Primary melanocytic lesions of the CNS: report of five cases

Primary melanocytic tumours of the central nervous system (CNS) form a rare entity which is histologically and clinically distinct from metastatic cutaneous or retinal malignant melanoma. They can be classified into diffuse melanocytosis (diffuse melanosis), malignant melanoma and benign melanocytoma with a small number of intermediate variants. In this paper, 5 cases treated neurosurgically in our department for spinal or cerebral primary CNS malignant melanoma are reported. Primary tumors and further metastases were ruled out. Radiological, histological and clinical features are discussed. Compared to metastatic disease, primary CNS malignant melanoma shows a more benign clinical course with long-term tumour control and a good quality of life. A review of the literature which mainly consists of individual case reports, confirms this assessment. Although therapeutic experience for primary melanocytic lesions of the CNS is based on a small number of published cases, prognosis seems highly dependent on complete tumour resection. Adjuvant radiation seems to be of additional therapeutic benefit. Except for meningeosis melanomatosa chemotherapy must be regarded as experimental. Unfortunately, a standardised therapy concept is still lacking.     

The diagnostic dilemma of primary central nervous system melanoma

Melanomas are malignant neoplasms of melanocytes developing predominantly in the skin, but occasionally arising from eyes, mucous membranes, and the central nervous system (CNS). The CNS can be affected by a spectrum of melanocytic lesions ranging from diffuse neurocutaneous melanosis, to a focal and benign neoplasm (melanocytoma), and to an overtly malignant tumor (melanoma). Primary melanocytic lesions involving the CNS are typically concentrated in the perimedullary and high cervical region. Primary CNS melanoma cannot be reliably distinguished from metastatic melanoma on neuroimaging and histopathological characteristics alone: its diagnosis is established only after exclusion of secondary metastatic disease from a cutaneous, mucosal or retinal primary. We present two patients with primary CNS melanoma and discuss relevant issues, available treatment options, and expected outcomes. Awareness of disease spectrum and clinico-biological differences may be used to guide therapeutic decision-making for a patient with a proven or suspected primary CNS melanoma.     

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.     

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。     

Primary cerebellopontine angle melanoma: a case report and review

Primary melanomas at the cerebellopontine (CP) angle are extremely rare and considered a diagnostic dilemma. With only 16 prior cases reported so far, there is not enough material in world literature. We report a 29-year-old male who presented with vertigo, headache and features of lower cranial nerve involvement with MRI revealing a melanotic lesion at CP angle. The patient underwent right suboccipital craniectomy and only subtotal excision of the tumor was possible. Histopathologically it turned out to be malignant melanoma. Since a thorough search for any possible primary was futile, it was considered a primary melanoma. Patient was given adjuvant radiotherapy. Ten months later, he presented with weakness and multiple spinal metastases and two months later he succumbed to his disease. We did a comprehensive review of literature about various melanocytic tumors at the CP angle. Pathologically, melanocytic tumors range from benign melanocytomas to malignant melanoma with variable prognosis. The clinical presentation depends upon whether the lesions are diffuse or discrete. Surgery is the primary modality of treatment and the amount of tumor excised is related to the prognosis. We conclude the discussion with a novel classification for melanotic tumors of CNS and the current diagnostic pathway for a melanotic lesion at the CP angle.     

中枢神经系统原发性黑色素瘤10例临床分析

目的 探讨中枢神经系统原发性黑色素瘤的诊治与随访结果.方法 回顾性分析自2002年1月至2013年1月收治的10例中枢神经系统原发性黑色素瘤患者的临床表现、影像学特点、病理结果、手术治疗与预后情况.结果 10例黑色素瘤患者中发生于颅内者8例,椎管内者1例,颅颈交界区1例.手术全切除8例,大部切除2例.病理检查黑色素瘤8例,脑脊膜黑色素细胞瘤2例.随访3月至11年,6例死亡,其中1例术后综合治疗后存活了7年,后因并发症死亡,术后中位生存期1.1年.4例术后放疗,恢复正常生活.结论 中枢神经系统原发性黑色素瘤发病率低,但术前诊断困难,误诊率较高.手术切除为首选,术后结合放、化疗,可延长生存时间,但总的预后差.     

Activating mutations of the GNAQ gene: a frequent event in primary melanocytic neoplasms of the central nervous system

Primary melanocytic neoplasms of the central nervous system (CNS) are uncommon neoplasms derived from melanocytes that normally can be found in the leptomeninges. They cover a spectrum of malignancy grades ranging from low-grade melanocytomas to lesions of intermediate malignancy and overtly malignant melanomas. Characteristic genetic alterations in this group of neoplasms have not yet been identified. Using direct sequencing, we investigated 19 primary melanocytic lesions of the CNS (12 melanocytomas, 3 intermediate-grade melanocytomas, and 4 melanomas) for hotspot oncogenic mutations commonly found in melanocytic tumors of the skin (BRAF, NRAS, and HRAS genes) and uvea (GNAQ gene). Somatic mutations in the GNAQ gene at codon 209, resulting in constitutive activation of GNAQ, were detected in 7/19 (37%) tumors, including 6/12 melanocytomas, 0/3 intermediate-grade melanocytomas, and 1/4 melanomas. These GNAQ-mutated tumors were predominantly located around the spinal cord (6/7). One melanoma carried a BRAF point mutation that is frequently found in cutaneous melanomas (c.1799 T>A, p.V600E), raising the question whether this is a metastatic rather than a primary tumor. No HRAS or NRAS mutations were detected. We conclude that somatic mutations in the GNAQ gene at codon 209 are a frequent event in primary melanocytic neoplasms of the CNS. This finding provides new insight in the pathogenesis of these lesions and suggests that GNAQ-dependent mitogen-activated kinase signaling is a promising therapeutic target in these tumors. The prognostic and predictive value of GNAQ mutations in primary melanocytic lesions of the CNS needs to be determined in future studies.     

Intraventricular melanocytoma diagnosis confirmed by gene mutation profile

Primary leptomeningeal melanocytic tumors (PLMTs) are rare. They usually arise along the spinal cord and at the skull base. Here we report on a patient with a very rare intraventricular melanocytoma. Histologically, a melanocytic tumor was clearly diagnosed. However, to make the uncommon diagnosis of an intraventricular melanocytoma, metastatic melanoma needed to be excluded. Next generation sequencing covering gene mutations that may occur in PLMTs and cutaneous melanoma was performed. The unique gene mutation profile detected, consisting of an activating CYSLTR2 L129Q mutation and EIF1AX G9R mutation and a lack of mutations in genes known to occur in metastatic melanoma (i.e. BRAF or NRAS) confirmed the diagnosis of an intraventricular melanocytoma. This case report is the second intraventricular melanocytoma published to date and demonstrates the value of applying novel genetic assays to make this diagnosis.     

Imaging appearances of meningeal melanocytoma

Meningeal melanocytoma is an uncommon, benign melanocytic tumour of the meninges. Only 15 cases have been reported to date. We present the MR and CT appearance of a case of compressive myelopathy due to cervical meningeal melanocytoma. Careful analysis of the imaging features, as illustrated in the present case, allows a preoperative diagnosis. The differential diagnosis includes malignant melanoma and melanocytic meningioma.     

Malignant transformation of intracranial meningeal melanocytoma. Case report and review of the literature

Meningeal melanocytoma is an uncommon pigmented neoplasm that affects the CNS and develops in the cranial and spinal leptomeninges. Here we report on a case of malignant transformation of intracranial supratentorial meningeal melanocytoma which recurred after 3 years as malignant melanoma. This case demonstrates that the biological behavior of melanocytoma is uncertain and that these lesions may recur as malignant melanoma.     

Primary meningeal intermediate grade melanocytic neoplasm: case report with radiologic-pathologic correlation

A case of primary meningeal intermediate grade melanocytic neoplasm involving the right C2 nerve root is presented. MRI findings may suggest this rare entity, especially when an extra-axial lesion is located in the posterior fossa or cervical spinal canal and demonstrates shortening of both T1 and T2. Eventually, definitive diagnosis relies on histology which demonstrates spindle-shaped melanocytic cells that are Fontana stained and positive for HMB:45 antigen. Cellularity, pleomorphism, mitotic rate, proliferation index and invasiveness are useful criteria to distinguish among the spectrum of primary melanocytic tumors of the central nervous system ranging from melanocytoma to malignant melanoma.     

Primary atypical melanocytoma arising from the cavernous sinus in a child

Introduction

Primary melanocytic lesions of the central nervous system originate from leptomeningeal melanocytes, with a spectrum ranging from well-differentiated benign meningeal melanocytomas to malignant melanomas. Atypical melanocytomas are borderline tumors, which have clinical and pathological characteristics between benign melanocytomas and malignant melanomas. Melanocytomas are rare in children and infrequently arise from the cavernous sinus. Approximately five patients with such an origin site have been reported.

Materials and methods

We report a 15-year-old girl with an atypical melanocytoma arising from the cavernous sinus. She underwent partial resection of the tumor and postoperative gamma knife surgery (GKS). She is stable 39 months after surgery.

Conclusion

We discuss the first pediatric case with an intracranial atypical melanocytoma arising from the cavernous sinus.

     

Primary amelanotic meningeal melanomatosis

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.     

Primary spinal melanoma with bilateral papilledema

A case of primary leptomeningeal malignant melanoma localized in the cervical region in a 41-year-old woman is presented. The only clinical finding was intracranial hypertension with papilledema. A diagnosis of primary CNS melanoma was made after dermatological and ophthalmological consultations, ruled out a metastatic lesion. Primary leptomeningeal melanoma is an extremely rare spinal tumor. Its clinical presentation with signs of increased intracranial pressure but without cord symptoms is unusual. Clinical features of this case including the radiological and histologic findings are described. Diagnosis as well as management is discussed.     

颅内转移性恶性黑色素瘤:一例报告并文献复习

目的探讨颅内转移性恶性黑色素瘤临床组织病理学及免疫组织化学特征。方法应用组织病理学及免疫组织化学检测方法对1例颅内多发转移性恶性黑色素瘤患者的两次手术标本进行观察,通过复习文献分析其组织病理学和免疫组织化学特征,提出诊断与鉴别诊断要点。结果男性患者,48岁。因颅内多发占位性病变、肿瘤卒中而行右侧额颞叶肿瘤切除术。两次手术标本组织病理学表现不一:首次右侧额叶病灶表现为异型性上皮样肿瘤细胞围绕毛细血管和纤维组织呈乳头状排列;再次手术标本为右侧颞叶,病灶表现为梭形细胞呈片巢状或束状排列,胞质丰富、淡染或透亮,胞核异型性明显、核仁呈明显嗜酸性。左侧腹股沟淋巴结活检提示肿瘤转移,且肿瘤组织局部可见大量黑色素颗粒。免疫组织化学染色肿瘤细胞弥漫表达S-100蛋白、人黑色素细胞瘤抗原45、Melan-A和波形蛋白,部分表达上皮膜抗原,而细胞角蛋白、高分子角蛋白、低分子角蛋白、胶质纤维酸性蛋白、突触素、神经微丝蛋白等表达阴性。结论颅内转移性恶性黑色素瘤的组织学表现复杂多样,临床病史和影像学资料对诊断具有重要参考价值,但明确诊断仍需依靠免疫组织化学检测结果。需注意与转移癌、脑膜肿瘤、淋巴瘤及其他含黑色素的颅内肿瘤相鉴别。     

颅内转移性恶性黑色素瘤：一例报告并文献复习

目的探讨颅内转移性恶性黑色素瘤临床组织病理学及免疫组织化学特征。方法应用组织病理学及免疫组织化学检测方法对1例颅内多发转移性恶性黑色素瘤患者的两次手术标本进行观察,通过复习文献分析其组织病理学和免疫组织化学特征,提出诊断与鉴别诊断要点。结果男性患者,48岁。因颅内多发占位性病变、肿瘤卒中而行右侧额颞叶肿瘤切除术。两次手术标本组织病理学表现不一：首次右侧额叶病灶表现为异型性上皮样肿瘤细胞围绕毛细血管和纤维组织呈乳头状排列;再次手术标本为右侧颞叶,病灶表现为梭形细胞呈片巢状或束状排列,胞质丰富、淡染或透亮,胞核异型性明显、核仁呈明显嗜酸性。左侧腹股沟淋巴结活检提示肿瘤转移,且肿瘤组织局部可见大量黑色素颗粒。免疫组织化学染色肿瘤细胞弥漫表达S一100蛋白、人黑色素细胞瘤抗原45、Melan—A和波形蛋白,部分表达上皮膜抗原,而细胞角蛋白、高分子角蛋白、低分子角蛋白、胶质纤维酸性蛋白、突触素、神经微丝蛋白等表达阴性。结论颅内转移性恶性黑色素瘤的组织学表现复杂多样,临床病史和影像学资料对诊断具有重要参考价值,但明确诊断仍需依靠免疫组织化学检测结果。需注意与转移癌、脑膜肿瘤、淋巴瘤及其他含黑色素的颅内肿瘤相鉴别。     

Improved discrimination of melanotic schwannoma from melanocytic lesions by combined morphological and GNAQ mutational analysis

The histological differential diagnosis between melanotic schwannoma, primary leptomeningeal melanocytic lesions and cellular blue nevus can be challenging. Correct diagnosis of melanotic schwannoma is important to select patients who need clinical evaluation for possible association with Carney complex. Recently, we described the presence of activating codon 209 mutations in the GNAQ gene in primary leptomeningeal melanocytic lesions. Identical codon 209 mutations have been described in blue nevi. The aims of the present study were to (1) perform a histological review of a series of lesions (initially) diagnosed as melanotic schwannoma and analyze them for GNAQ mutations, and (2) test the diagnostic value of GNAQ mutational analysis in the differential diagnosis with leptomeningeal melanocytic lesions. We retrieved 25 cases that were initially diagnosed as melanotic schwannoma. All cases were reviewed using established criteria and analyzed for GNAQ codon 209 mutations. After review, nine cases were classified as melanotic schwannoma. GNAQ mutations were absent in these nine cases. The remaining cases were reclassified as conventional schwannoma (n = 9), melanocytoma (n = 4), blue nevus (n = 1) and lesions that could not be classified with certainty as melanotic schwannoma or melanocytoma (n = 2). GNAQ codon 209 mutations were present in 3/4 melanocytomas and the blue nevus. Including results from our previous study in leptomeningeal melanocytic lesions, GNAQ mutations were highly specific (100%) for leptomeningeal melanocytic lesions compared to melanotic schwannoma (sensitivity 43%). We conclude that a detailed analysis of morphology combined with GNAQ mutational analysis can aid in the differential diagnosis of melanotic schwannoma with leptomeningeal melanocytic lesions.     

中枢神经系统恶性黑色素瘤的诊断与治疗

目的 探讨中枢神经系统恶性黑色素瘤的临床表现、影像学特点及诊治要点.方法 分析17例中枢神经系统恶性黑色素瘤的临床表现、影像学特点、诊治方法和疗效.结果 17例中13例位于幕上,幕下小脑半球3例,颈髓1例.其临床表现及体征无特异性,GT和MRI无法明确诊断.手术全切除12例,近全切除5例.病理检查均证实为恶性黑色素瘤.随访14例,均死于术后肿瘤复发,最短于术后1个月死亡,最长于术后14个月死亡,术后中位生存期6.5个月.结论 中枢神经系统恶性黑色素瘤发病率低,误诊率高,预后差,以手术切除为主,可辅以化疗、放疗等综合性治疗.     

中枢神经系统原发性黑色素肿瘤的临床特征及病理特征分析

目的探讨中枢神经系统原发性黑色素肿瘤的临床表现、病理特征及手术效果。方法回顾性分析2003年3月至2017年2月手术治疗的3例中枢神经系统原发性黑色素性肿瘤的临床资料,1例位于颞叶,1例位于小脑,1例位于右侧桥小脑角区。结果 2例全切,1例次全切。术后随访1~3个月,3例一般情况良好。结论中枢神经系统原发性黑色素肿瘤确诊依赖病理检查,临床分型对判断预后有重要意义。