Saba Saleem Qazi1, Syed Muhammad Ismail Shah2, Muhammad Waqas Saeed Baqai2, Syed Ather Enam3
  1. Department of Neurosurgery, Ziauddin Medical University, Karachi, Pakistan.
  2. Department of Neurosurgery, The Aga Khan University Hospital, Karachi, Pakistan.
  3. Department of Neurosurgery, Aga Khan University, Karachi, Pakistan.

Correspondence Address:
Muhammad Waqas Saeed Baqai, Department of Neurosurgery, The Aga Khan University Hospital, Karachi, Pakistan.


Copyright: © 2022 Surgical Neurology International This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-Share Alike 4.0 License, which allows others to remix, transform, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.

How to cite this article: Saba Saleem Qazi1, Syed Muhammad Ismail Shah2, Muhammad Waqas Saeed Baqai2, Syed Ather Enam3. Primary leptomeningeal melanoma in association with neurocutaneous melanosis: A case report. 25-Nov-2022;13:547

How to cite this URL: Saba Saleem Qazi1, Syed Muhammad Ismail Shah2, Muhammad Waqas Saeed Baqai2, Syed Ather Enam3. Primary leptomeningeal melanoma in association with neurocutaneous melanosis: A case report. 25-Nov-2022;13:547. Available from:

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Background: Primary melanocytic tumors of the central nervous system accounts for approximately 1% of all melanoma with a peak incidence in the fourth decade. The tumor originates from leptomeningeal melanocytes with a variable degree of belligerence. The proliferation of these melanocytes in large amounts in the dermis and nervous system can raise suspicion of neurocutaneous melanosis (NCM), which is an association between malignant melanoma and the presence of a giant intradermal nevus.

Case Description: We present a case of a 62-year-old South Asian male with a large congenital melanocytic nevus (>20 cm in size) in the left hemifacial, and head region who presented with complaints of a single episode of grand-mal seizure followed by neuropsychiatric symptoms. The patient was thoroughly evaluated both clinically and surgically leading to a rare diagnosis of primary leptomeningeal melanoma of the left temporal lobe. The patient subsequently underwent a neuronavigation guided left temporal craniotomy with gross total resection of the lesion.

Conclusion: Primary leptomeningeal melanoma with a clinical association with NCM is rarely ever reported within the literature. To date, our case is one of the very few instances where such an association is being reported in this age group along with rare neuropsychiatric symptoms.

Keywords: Leptomeningeal melanoma, Neural crest, Neurocutaneous melanosis, Nevus, Primary melanoma, Seizures


Primary central nervous system (CNS) melanomas are malignant melanocytic lesions of the CNS that have a high metastatic potential. They are rare entities and comprise approximately 1% of all cases of melanomas and 0.07% of all brain tumors.[ 3 ] These lesions arise from melanocytes that are normally present in the CNS. They tend to occur in the 4th–5th decades of life.[ 12 , 13 ] Melanocytes have a neural crest origin,[ 17 ] after which they migrate during embryonic development, incorporating into the skin, uvea, cerebral parenchyma, leptomeninges, and mucous membranes.[ 14 ]

Primary CNS melanomas are clinically and histologically unique from their cutaneous and retinal counterparts. They demonstrate a benign clinical course.[ 9 ] They arise from the melanocytes normally present in the leptomeninges. Radiologically, a melanocytic lesion in the CNS can be subclassified into either a diffuse type, characterized by having infiltrations into the subarachnoid space or a focal type of tumor.[ 14 ] Furthermore, malignant melanoma is closely related to congenital intradermal nevus, an association that exists in 40–60% of cases of neurocutaneous melanosis (NCM) disorder.[ 16 ] This association was described by Fox and later revised by Kadonaga and Frieden. However, the majority of the patients with NCM present with neurological deficits within the early 2 years of life.[ 10 ]


A 62-year-old man presented to the emergency room after one episode of a generalized tonic-clonic seizure preceded by an aura of generalized body numbness and right hemiparesis. The family later reported a 3-week history of depressed mood, personality changes, and short-term memory disturbances. The patient had no previous history of seizures, trauma, or any other neurological symptom. He had recently been diagnosed with diabetes mellitus, gastroesophageal reflux disease, and depression. His medications included sitagliptin, metformin, omeprazole, and risperidone.

A detailed physical examination revealed a large congenital melanocytic nevus of more than 20 cm in size. The giant nevus was distributed unilaterally across the left side of the patient’s face and head in a nondermatomal fashion [ Figure 1 ]. Neurologically, his cranial nerves and higher mental functions were intact and he had no sensory, motor deficits, or cerebellar defects.

Figure 1:

Cutaneous pigmentation (white arrows) of the periorbital and malar region on the unilateral left side of the face head in a nondermatomal fashion.


Subsequently, brain magnetic resonance imaging (MRI) showed a left temporal lesion in close approximation to the greater wing and petrous portion of the sphenoid bone and measured approximately 37 × 41 × 32 mm [ Figure 2 ]. The lesion also resulted in the obscuration of the temporal horn of the left lateral ventricle with mild uncal herniation. It was hyperintense on the T1-weighted images and isointense on the T-2 weighted images with perilesional edema and areas of signal dropout on susceptibility-weighted imaging. Computed tomography of the chest, abdomen, and pelvis was performed to look for any systemic involvement and was unremarkable.

Figure 2:

Preoperative multiplanar and multisequential MRI of the brain. (a) T1 without contrast shows a heterogeneous hyperintense lesion in the left temporal region, (b) T1 with contrast shows further enhancement on contrast administration, (c) T2 shows a hypointense lesion with surrounding hyperintense signals, (d) fluid-attenuated inversion recovery showing edema surrounding lesion, (e) T1 post contrast sagittal, and (f) susceptibility weighted image displaying areas of signal drop out.


A standard left temporal craniotomy was performed during which the tumor was recognized as a darkly pigmented mass in the anteromedial aspect of the left temporal lobe. The tumor was pigmented and firm. It was surrounded by a blood clot of variable ages and was separable from the brain parenchyma. During the procedure, patchy pigmented leptomeninges, islands of pial pigmentation, and perivascular dark arachnoid deposits were also noticed [ Figure 3 ]. Gross total resection (as confirmed by postoperative MRI) was performed and the patient was discharged on the 3rd postoperative day after smooth postoperative recovery.

Figure 3:

Surgical images of densely pigmented leptomeninges of the brain, as seen under the operating microscope. (a and b) Pattern of black multiple discrete clusters of hyper-pigmentation seen over the brain meninges (white arrow). (c) Extensive pigmentation seen as a sheet of dots spread over the leptomeninges (white arrows). (d) Dark, blotched, and pigmented vascularized (white arrows) meninges.


On histopathology, the tumor was revealed as a neoplastic lesion consisting of cells arranged in a solid sheet pattern. The cells individually possessed scanty cytoplasm, an abundance of dark brown pigment coupled with enlarged hyperchromatic round nuclei and prominent nucleoli. Moreover, scattered mitotic activity and reactive glial tissue were also highlighted. Immunohistochemical stains were performed which showed a reactivity pattern consistent with melanoma; Melan A Positive, HMB45 Positive with Ki-67 high proliferative index [ Figure 4 ].

Figure 4:

Histopathology of primary leptomeningeal melanoma. (a) Hematoxylin and Eosin stained sections show sheets of medium-sized polygonal cells with moderately pleomorphic nuclei (white arrows) containing dispersed chromatin, macronucleoli, and moderate amounts of eosinophilic cytoplasm. (b) Immunoperoxidase staining for Melan A shows diffuse cytoplasmic staining (white arrows) in tumor cells. (c) Positive staining for Ki-67 (white arrows) is observed.


Postoperatively, a multiplanar and multi sequential MRI of the brain was performed with and without IV gadolinium contrast that showed no post-contrast enhancement or visualization at the site of the previously seen lesion to suggest residual disease. He had a stable postoperative course and was discharged on tapering doses of steroids and anti-epileptics. His case was discussed in our multidisciplinary tumor board meeting and was referred to a medical and radiation oncologist for adjuvant therapy.


Melanocytes are pigment cells in the CNS that are normally localized in the pia mater, high cervical cord, and the frontal part of the medulla oblongata. One theory has described that the pigment cells have a neural crest origin, which eventually develops into mesodermal and neural elements and gives rise to tumors.[ 15 ] The tumor cells can spread to the leptomeninges such as the arachnoid and pia mater, and become visible as either discrete dots or clusters of branching pigmentation.[ 8 ] Primary CNS melanomas are characterized by the absence of melanocytic lesions outside the CNS along with histological confirmation. For comparison, metastatic melanomas are differentiated from primary lesions by findings of multiple intracerebral lesions, having a rapid and poor clinical course, and their appearance in relatively older patients.[ 20 ]

NCM is described as a neuroectodermal dysplasia, characterized by large (>20 cm) or multiple congenital nevi associated with meningeal melanosis or melanoma. The diagnosing criteria also include the following two clinical aspects: no evidence of cutaneous melanoma except in patients in whom the examined areas of the meningeal lesions are histologically benign; no evidence of meningeal melanoma except in patients in whom the examined areas of cutaneous lesions are histologically benign.[ 6 ] Our patient had a large benign congenital nevus on one half of the face. On MRI, our patient was seen to have a paramagnetic lesion, which was confirmed to be a primary CNS melanoma, with no evidence of metastasis from any other area of the body. Therefore, he fulfilled the criteria to be diagnosed as a case of NCM. The uniqueness of our case, however, lies in the fact that symptoms of NCM are majorly present in the first 2 years of life,[ 5 ] characterized by high intracranial pressure, hydrocephalus, cranial nerve palsy, hemiparesis, developmental delays, and seizures.[ 10 ] Our patient had only one episode of seizure at the age of 62, with psychiatric symptoms for years. It is very rare for NCM to present at a later age like in this patient. His neuropsychiatric symptoms are, however, consistent with the manifesting symptoms of NCM that are found in later years of life.[ 2 ]

CNS melanomas have a nonuniform histological pattern and are divided into four subtypes; the majority of the tumors are: (1) epithelioid,[ 9 ] however, (2) pleomorphic, (3) spindle-shaped,[ 11 ] and (4) mixed cell types are also found.[ 7 ] Primary leptomeningeal melanomas also show cellular pleomorphism, mitoses, necrosis,[ 4 ] and hemorrhage. Immunocytochemical tests aid in the diagnosis of these tumors. S-100 is a non-specific marker of melanomas as it also stains positive for gliomas and meningiomas. HMB-45 positivity has a higher specificity for melanomas.[ 12 ] However, unlike meningioma, CNS melanocytic lesions are usually negative for epithelial membrane antigen.[ 3 ]

Computed tomography (CT) is of limited diagnostic value for these tumors that produce isodense or hyperdense lesions.[ 14 ] Melanocytes demonstrate paramagnetism, causing shortening of both the T1 and T2 relaxation times. They appear as hyperintense and hypointense on T1- and T2-weighted imaging, respectively.[ 5 ] On postprocessed susceptibility-weighted images, signal dropout and blooming would be expected in the presence of diamagnetic (calcification) and paramagnetic (hemosiderin) properties. However, to distinguish between microhemorrhages in melanoma and calcification in meningioma, phase-filtered images are useful. They would show calcification as a hyperintensity due to a negative phase shift and loss of signal for hemosiderin due to a positive phase shift.[ 1 ] CT can also confirm the calcification in meningiomas. Although CT was not performed in our case, our patient had a left temporal lesion that was hyperintense on T1-weighted images and hypointense on T2-weighted images. Areas of signal dropout were seen on SW-images which signified microhemorrhages.

Treatment options for primary CNS melanoma include surgical excision which carries a good outcome, compared to radiotherapy and chemotherapy, which can be used as adjuvants.[ 18 ] Radiation can be given as whole-brain radiotherapy, or just involved-field radiotherapy at the site of the bulky lesion.[ 3 ] One patient underwent whole-brain radiotherapy with intra-CSR chemotherapy. Methotrexate (MTX) 15 mg and dexamethasone 5 mg were administered intrathecally for 8 weeks providing complete remission. However, the patient was required to undergo monthly intraCSF chemotherapy and noncompliance was eventually the cause of her death.[ 14 ] Other chemotherapeutic drugs that can be administered include MTX, dacarbazine, vincristine, temozolomide, and interferon, although due to the rarity of these tumors, no standardized guideline for treatment exists.[ 19 ] Table 1 further shows the reported treatment combinations used for melanoma and their outcomes.

Table 1:

Shows the treatment combinations used in various diffuse and focal leptomeningeal melanomas reported with/without benign congenital nevus and their outcomes.


Malignant manifestation of a primary CNS lesion without metastasis, in juxtaposition to congenital nevi in an older patient, is a unique rarity in clinical neuromedicine. What provides significance to our report is the rare presentation of lesions, late onset of symptoms, importance of neuroimaging, and prompt surgical approach that prevents tumor spread and ensures the longevity of life.


The peculiarity of our case lies in the fact that NCM was discovered late in a 62-year-old patient with neuropsychiatric symptoms, providing an addition to the rarity of such cases found in the literature. The presence of a giant nevus along with a malignancy in the CNS should raise the suspicion of NCM regardless of the age of a patient.

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Patient’s consent not required as patient’s identity is not disclosed or compromised.

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Conflicts of interest

There are no conflicts of interest


The views and opinions expressed in this article are those of the authors and do not necessarily reflect the official policy or position of the Journal or its management. The information contained in this article should not be considered to be medical advice; patients should consult their own physicians for advice as to their specific medical needs.


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