Primary diffuse meningeal melanomatosis – a rare form of meningeal melanoma: case report
Meningeal melanomatosis is a rare type of central nervous system neoplasm (with incidence ranging between 3 and 5%) that develops in the course of malignant melanoma. In a small percentage of cases, meningeal melanomatosis may develop without a primary focus. It affects the leptomeninx. The clinical activity of the disease is uncharacteristic, with a number of neurological symptoms developing over weeks or months.
A 45-year-old male patient presented with consciousness disturbance, cognitive dysfunctions, seizures and progressive paresis. None of the examinations performed, including cerebrospinal fluid examination, neuroimaging and biopsy of the leptomeninges, permitted us to establish a diagnosis during the patient’s hospital stay. The diagnosis of meningeal melanomatosis was established after an autopsy had been carried out.
In the absence of unequivocal test results, it is also worth taking into account the primary changes in the leptomeninx, including those caused by melanoma.
KeywordsMeningeal Melanomatosis Melanoma Leptomeninx
hepatitis B virus
hepatitis C virus
human immunodeficiency virus
positron emission tomography–computed tomography
Primary meningeal melanomatosis is a extreme, aggressive form of nonmetastatic invasion of the leptomeninges by malignant melanocytic cells. Melanocytes originate from the neural crest, and during the embryonic period, they can transfer to the eyes, skin, mucous membranes and leptomeninges. In exceptional cases, melanocytes may cause the growth of primary central nervous system (CNS) melanoma. There are two forms of primary CNS melanoma: solid tumours and diffuse meningeal melanomatosis. The diffuse form represents infiltrations into the subarachnoid space and the superficial parts of the brain without a solid mass. It can occur either as a local nodular infiltration or as meningitis . Primary diffuse meningeal melanomatosis is extremely rare and involves a high degree of malignancy and an unfavourable prognosis. The clinical manifestation is complex and includes seizures, verbal communication disorders, symptoms and signs of increased intracranial pressure, psychiatric disturbances, cranial nerve palsies, and spinal cord compression. A simultaneous manifestation of symptoms of damage to many CNS areas is typical. There are many diseases that they can mimic primary diffuse meningeal melanomatosis, including subacute meningitis, viral encephalitis, leukaemia, lymphoma, neurosarcoidosis, metastatic carcinoma, acute disseminated encephalomyelitis, viral encephalitis and subacute meningitis [2, 3]. If such symptoms are present in patients with no history or symptoms of cancer, they can pose a severe diagnostic and therapeutic problem.
Discussion and conclusions
We are presenting this case because of its rarity and the diagnostic difficulties that we encountered along the way. To date, the incidence of this disease has been reported to be 0.005 in 100,000 people. Meningeal melanomatosis is classified as a rare disease . Therapeutic failure is mainly associated with the lack of quick diagnosis and thus with the lack of effective treatment. The symptoms of meningeal melanomatosis are uncharacteristic and occur in patients between 20 and 70 years of age (: 42 years), although a child with this disease has been described . Meningeal melanomatosis affects the brain tissue in all of the cases described thus far and the spinal cord in 43% of cases. The most common symptoms include headache (46%), nausea or vomiting (37%), back or neck pain (24%) and weakness (22%). Other features include hydrocephalus, convulsions, ataxia, spinal cord cavity, cranial nerve palsies, intracranial haemorrhage and neuropsychiatric symptoms . In the present case, meningeal melanomatosis affected both the brain and the spinal cord, and most of these symptoms were observed in our patient. We primarily suspected our patient to have tuberculous meningitis, but no tests confirmed it. We did not decide to start any anti-tuberculosis treatment. In a similar case, Lee et al. also considered tuberculosis and decided to put the patient on an anti-tuberculosis regimen and steroids, but they did not achieve any improvement . In our patient, the CSF was tested many times, and the CSF was xanthochromic every time. The CSF showed inflammatory properties, CSF cultures were negative, and there were atypical cells, but the colour of the CSF remained unchanged. This was in contrast to Dean, who wrote that the brown colour of the CSF is suggestive of melanomatosis . Using MRI, we observed hyperintensity on T1-weighted images and hypointensity on T2-weighted images of the lesions. This was because of the paramagnetic effect of melanin, which contains stable organic free radicals and shortens both the T1 and T2 relaxation times in typical melanotic melanoma . On the other hand, the enhancement of the meninges with gadolinium contrast indicated a neoplastic process. Nevertheless, the diagnosis of neoplastic meningitis was suspected, and the paraclinical findings could be inconclusive. We did not perform 18F-choline PET/CT scans of the brain. Trinh et al. confirmed that an 18F-cholinethe PET/CT scan may show hypermetabolism in the affected tissue of the leptomeningeal [9, 10]. In most descriptions of meningeal melanomatosis, biopsy was recommended as a follow-up diagnosis. Our biopsy leptomeninges turned out to be nondiagnostic because of downloading probably part without changes. This was because the biopsy was performed on the frontal vault, but most of the melanomatotic changes were on the base of the brain. The fact that the diagnosis could not be established with biopsy is quite rare. Tekataş et al. repeated biopsy to confirm diagnosis . Our patient was not given any chemotherapy. Dacarbazine (16–20% efficacy) combined with radiotherapy and chemotherapy has recently proven to be the most effective treatment for melanomatosis . Schӓfer et al. described the first case of a patient with meningeal melanomatosis who achieved a good therapeutic effect from vemurafenib treatment . Oral doses of 960 mg twice a day caused the composition of the cerebrospinal fluid to normalize, and after some time, the neoplastic cells disappeared completely. Most surprisingly, neurological deficits subsided completely under conditions where a significant clinical improvement was uncommon. Vemurafenib is a BRAF inhibitor that has been shown to be effective in patients with BRAF V600E melanoma. For local changes, the efficacy of surgical treatment was confirmed . In summary, patients suffering from meningeal melanomatosis require very thorough clinical, radiological and, above all, histopathological diagnosis. Histopathological examinations should be performed in units with extensive experience. Early diagnosis gives us a chance to try the right treatment. Meningeal melanomatosis should be considered as a possible cause.
First, I would like to show my sincere gratitude to my colleagues MO and HB, who provided me with invaluable help and support in carrying out this study. Second, I want to thank my entire family.
TG analysed and interpreted the patient data regarding meningeal melanomatosis and was a major contributor in writing the manuscript. MO was responsible for collecting the material. He took part in the autopsy. He also chose suitable specimens and made the preparations with the appropriate staining. MO his knowledge contributed to the diagnosis. He gave valuable tips about the disease. HB made substantial contributions to the conception and design, acquisition of data, analysis and interpretation of data and was involved in drafting the manuscript or revising it critically for important intellectual content; this author also gave final approval of the version to be published. All authors read and approved the final manuscript.
No funding was received for this study.
Ethics approval and consent to participate
The authors declare that ethics approval was not required for this case report.
Consent for publication
Written informed consent was obtained directly from the patient’s mother for publication of this case report and any accompanying images at the same time.
The authors declare that they have no competing interests.
- 1.Aslan S, Gocmen R, Acar NP, Khasiyev F, Gumeler E, Soylemezoglu F, Tuncer A, Arsava EM, Topçuoglu MA, Unal Cevik I. Two cases of primary leptomeningeal melanomatosis mimicking subacute meningitis. Neuroradiol J 2018 Feb;31(1):42–46. doi: https://doi.org/10.1177/1971400917708581. Epub 2017 Jun 19.CrossRefGoogle Scholar
- 6.Harstad L., Hess K., Groves M. (2008) Prognostic factors and outcomes in patients with leptomeningeal melanomatosis. Society for Neuro-Oncology.Google Scholar
- 7.Hong Je Lee, Byeong-Cheol Ahn, Seong Wook Hwang, Suk Kyong Cho, Hae Won Kim, et al. (2013) F-18 Fluorodeoxyglucose PET/CT and post hoc PET/MRI in a case of primary meningeal Melanomatosis, Korean J Radiol kjronline.org 14(2), Mar/Apr 2013.Google Scholar
- 8.Seehusen DA, Reeves MM, Fomin DA. American family physician: cerebrospinal fluid analysis; 2003. p. 1103–8.Google Scholar
Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.