Atypical Melanocytic Cells in the Cerebrospinal Fluid of a 7‐Year‐Old Child With Headaches

A 7-year-old male presented with three episodes of headaches, aphasia, and right-sided hemiplegia within 3 months. Head CT scan and laboratory studies including complete blood counts were within normal limits. Brain magnetic resonance imaging (MRI) without contrast demonstrated subtle asymmetry of cerebral vasculature and no mass lesion. Magnetic resonance angiography (MRA) of the head was unremarkable. Cerebrospinal fluid (CSF) examination showed elevated CSF pressure, increased protein and cellularity, and decreased glucose. CSF cytospin showed many isolated or clustered large, atypical cells with round or oval nucleolated nuclei, and abundant basophilic cytoplasm with vacuoles and blebs (Figure 1A). Mitosis was present (red arrow). Flow cytometry study showed a cell population (orange) positive for CD117, and CD56, partially positive for CD13, negative for CD34, CD38, CD45, and CD61 (Figure 1B), and T-/B-cell markers. By immunohistochemical (IHC) stains (Figure 1C), the atypical cells were positive for HMB45 and Melan A, and negative for pan cytokeratin, GFAP, synaptophysin, and NeuN. The atypical cells were also positive for vimentin and S-100 (not shown). The diagnosis of melanocytic tumor was made with a comment favoring melanoma. Repeat MRI with and without contrast demonstrated diffuse enhancement of the meninges and linear enhancement around the spinal cord within the spinal canal, especially at lower thoracic levels. The patient had no evidence of cutaneous melanoma or giant congenital melanocytic nevi. A brain biopsy confirmed the presence of atypical melanocytic cells in the leptomeninges and cerebral cortical perivascular Virchow–Robin spaces. The diagnosis of primary meningeal melanomatosis was made. Primary meningeal melanoma (circumscribed) or melanomatosis (diffuse) is rare, especially in children [1, 2]. The clinical diagnosis can be delayed due to its nonspecific symptoms. The two most effective diagnostic techniques for leptomeningeal disease are imaging studies, especially T1-weighted MRI with gadolinium contrast, and cytological analyses [3]. Hydrocephalus commonly occurs in these patients due to tumoral obliteration of the basal cisterns [1]. Lumbar puncture typically shows elevated opening pressure, and decreased glucose and increased protein in CSF. As demonstrated in this case, the tumor cells can be seen in the CSF specimens of some patients. Molecular tests using tumor cells or cell-free DNA from CSF samples are also helpful in establishing the diagnosis [3]. Without clinical suspicion and the typical melanin pigment in the cells, as shown in this case, the recognition of melanoma cells in CSF can be difficult. For instance, this case required three rounds of IHC studies before arriving at the diagnosis. This case highlights the importance of awareness of rare diseases and proper workup when dealing with unusual cells in the CSF specimen. W.L. wrote up the article. S.S. and T.G. revised the final version of the article. All authors contributed to the diagnosis of this case. The authors have nothing to report. The authors have nothing to report. The authors declare no conflicts of interest. The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.