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Year : 2011  |  Volume : 7  |  Issue : 3  |  Page : 368-372

Malignant melanotic neuroectodermal tumor of infancy arising in the mandible

1 Department of Surgical Oncology, Cancer Institute (WIA), Chennai, India
2 Department of Pathology, Cancer Institute (WIA), Chennai, India

Date of Web Publication2-Nov-2011

Correspondence Address:
Arvind Krishnamurthy
Department of Surgical Oncology, Cancer Institute (WIA), 36, Sardar Patel Road, Adyar, Chennai - 600 020
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0973-1482.87018

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How to cite this article:
Krishnamurthy A, Vaidhyanathan A, Majhi U. Malignant melanotic neuroectodermal tumor of infancy arising in the mandible. J Can Res Ther 2011;7:368-72

How to cite this URL:
Krishnamurthy A, Vaidhyanathan A, Majhi U. Malignant melanotic neuroectodermal tumor of infancy arising in the mandible. J Can Res Ther [serial online] 2011 [cited 2020 Jun 4];7:368-72. Available from: http://www.cancerjournal.net/text.asp?2011/7/3/368/87018


Melanotic neuroectodermal tumor of infancy (MNTI) is a rare, rapidly growing pigmented neoplasm of neural crest origin that primarily develops in the maxilla of infants during the first year of life. [1],[2] Mandibular lesions are rare and account for 6% of all cases. Of more than 350 cases reported in the English literature, to the best of our knowledge only 23 cases of mandibular MNTI have been reported till date. We discuss the clinicopathological and immunohistochemical features of a malignant mandibular MNTI in a 6 month old infant.

A 6-month-old male infant with no prior relevant medical history reported to our center with a swelling in his right cheek. The parents first noticed the swelling two months prior to their first consultation. An incisional biopsy was performed, after which the infant was referred to our centre and a diagnosis of MNTI was made. Clinical examination showed a normally developed male infant weighing 6 kg. The maternal, birth and family histories were unremarkable. Extra oral examination revealed a single, immobile, well circumscribed lesion of approximately 2 × 1 cm over the right body of the mandible. The swelling was firm and non tender on palpation, and could not be appreciated on intraoral examination. There was no cervical lymphadenopathy. He presented with a scar in relation to the previous biopsy site. The rest of the physical examination was unremarkable.

The computerized tomogram (CT) of the head and neck scan revealed a 1.7 × 1 cm, well defined, mildly hyperdense lesion overlying the outer cortex of the right body of the mandible [Figure 1]a. The bone scan showed an uptake corresponding to the extra oral swelling [Figure 1]b. His chest skiagram, urinary vanillyl mandelic acid (VMA) levels, bone marrow aspiration and biopsy were normal. The tumor was accessed by an external approach along the previous incision overlying the mandible. [Figure 2]a and b The entire tumor was excised en bloc along with a vertical rim of the mandible (reverse marginal mandibulectomy). The right mandibular deciduous canine and the first molar tooth were extracted as it was significantly displaced to the buccal aspect and had no osseous support. Primary closure was achieved.
Figure 1: (a) Axial computerized tomogram scan image showing the tumor. (b) Bone scan image showing hot spot in the right horizontal ramus of mandible

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Figure 2: (a) Pre operative clinical photograph. (b) Post operative clinical photograph after en bloc excision

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The gross histopathology revealed a 3 × 3 × 2 cm specimen of marginal mandibulectomy along with overlying skin and soft tissue. The microscopic examination showed the eroded bone along with dense fibrocollagenous tissue, infiltrated by a biphasic tumor consisting of alveolar masses and nests of large atypical epithelioid cells, and nodular collections of poorly differentiated small round to oval neuroblastoma like cells. The neuroblastic cells showed scanty cytoplasm and hyperchromatic nuclei, mitotic activity was not well made out. The larger epithelioid cells showed moderate cytoplasm and round to oval vesicular nuclei with prominent nucleoli. The cytoplasm contained variable amounts of dark brown melanin pigment. Mitotic activity varied from 0-1/high power field. The mandible was focally involved; however, the resected bone and soft tissue margins were free of tumor. The immunohistochemical expression for the various epithelial, melanocytic and neural markers [Figure 3], [Figure 4] and [Figure 5], a-d is depicted in [Table 1]. The large epithelioid cells showed positivity to Human Melanoma Black (HMB- 45) and Melan A, additionally the Fontana stain for melanin pigment was positive and the melanin bleach confirmed the presence of the melanin pigment in these cells. 40% of the tumor cells showed nuclear positivity to Ki67. The stromal fibroblastic cells showed positive reaction to desmin, muscle actin and Smooth Muscle Actin (SMA), while the tumor cells were negative for the same.
Figure 3: (a) H and E ×100-Showing large pigmented epithelioid and small neuroblastoma cells. (b) - Immunohistochemical staining, ×100-Human Melanoma Black 45 positivity by pigmented epithelioid cells. (c) - Immunohistochemical staining, ×100-Fontana stain demonstrating the melanin pigment (d) Immunohistochemical staining, ×100-Bleach staining showing removal of melanin pigment

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Figure 4: (a) IHC ×100-Showing CD 99 positivity in both the pigmented epitheloid and neuroblastic cells. (b) Immunohistochemical staining, ×100-Showing CD 56 positivity in both the pigmented epithelioid and neuroblastic cells. (c) Immunohistochemical staining, ×100-Showing Chromogranin positivity in both the pigmented epithelioid and neuroblastic cells (d) Immunohistochemical staining, ×100-Showing S 100-P
positivity in both the pigmented epithelioid and neuroblastic cells

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Figure 5: (a) Immunohistochemical staining, ×100-Showing keratin positivity by large epitheloid cells. (b) Immunohistochemical staining, ×100-Showing mitosis in the tumor cells. (c) Immunohistochemical staining, ×100-Showing vimentin positivity in both the pigmented epithelioid and neuroblastic cells. (d) Immunohistochemical staining, ×100-Showing nuclear positivity to Ki-67

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Table 1: Immunohistochemistry profi le of our patient in the case report

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The final impression was malignant MNTI considering the cellular morphology, presence of mitosis and immunoreactivity to CD99 and Ki-67. The postoperative course of the infant was uneventful, he is disease free and on regular follow up for over a year, has shown a good cosmetic and functional outcome.

MNTI is an uncommon pigmented neoplasm of neural crest origin that primarily affects the jaws of newborn infants. Described as early as 1918 by Krompecher as a congenital melanocarcinoma, there have been numerous changes in its nomenclature, perhaps in uncertainty regarding its' histogenesis, a few of the popular terminologies being retinal anlage tumor, melanotic progonoma, and melanotic ameloblastoma.

Borello and Gorlin in the year 1966 observed that the tumor elaborated high levels of Vanillyl mandelic acid (VMA), classically found in pheochromocytomas as well as in other neuroectoblastic tumors suggesting a neuroectodermal origin for this lesion, and in turn their proposal to delineate the tumor as a melanotic neuroectodermal tumor of infancy was made. [3] Nevertheless, a significant number of cases of MNTI associated with normal levels of VMA appear in the literature.

Presently, based on biochemical, histochemical, ultrastructural, and immunophenotypic studies, there is a general agreement that that the tumor's origin is from the neural crest. [4],[5],[6] These tumors have a marked predilection (>90%) for the head and neck regions. [1],[2] Although occurrence in other intraosseous and extraosseous anatomic locations have been described, including the epididymis, testis, soft tissue of the cheek, and mediastinum, the lesions predominantly have been known to arise in the anterior maxilla (68% to 80%), skull (10.8%), mandible (5.8%) and brain (4.3%). [1],[2]

Although MNTI is considered a lesion with no sex predilection, the mandibular lesions show a slight male predominance, [1],[5] the median age of presentation being 5 months. The clinical presentation is usually as a rapidly growing, non ulcerative swelling. Although the tumor is known to produce melanin, pigmentation is not always clinically evident. [2],[3] Conventional radiographs and CT images are useful but not specific for assessment of the lesion. Some authors have demonstrated CT scan images typically revealing a well-demarcated, hyperdense lesion on contrast enhancement and hyperostosis of adjacent bone [7] as seen in our case. Microscopic examination shows melanin-producing cells of epithelial origin, and undifferentiated cells of neuroblastic origin along with the stromal fibroblasts. [1],[2],[3],[6] It is the epithelial cell population that characteristically distinguishes MNTI from other tumors expressing a small round cell phenotype; the differential diagnoses including small round blue cell tumors like neuroblastoma, lymphoma, rhabdomyosarcoma, Ewings sarcoma and primitive nueroectodermal tumor. [1],[4],[5] A distinctive morphology and demonstration of the multiphenotypical expression for the various epithelial, melanocytic and neural markers aid in the diagnosis of MNTI [6] The increased expression of Ki-67 and CD 99 has been correlated with more aggressive behavior, as has also been suggested in cases with malignant transformation. [4],[5]

Surgery remains the mainstay of treatment for patients with MNTI. [1],[2],[3],[4],[5],[6],[7],[8],[9],[10] There has however been some controversy over the issue of 'optimal surgical margins', given the benign nature of most tumors. The treatment options therefore include enucleation [5] and/or curettage with limited, wide, or en bloc excision. The initial surgery is generally a wide excision with a 5-mm free margin along with removal of the involved teeth. It has been suggested to reserve hemimandibulectomy for extensive or recurrent lesions because of the functional and cosmetic disturbance that it can cause in the young infants. [5],[8] Hemimandibulectomy, as a treatment option was carried out in only five of the earlier reported 23 cases of mandibular MNTI. [5] A more aggressive surgical approach with chemotherapy before or after surgery has been tried in extensive, recurrent multifocal lesions . [9]

Recurrence has been known to occur in 10%-20% of cases, [1],[2] however, higher rates up to 60% [6] have also been reported. The early recurrences, presenting within a few months after surgery are thought to result from 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. [2],[10] To conclude, the only modality with proven efficacy in the treatment for MNTI has been surgical excision with clear margins, and at the same time much mutilation is not recommended in young patients in order to achieve a good oncological, cosmetic and functional outcome.

 > References Top

1.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
2.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. 2
3.Borrello ED, Gorlin RJ. Melanotic neuroectodermal tumor of infancy - A neoplasm of neural crest origin. Cancer 1966;19:196-206.  Back to cited text no. 3
4.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. 4
5.Piperi EP, Rake SA, Tosios KI, Vasilopoulou EE, Rake AP, Sandler NA, et al. Mandibular melanotic neuroectodermal tumor of infancy treated conservatively with enucleation. J Craniofac Surg 2010;21:685-8.  Back to cited text no. 5
6.Kapadia SB, Frisman DM, Hitchcock CL, Ellis GL, Popek EJ. Melanotic neuroectodermal tumor of infancy. Clinicopathological, immunohistochemical, and flow cytometric study. Am J Surg Pathol 1993;17:566-73.  Back to cited text no. 6
7.Suzuki C, Maeda M, Matsushima N, Takamura M, Matsubara T, Taki W. Melanotic neuroectodermal tumor of infancy in the skull: CT and MRI features. J Neuroradiol 2007;34:212-3.  Back to cited text no. 7
8.Ahmed J, Chuckwulobelu R, Sebire NJ, Hartley BE, Dunaway DJ. Hemimandibulectomy and autologous costochondral rib graft reconstruction for a case of melanotic neuroectodermal tumor of infancy arising within the mandible. Int J Pediatr Otorhinolaryngol Extra 2007;2:189-93.  Back to cited text no. 8
9.Neven J, Kaa CH, 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. 9
10.Steinberg B, Shuler C, Wilson S. Melanotic neuroectodermal tumor of infancy: Evidence of multicentricity. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1988;66:666-9.  Back to cited text no. 10


  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]

  [Table 1]


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