Acta Neurochir (Wien) (2003) 145: 1121–1126 DOI 10.1007/s00701-003-0121-3
Case Report Aggressive management of orbital meningeal melanocytoma O. I. de Tella Jr2, C. Agner1, P. H. Aguiar3, M. A. Herculano4 , M. N. Prandini2 , and J. N. Stavile5 1
Department Department 3 Department 4 Department 5 Department 2
of of of of of
Neurology, Albany Medical Center, Albany, NY Neurosurgery, Federal University of Sao Paulo, Sao Paulo, Brazil Neurosurgery, State University of Sao Paulo, Sao Paulo, Brazil Neurosurgery, Jundiai Medical School, Jundiai, Brazil Pathology, Federal University of Sao Paulo, Sao Paulo, Brazil
Published online October 13, 2003 # Springer-Verlag 2003
Summary Objective. Meningeal melanocytoma generally occurs in the posterior fossa. Orbital manifestation is rarely encountered. Methods. A thirty-five year-old man presented with progressive proptosis of his right eye. Computed tomography (CT) and Magnetic Resonance Imaging (MRI) of the brain showed an expansive intraconal mass lesion occupying the superior orbital compartment, the entire orbital apex, and the optic foramen. Histological analysis and Immunohistochical staining for S-100 and HMB-45 monoclonal antibodies confirmed melanocytoma. Findings. Microsurgical removal was accomplished through a frontoorbital craniotomy. Chemotherapy and irradiation followed the initial intervention. The patient returned for follow up two years after surgery, complaining of headache and right visual loss. A subfrontal tumor with massive edema was found on follow up CT scan. Interpretation. Meningeal melanocytomas are rare benign pigmented tumors of the central nervous system. They are predominant in the posterior fossa and spinal cord and frequently mistaken for melanomas, especially on frozen sections. Orbital presentation is rare. The natural history is poorly defined. Keywords: Orbital tumor; meningeal neoplasm; melanocytoma.
Introduction According to the 1999 World Health Organization Classification of Tumors of the Nervous System, melanocytic lesions are diffuse or circumscribed, benign or malignant tumors arising from melanocytes of the leptomeninges. They are comprised of (1) diffuse melanocytosis and neuocutaneous melanosis, (2) melanocytoma, and (3) malignant melanoma. Melanocytomas correspond to solid masses in the cranial or spinal
segments and are somewhat difficult to be differentiated from other topographically similar intracranial lesions . Benign meningeal melanocytic lesions are called melanotic, pigmented meningioma, or meningeal melanocytoma . Meningeal melanocytoma may also describe a primary ultra structural leptomeningeal melanotic neoplasm with prolonged clinical course and benign histology . Meningeal melanocytoma generally manifests around the foramen magnum. We report an example of rare orbital presentation. Case report A thirty-five year-old right-handed man presented with proptosis of the right eye for six months. Visual acuity and external ocular motility were preserved. Contrast-enhanced computed tomography disclosed a contrast-enhancing intraconal mass around the optic nerve involving the superior aspect of the orbita and the optic foramen (Fig. 1). A T1weighted magnetic resonance imaging (MRI) of the brain and orbita showed an iso-intense intraconal lesion, invading the cranial cavity through the optic foramen (Fig. 2). There was no change in intensity on T2 and minimal enhancement after gadolinium. A fronto-orbital craniotomy was performed and the suprasellar and parasellar spaces inspected, revealing a darkened dura on the roof of the cavernous sinus. The optic foramen was identified and the periorbita, opened. Lateral retraction of the levator palpebra superioris and the superior rectus muscles exposed an encapsulated dark tumor. Removal by fragments or suction was accomplished without difficulty. There were no postoperative complications. Subtotal resection was seen on a followup MRI of the brain (Fig. 3). Radiotherapy cycles (5500 cGy) and chemotherapy (BCNU, DTIC and Cisplatin) followed subtotal resection. Two years later the patient
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Fig. 1. MRI in coronal and axial views, depicting in T1-weighted images without Gadolinium, an iso-intense mass before operation
Fig. 2. MRI sagittal and axial (T1 with GDTA) shows a subfrontal mass with a large amount of edema, suggestive of radio necrosis
returned for follow-up with loss of vision in the right eye and intense headache. CT scan revealed a sub frontal mass surrounded by massive edema (Fig. 4). MRI spectroscopy confirmed the intra-operative finding of radio necrosis on re-operation. Remission of symptoms occurred after high dose of oral steroids. He is now five-year post-surgery and doing well on anticonvulsants.
Pathology Multiple fragments of tumor tissue were processed for light microscopy and stained with hematoxylin and
eosin, Masson-Fontana method for melanin, Perl’s Prussian blue reaction for hemosiderin, and reticulin. Avidin biotinylated complex (ABC) immunohistochemistry was performed on paraffin sections using polyclonal antiserum to S-100 protein and monoclonal antibodies to epithelial membrane antigen (EMA) and vimentin. Positive sections were visualized with 3,3,diaminobenzidine tetrahydrochloride substrate (DAB).
Orbital meningeal melanocytoma
Fig. 3. Follow-up midline T1-weighted gadolinium enhanced post-operative sagittal and coronal MRI images of lesion, showing enhancement and surrounding edema
Fig. 4. Shows a highly cellular lesion without sharp outlines. The cells are oval or spindle shaped with large plump cytoplasm with dark brown granules of melanin pigment and the nuclei were vesicular with prominent nucleoli and no mitoses were seen. H.E. 400
Results A brownish soft tumor adherent to the meninges was seen on the initial gross specimen. Highly cellular lesions without sharp outlines were seen on light microscopy. Dark-brown melanin granules were seen within oval or spindle-shaped cells. After pigment removal, nuclei were vesicular with prominent nucleoli. Mitoses were not observed (Fig. 4). Immunohistochemistry was positive for diffuse staining with S-100 and HMB-45 monoclonal antibodies. Epithelial membrane antigen, cytokeratins, and vimentin were not observed.
Ray and Foot coined the term ‘‘pigmented’’ or ‘‘melanocytic’’ meningiomas in 1940  to histologically benign meningeal tumors with heavy melanin pigmentation. Attention was called to their resemblance to meningiomas and to the importance of differentiating these tumors from melanomas. The diagnosis of primary meningeal melanocytoma has been confronted by the occasional presence of melanin in meningiomas, as described on the electron microscopic study of a pigmented neoplasm of the foramen magnum by Limas and Tio, in 1972 . These tumors have been initially described as primary intracranial or intraspinal melanomas . The favorable long-term outcome suggested a different diagnosis and classification, proposed years later and supported by the World Health Organization Classification of Brain Tumors of 2000 [21, 28, 34]. Melanocytes are embryologically derived from the neural crest and occur in normal leptomeninges. Meningeal melanocytomas may arise from these cells , usually occurring in the craniocervical region and spinal cord due to increased amount of pigmented cells in the leptomeninges at these levels. Spinal meningeal melanocytomas were previously reported [2, 11, 13, 15, 16, 20, 25, 37, 39, 42, 47, 48]. Matsumoto et al. , published a case of thoracic meningeal melanocytoma associated with superficial siderosis of the central nervous system. Kawaguchi et al.  described a completely resected left frontal melanocytoma in a 45 year-old man
with recurrence after two years. The occurrence of meningeal melanocytoma in the foramen magnum [28, 46], cerebellopontine angle [23, 31, 34], and left sphenoid wing [9, 48] were previously reported. Faro et al. described, in 1996, the occurrence of meningeal melanocytoma in the cavernous sinus. The authors provide with an extensive review of the literature and a critical analysis of the imaging data available at that time . Meckel’s cave is the most common location for this type of tumor [6, 17, 44, 49]. Meckel’s cave is the most common location for this type of tumor [6, 8, 26, 49]. There are multiple descriptions, in the literature, of meningeal melanocytoms of the iris, the optic nerve, and the immediate retro-orbital region [3, 5–7, 14, 22, 29, 41, 45]. To our knowledge, there are no reports of orbital melanocytic neoplasms extending to the suprasellar spaces. Its occurrence indicates its close relationship to the meninges and the orbital bony landmarks. Meningeal melanocytoma and meningiomas containing melanin can be well differentiated histologically . Pigmented schwannomas and melanocytic neoplasms are more difficult to distinguish . Immunohistochemical study with antimelanoma antibody and epithelial membrane antigen helps to confirm the diagnosis . Meningeal melanocytoma is a benign pigmented neoplasm, usually well encapsulated with a tendency to compress neighboring structures. It can be easily mistaken for melanoma. Biological behavior and treatment is different in many situations, surgical management may be curative, and the differential diagnosis is important in order to avoid mistakenly giving the wrong diagnosis to the patient or family and, therefore, seal a grim fate when that is not so. Malignant behavior has been described [6, 40, 42, 43]. Prabhu et al. report a 71% recurrence rate at 5 years  and is dependent on the proliferation ratio, the presence of aneuploidy, and the ability to invade neighboring tissues. Immunostaining with Ki-67 and MIB is helpful in determining the potential for spread and also the fate after surgical excision, radiation, chemotherapy, or a combination of all the above forms of management. Radiotherapy may be recommended postoperatively, in recurrences, or when total removal cannot be achieved [4, 11, 18, 34, 36]. In most circumstances, it is an adjuvant treatment to resection, even if the latter is incomplete. Focused radiation is preferred on many occasions for orbital lesions, due to the proximity to the optic nerve and other vital structures. Radionecrosis is, how-
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ever, unavoidable in many conditions, in particular after long-term follow-up of patients. Kurita et al.  described a successful outcome in a patient with a Meckel’s cave melanocytoma subjected to Gamma knife radiation. There were no long-term complications reported. The rate of complications depends on the dose of radiation, the location of the tumor, the shape, and the pre-operative planning of the isocenter dose. Malignant degeneration may sometimes occur in patients. Patel et al.  report a case of oculodermal melanocytosis (nevus of Ota) in a 29-year-old patient, calling attention to the high frequency of malignant degeneration. High proliferation indexes and lack of genetic control predisposes melanocytomas to malignant degeneration. Thorough immunochemical analysis of surgical and=or pathological specimens of meningeal melanocytomas looking especially for proliferation index markers should be done in all cases. The natural history of meningeal melanocytomas is not well understood and the management is controversial . Orbital lesions such as the one described in this paper are rare and deserve consideration in the differential diagnosis of orbital neoplasms. In 2001, Rades et al. reviewed the rate of recurrence of meningeal melanocytoma and found it to be relatively high to justify radiation therapy when incomplete resection was suggested . Combination of surgery, radiation therapy, and chemotherapy seems to be the optimal management for lesions extending beyond and above the orbit and with possibly incomplete resection. Histological characteristics of tumors extending above the orbital limits may indicate a more malignant course. The role of neurosurgery is not yet well established for those lesions, as incidence is low and the topography is close to vital visual pathways. Observation is also precluded in some conditions, when treatment may be more harmful than a full-course management. In this paper, it was hard to predict whether resection was complete or not and full resection of the mass was pursued. Better intra-operative imaging and histological characterization of meningeal melanocytoma will determine the guidelines for management of these tumors and whether resection should always be followed by radiation, chemotherapy, or both.
Acknowledgment We are grateful to Karina Gazzonato Pereira for her expert assistance in the manuscript editorial review.
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