A Comprehensive Case Report of Metastatic Intracranial Melanoma with Brief Review of Literature

Abstract

Primary intracranial melanomas are an extremely rare entity and are a diagnosis of exclusion. Malignant melanoma represents the third most common site for cerebral metastasis. We hereby narrate a comprehensive and detailed case of metastatic intracranial melanomas with BRAF mutation, which later on had an extensive systemic spread. The imaging differentials include metastasis, intracranial hemorrhage, or granuloma. The final and definitive diagnosis was attained by detailed clinical, histological, and immunohistochemical evaluation as metastatic malignant pigmented tumor consistent with intracranial melanoma.

 

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Keywords

metastatic intracranial melanoma - BRAF mutation - malignant melanoma

Introduction

Primary intracranial melanomas are uncommon and constitute approximately 1% of all melanoma cases and 0.07% of all brain tumors.[1] It can be classified into two types—diffuse meningeal melanomatosis or solitary (discrete) solid tumors depending on imaging pattern.[2] Primary intracranial metastatic melanomas rarely metastasize beyond the central nervous system (CNS) and are histologically similar to melanomas of other sites. They are often diagnosed after excluding the presence of extracranial lesions by careful physical examinations and positron emission tomography-computed tomography (PET-CT) imaging.

Malignant melanoma represents the third most common cause of cerebral metastases after breast and lung cancer. The spread is hematogenous, because of the absence of lymphatics in the brain. Specific molecular alterations like GNAQ and GNA11 gene also help in distinguishing primary from metastatic melanomas. Primary CNS melanoma is generally diagnosed following the exclusion of a primary cutaneous or mucosal/retinal malignant melanoma. A very low incidence of 0.07 to 0.17% of primary CNS melanomas has been reported and carries a worse prognosis. Brain metastasis is associated with a poor prognosis, with median overall survival from diagnosis of brain metastasis in the range of 17 to 22 weeks.[2] [3] Herein we report a comprehensive case of metastatic malignant melanoma which was confirmed by detailed clinical, radiological, and histopathological evaluation and also related literature is reviewed.

 

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Case Report

A 54-year-old male presented to the Department of Neurosurgery with a history of sudden onset of fall followed by loss of consciousness, slurring of speech, and a history of seizures for a year. His vitals were stable at the time of presentation.

 

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Radiological Investigation

His initial MRI brain with contrast, revealed T1 hyperintense and T2 hypointense lesions with a bubbly appearance seen in the right frontal region, the possibility of cavernomas with internal hemorrhage is likely differential including infective granuloma and intracranial hemorrhage and metastasis. ([Fig. 1A, B])

Fig. 1 (A) MRI brain with contrast revealed T1 and T2 hypointense lesions with a bubbly appearance suggestive of cavernoma with internal hemorrhage. (B) CEMRI brain with spectroscopy revealed findings suggestive of hemorrhagic metastasis.

Contrast-enhanced MRI brain with spectroscopy revealed multiple altered signal intensity lesions in the right frontal, right basal ganglia, and left parietal lobe with significant surrounding vasogenic edema with mass effect, findings were suggestive of hemorrhagic metastasis, and further histopathological correlation was advised. CSF flow study showed preserved phase CSF flow at the level of the cerebral aqueduct.

 

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Pathological Evaluation

Based upon the clinical and radiological investigation, the patient was taken up for right front-parietal craniotomy with adjacent soft tissue excision. In intraoperative, multiple soft tissue bits were sent for frozen and reported as malignant pigmented tumors suggestive of melanoma. ([Fig. 2A]) On final histopathology, the biopsy showed mainly necrotic material, with sheets of viable tumor cells and heavy melanin pigment. ([Fig. 2B]) On immunohistochemical evaluation, the tumor cells were immunoreactive for SOX-10 (score 4 + ), HMB-45 (score 4 + ), Melan-A (score 4 + ; [Fig. 2C]), and S-100 (score 4 + ) with BRAF mutation (strong and diffuse cytoplasmic granular positivity by IHC; [Fig. 2D]). Based on the aforementioned, comprehensive detailed histopathological and immunohistochemical analysis, a final diagnosis of malignant melanoma was rendered. He was put on four cycles of pembrolizumab and received stereotactic radiotherapy (18Gy).

Fig. 2 (A) Gross image of the pigmented tissue received for frozen. (B) Microphotograph of tumor cells showing marked pigmentation (hematoxylin and eosin stain ×100). (C) Immunohistochemical stain for Melan-A (IHC stain for Melan-A ×400). (D) Immunohistochemical stain for BRAF (IHC stain for BRAF ×400).

 

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Follow-Up Radiological Investigation

After 2 months, a repeat contrast-enhanced MRI was done which revealed multiple well-defined T1 hyperintense lesions and T2 hypointense lesions, in the bilateral cerebral hemispheres, favoring metastases. Thin right frontal T1 hyperintense dural thickening overlying the right frontal lesion likely postoperative.

PET Imaging

Post right frontal craniotomy status multiple enhancing nodular lesions of multiple sizes with midline shift likely to be neuro parenchymal metastasis. The left subcutaneous lesion abutting the left ear msg 1.6 cm × 0.8 cm likely to be metastatic deposits. Pleura-based lobulated soft tissue density seen in the right lower lobe lung, bilateral proximal tibia, and D10 vertebral body likely metastatic lesions. He underwent five cycles of nanoxel and carboplatin.

On detailed clinical examination, the patient had a hypopigmented lesion on the scalp and over the upper lip mucosa. He underwent excision for the scalp lesion 3 years back. The histopathology report was lost to follow-up. Hence it was a considered case of metastatic intracranial melanoma, considering the primary lesion to be at the scalp and upper lip mucosa.

On 1 year of follow-up, his PET-CT revealed few metabolically active lesions in the brain, subcutaneous left scalp, and suboccipital deposits with few coalescent metabolically active lesions in the right lung and liver. CT-guided biopsy also showed morphology consistent with metastatic melanoma. The patient did not get permission for BRAF inhibitors, hence he was put on Nivolumab and Ipilimumab.

 

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Discussion

Since systemic melanomas frequently metastasize to the CNS, a definitive diagnosis of primary CNS melanoma can be made if no systemic focus considered to be primary is found. Terao et al,[4] reported clinical differences between metastatic and primary melanomas in the CNS.

The preoperative diagnosis of primary CNS melanoma is difficult, except in cases associated with neurocutaneous melanosis or when melanin or melanin-containing cells are detected in the cerebrospinal fluid. The CT findings of intracranial melanomas are not specific. On the other hand, recent magnetic resonance studies have demonstrated characteristic features of melanomas. Primary intracranial melanoma needs to be distinguished from other pigmented CNS tumors, particularly meningeal melanocytoma (posterior cranial fossa, tight cellular nests, or whorls).

Our present case was a metastatic intracranial melanoma, which was diagnosed after a detailed clinical examination. The presenting symptoms usually are headache, ocular symptoms, hemiparesis, and seizures. Excision of the tumor is the mainstay of treatment.

Since melanomas are not radiosensitive, chemotherapy is important in the treatment of systemic melanomas. In contrast to these systemic melanoma cases, several patients with primary CNS melanoma have achieved better outcomes by surgical intervention with or without additional treatment. The biological behavior of tumor cells of primary CNS melanomas may differ from those of systemic melanomas.

Patients with metastatic melanoma to the brain have been considered to have an extremely poor prognosis with a short median overall survival, and in a vast majority of cases, deaths observed are due to disease progression in the brain.

 

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Conclusion

Primary intracranial melanomas are always a diagnosis of exclusion and should be distinguished from metastatic melanomas as in our case. Controversy remains over the optimal treatment for primary or secondary intracranial melanomas. There is a need to explore other advanced therapies in the future to obtain better postoperative results and prolonged survival, however, up till now maximum micro-surgical excision followed by radiotherapy should be considered as the primary management for these patients.

 

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Conflict of Interest

None declared.

Note

All legal entities of this case report will be entitled to Dharamshila Narayana Superspeciality Hospital, New Delhi 110092.

Patients' Consent

All participants provided written informed consent for their participation in the study.

• References

• 1 Chiarion-Sileni V, Murr R, Pigozzo J, Sarti S, Tomassi O, Romanini A. Brain metastases from malignant melanoma. Forum (Genova) 2003; 13 (02) 170-182 , quiz 190
• 2 Spagnolo F, Picasso V, Lambertini M, Ottaviano V, Dozin B, Queirolo P. Survival of patients with metastatic melanoma and brain metastases in the era of MAP-kinase inhibitors and immunologic checkpoint blockade antibodies: a systematic review. Cancer Treat Rev 2016; 45: 38-45
• 3 Davies MA, Liu P, McIntyre S. et al. Prognostic factors for survival in melanoma patients with brain metastases. Cancer 2011; 117 (08) 1687-1696
• 4 Terao H, Yoshimatsu N, Sano K. [Intracranial melanoma]. No To Shinkei 1968; 20 (10) 991-999

Publication History

Article published online:
04 June 2025