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Table of Contents
Year : 2019  |  Volume : 2  |  Issue : 2  |  Page : 124-127

An unusual occurrence of melanotic neuroectodermal tumor of infancy with malignant features

1 Department of Neuropathology, National Institute of Mental Health and Neurosciences, Bengaluru, Karnataka, India
2 Department of Neurosurgery, National Institute of Mental Health and Neurosciences, Bengaluru, Karnataka, India
3 Department of Neuroimaging and Intervention Radiology, National Institute of Mental Health and Neurosciences, Bengaluru, Karnataka, India

Date of Submission23-Oct-2019
Date of Acceptance03-Nov-2019
Date of Web Publication10-Jan-2020

Correspondence Address:
Prof. Anita Mahadevan
Department of Neuropathology, National Institute of Mental Health and Neurosciences, Bengaluru - 560 029, Karnataka
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/IJNO.IJNO_17_19

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Melanotic neuroectodermal tumor of infancy (MNTI) is a rare, commonly benign, congenital pigmented neoplasm that originates from the neural crest. In contrast to peripheral MNTI usually found in the maxilla, cerebral MNTI has a much worse outcome. We report a case of intracranial MNTI with malignant features in a 2-year-old child. The clinical, radiological, histological, and immunohistochemical findings are described, and the published data on this rare entity are reviewed.

Keywords: Malignant, melanotic neuroectodermal tumor of infancy, outcome

How to cite this article:
Rao S, Chavali P, Tyagi G, Savardekar A, Saini J, Mahadevan A. An unusual occurrence of melanotic neuroectodermal tumor of infancy with malignant features. Int J Neurooncol 2019;2:124-7

How to cite this URL:
Rao S, Chavali P, Tyagi G, Savardekar A, Saini J, Mahadevan A. An unusual occurrence of melanotic neuroectodermal tumor of infancy with malignant features. Int J Neurooncol [serial online] 2019 [cited 2022 Jun 27];2:124-7. Available from: https://www.Internationaljneurooncology.com/text.asp?2019/2/2/124/275534

  Introduction Top

Melanotic neuroectodermal tumor of infancy (MNTI) is a rare tumor of the head and neck. They mainly occur in infants and have a benign course. However, recurrences, malignant transformation, and metastasis of MNTI are rare. We report a case of a 2-year-old girl who presented with a parieto-occipital mass diagnosed as MNTI on histopathological examination and review published reports of this rare entity.

  Case Report Top

A 26-month-old female, with normal perinatal and developmental history, presented with complaints of progressive left hemiparesis and gait ataxia of 5-month duration. She later developed difficulty in swallowing liquids, drooling of saliva from the angle of the mouth, and facial asymmetry. The patient became drowsy and refused feeds for 3 days when she was brought to the emergency services of our hospital. On examination, the child was drowsy, irritable with bilateral sixth and seventh nerve palsy. Gag and cough reflexes were impaired. Computed tomography (CT) scan of the brain revealed a large extra-axial, slightly hyperdense, intensely contrast-enhancing lesion arising from the left temporo-parieto-occipital convexity extending into the occipital base, causing thickening of the bone with enhancing soft-tissue growth causing parenchymal buckling.

The patient underwent placement of the right Kocher's point frontal external ventricular drain followed by internalization as ventriculoperitoneal shunt. The patient's sensorium improved following cerebrospinal fluid (CSF) diversion. On detailed clinical examination, she was found to have truncal ataxia, left hemiparesis (MRC grade 4/5), and bilateral extensor plantars. Magnetic resonance imaging (MRI) of the brain showed a large extra-axial, T1 and T2/fluid-attenuated inversion recovery heterointense lesion arising from the left temporo-parieto-occipital convexity with extension into the basiocciput and petrous temporal bone. Thickening of the calvarial bone as well as the petrous apex was observed. The lesion was compressing the brain parenchyma with a significant mass effect over the brainstem and left cerebellar hemisphere. On contrast administration, the lesion showed intense and homogeneous enhancement [Figure 1]a [Figure 1]b [Figure 1]c [Figure 1]d [Figure 1]e [Figure 1]f. The diagnoses considered as per radiological findings included high-grade dural lesions such as sarcoma/malignant meningioma or peripheral primitive neuroectodermal tumor (PNET).
Figure 1: Magnetic resonance and computed tomography imaging of the patient. (a and b) A large, T1 and T2 heterointense, extra-axial lesion involving the left temporo-parieto-occipital region on magnetic resonance imaging. (c) Susceptibility-weighted magnetic resonance imaging of the lesion showing multiple microbleeds suggestive of a high-grade tumor. (d and e) The lesion shows intense and homogeneous enhancement on contrast-enhanced T1-weighted magnetic resonance sequence (D-axial image, E-coronal image). (f) Axial computed tomography image demonstrates the unusual bony hypertrophy of the temporo-occipital and petrous bones. The T1-weighted magnetic resonance sequence showing hyperintense areas and computed tomography showing hypertrophic/hyperostotic bony changes are the highlights of the imaging studies

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The child underwent left temporo-parieto-occipital craniectomy with subtotal decompression of the lesion with augmentative duroplasty and titanium mesh cranioplasty. Intraoperatively, the calvarial bone was noted to be thickened, with blackish pigmentation. The underlying dura was found to be fibrotic and thickened with black discoloration. The tumor was primarily extra-axial, with a variegated consistency (firm to gritty in the central areas and fleshy, highly vascularized at the periphery), and densely adhered to the dura; however, no clear arachnoid plane was found between the tumor and brain tissue, suggestive of arachnoid and pial infiltration.

The child recovered well from the surgery and anesthesia. She was kept on ventilatory support in lieu of weak cough reflex due to lower cranial nerve palsy. On postoperative day 5, the child developed fever and deteriorated in sensorium. She was diagnosed to have surgical site infection and  Escherichia More Details coli was identified as the causative organism. The patient was started on appropriate antibiotics in accordance with the culture sensitivity reports; however, she deteriorated further in sensorium, and serial CT scans of the brain showed progressively increasing ventriculomegaly suggestive of shunt malfunction. The shunt was removed and an extraventricular drain was placed. E. coli was isolated from the shunt CSF. The child succumbed to sepsis secondary to meningitis/ventriculitis following surgical site infection on postoperative day 14.

Histopathological examination of the resected tissue revealed a tumor with a typical biphasic pattern infiltrating the dura and eliciting a dense desmoplastic stromal response. Two distinct tumor populations were identified – with small, round, primitive-appearing cells and large epithelioid/rhabdoid cells. An organoid pattern was observed with the small, round, primitive cells arranged in nests, alveoli, or long tubules surrounded by the larger rhabdoid cells. Some of the large cells contained intracytoplasmic brownish-black pigment (melanin) [Figure 2]a and [Figure 2]b. Synaptophysin was positive in both the components [Figure 2]c. CD99 revealed diffuse membrane labeling [Figure 2]d. The large cells were labeled by pancytokeratin and HMB-45 [Figure 2]e and [Figure 2]f. In the primitive neuronal component, mitosis was brisk and apoptosis was prominent with a proliferation index of >50% that was in contrast to a lower proliferative index of 20% in the larger/pigmented cells. INI-1 expression was retained in the tumor cells excluding the diagnosis of atypical teratoid/rhabdoid tumor [Figure 2]f. Lin28A and BRAFV600E were negative in the tumor cells.
Figure 2: Microphotograph of the tumor reveals a characteristic alveolar pattern of arrangement of tumor cells. The central nest is composed of primitive appearing cells with high nuclear-cytoplasmic ratio and scant cytoplasm (a) lying within alveolar spaces that are lined by rhabdoid-like cells having abundant cytoplasm (b, arrow). These cells at places demonstrate intracytoplasmic melanin pigment (b, inset). The central nest of primitive cells shows intense labeling by neuronal marker synaptophysin (c) and CD99 (d). The outer layer of rhabdoid-like cells lining the alveoli is labeled by pancytokeratin (e) and HMB-45 (f) but have retained INI-1 expression (e, inset). MIB-1 labeling is high in the small primitive-appearing tumor cells (f, inset). (a and b: H and E; c-f: immunoperoxidase; Magnification = scale bar)

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  Discussion Top

MNTI is a rare neoplasm affecting infants, with very few cases being reported in older children and adults. The mean age of the affected patients is 4.3 months. Of the documented cases, 8.9% of the MNTI are found in children older than 12 months of age. Male predilection has been noted in a few studies.[1] The tumor is commonly located in the maxilla, mandible, brain, and skull. Long bones, epididymis, mediastinum, soft tissues of the extremities, shoulder, ovary, uterus, and thigh are the extracranial sites recorded. It is commonly reported to be a benign tumor with a tendency for the local invasion.[2]

The tumor was first described by Krompecher in 1918 in a 2-month-old infant and was termed as congenital melanocarcinoma as it was associated with a developing tooth and elements of the dental lamina.[1] Twenty other synonyms have been used for this entity including pigmented epulis, melanotic ameloblastoma, melanotic progonoma, melanotic adamantinoma, and melanocytic neuroectodermal tumor, which reflect its uncertain histogenesis.

The histogenesis of MNTI has long been debated. Histological, immunohistochemical, and ultrastructural features point toward a neural crest origin. Halpert and Patzer suggested that the tumor arose from the entrapment of retinal anlage in the embryologic fusion lines of developing maxilla. Misugi et al. hypothesized the tumor's origin from the neural crest.[3] Borello and Gorlin also proposed neural crest origin and recommended the usage of the term MNTI, based on the increased excretion of Vanillyl mandelic acid (VMA) in a 3-month-old child with MNTI, which returned to normal following tumor removal.[4] Electron microscopic studies have revealed abundant premelanosomes and melanin granules in the pigmented epithelial cells with nonmelanotic neuroblastic cells and a poorly differentiated anaplastic cell component.[5]

CT imaging typically reveals a well-demarcated, hyperdense lesion with contrast enhancement and hyperostosis of the adjacent bone.[6] MRI shows a T1 hyperintense and T2 hypointense lesion due to the presence of melanin.

Histopathology of the tumor has a distinctive morphology with epithelioid/polygonal cells lining the tubules with primitive-looking cells in the center. Intracytoplasmic pigment is usually observed in the larger lining cells which are HMB-45 and cytokeratin positive, whereas the small round cells express synaptophysin and Neuron specific enolase (NSE) similar to our case. Immunohistochemical findings in other studies suggest that MNTI is a PNET with polyphenotypic expression of neural and epithelial markers, melanin production, and occasional rhabdomyoblastic, glial, ganglionic, and osseous differentiation.[7] Pettinato et al. evaluated 10 cases with immunohistochemistry, flow cytometry, and electron microscopy, and based on the findings, they suggested that MNTI represents a dysembryogenetic neoplasm that recapitulates the retina at 5 weeks of gestation.[8] Differential diagnoses include other small round cell tumors such as rhabdomyosarcoma, lymphoma, peripheral PNET, and atypical teratoid/rhabdoid tumor.[9]

MNTI, although considered to be benign, is known to be locally aggressive. They tend to invade the local structures. Recurrence rates range from 10% to 20% of cases.[1] Metastasis has been documented in 6.5% of MNTI, involving the lymph nodes, liver, bone, omentum, peritoneum, and pleura. Malignant MNTI has been reported in the maxilla, mandible, cerebellum, uterus, ovary, epididymis, and femur.[2] The increased expression of Ki-67 and CD99 has been correlated with more aggressive behavior, being observed in cases with malignant transformation, similar to our case. However, criteria to define malignant MNTI are not well established. Very few studies have observed these parameters in MNTI. The early recurrences, presenting within a few months after surgery, are attributed to incomplete excision or diffuse bone marrow invasion by tumor cells because of the lack of a fibrous capsule, tumor dissemination during surgery, or multicentricity of the lesion.[10]

Our patient was symptomatic for 1 year and presented with a large mass at the age of 2 years. Histopathology of the tumor had characteristic features of MNTI. In addition, the cells expressed CD99 and high MIB-1 labeling as described in the malignant MNTI. Malignant transformation of the tumor could have occurred during the 1 year that the patient was symptomatic.

Since MNTIs are rare, treatment strategies for malignant MNTIs have not yet been defined. Molecular studies on genetic alterations are also limited. Recent studies have tried to identify the molecular alterations in MNTI. Gomes et al. identified BRAFV600E mutation in MNTI.[11] Barnes et al. described germline mutation of CDKN2A and RPLP1-C19MC fusion in a case of MNTI.[12] In our case, BRAFV600E was negative. Lin28A, which is a surrogate marker for C19MC fusion, was also negative.

The treatment of choice for MNTI is a radical excision.[13] There is a suggestion that these tumors may be chemosensitive rather than radiosensitive. However, malignant MNTIs require aggressive treatment.[14] Adjuvant therapy has been used with varying results in malignant MNTI.

There is a need to identify more cases of malignant MNTIs and evolve definitive criteria for its diagnosis and determine the treatment protocol.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Kruse-Lösler B, Gaertner C, Bürger H, Seper L, Joos U, Kleinheinz J. Melanotic neuroectodermal tumor of infancy: Systematic review of the literature and presentation of a case. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2006;102:204-16.  Back to cited text no. 1
Rachidi S, Sood AJ, Patel KG, Nguyen SA, Hamilton H, Neville BW, et al. Melanotic neuroectodermal tumor of infancy: A systematic review. J Oral Maxillofac Surg 2015;73:1946-56.  Back to cited text no. 2
Misugi K, Okajima H, Newton WA Jr., Kmetz DR, Delorimier AA. Mediastinal origin of a melanotic progonoma or retinal anlage tumor: Ultrastructural evidence for neural crest origin. Cancer 1965;18:477-84.  Back to cited text no. 3
Borello ED, Gorlin RJ. Melanotic neuroectodermal tumor of infancy – A neoplasm of neural crese origin. Report of a case associated with high urinary excretion of vanilmandelic acid. Cancer 1966;19:196-206.  Back to cited text no. 4
Mendis BR, Lombardi T, Tilakaratne WM. Melanotic neuroectodermal tumor of infancy: A histopathological and immunohistochemical study. J Investig Clin Dent 2012;3:68-71.  Back to cited text no. 5
Atkinson GO Jr., Davis PC, Patrick LE, Winn KJ, Ball TI, Wyly JB. Melanotic neuroectodermal tumor of infancy. MR findings and a review of the literature. Pediatr Radiol 1989;20:20-2.  Back to cited text no. 6
Barrett AW, Morgan M, Ramsay AD, Farthing PM, Newman L, Speight PM. A clinicopathologic and immunohistochemical analysis of melanotic neuroectodermal tumor of infancy. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2002;93:688-98.  Back to cited text no. 7
Pettinato G, Manivel JC, d'Amore ES, Jaszcz W, Gorlin RJ. Melanotic neuroectodermal tumor of infancy. A reexamination of a histogenetic problem based on immunohistochemical, flow cytometric, and ultrastructural study of 10 cases. Am J Surg Pathol 1991;15:233-45.  Back to cited text no. 8
Goswami M, Bhushan U, Mohanty S. Melanotic neuroectodermal tumor of infancy. J Clin Diagn Res 2016;10:ZJ07-8.  Back to cited text no. 9
Mosby EL, Lowe MW, Cobb CM, Ennis RL. Melanotic neuroectodermal tumor of infancy: Review of the literature and report of a case. J Oral Maxillofac Surg 1992;50:886-94.  Back to cited text no. 10
Gomes CC, Diniz MG, de Menezes GH, Castro WH, Gomez RS. BRAFV600E mutation in melanotic neuroectodermal tumor of infancy: Toward personalized medicine? Pediatrics 2015;136:e267-9.  Back to cited text no. 11
Barnes DJ, Hookway E, Athanasou N, Kashima T, Oppermann U, Hughes S, et al. A germline mutation of CDKN2A and a novel RPLP1-C19MC fusion detected in a rare melanotic neuroectodermal tumor of infancy: A case report. BMC Cancer 2016;16:629.  Back to cited text no. 12
Dashti SR, Cohen ML, Cohen AR. Role of radical surgery for intracranial melanotic neuroectodermal tumor of infancy: Case report. Neurosurgery 1999;45:175-8.  Back to cited text no. 13
Neven J, Hulsbergen-van der Kaa C, Groot-Loonen J, de Wilde PC, Merkx MA. Recurrent melanotic neuroectodermal tumor of infancy: A proposal for treatment protocol with surgery and adjuvant chemotherapy. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2008;106:493-6.  Back to cited text no. 14


  [Figure 1], [Figure 2]


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