Keywords brainstem tumor - CNS melanoma - leptomeningeal tumors - malignant transformation
- meningeal melanocytoma
Introduction
Primary melanocytic tumors of the central nervous system (CNS) are uncommon entities
originating from leptomeningeal melanocytes, with an estimated incidence of 1 per
10 million annually. These tumors include a spectrum of lesions: benign (melanocytoma
and diffuse melanocytosis) and malignant (melanoma and melanomatosis).[1 ]
[2 ] Although melanocytomas are typically slow-growing and noninvasive, their potential
for malignant transformation remains poorly understood. Here, we present a case of
a histopathologically benign brainstem meningeal melanocytoma with subsequent systemic
metastasis, offering insights into its aggressive biological potential and emphasizing
the diagnostic and prognostic uncertainty that often accompanies these lesions.
Case Report
A 33-year-old male presented with occipital headache, Valsalva-induced respiratory
difficulty, and dysphagia. Neurological examination revealed bilateral nystagmus.
Magnetic resonance imaging (MRI) revealed a T1-hyperintense, contrast-enhancing lesion
centered in the right bulbopontine region, extending into the prepontine, premedullary,
and right lateral cerebellomedullary cistern ([Fig. 1 ]).
Fig. 1 Preoperative axial (A ), coronal (B ), sagittal (C ), and postoperative axial (D ), coronal (E ), sagittal (F ) contrast-enhanced T1-weighted MRI demonstrating a hyperintense mass in the bulbopontine
region.
After the evaluation by a multidisciplinary council, surgery was planned as two sessions.
During the first surgical procedure, suboccipital craniotomy with C1 laminectomy for
decompression and tumoral mass excision with biopsy from the anterior part of the
bulbus were performed. A biopsy sample was reported as benign melanosis on the bone.
One month later, the second surgical procedure was performed by an endoscopic endonasal
transsphenoidal approach for the resection. A firm, gray–black colored, dural-based
mass invading the clival and sellar bones was identified and subtotally resected with
the help of the neuronavigation[3 ] ([Fig. 2 ]). Histopathology showed well-differentiated, melanin-rich spindle cells without
mitotic activity, necrosis, or nuclear atypia—consistent with a diagnosis of meningeal
melanocytoma ([Fig. 3 ]). Additional biopsies from the sphenoid sinus and dura also revealed benign melanosis.
Since it revealed the melanosis patient was referred to the departments of dermatology
and ophthalmology for further evaluation. No skin and choroidal lesions were identified,
and BRAF mutation testing was negative.
Fig. 2 Intraoperative view of black–gray dural-based tumor invading skull base structures
(A, B ).
Fig. 3 H&E stain of tumor cells showing melanin-rich spindle morphology with minimal atypia
(A , ×200; B , ×400). Benign melanosis in the sphenoid sinus (C , ×200; D , ×100).
During follow-up, the patient developed hepatic lesions detected by abdominal computed
tomography. A liver biopsy was done and confirmed metastatic melanoma with HMB45-MART1-Tyrosinase
antibody positivity. The tests for BRAF mutation and PD-L1 expression were negative.
Since the histopathological diagnosis was uncertain before surgery, systemic screening—including
whole-body positron emission tomography (PET)—was not deemed necessary in the preoperative
period. However, after the diagnosis of melanocytoma was made intraoperatively and
the disease progressed, whole-body PET demonstrated widespread osseous metastases.
Despite adjuvant radiotherapy, the patient died of progressive disease.
Discussion
This case illustrates a paradoxical clinical course: a histologically benign meningeal
melanocytoma with subsequent rapid systemic dissemination. Several hypotheses may
explain this discrepancy:
Sampling error: histologic sections may not represent the entire lesion; focal malignant
areas could have been missed.
Biological spectrum: melanocytomas may occupy a continuum with melanomas, especially
in the CNS, where neural crest–derived melanocytes may harbor latent oncogenic potential.
Immunophenotypic silence: the absence of classic melanoma markers (e.g., BRAF mutation,
mitosis) does not preclude aggressive behavior, as supported by recent molecular profiling
studies.[4 ]
[5 ]
Radiologically, both melanocytomas and melanomas demonstrate T1 hyperintensity and
T2 hypointensity due to melanin's paramagnetic effects. However, radiology alone cannot
reliably differentiate benign from malignant lesions. Furthermore, diffuse leptomeningeal
melanocytosis and melanomatosis, though rare, may resemble infectious or inflammatory
conditions on imaging and cerebrospinal fluid analysis.[6 ]
[7 ]
No standardized treatment protocol exists for primary CNS melanocytic tumors.[8 ] Gross total resection remains the cornerstone of treatment, particularly for localized
masses. In our case, complete resection was not feasible due to brainstem adherence.
Although radiotherapy was administered postoperatively, it failed to prevent systemic
spread. There is limited evidence regarding the efficacy of systemic therapies in
primary CNS melanocytomas, particularly those undergoing malignant transformation.
This case raises two essential clinical considerations: (1) even histologically benign
melanocytic CNS tumors warrant long-term surveillance; (2) absence of systemic disease
at presentation does not rule out future metastasis.
Conclusion
Meningeal melanocytomas, while typically benign, can exhibit aggressive biological
behavior and metastasize. Long-term follow-up and a high index of suspicion are essential,
even when histologic and molecular findings suggest indolence. This case emphasizes
the need for multidisciplinary vigilance and may support broader resection and earlier
adjunctive therapy in select patients.
