activity biosensor to detect GTP‐bound Gαq in live cells based on the principle of Bioluminescence Resonance Energy Transfer (BRET). First, we validated that our sensor specifically detects Gαq activity, and that it can faithfully report its modulation by G protein‐coupled receptors (GPCRs) and by Regulators of G protein signaling (RGS) in real time with sub‐second resolution. After benchmarking our sensor against well‐characterized Gαq oncogenic mutants, we implemented it in a battery of cancer‐associated Gαq mutants that had not been characterized before. Our findings reveal that a hotspot mutation present in &gt;10% of hepatocellular carcinomas does not give rise to a hyperactive Gαq, whereas other infrequent mutations enhance Gαq activity. More specifically, the latter mutations are insensitive to deactivation by GTPase activating proteins (GAPs) of the RGS family, which sensitizes Gαq activation and delays inactivation upon GPCR‐mediated modulation. In conclusion, we have developed a G protein activity biosensor that directly monitors the formation of Gαq‐GTP, and showed that it is useful to rapidly profile disease‐associated G protein mutants and reveal novel mechanisms of aberrant activation.Support or Funding InformationFunding: R01GM130120, R21MH118745This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Abstract 1617: Utility of a solid-tumor NGS panel in the differential diagnosis of composite neoplasms with divergent phenotypes

Abstract Introduction: Composite neoplasms (CN) are rare, diagnostically challenging lesions that require differentiating between three possibilities: clonal tumors with divergent phenotypes (mixed tumors, MT), collision of two synchronous adjacent tumors (CT) and tumor-to-tumor metastasis (TTM). To make this distinction, pathologists have relied on morphology, immunohistochemistry and limited molecular techniques such as single-gene sequencing. In this study, we performed next-generation sequencing (NGS) on 4 CN to illustrate the diagnostic utility of NGS-based approach in these rare tumors. Materials and Methods: Of the 4 CN included in the study, 2 had been diagnosed as MT containing phenotypically different cell populations (mixed adenoneuroendocrine carcinoma of the gallbladder and metastatic papillary thyroid carcinoma with squamous dedifferentiation), while the remaining 2 had been interpreted as TTM (esophageal adenocarcinoma to lung adenocarcinoma and small cell carcinoma of the lung to meningeal melanoma). Pathology diagnoses were made using clinical, histologic and immunophenotypic information. Manual dissection of the tumor components was performed on formalin-fixed, paraffin-embedded tissue sections for extraction of DNA and RNA. NGS was performed using the Oncomine Comprehensive Panel on Ion S5XL sequencer. Ion Reporter variant caller pipeline was used for data analysis. Results: Sequencing results confirmed the histopathologic diagnosis in all cases (Table 1). Importantly, comparison of our results with data from TCGA studies allowed a meaningful interpretation of the genetic aberrations found, and shed light on the biology of these lesions. Table 1 – Integration of immunophenotypic and massively parallel sequencing data from 4 composite neoplasmsNDiagnosisComponentsIHCGeneType of aberrationVariant effect (AA change)InterpretationCN1Mixed adenoneuroendocrine carcinomaAdenocarcinomaCK20 -/p53 -/p63 -/CK7 +/ CDX2 +ERBB2CNV–Amplification8.57CCNE1CNV–Amplification16.7Large cell neuroendocrine carcinomaCK20 -/p53 -/p63 -/CK7 +/ CDX2 +/Chromo +/Synapto +CCND1CNV–Amplification4.63ATMCNV–Deletion0.39TP53CNV–Deletion0.56CCNE1CNV–Amplification402Metastatic papillary thyroid carcinoma with squamous dedifferentiationPapillary thyroid carcinomaCK 5/6 -/p40 -/PAX8 +/TTF1 +/TG +BRAFMutation (c.1799T&amp;gt;A)Missense (p.Val600Glu)Deleterious (GOF)–Squamous cell carcinomaCK5/6 +/p40 +/PAX8 +/TTF1 -/TG -BRAFMutation (c.1799T&amp;gt;A)Missense (p.Val600Glu)Deleterious (GOF)–PIK3CAMutation (c.1633G&amp;gt;A)Missense (p.Glu545Lys)Deleterious (GOF)–3Esophageal adenocarcinoma metastatic to lung adenocarcinomaLow grade adenocarcinoma (lung)TTF1 +/HER2 -CDKN2ACNV–Deletion0.76CDKN2AMutation (c.170C&amp;gt;T)Missense (p.Ala57Val)Deleterious (LOF)–KRASMutation (c.35G&amp;gt;T)Missense (p.Gly12Val)Deleterious (GOF)–STK11Mutation (c.580G&amp;gt;T)Missense (p.Asp194Tyr)Deleterious (LOF)–High grade adenocarcinoma (lung)TTF1 -/HER2 +CDKN2AMutation (c.170C&amp;gt;T)Missense (p.Ala57Val)Deleterious (LOF)–KRASMutation (c.35G&amp;gt;T)Missense (p.Gly12Val)Deleterious (GOF)–STK11Mutation (c.580G&amp;gt;T)Missense (p.Asp194Tyr)Deleterious (LOF)–High grade adenocarcinoma (esophagus)–CDKN2AMutation (c.170C&amp;gt;T)Missense (p.Ala57Val)Deleterious (LOF)–KRASCNV–Amplification22.01TP53Mutation (c.614A&amp;gt;G)Missense (p.Tyr205Cys)Deleterious (LOF)–4Small cell carcinoma of the lung combined metastatic to meningeal melanomaSmall cell carcinomaTTF1 +/Synapto +/Chromo +/AE1+3 +/CAM 5.2 +/MelanA -/HMB 45 -RB1Mutation (c.1183C&amp;gt;T)NonsenseDeleterious (LOF)GAS6CNV–Amplification6.14TP53Mutation (c.473G&amp;gt;T)Missense (p.Arg158Leu)Deleterious (LOF)MelanomaTTF1 -/Synapto -/Chromo -/AE1+3 -/CAM 5.2 -/Melan-A +/Pan-M +/MITF +NRASMutation (c.35G&amp;gt;A)Missense (p.Gly12Asp)Deleterious (GOF)TERTCNV–Amplification21.34 Conclusion: This study illustrates the diagnostic utility of NGS in tumors with more than a single histologic component. Additionally, it demonstrates a potential role for NGS in the detection of clinically actionable targets in a group of neoplasms that lack standardized treatment. Citation Format: Andres M. Acosta, Mohamed Rizwan H. Al Rasheed, Dipti Panchal, Magdalena Rogozinska, Frederick G. Behm, Gayatry Mohapatra. Utility of a solid-tumor NGS panel in the differential diagnosis of composite neoplasms with divergent phenotypes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1617.

The role of next-generation sequencing in the differential diagnosis of composite neoplasms

Composite neoplasms (CNs) are rare and diagnostically challenging lesions that require differentiating between mixed clonal tumors with divergent phenotypes (MT), collision of 2 independent tumors adjacent to each other (CT), and tumor-to-tumor metastasis (TTM). To that end, pathologists have traditionally used immunohistochemistry and limited molecular studies, such as Sanger sequencing. Herein we evaluate the potential application of NGS in the differential diagnosis of these rare neoplasms. Four CNs were included in the study. Two were diagnosed as MT (mixed adenoneuroendocrine carcinoma of the gallbladder and metastatic papillary thyroid carcinoma with squamous dedifferentiation) and 2 were interpreted as TTM (esophageal adenocarcinoma to lung adenocarcinoma and small cell carcinoma of the lung to meningeal melanoma). Diagnoses were made using clinical, histologic, and immunophenotypic information, with the aid of limited molecular studies in 2 cases. Formalin-fixed, paraffin-embedded tissue was dissected for DNA and RNA extraction, and NGS was performed using the Oncomine Comprehensive Panel. The 2 tumors initially interpreted as MT showed shared genetic aberrations in the different neoplastic components, supporting the pathologic diagnosis. NGS results for the lesion diagnosed as esophageal adenocarcinoma metastatic to lung adenocarcinoma did not support the histopathologic interpretation and were deemed inconclusive. However, the identification of an identical CDKN2A mutation in all components and in the adjacent benign lung parenchyma suggests a possible germline aberration. Sequencing results in the last case were clearly supportive of TTM. This study illustrates the role of NGS in the diagnostic workup of CNs, as an adjunct to light microscopy and immunohistochemistry.

Meningeal Melanocytes in the Mouse: Distribution and Dependence on Mitf.

Summary: Melanocytes are pigment producing cells derived from the neural crest. They are primarily found in the skin and hair follicles, but can also be found in other tissues including the eye, ear and heart. Here, we describe the distribution of pigmented cells in C57BL/6J mouse meninges, the membranes that envelope the brain. These cells contain melanosomes of all four stages of development and they depend on Microphthalmia associated transcription factor (MITF), the master regulator of melanocyte development, suggesting that they are bona-fide melanocytes. The location of these pigmented cells is consistent with the location of meningeal melanomas in humans and animal models.Significance: Here, we document and define pigmented cells in the meninges of the mouse brain and confirm that they are melanocytes. This is important for understanding the role of this cell type and for understanding primary meningeal melanoma, a rare disease that likely arises from normal meningeal melanocytes.

Microsurgical treatment of meningeal malignant melanoma accompanied by nevus of Ota

Microsurgical treatment of meningeal malignant melanoma accompanied by nevus of Ota

Liposomal cytarabine in neoplastic meningitis from primary brain tumors: a single institutional experience

Neoplastic meningitis (NM) is diagnosed in 1-2 % of patients with primary brain tumors. Standard treatment of NM includes single-agent or combination chemotherapy, with compounds such as methotrexate, thiotepa, and cytarabine (Ara-C) or its injectable, sustained-release formulation Depocyte(®). In this Report, we reported the data of efficacy and tolerability of an intrathecal Depocyte(®) regimen for patients presenting with NM from primary brain tumors. We described 12 patients with NM confirmed at magnetic resonance imaging (MRI) and with a positive cerebrospinal fluid (CSF) cytology. Patients were treated with repeated courses of intrathecal Depocyte(®) (once every 2 weeks for 1 month of induction therapy and as consolidation therapy on a monthly base in responding patients). Twelve patients (10 males and 2 females) were treated by our Institution. The diagnosis of primitive brain tumor was medulloblastoma in six patients, germinoma in two patients, pylocitic astrocytomas with spongioblastic aspects, teratocarcinoma, meningeal melanoma, and ependimoma in the other four patients. The total number of Depocyte(®) cycles ranged from one to nine. In 7/12 patients, there was clinical and/or radiological response after Depocyte(®), and the toxicity was moderate and transient, mainly due to the lumbar puncture procedure. In the two patients with germinoma, we observed a normalization of MRI Imaging and negativization of CSF with disappearance of the tumor cells. OS was 180 days (range 20-300, CI 95 %).

Primäre amelanotische meningeale Melanomatose

Primary melanocytic lesions of the central nervous system are rare. The spread of melanoma cells primarily into the meningeal layers is referred to as meningeal melanomatosis. A few case reports about either intracranial or intraspinal primary meningeal melanoma were published in the past. The amelanotic variation of primary melanoma in the central nervous system is a very rare event and so far no cases of primary amelanotic meningeal melanomatosis have been described in the current literature. We present a case with combined multiple intracranial and intraspinal primary malignant amelanotic melanomas.

Clinical characteristics and risk of melanoma development from giant congenital melanocytic naevi in Korea: a nationwide retrospective study

Giant congenital melanocytic naevi (GCMN) are known risk factors for the development of melanoma. However, melanoma risk among Asians is rarely evaluated. To evaluate the clinical characteristics and risk of melanoma development from GCMN in Koreans, we performed a nationwide retrospective cohort study in Korea. GCMN were defined as those comprising ≥5% body surface area in children or measuring ≥20cm in adults. In total, 131 patients with GCMN were enrolled, with a mean age of 10·3years (range: birth-70years). The posterior trunk was the most common site (67, 51·1%), followed by lateral trunk, anterior trunk, legs, both anterior and posterior trunk, buttocks, and arms. Satellite naevi were present in 69 cases (52·7%), and axial areas were more commonly involved in patients with satellite naevi than in those without satellite lesions. Atypical features such as rete ridge elongation and bridges were seen, and, among these, pagetoid spread and ballooning cell changes were more common in patients <4years old. Proliferative nodules were found in three cases. Melanomas had developed in three of 131 patients (2·3%; a 6-year-old girl, a 14-year-old girl and a 70-year-old man), and the incidence rate was 990 per 100000 person-years. Melanomas in these three patients consisted of two cutaneous melanomas and one extracutaneous meningeal melanoma. We should be aware of melanoma development from GCMN, and lifelong follow-up is required due to the risk of melanoma arising in GCMN.