Primary intradural cervical spine melanocytoma: A rare tumor and review of literature
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/neuroindia.NI_171_16
Source of Support: None, Conflict of Interest: None
Primary central nervous system (CNS) melanocytoma is a rare disease originating from leptomeningeal melanocytes. It is considered to be the benign end of the neoplastic lesions of the leptomeningeal melanocytes. The most common site of involvement in the spinal cord is the cervical region. The differential diagnosis of other pigmented CNS lesions producing melanin include melanoma, schwannoma, and meningioma. We present a case of primary CNS melanocytoma having an intradural location in the cervical spine, describing its symptoms, radiological features, histological findings, treatment given, and discuss current management option, prognosis, and the review of literature.
A 20-year old male patient presented with progressively increasing right-sided weakness, gait instability, numbness, and a tingling sensation in bilateral upper and lower limbs, as well as decreased urinary flow for 4 months. There were no symptoms suggestive of increased intracranial tension, seizures or an episode of unconsciousness.
Clinical examination revealed an increased tone of lower limbs with no sensory/motor deficits. Magnetic resonance imaging (MRI) of the brain and cervical spine revealed a 1.2 × 1.3 × 1.4 cm intradural, extramedullary space occupying lesion at the C1–C2 vertebra level. The lesion was isointense on T2-weighted images (T2WI) as well as short T1 inversion recovery (STIR), and mildly hyperintense on T1-weighted images (T1WI), causing compression and displacement of the spinal cord with focal cord edema. Diffuse homogenous enhancement of the lesion was noted on post-contrast study. Punctate hypointensity was noted within the lesion on gradient echo sequences (GRE) suggestive of intralesional hemorrhage or calcification. A radiological diagnosis of a meningioma with intralesional hemorrhage or calcification was suggested [Figure 1]. Following a C1–C2 laminectomy with excision of the space occupying lesion, a referral for radiotherapy (RT) was made.
Histopathologically, the gross examination showed multiple dark brown soft tissue bits together measuring 2.2 × 1.8 × 0.5 cm. On microscopic examination, the tumor cells were disposed in sheets and nests. The tumor cells were large, oval-to-polygonal in shape with oval nuclei, finely dispersed chromatin, occasionally prominent small eosinophilic nucleoli, and moderate-to-abundant cytoplasm filled with melanin pigment. Mitosis was <1/10 high power field. There was no necrosis or invasion seen. On immunohistochemistry, tumor cells were HMB-45, epithelial membrane antigen (EMA), and S100 positive. Ki-67 was inconclusive. Due to the absence of pleomorphism, mitosis, and necrosis, as well as the characteristic immunohistomorphological features, the diagnosis of melanocytoma was confirmed [Figure 2],[Figure 3],[Figure 4].
Following surgery, there was no residual neurological deficit. No pigmented lesions in the skin or mucosa were discovered; the chest X-ray and abdominal ultrasonography were normal.
A postoperative MRI of the cervical spine revealed mild expansion of the upper cervical cord at the C1–C2 level with T2W1 hyperintensity, predominantly involving the posterior and bilateral lateral columns. However, no post-contrast enhancement was seen. Postoperative bony changes were seen at the C1–C2 level with a 3.8 × 2.2 × 2.5 cm collection in the suboccipital region. Thus, there was no overt residual disease [Figure 5]. Cerebrospinal fluid (CSF) cytology was negative.
He was offered adjuvant radiotherapy (RT) to decrease the probability of local recurrence and was treated with three-dimensional conformal radiotherapy (3D-CRT) to the tumor bed in a dose of 45 Gy in 25 fractions over 5 weeks with 6 MV photons, which he tolerated well and remained asymptomatic. He has been advised a periodic follow-up with MRI imaging. He is currently without clinical recurrence at a 12 months follow up.
The World Health Organization's (WHO) classification of tumors of the central nervous system classify primary melanocytic lesions into four categories – diffuse melanocytosis, melanocytoma, malignant melanoma, and meningeal melanomatosis. Of these four categories, only melanocytomas and malignant melanomas present as solitary lesions. Meningeal melanocytomas and primary malignant melanomas are similar in their origin from leptomeningeal melanocytes; however, they represent both ends of the spectrum, ranging from a lesion that is benign in appearance and behaviour to one that is overtly malignant. Brat et al., have classified melanocytic lesions of the CNS as low grade (melanocytoma), intermediate grade, and high grade melanoma. The differential diagnosis of other pigmented CNS lesions producing melanin include schwannoma, medulloblastoma, neurofibroma, meningioma, and astrocytoma. Immunohistochemistry, ultrastructural and radiological features are usually helpful in distinguishing these lesions.
The term melanocytoma was first given by Limas and Tio in 1972 to describe a heavily pigmented foramen magnum tumor. Melanocytes are found in the highest concentration in the medulla oblongata and upper cervical levels of spinal leptomeninges., Therefore, the most common site for its presence is the cervical region of the spinal cord. Clinically, the tumor presents commonly in the fifth decade of life and females are affected more than males. In the spinal cord, the lesions usually present with a myeloradiculopathy.
Liubinas et al., reviewed the literature of a primary melanocytic neoplasm consisting of case reports and case series and reported the lack of a strict diagnostic criteria in literature.
Radiologically, on MRI, melanocytomas are typically hyperintense on T1WI, hypointense on T2WI, and hyperintense on FLAIR images, enhancing homogenously with gadolinium., These variations are thought to be due to the degree of the paramagnetic effect of the stable free radicals in melanin and also due to intratumoral hemorrhage., Although MRI features point towards the presence of melanin, it is difficult to determine whether the lesion is benign or malignant. Melanocytomas are generally dense, extra-axial lesions with a dural attachment, which may not show distinct margins.,
Melanocytomas on immunohistochemistry show positivity for monoclonal melanoma antibody (HMB-45), S-100 protein, and vimentin antibodies (which rarely appear in malignant melanoma) and are negative for epithelial membrane antigen [EMA] (indicator of meningioma) and Leu7 (indicator of schwannoma).,, Halder et al., reported the use of an intraoperative squash cytopathology for the diagnosis of primary meningeal melanocytoma.
Based on multiple small case reports and series, surgical excision is the primary mode of treatment for melanocytoma, as shown in [Table 1].,,,,,, Total excision is better than subtotal excision.,,,, Although melanocytomas are benign tumors, they may show an aggressive behaviour after complete or incomplete surgery, with recurrence possible even after apparently complete excision.,,, Therefore, adjuvant radiation therapy has been advised in cases of both complete and incomplete resection. Rades et al., in a series of 89 intracerebral and spinal melanocytomas, found that the 5-year survival rate was 100% when RT was added in either complete or incomplete resection and only 46% after only a incomplete resection. RT was given to the tumor bed region in most of the cases. Patients receiving 30–40 Gy were compared with those receiving 45–55 Gy for local control. It revealed a trend toward better local control for radiation doses of 45–55 Gy versus doses of 40 Gy. Rades and Schild have proposed a high-dose local radiation, even in cases in whom complete tumor resection has been achieved, in order to prevent local recurrence., Very few long-term follow-up studies have been presented, especially in patients with recurrence after radiographic gross total resection, to show which treatment provides the best survival benefit.
Local control rates have been shown to be four times higher if complete resection is done; incomplete resection mandates the use of adjuvant radiation therapy.,,,, More aggressive approaches have also been advocated, including re-resection of the recurring tumor and reservation of adjuvant radiotherapy for lesions that cannot be completely resected.,
Jaiswal et al., reported local recurrence following survival of 12 years. A few cases have shown CNS invasion as well as local recurrence, if incompletely removed. Malignant transformation of a melanocytoma and associated leptomeningeal spread throughout the neuraxis have been reported.,
Radiosurgery has been given in some cases who have subsequently showed an improved clinical outcome; however, very limited data is available regarding radiosurgery for this entity at present. There is no definite evidence for giving chemotherapy. A few studies using agents such as methotrexate and interleukins have shown a promising result. However, questions remain regarding the optimal treatment after incomplete total resection and how recurrences should be managed. Melanocytoma of the CNS is a rare benign tumor and complete excision of the tumor should be attempted, whenever feasible. Adjuvant RT decreases the chances of local recurrence, however, there is no consensus regarding the adjuvant management.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]