Primary melanocytic neoplasms of the central nervous system

Primary melanocytic neoplasms of the central nervous system (CNS) are rare lesions arising from melanocytes of the leptomeninges. They include diffuse leptomeningeal melanocytosis or melanomatosis, melanocytoma and primary malignant melanoma. We have reviewed the English literature regarding these lesions, which consists of case reports and a small number of larger case series. The presenting features, radiological, surgical and histological findings are reviewed, as are current management options and prognosis. We also present illustrative case reports of diffuse leptomeningeal melanocytosis and primary melanoma of the CNS.     

GNA11 and N‐RAS mutations: alternatives for MAPK pathway activating GNAQ mutations in primary melanocytic tumours of the central nervous system

M. Gessi, J. Hammes, L. Lauriola, E. Dörner, J. Kirfel, G. Kristiansen, A. zur Muehlen, D. Denkhaus, A. Waha and T. Pietsch (2013) Neuropathology and Applied Neurobiology 39, 417–425 GNA11 and N‐RAS mutations: alternatives for MAPK pathway activating GNAQ mutations in primary melanocytic tumours of the central nervous system Aim: Primary melanocytic tumours are uncommon neoplasms of the central nervous system. Although similarities with uveal melanomas have been hypothesized, data on their molecular features are limited. Methods: In this study, we investigated the mutational status of BRAF^V600E, KIT, GNAQ, GNA11, N‐RAS and H‐RAS in a series of 19 primary melanocytic tumours of the central nervous system (CNS). Results: We identified six cases harbouring mutations in the hotspot codon 209 of the GNAQ gene and two cases with mutations in the hotspot codon 209 of the GNA11 gene. Two mutations in codon 61 of N‐RAS were also found. In the single strand conformation polymorphism (SSCP) analysis, no shifts corresponding to BRAF^V600E mutations or suggesting activating mutations in the KIT gene were observed. Conclusions: In primary melanocytic tumours of the CNS, GNA11 and N‐RAS mutations represent a mechanism of MAPK pathway activation alternative to the common GNAQ mutations. On the other hand, BRAF^V600E mutations and activating KIT mutations seem to be absent or very rare in these tumours.     

Immunolocalization of cathepsin D in the human central nervous system and central nervous system neoplasms

The cellular distribution of the lysosomal proteinase cathepsin D was studied in a series of 76 neoplasms and 18 non-neoplastic tissues from the human central nervous system, using a well-characterized polyclonal antibody in a peroxidase-antiperoxidase technique. In the normal and developing brain, cathepsin D is confined to neurons and choroid plexus epithelium. Strong granular cytoplasmic staining was present in neuronal and choroid plexus neoplasms, and in reactive macrophages. A large variety of other neoplasms also exhibited positive cytoplasmic staining, albeit usually of a weaker diffuse type. Cathepsin D cannot be considered a specific marker for neuronal or choroid plexus neoplasms, but the antiserum used in this study may be of value in antibody panels for the investigation of these tumours. Its localization may also be of value in embryological studies, particularly in the cerebellum, and in investigations of steroid hormone receptor-associated proteins in meningiomas and Schwannomas.     

Regulatory peptides in neuronal neoplasms of the central nervous system

Neuronal tumors of CNS were examined immunohistochemically for regulatory peptides. Thirteen ganglion cell neoplasms, one cerebellar ganglioneuroblastoma, one cerebellar neuroblastoma, and four medulloblastomas were studied. Sixteen non-neuronal intracranial neoplasms were examined as controls. Immunoreactive vasoactive intestinal polypeptide (VIP) was observed in seven cases of ganglion cell neoplasm and in the one cerebellar ganglioneuroblastoma. The cerebellar neuroblastoma, all of the medulloblastomas, and all of the non-neuronal intracranial neoplasms were negative. Four additional ganglion cell neoplasms were tested for the presence of neurotensin and somatostatin. Two contained neurotensin. The results suggest that CNS ganglion cell neoplasms share with their extracranial counterparts the production of certain hormonal polypeptides. Since these peptides are presumed to be specific markers for neurons, the immunohistochemical detection of these substances may provide diagnostically useful technique in the diagnosis of such lesions.     

An immunohistochemical study of glial and neuronal markers in primary neoplasms of the central nervous system

Summary Paraffin-embedded tissues from 56 primary neoplasms of the central nervous system and seven cases of non-neoplastic reactive astrocytosis were examined by immunoperoxidase techniques on serial sections using monoclonal antibodies to glial fibrillary acidic protein (GFAP) and the 68 kDa neurofilament subunit and monospecific polyclonal antibodies to -and -enolase. -Enolase was present in all neoplasms of neuronal origin, but was also present in anaplastic gliomas (particularly in giant cells), in some well-differentiated astrocytomas and reactive astrocytes. The cells containing -enolase in these cases appeared morphologically identical to those containing -enolase and GFAP in adjacent serial sections. No relationship was found between -enolase immunoreactivity and cellular anaplasia in the gliomas studied. Subependymal neoplasms from patients with tuberose sclerosis exhibited evidence of both astrocytic and neuronal differentiation, sometimes in morphologically distinct cell populations, consistent with their suggested origin from a primitive cell line.Supported by Wellcome Trust Grant No. 11353/1.5     

Multiple sclerosis and malignant neoplasms in the central nervous system

Summary There is some evidence that the incidence of malignant neoplasms in the central nervous system of patients with multiple sclerosis (MS) is more infrequent than among the general population. The examination of 3 MS cases with different type of neoplasms in the central nervous system revealed mainly inactive demyelinated plaques. These plaques and the neoplastic lesions were dispersed diffusely and coincidentally all over the brain and spinal cord. The benign course of MS in all three cases is discussed in relation to the malignant diseases.Supported by the Deutsche Forschungsgemeinschaft, Schwerpunktprogramm Ätiologie und Pathogenese der Multiplen Sklerose und verwandter Erkrankungen     

Recurrent inactivation of the PRDM1 gene in primary central nervous system lymphoma

Primary lymphomas of the CNS (PCNSLs) show molecular features of the late germinal center exit B-cell phenotype and are impaired in their terminal differentiation as indicated by a lack of immunoglobulin class switching. Because the positive regulatory domain I protein with ZNF domain (PRDM1/BLIMP1) is a master regulator of terminal B-cell differentiation into plasma cells, we investigated a series of 21 PCNSLs for the presence of mutations in the PRDM1 gene and alterations in the expression pattern of the PRDM1 protein. Direct sequencing of all coding exons of the PRDM1 gene identified deleterious mutations associated with abrogation of PRDM1 protein expression in 4 of 21 (19%) PCNSLs. Thus, similar to systemic diffuse large B-cell lymphomas, PRDM1 may be a tumor suppressor in some PCNSL and contribute to lymphomagenesis by impairing terminal differentiation.     

Immunohistochemical analysis of metastatic neoplasms of the central nervous system

Metastatic neoplasms to the central nervous system are often encountered in the practice of surgical neuropathology. It is not uncommon for patients with systemic malignancies to present to medical attention because of symptoms from a brain metastasis and for the tissue samples procured from these lesions to represent the first tissue available to study a malignancy from an unknown primary. In general surgical pathology, the evaluation of a metastatic neoplasm of unknown primary is a very complicated process, requiring knowledge of numerous different tumor types, reagents, and staining patterns. The past few years, however, have seen a remarkable refinement in the immunohistochemical tools at our disposal that now empower neuropathologists to take an active role in defining the relatively limited subset of neoplasms that commonly metastasize to the central nervous system. This information can direct imaging studies to find the primary tumor in a patient with an unknown primary, clarify the likely primary site of origin in patients who have small tumors in multiple sites without an obvious primary lesion, or establish lesions as late metastases of remote malignancies. Furthermore, specific treatments can begin and additional invasive procedures may be prevented if the neuropathologic evaluation of metastatic neoplasms provides information beyond the traditional diagnosis of "metastatic neoplasm." In this review, differential cytokeratins, adjuvant markers, and organ-specific antibodies are described and the immunohistochemical signatures of metastatic neoplasms that are commonly seen by neuropathologists are discussed.     

椎管内原发性黑色素细胞肿瘤(附5例报告)

目的总结椎管内原发性黑色素细胞肿瘤的临床特点。方法分析5例椎管内黑色素细胞起源肿瘤病人的临床资料，结合文献，对其流行病学、病理类型、影像特征、诊治和预后等进行讨论。结果本组男3例，女2例；年龄31-47，平均38-2岁。椎管内肿瘤单发4例，多发1例；髓外硬膜下4例，髓内1例。短T1、短T2信号为其典型MRI特征。病理诊断为恶性黑色素瘤3例，黑色素细胞瘤2例。不同病理类型的治疗方法和预后迥然不同。结论早期诊断、显微手术全切除是获得良好预后的关键；应根据不同病理类型采取适宜的放、化疗措施。     

Treatment of primary central nervous system lymphoma

Primary central nervous system lymphoma (PCNSL) is a rare form of extranodal non-Hodgkin’s lymphoma that is typically confined to brain, eyes, and cerebrospinal fluid without evidence of systemic spread. The prognosis of patients with PCNSL has improved during the past decade with the introduction of high-dose methotrexate with or without whole brain radiotherapy. However, despite recent progress, results following treatment are durable in few patients, and therapy can be associated with late neurotoxicity. PCNSL is an uncommon tumor, and no phase III trial has been completed so far, leaving many questions about its optimum first-line and salvage treatments unanswered. This review summarizes the literature regarding the treatment of PCNSL in immuno-competent patients.     

Management of primary central nervous system lymphoma

Primary CNS lymphoma is the malignant brain tumor whose prognosis has improved the most the two past decades. The majority of the patients achieve a complete remission with treatment and a substantial minority may hope to be cured. The treatment includes high-dose methotrexate polychemotherapy combined or not with whole brain radiotherapy (WBRT). Elderly patients who are exposed to a high risk of treatment induced neurotoxicity need a specific management avoiding or defering WBRT. In young patients, the main questions concerning the treatment are the role of consolidation WBRT and intensive chemotherapy with peripheral blood stem cell rescue in the initial treatment of PCNSL. As recently shown, national and international collaborative efforts make now possible randomized trials for this rare disease, which would contribute to better define the treatment strategy. New insights in PCNSL tumorigenesis would help to better understand the heterogeneity of outcome and to develop efficient targeted therapies.