Accepted Manuscript Primary Meningeal Melanocytoma in the Left Temporal Lobe Associated with Nevus Ota: a Case Report and Review of the Literature Mohammad Samadian, Ali Mousavi Nejad, Mehrdad Hosseinzadeh Bakhtevari, Shahram Sabeti, Guive Sharifi, Reza Jabbari, Omidvar Rezaei PII:
S1878-8750(15)00358-7
DOI:
10.1016/j.wneu.2015.03.061
Reference:
WNEU 2820
To appear in:
World Neurosurgery
Received Date: 20 January 2015 Revised Date:
29 March 2015
Accepted Date: 31 March 2015
Please cite this article as: Samadian M, Nejad AM, Bakhtevari MH, Sabeti S, Sharifi G, Jabbari R, Rezaei O, Primary Meningeal Melanocytoma in the Left Temporal Lobe Associated with Nevus Ota: a Case Report and Review of the Literature, World Neurosurgery (2015), doi: 10.1016/ j.wneu.2015.03.061. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
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Primary Meningeal Melanocytoma in the Left Temporal Lobe Associated with Nevus Ota: a Case Report and Review of the Literature
Sabeti4, Guive Sharifi5, Reza Jabbari6, Omidvar Rezaei7
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Mohammad Samadian1, Ali Mousavi Nejad2, Mehrdad Hosseinzadeh Bakhtevari3*, Shahram
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Associate Professor of Neurosurgery, Department of Neurosurgery, Loghman e Hakim hospital, Shahid Beheshti University of Medical Sciences -Tehran-Iran. E-mail: [email protected]
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E-mail: [email protected] *3
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Resident of Neurosurgery, Department of Neurosurgery, Loghman e Hakim Hospital, Shahid Beheshti University of Medical Sciences - Tehran-Iran
Resident of Neurosurgery, Department of Neurosurgery, Loghman e Hakim Hospital, Shahid Beheshti University of Medical Sciences - Tehran-Iran
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E-mail: [email protected] 4
Assistant Professor of Pathology, Department of Neuropathology, Loghman e Hakim hospital, Shahid Beheshti University of Medical Sciences -Tehran-Iran. E-mail: [email protected] 5
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Associate Professor of Neurosurgery, Department of Neurosurgery, Loghman e Hakim hospital, Shahid Beheshti University of Medical Sciences -Tehran-Iran.
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E-mail: [email protected]
Assistant Professor of Neurosurgery, Department of Neurosurgery, Loghman e Hakim hospital, Shahid Beheshti University of Medical Sciences -Tehran-Iran. E-mail: [email protected]
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Professor of Neurosurgery, Department of Neurosurgery, Loghman e Hakim hospital, Shahid Beheshti University of Medical Sciences -Tehran-Iran. E-mail: [email protected]
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* Correspondence should be sent to:
Mehrdad Hosseinzadeh Bakhtevari
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Department of Neurosurgery, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran-Iran. Tel: +9821-55414065 Fax: +9821-55414065
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Mobile: +98912-1874506
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Email: [email protected]
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Abstract Background: Primary melanocytic neoplasms of the central nervous system (CNS) are rare lesions arising
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from melanocytes of the leptomeninge that are found at highest density underneath the brain stem and along the upper cervical spinal cord. Thus, most reported cases of meningeal melanocytomas are located in the posterior fossa and the spinal cord, and presentation of the tumor in supratentorial is very rare. Methods: A 19-year-old man presented with headache and seizure at our department. Neurological exams
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were otherwise normal. On physical examination He had asymptomatic, bluish, speckled and welldemarcated hyperpigmented macules on the left midface extraorally. A left temporal space-occupying
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lesion was seen on magnetic resonance imaging. The mass was hyper-intense on T1-weighted images and isointense on T2-weighted images. Enhancement was shown on contrast-enhanced MRI. Preoperative diagnosis was meningioma.
Result: Gross complete resection was performed. Pathological studies led to the diagnosis of
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meningeal melanocytoma WHO grade I. Oncologic consultation done for patient. Because total resection of the tumor was achieved and its histopathologic grade was benign (WHO grade I) radiotherapy did not advise for patient and he fallowed up each 6 months. No tumor was seen on follow-up MRI one year after
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surgery.
Conclusion: Presentation of meningeal melanocytoma in supratentorial compartment is very rare and its
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combination with nevus Ota has been reported in very few cases. Although this lesion is benign, it might behave aggressively. Complete surgical resection of the lesion is the preferred therapeutic option.
Keywords: Meningeal melanocytoma, Neoplasm, Nevus Ota, Supratentorial
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Introduction
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Primary meningeal melanocytoma (MM) is a benign central nervous system (CNS) neoplasm rarely seen by neurosurgeons in clinical practice. It accounts for 0.06-0.1% of brain tumors with an estimated incidence of 1 in every 10 million individuals. This rare lesion mostly affects adult patients between the
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ages of 45 and 50 years, with slight predominance (1.5: 1) among females [15].
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First reported by Limas and colleagues in 1972 [23], the tumor is derived from melanocytic cells of leptomeninge and thus mainly found in the locations with high density of melanocytes that include underneath the brainstem and along the cervical spinal cord [25]. Melanocytomas have been shown to occur anywhere along the neuraxis, but are most commonly found in the region of the foramen magnum, the posterior fossa, meckel’s cave, or adjacent to cranial nerve nuclei. Within the spine, melanocytomas present as intradural masses, and may be intradural extramedullary or rarely intramedullary. They are most commonly found in the upper cervical region, as melanocytes are
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most concentrated at this location.
The term “meningeal melanocytoma” was assigned to these neoplasms after the demonstration of their melanocytic origin [23].
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Although prognosis is generally good, recurrence is common along with possible local aggressive behaviour [2,5,8,25,33,35,48,49]. Most reported cases are solitary lesions with slow growth and low
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infiltration activity; however, there have been reports of malignant transformation to melanoma with leptomeningeal or multifocal diffusion [2,16,355,48,49]. We present a clinical case of a young patient with the leptomeningeal form of MM in the left temporal lobe, with ipsilateral nevus Ota, and discuss the diagnostic and therapeutic aspects of this rare neoplasm.
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Case report
A 19 years old man with a history of headache for 3 years was referred to our clinic for new onset
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generalized tonic-clonic seizure (GTC). On physical examination He had asymptomatic, bluish, speckled and well-demarcated hyperpigmented macules on the left midface extraorally (figure1). The neurological exam was otherwise normal.
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Non-contrast head computed tomography (CT) scan showed a hyperdense lesion in the left temporal lobe (figure2). Following with magnetic resonance imaging (MRI), the left temporal space-occupying lesion
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was confirmed with enhancement on contrast-enhanced scan. The lesion appeared hyperintense on T1weighted images and iso-intense on T2-weighted images (figure 3).
The mass enhanced severely after contrast injection (figure 4).Preoperative diagnosis was meningioma or melanoma. Surgery was performed using middle fossa approach. Direct observation during surgery showed that the lesion was located at the middle cranial fossa with close adherence to the dura and
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tentorium. Grossly, the tumor was a soft, capsulated, well-circumscribed pigmented lesion (figure 5).
The tumor was grossly removed following Simpson’s grade II resection (complete removal + coagulation
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of dural attachment).
Paraffin sections of the tumor revealed uniform sheets of epithelioid to spindle cells with regular nuclei,
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prominent nucleoli and dusty pigmentation of the cytoplasm (fig.6B&C). Focal minimal brain invasion was evident (Fig.6A). Mitotic activity was inconspicuous and necrosis was absent. Tumor cells were CAM5.2, CK7, CK20 and EMA negative and Melan A and S100 positive. Other immunehistochemical findings were focal positivity for HMB45 and MIB-1 index of nearly 1%. Final histopathologic diagnosis was “Intermediate grade melanocytic neoplasm”. After the definite diagnosis, a detailed physical examination was performed in which no skin melanoma was found. Post-operative neurological examination showed right superior-quadrant anopia. No signs of recurrence were seen on the follow-up MRI one year after surgery (figure 7). 5
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Discussion Meningeal melanocytoma: Meningeal melanocytoma is a pigmented tumor from melanocytic origin. It can present as spinal cord and,
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less commonly, brain lesions. The majority of spinal cord forms are reported in the upper cervical and thoracic regions and the brain forms are mostly observed in infratentorial locations [16,25]; however few cases of intracranial MM have been reported in supratentorial location [3,20] (Table 1) .
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This neoplasm must be distinguished from other melanotic neoplasms of the CNS, that according to World Health Organization (WHO) 2007 classification include diffuse melanocytosis, melanomatosis, and malignant melanoma (metastatic or primary) as well as meningiomas, schwannomas or neurofibroma containing melanotic pigment [38]. The process of differential diagnosis can be difficult if the clinical and radiological features of the tumor are not definitive. Pathological examination and
immunohistochemistry of the primary CNS melanocytic lesions are critical to diagnose and distinguish it from primary or metastatic melanomas, melanotic schwannoma, melanotic neuroectodermal tumors [48].
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Patients with meningeal melanocytoma may present with a wide variety of neurological symptoms, including the frequent occurrence of hydrocephalus, seizures, multiple cranial nerve palsies, psychiatric disturbances, intracranial hemorrhage of the meninges or subdural space and myeloradiculopathy [27,33]. Preoperative imaging studies, although suggestive, are inconclusive and non-specific for the lesion. On CT scan, this tumor generally appears as an iso to hyper-dense extra-axial lesion with dural attachment,
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no distinct margins and variable contrast enhancement. In our case however the tumor was hyper-dense on CT scan and was homogenously enhancing on contrast. In MRI, these lesions generally show high
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signal intensity on T1-weighted images, diminished signal on T2-weighted images and diffuse enhancement after contrast administration [27,33,41] as seen in our case. The definite diagnosis of MM is best achieved post-operatively through histopathologic and immunohistochemical studies. Grossly, the tumor usually appears as a black lesion firmly attached to the underlying meninges. Melanin granules are commonly seen in microscopic view [25,33]. Characteristic immunohistochemical reactions of meningeal melanocytoma include a positive response to anti-
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melanoma (HMB-45), S-100 protein and vimentin antibodies (an indicator of cells with mesenchymal origin, which rarely appears in malignant melanoma) and a negative reaction to epithelial membrane
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antigen (EMA) (indicator of meningioma) and Leu7 (indicator of schwannoma) [2,27,33,42,43,48,49]. The generally accepted management plan is complete tumor resection whenever possible as the best therapeutic option. In cases with incomplete resection of the lesion, adjuvant postoperative radiotherapy seems to be beneficial leading to higher patient survival [39]. In addition, radiosurgery has been used as a
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new option in a few cases described in the literature [3]. There is no evidence supporting the use of chemotherapy, albeit Doglietto et al. [11] reported a 20-year-old male with a tumor in left cavernous sinus
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which was followed conservatively for 2 years, until a new space occupying lesion was evident at the level of the right frontal convexity which removed surgically. Three years later, due to a symptomatic growth, he underwent partial removal of the lesion in the cavernous sinus. Histological examination was unchanged. He then received adjuvant Temozolomide with Low
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Dose Fractionated Radiation Therapy (LD-FRT). Due to further disease progression cisplatin plus fotemustine were administered, concomitant with LD-FRT: after two cycles MRI documented significant disease regression. After a period of apparent disease control, the patient
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presented with persistent cough and evidence of multiple thoracic metastases, which lead to his
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death, seven years after presentation. Although meningeal melanocytoma is benign, several cases of relapse, leptomeningeal or multifocal diffusion and malignant transition have been reported even years after the first diagnosis despite the complete cure of the primary neoplasm [8,15,47]. Roser et al reported this transition 10 years after complete treatment with a subsequently rapid diffuse meningeal spread throughout the brain and spine that led to death in 4 months despite whole-brain and stereotactic radiation therapy as well as chemotherapy [42]. Accordingly, long-term close follow-ups with continuous regular imaging studies are necessary in these patients.
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Nevus Ota and Ito:
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The proliferation of dendritic melanocytes in the dermis gives rise to congenital and acquired lesions characterized by the presence of dendritic cells that have migrated from the neural crest towards the epidermis. These lesions are classified as dermal melanocytoses (Mongolian spot, nevus of Ota, and nevus of Ito) and blue nevi. Malignant transformation of dermal melanocytoses is extremely rare, with very few cases reported in the literature. Nevus of Ota presents as bluish hyperpigmentation of the eyelid and the periocular region. Tympanic membrane, ocular, and nasal mucosa also may be involved. First description of oculodermal melanosis was made by Hulke in 1861 [18]. Later, Pusey in 1916 described a case of scleral and facial pigmentation [17]. However, in 1939, Ota from Tokyo coined the name nevus fuscoceruleus ophthalmo-maxillaris and melanosis bulbi. Since then, the condition is known as nevus of Ota. Nevus of Ota, which originally was described by Ota and Tanino in 1939, is a hamartoma of dermal melanocytes. Clinically, nevus of Ota presents as a blue or gray patch on the face, which is congenital or acquired and is within the distribution of the ophthalmic and maxillary branches of the trigeminal nerve. The nevus can be unilateral or bilateral, and, in addition to skin, it may involve ocular and oral mucosal surfaces.
Types:
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Type IA: mild orbital type - distribution over upper and lower eyelids, periocular and temple region Type IB: mild zygomatic type - pigmentation in infrapalpebral fold, nasolabial fold and zygomatic region Type IC: mild forehead type - involvement of forehead alone Type ID: involvement of ala nasi alone Type II: moderate type - distribution over upper and lower eyelids, periocular, zygomatic, cheek and temple regions Type III: involves scalp, forehead, eyebrow and nose Type IV: bilateral Hori’s nevus: acquired bilateral nevus of Ota-like macules; usually Chinese women with family history, becomes more confluent and gray over time Sun’s nevus: acquired unilateral nevus of Ota
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Nevus of Ito, initially described by Minor Ito in 1954, is a dermal melanocytic condition affecting the shoulder area. Nevus of Ito often occurs in association with nevus of Ota in the same patient but is much less common, although the true incidence is unknown. It occurs commonly in Asians (0.014–0.034% prevalence) but rarely in Caucasians, [17] with female preponderance [26]. Variable prevalence among different population groups indicates genetic influences [45]. Two peak ages of onset, in early infancy (50%) and in early adolescence, suggested hormonal influence [45]. Even though nevus of Ota is common in the Orientals, malignant transformation of the melanocytoses, though very rare, has been reported in cases of 8
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nevus of Ota and, more frequently, in blue nevi [46]. In contrast with ocular lesions, nevi of Ota rarely transform into malignant melanoma [12,28]. Radhadevi et al reported a 45-year-old male with malignant melanoma of the left orbit in association with nevus of Ota and MartínezPe˜nuela et al reported a 24-year-old man who presented with a subcutaneous nodule that had developed in the anterolateral region of the thorax over the previous 8 months. The nodule was located beneath a faint bluegray macule with poorly defined borders. Biopsy of the nodule revealed malignant melanoma; biopsies of the adjacent skin lesion showed a diffuse proliferation of scattered melanocytes in a collagen stroma in the reticular dermis. Patel et al reported 29-yearold white man, with oculodermal melanocytosis, which had a rapidly enlarging, erythematous, painful nodule over his left brow, within the nevus. The lesion was excised and diagnosed as a malignant melanoma
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Conclusion
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The etiology and pathogenesis of nevi of Ota and Ito are not known. Although unconfirmed, nevus of Ota and other dermal melanocytic disorders, such as nevus of Ito, blue nevus, and mongolian spots, may represent melanocytes that have not migrated completely from the neural crest to the epidermis during the embryonic stage. Abnormalities of neural crest migration lead to the development of these congenital dermal melanoses. The exact embryologic events that produce such abnormalities are unknown, but changes in the local embryonic environment could be important. Changes in glycosaminoglycans, which fill the cell free space in early embryologic development, may play an important role in the neural crest migration, leading to dermal melanosis.[17] Exact pathophysiology is not yet known. However, suggested theories include failure of dermal melanocytes to disappear during fetal life, arrested migration of melanocytes in the dermis, and active melanin production by intradermal melanocytes [28].
Meningeal melanocytoma is a rare primary brain tumor; however it must be considered in the differential
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diagnosis of all pigmented lesions of CNS even in uncommon locations since its prognosis and biological behavior might be different and potentially lethal. Combination of this tumor with nevus Ota has been reported in very few cases such as ours (Table 2). Although these tumors are benign, they might demonstrate aggressive behavior or malignant transition. In most cases total resection of the tumor is the best curative option. Whenever total resection is not possible radiotherapy is essential to prevent recurrence. Regular long-term follow-ups are highly recommended.
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“There is no financial disclosures”
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“There is no funding or conflict of interest”
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Table 1: Literature Review of 28 cases of the supratentorial meningeal melanocytoma
Table 2: Eight cases of nevus Ota with meningeal melanocytoma
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Figure Legends:
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Figure 1: He had asymptomatic, bluish, speckled and well-demarcated hyperpigmented macules on the
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left midface extra orally
Figure 2: Axial brain CT scan shows a hyper-dense lesion in left temporal lobe
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weight MRI
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Figure 3: Brain MRI shows a hyper-intense lesion in T1-weight and iso-intense lesion in cronal T2-
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Figure 4: The lesion shows homogenous enhancement in MRI with contrast
Figure 5: Gross view of the lesion
FIGURE6: A.Focus of brain invasion (Brain tissue located at the upper right corner) and B: Spindle cell neoplasm with fascicular arrangement (×10). C: Epithellioid cell proliferation with slight dusty pigmentation (×40)
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Figure 7: post-operative MRI with contrast one year after surgery were seen no signs of recurrence.
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Table 1: Literature Review of 28 cases of the supratentorial meningeal melanocytoma Location
TREATMENT
RECURRENCE
Age/Sex
Aimar et al., 2003 (1) K. Beseoglu et al., 2006(3)
Temporal lobe
Surgery
No
27y/M
Convexity
Surgery
NO
55y/M
Botticelli et al., 1983 (4)
Meckle`s cave
Surgery
No
43y/F
Chen, et al., 1997 (6)
Meckle`s cave
Surgery
No
41y/F
Chow et al., 2001 (7)
Planum sphenoidale
Surgery
Classen et al., 2002 (9)
Suprasellar
Biopsy + Radiotherapy
Das et al., 2015 (10)
Right frontal
Doglietto et al., 2012 (11)
Cavernous sinus and right frontal convexity
Faro et al ., 1996 (13)
Cavernous sinus
Hino et al., 2005 (18)
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46/M
No
57y/M
Surgery
No
17y/M
1.Surgery for frontal portion 2.After 3 years second surgery for cavernous portion + temozolamide low dose fractionated radiotherapy Surgery
No
20y/M
No
30y/F
Anterior cranial fossa
Surgery
No
75y/F
Occipital
Surgery
Yes After 60 months
27y/F
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No
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Jellinger et al., 1988 (19)
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Kawaguchi et al., 1998 (20)
Left frontal
Surgery
Yes, after 2 years
45y/M
Kumar et al., 2013 (21)
Meckel’s cave
SURGERY
NO
25y/M
Leonardi et al., 1998 (22)
Meckel’s cave
Surgery
No
67y/M
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Table 1: Literature Review of 28 cases of the supratentorial meningeal melanocytoma Left frontal
Surgery + Radiotherapy
No
25y/M
Maiuri, et al., 1995 (27)
Frontal
Biopsy + Radiotherapy
No
69y/M
MuñozHidalgo et al., 2014 (29) Nakahara et al., 2010 (30)
Two lesions in right temporal
Surgery
No
15y/M
Occipital
Surgery
Navas et al., 2009 (31)
frontotemporal
Surgery
O’Brien et al., 1995 (32)
Temporal
Surgery + Radiotherapy
Died because of massive bleeding during surgery The patient did not recover from the operation due to a malignant infarct of the right hemisphere No
Pan et al., 2011 (34)
Cavernous sinus
PiercecchiMarti et al., 2002 (36) Prabhu et al., 1993 (37)
Left frontal
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39y/F
No
36y/M
Surgery
Yes
46y/M
Surgery + Radiotherapy
No
27y/F
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Surgery
No
17y/M
Anterior caranial fossa
1.Surgery 2. Surgery + Radiotherapy
Yes, 5 years after the first surgery
37y/F
Surgery
No
34y/M
1.Surgical resection in 1994, 2.Gammaknife for recurrence in1998, 3.Surgery in 1999 (malignant transformation) Surgery
Yes, Died six months after his 3rd surgery
49y/M
Yes after 15 months
9y/M
Suprasellar
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Tewari et al., 1990 (47)
21 weeks of gestation/M
Left parietal
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Meckle`s cave
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Uozumi et al., 2003 (49)
Left frontal
Winston et al., 1987 (51)
Meckle`s cave
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Table 1: Literature Review of 28 cases of the supratentorial meningeal melanocytoma
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Table 2: Eight cases of nevus Ota with meningeal melanocytoma Location of Tumor
Nevus Ota
Age / Sex
Outcome & Treatment
Botticelli et al., 1983 (4)
Left meckle`s cave
Ipsilateral frontal
43y / F
Surgical resection
Hino et al., 2005 (10)
Right intracranial and orbital with hemorrhage
75y / F
Surgical resection
MuñozHidalgo et al., 2014 (29) Navas et al., 2009 (31)
Two lesions in right temporal
Ipsilteral (first and second divisions of the right trigeminal nerve territory, which had been treated with a skin graft 40 years earlier) Ipsilateral frontoparietal
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25y / M
Surgical resection
Surgical resection (the patient did not recover from the operation due to a malignant infarct of the right hemisphere)
36y / M
Surgical resection
Ipsilateral forehead and scalp
46y / M
Surgical resection
Left parietal
Ipsilateral frontal and scalp
17y / M
Surgical resection
Ipsilateral periorbital (first division of trigeminal nerve)
37y / F
1.Surgical resection in 1997 2.Surgical resection + radiotherapy in 2002
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Ipsilateral side of the face
Right olfactory groove and orbital wall
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PiercecchiMart et al., 2002 (36) RahimiMovaghar and Karimi, 2003 (41) Rutten et al., 2005 (44)
Ipsilateral frontal
15y / M
Right cavernous sinus Left frontal
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Right frontotemporal
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CNS: central nervous system GTC: generalized tonic-clonic seizure
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MM: meningeal melanocytoma
S1878-8750(15)00358-7
DOI:
10.1016/j.wneu.2015.03.061
Reference:
WNEU 2820
To appear in:
World Neurosurgery
Received Date: 20 January 2015 Revised Date:
29 March 2015
Accepted Date: 31 March 2015
Please cite this article as: Samadian M, Nejad AM, Bakhtevari MH, Sabeti S, Sharifi G, Jabbari R, Rezaei O, Primary Meningeal Melanocytoma in the Left Temporal Lobe Associated with Nevus Ota: a Case Report and Review of the Literature, World Neurosurgery (2015), doi: 10.1016/ j.wneu.2015.03.061. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
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Primary Meningeal Melanocytoma in the Left Temporal Lobe Associated with Nevus Ota: a Case Report and Review of the Literature
Sabeti4, Guive Sharifi5, Reza Jabbari6, Omidvar Rezaei7
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Mohammad Samadian1, Ali Mousavi Nejad2, Mehrdad Hosseinzadeh Bakhtevari3*, Shahram
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Associate Professor of Neurosurgery, Department of Neurosurgery, Loghman e Hakim hospital, Shahid Beheshti University of Medical Sciences -Tehran-Iran. E-mail: [email protected]
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E-mail: [email protected] *3
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Resident of Neurosurgery, Department of Neurosurgery, Loghman e Hakim Hospital, Shahid Beheshti University of Medical Sciences - Tehran-Iran
Resident of Neurosurgery, Department of Neurosurgery, Loghman e Hakim Hospital, Shahid Beheshti University of Medical Sciences - Tehran-Iran
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E-mail: [email protected] 4
Assistant Professor of Pathology, Department of Neuropathology, Loghman e Hakim hospital, Shahid Beheshti University of Medical Sciences -Tehran-Iran. E-mail: [email protected] 5
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Associate Professor of Neurosurgery, Department of Neurosurgery, Loghman e Hakim hospital, Shahid Beheshti University of Medical Sciences -Tehran-Iran.
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E-mail: [email protected]
Assistant Professor of Neurosurgery, Department of Neurosurgery, Loghman e Hakim hospital, Shahid Beheshti University of Medical Sciences -Tehran-Iran. E-mail: [email protected]
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Professor of Neurosurgery, Department of Neurosurgery, Loghman e Hakim hospital, Shahid Beheshti University of Medical Sciences -Tehran-Iran. E-mail: [email protected]
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* Correspondence should be sent to:
Mehrdad Hosseinzadeh Bakhtevari
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Department of Neurosurgery, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran-Iran. Tel: +9821-55414065 Fax: +9821-55414065
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Mobile: +98912-1874506
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Email: [email protected]
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Abstract Background: Primary melanocytic neoplasms of the central nervous system (CNS) are rare lesions arising
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from melanocytes of the leptomeninge that are found at highest density underneath the brain stem and along the upper cervical spinal cord. Thus, most reported cases of meningeal melanocytomas are located in the posterior fossa and the spinal cord, and presentation of the tumor in supratentorial is very rare. Methods: A 19-year-old man presented with headache and seizure at our department. Neurological exams
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were otherwise normal. On physical examination He had asymptomatic, bluish, speckled and welldemarcated hyperpigmented macules on the left midface extraorally. A left temporal space-occupying
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lesion was seen on magnetic resonance imaging. The mass was hyper-intense on T1-weighted images and isointense on T2-weighted images. Enhancement was shown on contrast-enhanced MRI. Preoperative diagnosis was meningioma.
Result: Gross complete resection was performed. Pathological studies led to the diagnosis of
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meningeal melanocytoma WHO grade I. Oncologic consultation done for patient. Because total resection of the tumor was achieved and its histopathologic grade was benign (WHO grade I) radiotherapy did not advise for patient and he fallowed up each 6 months. No tumor was seen on follow-up MRI one year after
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surgery.
Conclusion: Presentation of meningeal melanocytoma in supratentorial compartment is very rare and its
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combination with nevus Ota has been reported in very few cases. Although this lesion is benign, it might behave aggressively. Complete surgical resection of the lesion is the preferred therapeutic option.
Keywords: Meningeal melanocytoma, Neoplasm, Nevus Ota, Supratentorial
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Introduction
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Primary meningeal melanocytoma (MM) is a benign central nervous system (CNS) neoplasm rarely seen by neurosurgeons in clinical practice. It accounts for 0.06-0.1% of brain tumors with an estimated incidence of 1 in every 10 million individuals. This rare lesion mostly affects adult patients between the
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ages of 45 and 50 years, with slight predominance (1.5: 1) among females [15].
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First reported by Limas and colleagues in 1972 [23], the tumor is derived from melanocytic cells of leptomeninge and thus mainly found in the locations with high density of melanocytes that include underneath the brainstem and along the cervical spinal cord [25]. Melanocytomas have been shown to occur anywhere along the neuraxis, but are most commonly found in the region of the foramen magnum, the posterior fossa, meckel’s cave, or adjacent to cranial nerve nuclei. Within the spine, melanocytomas present as intradural masses, and may be intradural extramedullary or rarely intramedullary. They are most commonly found in the upper cervical region, as melanocytes are
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most concentrated at this location.
The term “meningeal melanocytoma” was assigned to these neoplasms after the demonstration of their melanocytic origin [23].
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Although prognosis is generally good, recurrence is common along with possible local aggressive behaviour [2,5,8,25,33,35,48,49]. Most reported cases are solitary lesions with slow growth and low
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infiltration activity; however, there have been reports of malignant transformation to melanoma with leptomeningeal or multifocal diffusion [2,16,355,48,49]. We present a clinical case of a young patient with the leptomeningeal form of MM in the left temporal lobe, with ipsilateral nevus Ota, and discuss the diagnostic and therapeutic aspects of this rare neoplasm.
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Case report
A 19 years old man with a history of headache for 3 years was referred to our clinic for new onset
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generalized tonic-clonic seizure (GTC). On physical examination He had asymptomatic, bluish, speckled and well-demarcated hyperpigmented macules on the left midface extraorally (figure1). The neurological exam was otherwise normal.
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Non-contrast head computed tomography (CT) scan showed a hyperdense lesion in the left temporal lobe (figure2). Following with magnetic resonance imaging (MRI), the left temporal space-occupying lesion
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was confirmed with enhancement on contrast-enhanced scan. The lesion appeared hyperintense on T1weighted images and iso-intense on T2-weighted images (figure 3).
The mass enhanced severely after contrast injection (figure 4).Preoperative diagnosis was meningioma or melanoma. Surgery was performed using middle fossa approach. Direct observation during surgery showed that the lesion was located at the middle cranial fossa with close adherence to the dura and
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tentorium. Grossly, the tumor was a soft, capsulated, well-circumscribed pigmented lesion (figure 5).
The tumor was grossly removed following Simpson’s grade II resection (complete removal + coagulation
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of dural attachment).
Paraffin sections of the tumor revealed uniform sheets of epithelioid to spindle cells with regular nuclei,
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prominent nucleoli and dusty pigmentation of the cytoplasm (fig.6B&C). Focal minimal brain invasion was evident (Fig.6A). Mitotic activity was inconspicuous and necrosis was absent. Tumor cells were CAM5.2, CK7, CK20 and EMA negative and Melan A and S100 positive. Other immunehistochemical findings were focal positivity for HMB45 and MIB-1 index of nearly 1%. Final histopathologic diagnosis was “Intermediate grade melanocytic neoplasm”. After the definite diagnosis, a detailed physical examination was performed in which no skin melanoma was found. Post-operative neurological examination showed right superior-quadrant anopia. No signs of recurrence were seen on the follow-up MRI one year after surgery (figure 7). 5
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Discussion Meningeal melanocytoma: Meningeal melanocytoma is a pigmented tumor from melanocytic origin. It can present as spinal cord and,
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less commonly, brain lesions. The majority of spinal cord forms are reported in the upper cervical and thoracic regions and the brain forms are mostly observed in infratentorial locations [16,25]; however few cases of intracranial MM have been reported in supratentorial location [3,20] (Table 1) .
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This neoplasm must be distinguished from other melanotic neoplasms of the CNS, that according to World Health Organization (WHO) 2007 classification include diffuse melanocytosis, melanomatosis, and malignant melanoma (metastatic or primary) as well as meningiomas, schwannomas or neurofibroma containing melanotic pigment [38]. The process of differential diagnosis can be difficult if the clinical and radiological features of the tumor are not definitive. Pathological examination and
immunohistochemistry of the primary CNS melanocytic lesions are critical to diagnose and distinguish it from primary or metastatic melanomas, melanotic schwannoma, melanotic neuroectodermal tumors [48].
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Patients with meningeal melanocytoma may present with a wide variety of neurological symptoms, including the frequent occurrence of hydrocephalus, seizures, multiple cranial nerve palsies, psychiatric disturbances, intracranial hemorrhage of the meninges or subdural space and myeloradiculopathy [27,33]. Preoperative imaging studies, although suggestive, are inconclusive and non-specific for the lesion. On CT scan, this tumor generally appears as an iso to hyper-dense extra-axial lesion with dural attachment,
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no distinct margins and variable contrast enhancement. In our case however the tumor was hyper-dense on CT scan and was homogenously enhancing on contrast. In MRI, these lesions generally show high
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signal intensity on T1-weighted images, diminished signal on T2-weighted images and diffuse enhancement after contrast administration [27,33,41] as seen in our case. The definite diagnosis of MM is best achieved post-operatively through histopathologic and immunohistochemical studies. Grossly, the tumor usually appears as a black lesion firmly attached to the underlying meninges. Melanin granules are commonly seen in microscopic view [25,33]. Characteristic immunohistochemical reactions of meningeal melanocytoma include a positive response to anti-
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melanoma (HMB-45), S-100 protein and vimentin antibodies (an indicator of cells with mesenchymal origin, which rarely appears in malignant melanoma) and a negative reaction to epithelial membrane
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antigen (EMA) (indicator of meningioma) and Leu7 (indicator of schwannoma) [2,27,33,42,43,48,49]. The generally accepted management plan is complete tumor resection whenever possible as the best therapeutic option. In cases with incomplete resection of the lesion, adjuvant postoperative radiotherapy seems to be beneficial leading to higher patient survival [39]. In addition, radiosurgery has been used as a
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new option in a few cases described in the literature [3]. There is no evidence supporting the use of chemotherapy, albeit Doglietto et al. [11] reported a 20-year-old male with a tumor in left cavernous sinus
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which was followed conservatively for 2 years, until a new space occupying lesion was evident at the level of the right frontal convexity which removed surgically. Three years later, due to a symptomatic growth, he underwent partial removal of the lesion in the cavernous sinus. Histological examination was unchanged. He then received adjuvant Temozolomide with Low
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Dose Fractionated Radiation Therapy (LD-FRT). Due to further disease progression cisplatin plus fotemustine were administered, concomitant with LD-FRT: after two cycles MRI documented significant disease regression. After a period of apparent disease control, the patient
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presented with persistent cough and evidence of multiple thoracic metastases, which lead to his
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death, seven years after presentation. Although meningeal melanocytoma is benign, several cases of relapse, leptomeningeal or multifocal diffusion and malignant transition have been reported even years after the first diagnosis despite the complete cure of the primary neoplasm [8,15,47]. Roser et al reported this transition 10 years after complete treatment with a subsequently rapid diffuse meningeal spread throughout the brain and spine that led to death in 4 months despite whole-brain and stereotactic radiation therapy as well as chemotherapy [42]. Accordingly, long-term close follow-ups with continuous regular imaging studies are necessary in these patients.
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Nevus Ota and Ito:
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The proliferation of dendritic melanocytes in the dermis gives rise to congenital and acquired lesions characterized by the presence of dendritic cells that have migrated from the neural crest towards the epidermis. These lesions are classified as dermal melanocytoses (Mongolian spot, nevus of Ota, and nevus of Ito) and blue nevi. Malignant transformation of dermal melanocytoses is extremely rare, with very few cases reported in the literature. Nevus of Ota presents as bluish hyperpigmentation of the eyelid and the periocular region. Tympanic membrane, ocular, and nasal mucosa also may be involved. First description of oculodermal melanosis was made by Hulke in 1861 [18]. Later, Pusey in 1916 described a case of scleral and facial pigmentation [17]. However, in 1939, Ota from Tokyo coined the name nevus fuscoceruleus ophthalmo-maxillaris and melanosis bulbi. Since then, the condition is known as nevus of Ota. Nevus of Ota, which originally was described by Ota and Tanino in 1939, is a hamartoma of dermal melanocytes. Clinically, nevus of Ota presents as a blue or gray patch on the face, which is congenital or acquired and is within the distribution of the ophthalmic and maxillary branches of the trigeminal nerve. The nevus can be unilateral or bilateral, and, in addition to skin, it may involve ocular and oral mucosal surfaces.
Types:
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Type IA: mild orbital type - distribution over upper and lower eyelids, periocular and temple region Type IB: mild zygomatic type - pigmentation in infrapalpebral fold, nasolabial fold and zygomatic region Type IC: mild forehead type - involvement of forehead alone Type ID: involvement of ala nasi alone Type II: moderate type - distribution over upper and lower eyelids, periocular, zygomatic, cheek and temple regions Type III: involves scalp, forehead, eyebrow and nose Type IV: bilateral Hori’s nevus: acquired bilateral nevus of Ota-like macules; usually Chinese women with family history, becomes more confluent and gray over time Sun’s nevus: acquired unilateral nevus of Ota
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Nevus of Ito, initially described by Minor Ito in 1954, is a dermal melanocytic condition affecting the shoulder area. Nevus of Ito often occurs in association with nevus of Ota in the same patient but is much less common, although the true incidence is unknown. It occurs commonly in Asians (0.014–0.034% prevalence) but rarely in Caucasians, [17] with female preponderance [26]. Variable prevalence among different population groups indicates genetic influences [45]. Two peak ages of onset, in early infancy (50%) and in early adolescence, suggested hormonal influence [45]. Even though nevus of Ota is common in the Orientals, malignant transformation of the melanocytoses, though very rare, has been reported in cases of 8
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nevus of Ota and, more frequently, in blue nevi [46]. In contrast with ocular lesions, nevi of Ota rarely transform into malignant melanoma [12,28]. Radhadevi et al reported a 45-year-old male with malignant melanoma of the left orbit in association with nevus of Ota and MartínezPe˜nuela et al reported a 24-year-old man who presented with a subcutaneous nodule that had developed in the anterolateral region of the thorax over the previous 8 months. The nodule was located beneath a faint bluegray macule with poorly defined borders. Biopsy of the nodule revealed malignant melanoma; biopsies of the adjacent skin lesion showed a diffuse proliferation of scattered melanocytes in a collagen stroma in the reticular dermis. Patel et al reported 29-yearold white man, with oculodermal melanocytosis, which had a rapidly enlarging, erythematous, painful nodule over his left brow, within the nevus. The lesion was excised and diagnosed as a malignant melanoma
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The etiology and pathogenesis of nevi of Ota and Ito are not known. Although unconfirmed, nevus of Ota and other dermal melanocytic disorders, such as nevus of Ito, blue nevus, and mongolian spots, may represent melanocytes that have not migrated completely from the neural crest to the epidermis during the embryonic stage. Abnormalities of neural crest migration lead to the development of these congenital dermal melanoses. The exact embryologic events that produce such abnormalities are unknown, but changes in the local embryonic environment could be important. Changes in glycosaminoglycans, which fill the cell free space in early embryologic development, may play an important role in the neural crest migration, leading to dermal melanosis.[17] Exact pathophysiology is not yet known. However, suggested theories include failure of dermal melanocytes to disappear during fetal life, arrested migration of melanocytes in the dermis, and active melanin production by intradermal melanocytes [28].
Meningeal melanocytoma is a rare primary brain tumor; however it must be considered in the differential
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diagnosis of all pigmented lesions of CNS even in uncommon locations since its prognosis and biological behavior might be different and potentially lethal. Combination of this tumor with nevus Ota has been reported in very few cases such as ours (Table 2). Although these tumors are benign, they might demonstrate aggressive behavior or malignant transition. In most cases total resection of the tumor is the best curative option. Whenever total resection is not possible radiotherapy is essential to prevent recurrence. Regular long-term follow-ups are highly recommended.
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“There is no financial disclosures”
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References:
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“There is no funding or conflict of interest”
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21. Kumar M, Gokden M: Primary intracranial meningeal melanocytoma. J Biomed Graph Comput. 2013; 3:14-18. 22. Leonardi MA, Lumenta CB, Stölzle A, Müller-Höcker J. Unusual clinical presentation of a meningeal melanocytoma with seizures: case report and review of the literature. Acta Neurochir. 1998;140(6):621-8.
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24. Lin B, Yang H, Qu L, Li Y, Yu J. Primary meningeal melanocytoma of the anterior cranial fossa: a case report and review of the literature. World J Surg Oncol. 2012; 3;10:135.
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melanocytosis (nevus of Ota): case report and literature review. Surg Neurol. 2003 Mar;59(3):200-10. 42. 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(3):528-31.
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Table 1: Literature Review of 28 cases of the supratentorial meningeal melanocytoma
Table 2: Eight cases of nevus Ota with meningeal melanocytoma
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Figure Legends:
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Figure 1: He had asymptomatic, bluish, speckled and well-demarcated hyperpigmented macules on the
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left midface extra orally
Figure 2: Axial brain CT scan shows a hyper-dense lesion in left temporal lobe
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Figure 3: Brain MRI shows a hyper-intense lesion in T1-weight and iso-intense lesion in cronal T2-
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Figure 4: The lesion shows homogenous enhancement in MRI with contrast
Figure 5: Gross view of the lesion
FIGURE6: A.Focus of brain invasion (Brain tissue located at the upper right corner) and B: Spindle cell neoplasm with fascicular arrangement (×10). C: Epithellioid cell proliferation with slight dusty pigmentation (×40)
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Figure 7: post-operative MRI with contrast one year after surgery were seen no signs of recurrence.
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Table 1: Literature Review of 28 cases of the supratentorial meningeal melanocytoma Location
TREATMENT
RECURRENCE
Age/Sex
Aimar et al., 2003 (1) K. Beseoglu et al., 2006(3)
Temporal lobe
Surgery
No
27y/M
Convexity
Surgery
NO
55y/M
Botticelli et al., 1983 (4)
Meckle`s cave
Surgery
No
43y/F
Chen, et al., 1997 (6)
Meckle`s cave
Surgery
No
41y/F
Chow et al., 2001 (7)
Planum sphenoidale
Surgery
Classen et al., 2002 (9)
Suprasellar
Biopsy + Radiotherapy
Das et al., 2015 (10)
Right frontal
Doglietto et al., 2012 (11)
Cavernous sinus and right frontal convexity
Faro et al ., 1996 (13)
Cavernous sinus
Hino et al., 2005 (18)
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46/M
No
57y/M
Surgery
No
17y/M
1.Surgery for frontal portion 2.After 3 years second surgery for cavernous portion + temozolamide low dose fractionated radiotherapy Surgery
No
20y/M
No
30y/F
Anterior cranial fossa
Surgery
No
75y/F
Occipital
Surgery
Yes After 60 months
27y/F
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No
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Jellinger et al., 1988 (19)
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Kawaguchi et al., 1998 (20)
Left frontal
Surgery
Yes, after 2 years
45y/M
Kumar et al., 2013 (21)
Meckel’s cave
SURGERY
NO
25y/M
Leonardi et al., 1998 (22)
Meckel’s cave
Surgery
No
67y/M
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Table 1: Literature Review of 28 cases of the supratentorial meningeal melanocytoma Left frontal
Surgery + Radiotherapy
No
25y/M
Maiuri, et al., 1995 (27)
Frontal
Biopsy + Radiotherapy
No
69y/M
MuñozHidalgo et al., 2014 (29) Nakahara et al., 2010 (30)
Two lesions in right temporal
Surgery
No
15y/M
Occipital
Surgery
Navas et al., 2009 (31)
frontotemporal
Surgery
O’Brien et al., 1995 (32)
Temporal
Surgery + Radiotherapy
Died because of massive bleeding during surgery The patient did not recover from the operation due to a malignant infarct of the right hemisphere No
Pan et al., 2011 (34)
Cavernous sinus
PiercecchiMarti et al., 2002 (36) Prabhu et al., 1993 (37)
Left frontal
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25y/M
39y/F
No
36y/M
Surgery
Yes
46y/M
Surgery + Radiotherapy
No
27y/F
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Surgery
No
17y/M
Anterior caranial fossa
1.Surgery 2. Surgery + Radiotherapy
Yes, 5 years after the first surgery
37y/F
Surgery
No
34y/M
1.Surgical resection in 1994, 2.Gammaknife for recurrence in1998, 3.Surgery in 1999 (malignant transformation) Surgery
Yes, Died six months after his 3rd surgery
49y/M
Yes after 15 months
9y/M
Suprasellar
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Tewari et al., 1990 (47)
21 weeks of gestation/M
Left parietal
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Meckle`s cave
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Uozumi et al., 2003 (49)
Left frontal
Winston et al., 1987 (51)
Meckle`s cave
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Table 2: Eight cases of nevus Ota with meningeal melanocytoma Location of Tumor
Nevus Ota
Age / Sex
Outcome & Treatment
Botticelli et al., 1983 (4)
Left meckle`s cave
Ipsilateral frontal
43y / F
Surgical resection
Hino et al., 2005 (10)
Right intracranial and orbital with hemorrhage
75y / F
Surgical resection
MuñozHidalgo et al., 2014 (29) Navas et al., 2009 (31)
Two lesions in right temporal
Ipsilteral (first and second divisions of the right trigeminal nerve territory, which had been treated with a skin graft 40 years earlier) Ipsilateral frontoparietal
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25y / M
Surgical resection
Surgical resection (the patient did not recover from the operation due to a malignant infarct of the right hemisphere)
36y / M
Surgical resection
Ipsilateral forehead and scalp
46y / M
Surgical resection
Left parietal
Ipsilateral frontal and scalp
17y / M
Surgical resection
Ipsilateral periorbital (first division of trigeminal nerve)
37y / F
1.Surgical resection in 1997 2.Surgical resection + radiotherapy in 2002
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Ipsilateral side of the face
Right olfactory groove and orbital wall
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PiercecchiMart et al., 2002 (36) RahimiMovaghar and Karimi, 2003 (41) Rutten et al., 2005 (44)
Ipsilateral frontal
15y / M
Right cavernous sinus Left frontal
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Right frontotemporal
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CNS: central nervous system GTC: generalized tonic-clonic seizure
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MM: meningeal melanocytoma
