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 » Introduction
 » Material and Methods
 » Results
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Table of Contents    
BRIEF REPORT
Year : 2011  |  Volume : 59  |  Issue : 3  |  Page : 413-419

Primary melanocytic tumors of the central nervous system: A neuroradiological and clinicopathological study of five cases and brief review of literature


1 Department of Pathology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Raebareli Road, Lucknow, Uttar Pradesh, India
2 Department of Neurosurgery, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Raebareli Road, Lucknow, Uttar Pradesh, India

Date of Submission26-Dec-2010
Date of Decision14-Jan-2011
Date of Acceptance27-Jan-2011
Date of Web Publication7-Jul-2011

Correspondence Address:
Sushila Jaiswal
Department of Pathology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Rae Bareli Road, Lucknow - 226 014, Uttar Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0028-3886.82758

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 » Abstract 

Primary melanocytic tumors of the central nervous system (CNS) are uncommon lesions. These lesions arise from the melanocytes located within leptomeninges and include diffuse melanocytosis and meningeal melanomatosis (seen in neurocutaneous melanosis), melanocytoma, and malignant melanoma. To study, the clinical course, neuroradiological features, morphology and immunohistochemistry of primary melanocytic tumor of CNS. Demographic, clinical and surgico-pathologic findings of five patients with melanocytic tumors seen between 1996 and 2003 were studied. In this study, five cases of primary melanocytic tumors have been reported: four cases of malignant melanoma and one case of melanocytoma. Three of the 5 cases were intracranial and 2 were spinal. The mean age in the present study was 26 years. Presenting features varied according to the location. Primary melanocytic tumor of CNS are rare. Whenever possible, complete surgical excision is the best treatment.


Keywords: Central nervous system, malignant melanoma, melanocytoma, primary melanocytic neoplasm


How to cite this article:
Jaiswal S, Vij M, Tungria A, Jaiswal AK, Srivastava AK, Behari S. Primary melanocytic tumors of the central nervous system: A neuroradiological and clinicopathological study of five cases and brief review of literature. Neurol India 2011;59:413-9

How to cite this URL:
Jaiswal S, Vij M, Tungria A, Jaiswal AK, Srivastava AK, Behari S. Primary melanocytic tumors of the central nervous system: A neuroradiological and clinicopathological study of five cases and brief review of literature. Neurol India [serial online] 2011 [cited 2019 Jun 18];59:413-9. Available from: http://www.neurologyindia.com/text.asp?2011/59/3/413/82758



 » Introduction Top


Primary melanocytic tumors of central nervous system (CNS) are rare tumors and the spectrum ranges from diffuse leptomeningeal melanocytosis, melanocytoma to its overtly malignant counterpart, melanoma. [1] Diagnostically difficult intermediate lesions lie between these extremes. [2] Melanocytomas are solitary low-grade tumors and do not invade the surrounding structures. They are usually characterized by a benign clinical course, but local recurrences can occur. The diagnosis of primary CNS melanoma is generally made after exclusion of a primary cutaneous or mucosal/retinal melanoma. Primary melanocytic lesions of the CNS occur throughout the neuroaxis, with a predilection for the spinal cord and posterior fossa. Studies on primary CNS melanocytic tumors are few and mostly limited to case reports or small case series. [3],[4],[5],[6],[7],[8],[9] In this study, we describe the clinical course, neuroradiological features, morphology and immunohistochemistry of five patients with primary melanocytic tumor of CNS.


 » Material and Methods Top


Demographic, clinical and surgico-pathologic findings of five patients with melanocytic tumors (one melonocytoma and four malignant melanoma), seen between 1996 and 2003, were retrieved from the medical case records. The pathological data included tumor location, gross appearance, tumor size (cm), growth pattern, cellular atypia, mitosis and necrosis. The formalin-fixed, paraffin embedded tissue blocks and tissue sections were retrieved and reviewed. Additional sections of 3-5 μm were cut and stained with hematoxylin and eosin (H and E), Masson Fontana's for melanin, and potassium permanganate bleach for melanin. Neuropathologic reevaluation of melanocytic tumor involved assessment of histologic features proposed by the current World Health Organization (WHO) classification. The presence or absence of high cellularity, fascicles, solid growth, necrosis, and nuclear pleomorphism and prominent nucleoli was assessed. Mitotic activity was assessed by counting mitoses in 10 randomly selected high-power fields (HPF). Based on light microscopic examination, representative sections were selected for immunohistochemistry for HMB-45, S-100 and glial fibrillary acidic protein (GFAP).


 » Results Top


Clinical and neuroradiological details

Clinical and neuroradiological features are summarized in [Table 1]. Case 1 presented with features of cerebellopontine (CP) angle syndrome of 4 months duration. Neurological examination revealed left-sided fifth, seventh and eight cranial neuropathy and cerebellar signs. Computed tomography (CT) head scan revealed a hyperdense mass in the left CP angle [Figure 1]a. Case 2 presented with headache and sensory seizure of 9 months duration. Neurological examination was normal. Case 3 presented with progressive headache of 6 months duration. Neurological examination was otherwise normal except for bilateral papilledema. CT scan head showed a hyperdense mass in right posterior frontal region with heterogonous contrast enhancement. Magnetic resonance imaging (MRI) revealed the mass to be hyperintense on T1-weighted (T1W), isointense on T2-weighted (T2W) images with diffuse contrast enhancement [Figure 1]b. Case 4 and 5 presented with neck pain and quadriparesis. MRI spine showed lesion in the cervical spine which was hyperintense on T1W and hypointense on T2W images with intense enhancement on contrast administration [Figure 2]a and b. General examination did not reveal any mucocutaneous or ocular pigmented lesions in any of the five cases.
Table 1: Clinical and neuroradiological features of melanocytoma and primary CNS melanoma

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Figure 1: (a) Plain CT head axial sections, showing hyperdense mass (arrow) in the left CP angle, (b) Contrast MRI brain coronal section, showing enhancing mass (arrow) in the posterior frontal areas, (c) Intra operative image showing blackish color of tumor

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Figure 2: (a) MRI scans of spinal melanoma: Sagittal section T1 image showing intradural hyperintense lesion at C2 level, (b) T2 image showing hypointense lesion

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Operative findings

All the patients underwent surgical excision of the lesion. Excision of CP angle melanocytoma was done via retromastoid suboccipital approach. Intraoperatively, the tumor was dark black, vascular and adherent to the fifth, seventh and eighth cranial nerve complex. For frontal and parietal melanoma, craniotomy and total tumor excision was done. Firm nodular, highly vascular, black lesion attached to dura was identified in both the patients [Figure 1]c. In cervical melanomas, cervical laminenctomy and total excision of the lesions were performed. The tumors were black in color and attached to dura.

Gross and histopathologic findings

On macroscopy, melanocytoma and melanoma were solitary mass lesions and appeared reddish brown to black. Complete to partial capsulation was identified. On sections stained with H and E, melanocytoma displayed sheets of well-differentiated epithelioid melanocytes having round to oval nuclei with finely dispersed chromatin, occasional single eosinophilic nucleoli and moderate amount of cytoplasm with abundant granular melanin pigment [Figure 3]a. Absence of mitosis and macronucleoli was noticed [Figure 3]b. Tumor cells contained finely to coarsely abundant brownish-black pigment in the cytoplasm which bleached with potassium permanganate and stained black with Masson Fontana staining [Figure 3]c and d. Melanin pigment was identified in stroma of the tumor. Melanophages were also identified in between the tumor cells. On immunohistochemisty, the tumor cells showed diffuse strong HMB45 and S-100 immunopositivity. Light microscopy of leptomeningeal melanoma showed a solid growth pattern in all the cases. In contrast to melanocytoma, these neoplasms were more densely cellular. The tumor cells were arranged in sheets of epithelioid cells, ill-defined fascicles of anaplastic spindle-shaped cells along with loose nests and displayed a moderate grade of cellular and nuclear pleomorphism, prominent nucleoli and mitoses (≥4/10 HPF) with variable finely granular melanin pigment in the cytoplasm [Figure 4]a-d. The nuclear features were better appreciated after melanin bleach. Few multinucleated cells and occasional large cells with bizarre nuclei were also identified. Singly scattered and groups of tumoral macrophages containing coarsely granular melanin pigment were noted in between the tumor cells. The pigment positively stained with Masson Fontana. The tumor cells were positive for HMB-45 and for S-100.
Figure 3: Photomicrograph of melanocytoma. (a) Tumor cells arranged in sheets and containing melanin in cell cytoplasm (H and E, ×100); (b) higher magnification of tumor cells showing no mitosis and macronucleoli (H and E, ×200); (c) Masson Fontana staining for melanin pigment; (d) tumor cells after melanin bleach

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Figure 4: Photomicrograph of malignant melanoma. (a) Tumor cells arranged in solid sheets (H and E, ×100); (b) tumor cells displaying ill-defined fascicles of spindle-shaped cells and containing melanin in cell cytoplasm (H and E, ×200); (c) epithelioid morphology of tumor cells (H and E, ×200); (d) pleomorphic tumor cells with prominent central nucleoli and mitotic activity admixed with melanophages (H and E, ×400)

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Follow-up

Patient with melanocytoma had uneventful postoperative phase and was discharged with advice to undergo radiotherapy. Initially, he was lost for follow-up; later, in 2008, he became symptomatic. MRI head showed local recurrence and he had excision of the lesion. In patients with melanoma, subsequent evaluation by oncologists failed to find any other melanotic lesions or primary melanoma. Case 2 received radiotherapy following surgery and required ventriculo-periotoneal shunt after 3 months for hydrocephalus and died during the follow-up. Case 3 received radiotherapy following surgery and was lost to follow-up. Case 4 and 5 improved symptomatically after surgery and were well at 4 months of follow-up.


 » Discussion Top


As for the WHO 2007 blue book, CNS melanotic tumors include diffuse melanocytosis and melanomatosis, melanocytoma and malignant melanoma. [1] Melanocytic lesions of the nervous system and the coverings are thought to arise from leptomeningeal melanocytes, derived from the neural crest during early embryonic development. In the CNS, melanocytes are preferentially localized at base of brain, around ventral medulla and along upper cervical spinal cord. [1] All the five patients fulfilled the Hayward criteria [3] for the diagnosis of primary CNS melanoma: absence of melanoma outside the CNS, absence of melanoma in other sites in the CNS, and histologic confirmation of melanoma.

Diffuse melanocytosis and melanomatosis involve the supra- and infra-tentorial leptomeninges and the superficial brain parenchyma and generally occur in the setting of dermatologic syndromes (e.g., neurocutaneous melanosis syndrome and nevus of Ota). [1],[10] Primary leptomeningeal melanomatosis is a rare, aggressive tumor and arises from melanocytes within the leptomeninges and carries a poor prognosis. This tumor is also referred to as a meningeal variant of primary malignant melanoma. The malignant melanocytes spread in the leptomeninges, into the Virchow-Robin spaces, and superficially within the brain substance. [10]

Meningeal melanocytoma is a rare tumor and was first described by Limas and Tio in 1972 [4] and accounts for 0.06-0.1% of the brain tumors. [5] These tumors are solitary, benign, low-grade tumors and occur in all the age groups (9-73 years) and are most frequent in the fifth decade, with slight female predominance. They mostly occur in the extramedullary intradural compartment of cervical and thoracic spine and less frequently occur intracranially in the posterior fossa, Meckel's cave and CP angle [5] and also in the supratentorial compartment. [1]

Primary CNS melanoma is a rare and aggressive tumor and accounts for approximately 1% of all cases of melanoma. The peak incidence of cutaneous melanoma is in the seventh decade; for primary leptomeningeal melanoma, it is in the fourth decade. [2] The mean age at diagnosis was 29 years (range 9-62 years). The mean age in the present study was 26 years. In this study, there was only one patient who presented under the age of 18 years, illustrating the rarity of this lesion in children. Both males and females are affected equally in the reported literature. All the patients were males in the present study. Primary CNS melanomas are dural based and have been reported in spine, suprasellar, pineal, CP angle and cerebrum regions.[1],[2],[7],[8],[9],[10]

Radiological studies may not be specific, especially in the absence of primary disease. The rarity of a primary melanotic lesion in the CNS as well as radiological similarities with other pigmented tumors like pigmented schwannomas or pigmented medulloblastomas most often preclude the preoperative radiological diagnosis of this lesion. Definitive diagnosis is based solely on histopathologic and immunohistochemical examination. On CT, these lesions appear isodense or hyperdense and demonstrate homogenous enhancement with contrast. Similar findings are seen in meningiomas. According to most descriptions, the MR imaging pattern of melanotic lesions includes hyperintensity on T1W images and iso- or hypointensity on T2W images. [1],[2],[10],[11],[12] T2W hyperintensity surrounding the melanoma is due to vasogenic edema. Uematsu et al. [11] reported that this unique MRI pattern is due to the presence of stable free radicals within the melanin. However, patterns of melanoma on MRI depend not only on the content of free paramagnetic radicals from melanin, but also on the paramagnetic products from acute or chronic intratumoral hemorrhages and fat deposits. Our patients had classical MRI findings.

Pathological examination and immunohistochemistry of the primary CNS melanocytic lesions are critical to diagnose and distinguish it from other different CNS tumors undergoing melanization, such as meningioma, schwannoma, medulloblastoma, paraganglioma, and gliomas. [1],[2],[10],[13],[14] There is little evidence to support the existence of true melanotic meningioma. Melanotic meningioma or pigmented meningioma terminology has been abandoned as these tumors, when reviewed by Limas and Tio, were found to be ultrastructurally immature premelanosomes and mature melanosomes and lacked the characteristics of meningiothelial cells, viz. desmosomes, interdigitating cytoplasmic processes and intracytoplasmic fibrils. [4] Melanotic neuroectodermal tumor of infancy has also been reported at intracranial locations. [1]

From a combined pathological and clinical point of view, the principle differential is between melanocytoma and melanoma. [1],[2],[10] Meningeal melanocytomas are histologically characterized as cellular lesions, and the cytoplasm contains variable amounts of melanin pigment in intracellular granules. Amelanotic examples have been reported. Melanocytoma typically should not have nuclear pleomorphism, atypia or macronucleoli, contain no more than the (very) occasional mitotic figure, or exhibit necrosis. It may be necessary to bleach the melanin to study the nuclear morphology, mitosis and before performing immmunohistochemistry. An indolent growth pattern spanning more than 4 years, also indicate a melanocytoma rather than a melanoma. Melanomas are more pleomorphic, have more anaplastic nuclei and have higher cell density than melnocytoma and often demonstrate tissue invasion and necrosis. However, a small subset of meningeal melanocytic tumors may be difficult to classify as either a melanocytoma or a malignant melanoma because they demonstrate intermediate histologic features. In such cases, a designation such as "melanocytic neoplasm of indeterminate biologic potential" is sometimes applied. It is obviously important to determine if the melanoma is primary or secondary. Absolute determination is only approached by a thorough examination at autopsy, including sectioning of the eyes. Even then, the possibility of previous regression of a primary site cannot be eliminated entirely.

Meningeal melanocytomas may cause neurological deficits through their expanding growth. Hence, an early complete surgical removal of the lesion may result in prolonged remission or even cure before neurological complications become fatal. Few cases show CNS invasion and local recurrence if incompletely removed. [10] Reports have been published that describe the transition of a melanocytoma to a primary malignant melanoma. [15],[16] Our case had local recurrence following a survival of 12 years. Malignant melanomas are considered to be highly aggressive and radioresistant tumors with poor prognosis. [1] Beresford reported only 1 of 37 patients with intracranial melanoma responding to radiation therapy. [17] However, an increase in the response rate has been reported by using fractionated irradiation in high dose. [18] It has been suggested that primary leptomeningeal melanoma exhibits slow progression and the tumor is less aggressive than the more common melanoma of the skin with metastases to the CNS. [1],[2] Metastatic melanomas grow rapidly and usually lead to fatal outcome in less than 6 months. Although primary CNS melanomas are potentially malignant and prone to local recurrence or systemic spread, Larson et al. [19] concluded that the average survival after surgery and radiotherapy was 6 years and 7 months.

Generally, diffuse melanosis carries poor prognosis even in the absence of anaplastic histology. [1],[10] It has also been reported that the focal tumors with the most favorable prognosis are most often localized to the spinal canal and the posterior fossa. Complete surgical excision of the tumor is usually possible with localized leptomeningeal melanomas, which may account for the longer survival periods with this form of the disease. [1] Most authors agree that whenever possible, complete surgical excision is the best treatment. The role and efficacy of radiotherapy and chemotherapy remain controversial. Clinical trials with intrathecally administered, radiolabeled immunoconjugates hold particular promise in this regard. [20]

 
 » References Top

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2.Brat DJ, Giannini C, Scheithauer BW, Burger PC. Primary melanocytic neoplasms of the central nervous systems. Am J Surg Pathol 1999;23:745-54.   Back to cited text no. 2
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3.Hayward RD. Malignant melanoma and the central nervous system. A guide for classification based on the clinical findings. J Neurol Neurosurg Psychiatry 1976;39:526-30.   Back to cited text no. 3
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4.Limas C, Tio FO. Meningeal melanocytoma ("melanotic meningioma"). Its melanocytic origin as revealed by electron microscopy. Cancer 1972;30:1286-94.  Back to cited text no. 4
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5.Gupta A, Ahmad FU, Sharma MC, Garg A, Mehta VS. Cerebellopontine angle meningeal melanocytoma: a rare tumor in an uncommon location. J Neurosurg 2007;106:1094-7.  Back to cited text no. 5
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6.Francois P, Lioret E, Jan M. Primary spinal melanoma: case report. Br J Neurosurg 1998;12:179-82.   Back to cited text no. 6
    
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9.Martin-Blondel G, Rousseau A, Boch AL, Cacoub P, Sène D. Primary pineal melanoma with leptomeningeal spreading: case report and review of the literature. Clin Neuropathol 2009;28:387-94.  Back to cited text no. 9
    
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11.Uematsu Y, Yukawa S, Yokote H, Itakura T, Hayashi S, Komai N. Meningeal melanocytoma: magnetic resonance imaging characteristics and pathologic features Case report. J Neurosurg 1992;76:705-9.  Back to cited text no. 11
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13.Dulai MS, Moes GS, Briley AL, Galperin IB, Smyth L, Cherry AM, et al., Gliosarcoma with melanocytic differentiation. Acta Neuropathol 2008;115:357-61.   Back to cited text no. 13
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14.Jaiswal S, Agrawal V, Vij M, Sahu RN, Jaiswal AK, Behari S. Glioblastoma with melanotic differentiation. Clin Neuropathol 2010;29:330-3.   Back to cited text no. 14
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15.Roser F, Nakamura M, Brandis A, Hans V, Vorkapic P, Samii M. Transition from meningeal melanocytoma to primary cerebral melanoma. Case report. J Neurosurg 2004;101:528-31.  Back to cited text no. 15
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16.Uozumi Y, Kawano T, Kawaguchi T, Kaneko Y, Ooasa T, Ogasawara S, et al., Malignant transformation of meningeal melanocytoma: a case report. Brain Tumor Pathol 2003;20:21-5.  Back to cited text no. 16
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    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]
 
 
    Tables

  [Table 1]

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