Melanocytes in the CNS arise from the multipotential cells residing in the lateral parts of the neural crest. They appear on the 22th day of embryonal development and become part of the pia mater and the arachnoid mater of the cerebrum and spinal cord. They are present in the highest concentration in parts of the meninges lining the posterior cranial fossa near the pons, cerebellum, medulla oblongata as well as the cervical segment of the spinal cord explaining why primary melanocytic tumours of the CNS are most commonly seen in these locations. Less frequent structures to be affected include the spinal cord, the pineal body, Meckel's cavity, the pontocerebellar angle and the remaining structures of the skull base.
Among the primary melanocytic tumours of the CNS originally described by Hayward (7), the WHO classification distinguishes generalised forms (diffuse melanocytosis and neurocutaneous melanosis) and focal forms: melanocytoma and malignant melanoma, which differ in histologic features and malignant potential determining the clinical course and prognosis. Focal neoplasms form isolated, often encapsulated and usually black, brownish or bluish foci. Pigment-free tumours have also been reported (8). The microscopic appearance of melanocytoma, which is considered to be a benign tumour, is dominated by arrangements of melanocytes of high maturity that form nests, whorls or intertwining fascicules that locally form storiform (wheel-and-spokes) structures. The tumour cells are morphologically similar, of spindle-like or epithelioid nature, with high content of melanin in the cytoplasm. Only exceptionally, areas of necrosis or bleeding are seen. The mitotic index is usually low (MIB-1 0-1%). Malignant melanoma, on the other hand, is a high-grade tumour characterised by cellular polymorphism, presence of multinucleated giant cells of variable pigment content. Areas of necrosis, bleeds and infiltration of the neural tissue adjacent to the tumour are more commonly seen, and the proliferative activity of the cells is high (MIB 1 usually exceeds 3%). Brat et al. distinguished also intermediate-grade tumours, characterised by an elevated MIB-1 (1-4%) and traits of neural tissue infiltration despite benign histologic appearance of the tumour (2). There have also been reports of several cases of malignant transformation of the tumour (13, 15, 23, 25, 26) confirmed by histopathological examinations of specimens obtained during subsequent surgeries. The histopathological features that would allow to predict the course of the disease have not been established.
An overwhelming majority of melanocytic tumours of the CNS are malignant melanoma metastases. No radiological or histopathological criteria have been established to differentiate a primary tumour from a metastasis and a thorough search for a potential melanoma in other regions of the body is mandatory.
Melanocytic tumours of the CNS have a specific presentation on MRI associated with their high content of melanin. These include tumour hyperintensity in T1-weighted and FLAIR sequences and hypointensity in the T2-weighed images. The degree of concentration of melanin corresponds with the T1WI hyperintensity (11, 20). They undergo a homogenous contrast enhancement, however as they are hyperintense before contrast administration, their enhancement cannot always be assessed. Owing to their rarity they are routinely misdiagnosed, the most common diagnosis being a meningioma. This is also what happened in our case; radiological suspicion of an atypical meningioma was supported by the narrowing of the cavernous segment of the internal carotid artery and contrast enhancement of the dura mater lining the middle cranial fossa adjacent to the parasellar region. Another common diagnosis is a pituitary macroadenoma with signs of intratumour bleeding (1, 3, 27); the T1-hyperintensity could be explained by the presence of blood degradation products. The radiological presentation of the tumour was not suggestive of other diseases of this region which could match those MRI characteristics, e.g. a craniopharyngioma containing a calcification or a spindle cell oncocytoma.
Sakata underlined the importance of distinct angiographic features of a sellar melanocytoma (17). In their case, angiography clearly demonstrated hypervascularity of the tumor explaining the massive intraoperative bleeding unusual for a pituitary adenoma which was also encountered in our case. We did not however regard a preoperative angiography to be necessary.
The sella turcica and the optic chiasm area are an exceptional location of these rare tumours. There have been 16 reports of sellar melanocytic tumours, 8 of which were diagnosed as primary melanoma (1, 3, 5, 8, 12, 18, 19, 22), 7 as melanocytoma (4, 6, 16, 17, 21, 24, 27) (table 1); in one case the exact diagnosis was not précised (10). Clinical presentation is uncharacteristic and the symptoms are typically related to the compression of the surrounding structures by the tumour. The most common manifestation was deterioration of vision, visual field impairment and endocrine abnormalities (hyperprolactinemia and pituitary insufficiency) caused by compression of the stalk and the anterior lobe of the pituitary gland. Diplopia and eye pain resulting from infiltration of the cavernous sinus were less frequent. The treatment of choice is gross total removal of the tumour which allows to improve vision and the endocrine function of the pituitary. As regards efficiency of adjuvant treatment (radiotherapy), there is no clear proof of its utility (14). Radiotherapy was offered to 5 of the 8 reported patients including our case however the longest survival periods have been reported for the two patients who both underwent complete tumour removal and did not receive radiation (17, 27). This may show that radiation therapy does not offer any substantial benefits and surgery is the most valuable treatment for melanocytoma. There is also uncertainty concerning potential negative effects of radiation treatment on tumour behaviour and the incidence of malignant transformation. Owing to the rarity of these tumours and little data this problem, however, remains unsolved.
The efficacy of treatment of primary intrasellar melanocytic tumours is limited, with patients diagnosed of a melanocytoma faring much better than those with a primary melanoma. In case of the latter diagnosis survival period has rarely exceeded few years irrespectively of the extent of resection nor the use of adjuvant therapy (radiation and chemotherapy in one case (5)). The results of treatment of melanocytoma have been more favorable; the longest survival has exceeded for this moment 7 years in the case reported by Sakata (17). The most probable reason of relapse is incomplete tumour resection with its subsequent regrowth or malignant transformation. It is worth to underline, however, that in our case the results of histologic examination even at the second surgery just before the rapid expansion of the tumour were unanimously characteristic of a benign lesion. It could be still possible that the specimens might have not included the areas of maximum malignancy of the tumour which in turn could have been underestimated.
In conclusion, diagnosis of a melanocytoma or other melanocytic tumours should be taken into consideration in case of an unusual MRI appearance of a sellar mass (hyperintensity on T1 weighted images before contrast administration). As in surgery for pituitary adenoma, the extrasellar expansion of a melanocytoma is an important factor limiting the feasibility of its complete removal. Radiotherapy should probably be offered after incomplete tumour resection, however its benefits following total removal could be outweighed by an increased possibility of the malignant transformation of the tumour. In spite of benign histopathological features, the course of the disease is unpredictable and warrants close surveillance and serial MRI imaging.
Conflict of interest: The authors declare that they have no conflict of interest.
Contributed by Zielinski Grzegorz, Podgorski Andrzej, Maksymowicz Maria, Witek Przemyslaw, Koziarski Andrzej