Childs Nerv Syst DOI 10.1007/s00381-015-2741-3


Primary atypical melanocytoma arising from the cavernous sinus in a child Na-Kyoung Lee 1 & Ji Yeoun Lee 1 & Kyu-Chang Wang 1 & Dong Gyu Kim 1 & Sung-Hye Park 2 & Jung-Eun Cheon 3 & Ji Hoon Phi 1 & Seung-Ki Kim 1

Received: 25 November 2014 / Accepted: 29 April 2015 # Springer-Verlag Berlin Heidelberg 2015

Abstract 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. Keywords Intracranial meningeal melanocytoma . Atypical melanocytoma . Cavernous sinus . Children * Seung-Ki Kim [email protected] 1

Division of Pediatric Neurosurgery, Seoul National University Children’s Hospital, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul 110-744, Republic of Korea


Department of Pathology, Seoul National University Children’s Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea


Division of Pediatric Radiology, Seoul National University Children’s Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea

Introduction Melanocytomas of the central nervous system (CNS) are rare, benign lesions derived from leptomeningeal melanocytes [10]. They may develop from anywhere in the cranial and spinal meninges [20]. Approximately two thirds of meningeal melanocytomas are found in the intracranial compartment and the remaining one third in the spine [7]. Among intracranial melanocytomas, the most frequently occurring site is the posterior cranial fossa because the melanocyte concentration in the leptomeninges is higher on the ventrolateral side of the medulla oblongata [4, 17]. In contrast, primary melanocytic tumors in the cavernous sinus are extremely rare. To the best of our knowledge, only five cases have been reported previously (Table 1) [2, 5, 6, 8, 13]. Intracranial melanocytomas can occur at any age, but most commonly occur in the fourth and fifth decades. These tumors are extremely rare in children and adolescence. We report the first pediatric patient and the youngest patient with an intracranial atypical melanocytoma arising from the cavernous sinus.

Case report History A 15-year-old girl presented with left facial hyperesthesia and paresthesia for 4 months. She also suffered from diplopia. Neurologic examination revealed left eye medial gaze limitation and ptosis and left facial hyperesthesia. Computed tomography (CT) imaging from an outside hospital showed a well-circumscribed extra-axial mass in the left middle cranial fossa, which was homogeneously hyperdense to the grey matter. There was no calcification

Pan et al., 36, M Headache, Rt. ptosis, nevus of Ota 2011

evidence of tumor recurrence until 1 year after surgery Doglietto 20, M Diplopia, melanosis oculi et al., 2012



evidence of tumor progression until 3 years after GKS

15, F Lt. facial hypesthesia, Lt. facial paresthesia, diplopia, Lt. ptosis

Meningeal melanocytoma


T1: hyperintense T2: hypointense GRE: isointense enhancement

Surgery (STR), radiosurgery

Surgery (GTR)

Surgery (GTR)

Surgery (PR), radiotherapy

Initial management

progression in cavernous sinus lesion → Chemotherapy (cisplatin, fotemustine), LDF-RT → Multiple thoracic metastasis, death 7 years after presentation Hyperdense T1: hyperintense Surgery (PR) radiosurgery (GKS) T2: hypointense GRE: hypointense No enhancement


Iso- to

Hyperdense T1: hyperintense T2: isointense to hypointense Enhancement

Hyperdense T1: hyperintense T2: hyperintense with multifocal areas of lowsignal intensity No enhancement Hyperdense T1: hyperintense T2: hypointense No enhancement

Hyperdense N.D.

CT findings MR findings



Tumor recurrence 6 months after 1st operation → 2nd operation, radiotherapy



Atypical meningeal


Cavernous chemotherapy sinus lesion: (temozolomide), LDF-RT surgery (PR), Frontal lesion: surgery (GTR) adjuvant







Multiple lesions in the left cavernous sinus, left frontal convexity, and right petrous apex

Rt. right, Lt. left, GTR gross total resection, STR subtotal resection, PR partial resection, T1 T1-weighted image, T2 T2-weighted image, GRE gradient echo image, LDF-RT low-dose fractionated radiotherapy, GKS gamma knife surgery, N.D. not described



Present case

Faro et al., 1996 N.D.



el-Kalliny et al., 1992


30, F Headache

43, F Orbital pain, Lt. facial paresthesia, diplopia, Lt. ptosis, Lt. enophthalmos, nevus of Ota recurrence 2 years after initial management → 2nd operation (PR), radiotherapy 61, F Lt. facial pain, diplopia

Botticelli et al., 1983 Tumor



Age, sex

Summary of the reported cases of primary melanocytic tumor of cavernous sinus

No. Authors, year

Table 1

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(Fig. 1a). Magnetic resonance imaging (MRI) demonstrated a 33×27 mm lobulated lesion in the left middle cranial fossa, mainly located along the left cavernous sinus and extending posteromedially to the anterior aspect of the left pons. The mass showed bright signal intensity on T1weighted imaging (T1 WI), low signal intensity on T2weighted imaging (T2 WI), and dark signal intensity on gradient echo imaging (GRE). Contrast-enhanced T1 WI showed no significant enhancement of the lesion. There was no surrounding brain edema or dural tail sign (Fig. 1b–f). MR angiography revealed absence of flow within the mass (Fig. 2a). Based on the CT and MRI findings, the presumptive diagnosis was an extra-axial mass with hemorrhage. The differential diagnosis should include cavernous hemangioma, neurogenic tumor, meningioma, or thrombosed aneurysm in the cavernous sinus. On conventional cerebral angiography, there was no demonstrable tumor vascularity or aneurysm in the left cavernous sinus (Fig. 2b). Therefore, the patient underwent exploratory craniotomy and tumor removal.

Fig. 1 A 15-year-old girl with an atypical melanocytoma arising from the left cavernous sinus. a Precontrast CT imaging demonstrates a welldefined, hyperdense mass in the left middle cranial fossa. The mass is mainly located along the left cavernous sinus and extends to the anterior side of the pons. b Axial T1-weighted MRI demonstrates a 33×27 mm lobulated mass in the left middle cranial fossa extending posteromedially to the anterior aspect of the left pons. The mass shows a bright, high signal intensity compared to the grey matter. c On axial T2-weighted MRI, the mass shows a heterogeneous dark signal intensity compared to the grey

Operation After left temporal craniotomy and dural opening, the temporal lobe was gently retracted upward. The mass was located extra-axially. The medial dura bulged and a brown to black pigmented mass was observed beneath the dura (Fig. 3a). After incision on the bulging dura, a mud-like material poured out (Fig. 3b). We suctioned it and performed a partial tumor resection of approximately 60 % of the total mass. To avoid intrusion of the cavernous sinus, the tumor was left in the cavernous sinus.

Histopathologic findings Histopathologically, the tumor showed sheets of highly cellular epithelioid cells with abundant cytoplasmic melanin pigments (Fig. 4). On bleach examination, there was mild nuclear pleomorphism, hemorrhage, and necrosis without mitotic cells. Some tumor cells showed prominent nucleoli.

matter. There is no surrounding edema. Note the anteriorly displaced left cavernous internal carotid artery (arrow). d The hourglass-shaped, left cavernous sinus lesion shows dark signal intensity on gradient echo imaging. Bright signal intensity on T1-weighted imaging, dark signal intensity on T2-weighted imaging and gradient echo imaging reflect the paramagnetic products within the mass. e, f No significant contrast enhancement is noted in the left cavernous sinus lesion on contrastenhanced, T1-weighted axial, and coronal images. There is no evidence of a dural tail sign

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Fig. 2 MR angiography and conventional cerebral angiography. a MR angiography shows a large lobulated, mass-like lesion in the left middle cranial fossa. The mass seems to be a vascular lesion, like a cavernous malformation, thrombosed aneurysm, or mass with paramagnetic

products, such as methemoglobin or other paramagnetic substrates. b On conventional cerebral angiography, there was no evidence of an internal carotid artery aneurysm in the left cavernous sinus or other remarkable abnormal findings

Immunohistochemically, the tumor cells were strongly positive for S-100 and human melanoma black (HMB)-45 after bleaching. The tissue stained negative for glial fibrillary acidic protein (GFAP), CD31, CD34, and phospho-histone H3 (pHH3). The proliferation index with MIB-1 was 1 %. These findings are consistent with a melanocytic tumor. There was no evidence of overt malignant features, such as marked nuclear pleomorphism, mitoses, necrosis, or brain invasion; however, the tumor was not entirely benign, because of the presence of necrosis and epithelioid tumor cells with focal presence of prominent nucleoli. An atypical melanocytoma with uncertain malignant potential was reported on the pathological examination.

After GKS, the residual tumor shrank gradually until 2 years after GKS (Fig. 5b, c). At the follow-up 36 months after GKS, the patient was stable except for a nonspecific headache. MRI showed no interval change in the extent of residual tumor (Fig. 5d).

Postoperative course Postoperatively, the patient was neurologically stable with no additional deficits. Her diplopia and left facial hyperesthesia improved gradually. A postoperative MRI demonstrated a residual mass involving the left cavernous sinus (Fig. 5a). Based on the pathological diagnosis of atypical melanocytoma with borderline malignant potential and imaging findings of a residual mass, the patient received gamma knife surgery (GKS) with 17 Gy of radiation for the residual tumor 3 months after surgery. Fig. 3 Intraoperative photographs. a After temporal lobe retraction, a brown to black pigmented lesion is seen beneath the medial dura. b Brown to black mud-like material is revealed after medial dural incision

Discussion The diagnosis and management of primary atypical melanocytoma is a challenge for neurosurgeons and neuro-oncologists. CT and MRI findings of primary melanocytic lesions are similar to other extra-axial masses. Typically, meningeal melanocytomas appear as iso- to hyper-dense lesions on CT and show homogeneous high signal intensity on T1 WI MRI and low signal intensity on T2 WI MRI and show homogeneous enhancement after gadolinium administration [12, 16]. However, this signal pattern may be variable depending on the melanin content and intratumoral bleeding [12, 13]. Although our patient showed compatible MRI findings with melanocytic tumors, making the correct diagnosis was difficult because of its rarity in this age group and location. The histological features of atypical melanocytomas are more aggressive than well-differentiated melanocytomas

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but lack the overt cytoplasmic and nuclear atypia of malignant melanomas [17, 19]. They are relatively hypercellular and have increased mitotic activity compared to low-grade melanocytomas but not to the degree of malignant melanomas. Additionally, they lack the anaplasia of malignant melanomas. However, microscopic brain parenchyma invasion and necrosis may be present in atypical lesions [11, 19]. The MIB-1 index might be useful for classifying primary melanocytic lesions. Although a definite cutoff value is not established, the value may roughly divide into some ranges. Benign meningeal melanocytoma shows less than 1–5 %, intermediate melanocytoma shows 5–10 %, and malignant melanoma shows more than 10 % [11]. In our patient, although the tumor tissue showed mild pleomorphism and necrosis, there was neither mitotic cell nor parenchymal invasion, and the MIB-1 index was 1 %. The pathological diagnosis was consistent with a borderline melanocytoma with uncertain malignant potential, which is an atypical melanocytoma. Complete resection is the primary treatment strategy for melanocytomas. However, in cases where complete resection

is not possible, adjuvant radiotherapy is recommended. Incomplete resection with radiotherapy had a 72 % control rate but incomplete resection only showed an 18 % control rate [15]. Due to the possibility of malignant transformation or recurrence, some have advised radiotherapy even after complete removal [3, 14]. According to Rades et al., the 5-year local control rate was 80 % after complete resection and 100 % with complete resection and subsequent radiotherapy [15]. We chose GKS as the adjuvant radiotherapy because the residual tumor in the cavernous sinus was located close to the optic nerve. Although not much literature is available, our experience shows that GKS may also be a viable adjuvant tool, especially when the remnant mass is small [9, 15, 18]. Looking into five previous cases of primary melanocytic tumor from cavernous sinus (Table 1), gross total resection with radiotherapy is the best option for treatment. However, complete tumor resection may be difficult when the tumor is located very close to the cavernous sinus wall. In such cases, subtotal resection with radiotherapy shows a better prognosis than partial resection with radiotherapy. Therefore, the best treatment choice is resection of tumor as much as possible with adjuvant radiotherapy, when complete resection is difficult. Primary intracranial meningeal melanocytoma has been reported to have quite a good clinical outcome in previous cases, especially when completely removed [1, 11, 15]. However, there have been some cases of transformation to malignant melanoma. The time to tumor recurrence varies from a few months to more than 10 years [11, 19]. The clinical outcome of meningeal melanocytomas arising from the cavernous sinus seems to be borderline because complete tumor resection is difficult. In the previous five patients (Table 1), two patients with partial resection and adjuvant radiotherapy had tumor recurrence. One had a recurrence 2 years after surgery, and the other died with a distant metastasis 5 years after surgery. Therefore, longterm follow-up is required for atypical melanocytoma patients after treatment due to its potential for delayed recurrence and malignant transformation.

Fig. 5 Serial MRIs after the initial management. Gamma knife surgery (GKS) was performed 3 months after partial tumor resection. Coronal T1weighted images with contrast enhancement show a residual mass after

partial resection and a stable residual mass after GKS (a 2 days after resection, b 12 months after GKS, c 24 months after GKS, d 36 months after GKS)

Fig. 4 Photomicrographs showing an atypical melanocytoma. Histopathologically, the tumor is composed of heavily pigmented polygonal cells with focal geographic necrosis (arrows). However, there is no mitotic figure on bleaching examination (H&E, ×200)

Childs Nerv Syst Acknowledgments This study was supported by a grant from the Korea Healthcare Technology R&D Project, Ministry for Health, Welfare and Family Affairs, Republic of Korea (A120099).


11. Conflict of interest The present authors have no potential conflicts of interest to disclose.

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Primary atypical melanocytoma arising from the cavernous sinus in a child.

Primary melanocytic lesions of the central nervous system originate from leptomeningeal melanocytes, with a spectrum ranging from well-differentiated ...
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