Primary melanocytic tumors of the central nervous system (CNS) are rare neoplasms that evolve from leptomeningeal melanocytes with an incidence of 1 per 10 million person-years. ^{Reference Guo, Wei, Guo and Wu1} These tumors range from benign melanocytomas to malignant melanomas and may present as solitary or multifocal lesions. Diagnosis is often challenging due to radiologic and histologic overlap with other CNS tumors and the difficulty in distinguishing them from metastatic disease. ^{Reference Lang-Orsini, Wu and Heilman2} Although prognosis is variable and influenced by tumor location, these lesions are frequently aggressive, with the focal and diffuse presentations of primary CNS melanoma having a median survival of two years and five months, respectively. ^{Reference Guo, Wei, Guo and Wu1} The mainstay of treatment includes a combination of surgical excision, chemotherapy and/or radiation therapy. In cases of advanced CNS melanoma where meaningful resection is not feasible, systemic chemotherapy is generally indicated. However, outcomes remain poor, with a median progression-free survival of approximately 5 months and a median overall survival of 12.5 months.

When multifocal, these tumors can radiologically mimic the appearance of other CNS neoplasms such as meningiomas, schwannomas and ependymomas, further complicating diagnosis. This overlap is particularly pertinent in neurofibromatosis type 2 (NF2), a genetic disorder caused by NF2 gene mutations characterized by multiple benign tumors of the nervous system, most notably bilateral vestibular schwannomas. The presence of bilateral internal auditory canal (IAC) lesions alone is sufficient to make a presumptive radiologic diagnosis of NF2. ^{Reference Plotkin, Messiaen and Legius3} However, rare cases of multifocal CNS melanocytic tumors may initially exhibit similar imaging patterns, potentially masquerading as NF2 and resulting in misdiagnosis and delays in appropriate management. ^{Reference Suranagi, Maste and Malur4–Reference Lewis, Dawson and Hyde5} The symptoms of CNS melanoma also vary depending on the lesion’s location, further complicating diagnosis. Given that CNS melanomas are often aggressive lesions, tissue biopsy for definitive confirmation should be considered, especially in cases with an unusual degree of disease progression. Herein, we present the youngest known case of diffuse primary CNS melanoma with IAC tumors mimicking NF2 and review similar cases.

A 28-year-old male presented with one week of painless bilateral decreased visual acuity in the context of a two-year history of occasional recurrent dizziness and tinnitus. His medical history was significant for benign paroxysmal positional vertigo and celiac disease, and his family history was notable for his maternal grandfather, who died of an unknown brain cancer in his twenties. He endorsed occasional transient oral paresthesia, transient episodes of hearing loss over the past two years and decreased visual acuity bilaterally with no visual field cuts. Complete blood count and electrolytes were noncontributory, and he denied any recent substance use or any recent medication usage. He was normotensive and afebrile.

He received a contrast-enhanced MRI head, which demonstrated bilateral IAC lesions suggestive of vestibular schwannomas. His scans also demonstrated bilateral lesions in Meckel’s cave suggestive of trigeminal schwannomas and multiple extra-axial lesions consistent with meningiomas, including a suprasellar lesion compressing the optic chiasm. In addition, there were diffuse atypical leptomeningeal deposits of uncertain etiology in the supratentorial and infratentorial compartments (Figure 1A–C). A contrast-enhanced MRI spine demonstrated enhancing intradural, extramedullary lesions radiologically consistent with meningiomas or schwannomas. A detailed dermatologic examination was unremarkable.

Figure 1.

Axial T1 MRI at initial presentation shows bilateral internal auditory canal (IAC) lesions (A), suprasellar lesion contacting the optic chiasm on the right (B) and multiple leptomeningeal lesions (C). Repeat Axial T1 with contrast shows diffuse enlargement of IAC (D) and optic chiasm lesions (E), as well as multiple new leptomeningeal lesions with an arrow designating selected surgical target (F).

Figure 1 Long description

The image consists of six axial T1 MRI scans. Image A shows bilateral internal auditory canal lesions. Image B displays a suprasellar lesion contacting the optic chiasm on the right. Image C highlights multiple leptomeningeal lesions. Image D, a repeat axial T1 with contrast, shows diffuse enlargement of the internal auditory canal lesions. Image E shows enlargement of the optic chiasm lesions. Image F, another repeat axial T1 with contrast, depicts multiple new leptomeningeal lesions with an arrow indicating a selected surgical target.

Due to his symptoms and the presence of radiologically presumed bilateral vestibular schwannomas and other lesions suggestive of meningiomas, schwannomas and spinal ependymomas, the presumptive diagnosis of NF2 was rendered. ^{Reference Plotkin, Messiaen and Legius3,Reference Evans, Huson and Donnai6} He was booked for outpatient ophthalmologic and auditory testing, as well as genetic testing for his new diagnosis of NF2.

Over the following six months, he experienced rapidly progressive bilateral vision decline, near-complete right-sided hearing loss, worsening postural headaches, progressive gait deterioration and radiating left arm pain. This was atypical for NF2, and he was referred to our tertiary center, where his presumed diagnosis was called into question. A repeat ophthalmologic exam revealed bilateral optic neuropathy with visual acuity OS 20/400 and OD 20/500. Audiogram testing revealed right sensorineural hearing loss with only 12% speech discrimination. Whole genome sequencing was unremarkable, and mitochondrial DNA testing was negative. We obtained a repeat MRI head, which demonstrated progressive growth in multiple lesions, including bilateral IAC lesion growth, enlargement of the suprasellar lesion causing increased optic chiasm compression and multiple new diffuse leptomeningeal lesions (Figure 1D–F). A repeat MRI spine with gadolinium demonstrated multiple intradural extramedullary contrast-enhancing lesions, including a large C5/C6 right spinal canal lesion causing extensive cord compression.

Due to his clinical deterioration and atypical imaging progression, he underwent a right occipital craniotomy for biopsy of the right tentorial lesion. Intraoperatively, the lesion was highly vascular with dark purple and black pigmentation. Pathology showed a spindled cell neoplasm with abundant brown pigmentation, an elevated mitotic count and small foci of necrosis invading the adjacent parenchyma. A Masson-Fontana stain confirmed the pigment to be melanin, and immunohistochemistry testing was positive for S100, Melan A, HMB45 and SOX10 but negative for PRAME and BRAF V600E. Amplicon NGS panel (AmpliSeq for Illumina panel) testing identified a GNAQ mutation (Q201L) with no BRAF, KRAS, NRAS or KIT mutations. This was indicative of a melanocytic neoplasm, specifically a melanoma.

He also underwent a C4–C6 decompressive laminoplasty to remove the C5/C6 intradural lesion to address his progressive myelopathy and motor deficits. Intraoperatively, the dura was darkly tinted, with a large deposit of highly pigmented subarachnoid tumor (Figure 2). Pathology of the spinal lesion demonstrated similar histology, immunohistochemical profile and focus panel as the tentorial lesion. Based on the histopathological findings, he was diagnosed with primary CNS meningeal melanoma and started on ipilimumab/nivolumab chemotherapy. An extensive genetic workup, including germline exome, demonstrated no pathologic variants, including those suggestive of NF2, making an additional superimposed neoplastic process unlikely. Despite the initial response to chemotherapy, the patient, unfortunately, passed away 13 months after his official diagnosis.

Figure 2.

Intraoperative and post-op imaging where * denotes cranial end. The dura was darkly pigmented (A) and overlying the pigmented hyper-vascular C5/C6 lesion (B). The tumor was resected, with an arrow denoting residual foraminal lesion (C). Postoperative T2 MRI shows C4–C6 laminoplasty and cervical cord decompression (D) and known residual foraminal lesion (E).

Figure 2 Long description

The image contains five elements: four intraoperative photos and one postoperative MRI scan. The first photo shows a darkly pigmented dura marked with an asterisk at the cranial end. The second photo displays the pigmented hyper-vascular lesion at C5/C6, also marked with an asterisk. The third photo illustrates the resected tumor with an arrow indicating residual foraminal lesion. The fourth and fifth elements are postoperative T2 MRI scans. The fourth scan shows C4-C6 laminoplasty and cervical cord decompression. The fifth scan highlights the known residual foraminal lesion.

This case highlights the diagnostic challenges posed by CNS melanocytic tumors, which can mimic NF2 due to overlapping clinical and radiologic features. A systematic review of Embase and Medline identified only two other cases of bilateral IAC CNS melanomas. ^{Reference Lang-Orsini, Wu and Heilman2,Reference Rosa Júnior, Da Motta and Scardino7} Both were single-patient case reports that presented with sensorineural hearing loss, headaches and/or unilateral paresis with no dermatologic findings. Rosa et al. detailed the case of a 38-year-old male with primary malignant meningeal melanoma with CSF dissemination and a frontal lesion. Lang-Orsini et al. described a similar primary meningeal melanoma with additional extra-axial enhancing Sylvian fissure and middle cranial fossa lesions, along with multiple small intradural extramedullary enhancing lesions in the spinal canal and an enhancing intramedullary C6–C7 spinal lesions.

In addition to bilateral IAC lesions, other clinical and radiographic findings common with this unique presentation of NF2 and CNS melanoma include hearing loss, tinnitus, headaches and multiple extra-axial cranial and spinal tumors suggestive of meningiomas and ependymomas, respectively. ^{Reference Evans8} However, unexpected clinical deterioration noncongruent with the course of NF2 or rapid lesion progression on follow-up imaging should raise suspicion for an alternative pathology, and more frequent imaging is beneficial in these cases. Such patients should also be carefully considered for diagnostic tissue biopsy to rule out unusual NF2 mimics, as demonstrated in our case. Indeed, early diagnosis of CNS melanoma can prevent delays in treatment thereby improving a patient’s prognosis. ^{Reference Lewis, Dawson and Hyde5} The literature should continue to be updated on similarly presenting cases to understand better the recognition, optimal management and prognosis of this rare pathology.