Melanotic neuroectodermal tumor of infancy: A rare case report.

Melanotic neuroectodermal tumor of infancy (MNTI) is a relatively uncommon osteolytic-pigmented neoplasm that primarily affects the jaws of infants. The early onset and its rapid disfiguring spread necessitate early diagnosis. A 4-month-old male child reported with the complaint of swelling in the right back tooth region of the upper jaw, which rapidly increased in size causing disfigurement of the face. Radiographic examination showed a diffuse osteolytic radiolucent lesion in the right maxilla and displacement and dysmorphic changes in the developing primary tooth buds. Wide surgical excision was performed under general anesthesia. Histopathological report revealed characteristic large pigmented epitheloid cells (melanocyte like cells). The biphasic tumor cell population arranged in a background of fibrous connective tissue stroma is suggestive of MNTI involving the cancellous bone. Early diagnosis and management of such aggressive tumors precludes significant morbidity of the patient.

Introduction

Melanotic neuroectodermal tumor of infancy (MNTI) is a rare clinical condition, which occurs in infants within the first 6 months of life. MNTI is usually a benign tumor of neural crest origin composed of relatively primitive pigment producing cells. Krompecher made the first description of this tumor in 1918 as a congenital melanocarcinoma.[1] In 1966, Borello and Gorlin reported a case characterized by a high urinary excretion of vanillylmandelic acid (VMA), classically found in a pheochromocytoma as well as in other neuroblastic tumors, suggesting a neuroectodermal origin of the lesion.[1]

Alternative terminologies for MNTI are pigmented neuroectodermal tumor of infancy, melanotic prognoma, retinal anlage tumor,[2] pigmented epulis of infancy, melanotic adamantinoma, pigmented ameloblastoma, melanotic epithelial odontoma, retinal choristoma, pigmented teratoma, atypical melanoblastoma. Previous literature mentioned that this condition has 23 different terminologies. The multitude of names reflects the uncommon occurrence and uncertain histogenesis. It is described as a pigmented, non-ulcerative, fast growing tumefaction. It is well-known to be locally aggressive which may result in tooth displacement as the tumor cells invade the surrounding bone.[34]

Case Report

This was a case report of a 4-month-old patient who presented with the complaint of swelling in the right back tooth region of the upper jaw reported to the Department of Pedodontics and Preventive Dentistry, Kamineni Institute of Dental Sciences, Narketpally, Nalgonda District. Difficulty in feeding was the chief concern of the parents. A swelling was observed for the first time when the child was 2 months old which rapidly increased in size, which caused disfigurement of face [Figure 1].

Figure 1

Pre-operative extra-oral view

On clinical examination, the swelling was diffuse, extending from the maxillary right second primary molar region to the canine region anteroposteriorly and caused expansion of the buccal cortical plate and palate up to the midline, but did not cross the midline. The mucosa over the swelling was normal and not ulcerated [Figure 2]. On palpation, the swelling was hard with ill-defined margins. The rapid increase in the size of the swelling suggested a malignant nature of the enlargement. Hence the lymph nodes were checked for any metastasis, but found none.

Figure 2

Pre-operative intra-oral view

Normal radiographic examination (occlusal radiograph) showed a diffuse osteolytic radiolucent lesion in the right maxilla and showed displacement and dysmorphic changes in the developing primary tooth buds. Plain and contrast enhanced computerized tomographic analysis of the para nasal sinuses performed on a 64 slice computed tomography (CT) scanner, with coronal reconstructions revealed evidence of an expansile lytic lesion arising from right maxillary sinus showing cortical defects with associated soft-tissue components and calcific densities within. The lesion is seen extending into right infratemporal region inferiorly and subcutaneous region anteriorly. The lesion measured 3.2 cm × 2.1 cm × 2.3 cm (Anterio-Posterior (AP) × trans × height), which displaced the primary teeth inferiorly. The lesion showed moderate contrast enhancement [Figures 3 and 4]. This CT analysis gave the impression of a primitive neuroectodermal tumor.

Figure 3

Pre-operative computed tomography scan image frontal view

Figure 4

Pre-operative computed tomography scan image lateral view

Initial wedge biopsy was planned and performed to aid in proper diagnosis. The histopathological report revealed nests of cells arranged in alveolar pattern and small basophilic neuroblast like cells arranged in clusters. The differential diagnosis given was myxoma or MNTI. Wide surgical excision with removal of the tooth buds involved in the lesion to avoid local recurrence was performed under general anesthesia.

The excised tumor mass was grayish black in color, circumscribed, but unencapsulated. The histopathological analysis revealed, tumor cells arranged in alveolar pattern within a delicate fibrous connective tissue stroma. Large epithelioid cells containing pigment (melanocyte like cells) are arranged peripherally in the clusters enclosing central small basophilic neuroblast like cells. Infiltration of these cells into the surrounding bone and in between developing tooth buds is appreciated. The biphasic tumor cell population arranged in a background of fibrous connective tissue stroma is suggestive of MNTI involving the cancellous bone [Figures 5 and 6].

Figure 5

Low power microscopic view showing tumor cells arranged in alveolar pattern

Figure 6

High power magnification view showing epithelioid cells containing pigment (melanocyte like cells)

Discussion

Early diagnosis and treatment of any pathological condition is the key to avoid serious sequelae. MNTI is a rare clinical condition. According to the literature, only around 365 cases were reported.[5] Though very rare, good knowledge about lesions like MNTI is crucial because of its early age of involvement and rapidity of its spread. Delay in the diagnosis may lead to rapid encroachment of the tumor onto the adjacent vital structures, which may necessitate a radical resection, leading to increased morbidity. Liu et al. in 2004 explained the possibility of obstruction of infant airway by fairly aggressive expansion of the lesion.[6]

In 90% of the instances, many authors confirmed the fact that the tumor affects children less than 1 year.[7891011] Although rare, some cases were reported in adults also. No gender predilection was reported by Stowens and Lim (1974) and Lopez (1976),[1213] but a male to female ratio of 1.48 was given by Kruse-Losler in 2006 after a review of 140 cases.[14] Most commonly MNTI occurs in the anterior region of maxilla. Other sites reported were mandible, brain, skull, epididymis, shoulder, scapula, fontanelle, mediastenum and uterus.[151617]

MNTI is described in literature as a benign, rapidly growing, non-ulcerated, locally aggressive tumefaction. Though it is a pigmented tumor, the pigmentation cannot always be observed through the overlying tissues.[1819] They are usually unencapsulated and frequently tend to occur as a single unilateral lesion.[14]

It is considered as a tumor of neural crest origin composed of primitive pigment producing cells. Several theories have been put forward to elucidate the pathogenesis of the tumor. Krompecher suggested that this tumor derives from epithelial islands trapped during embryonic fusion of facial buds. He called the tumor “melanocarcinoma congenitum processus alveolaris” owing to its aggressive behavior. Halpert,[3] was of the opinion that the tumor arises from retinal anlage by a process of pinching-off of the neuroectoblast eye. Similarity in the tissue organization between MNTI and fetal pineal gland suggested a pineal origin.[20]

Borello and Gorlin suggested the term “MNTI” which has now been universally accepted.[21] They observed increase in urinary VMA, which is a major catabolite of the catecholamines. Its free form when found in great quantity is regarded as a marker of the neuroectodermal tumors. They proved this by showing decreased VMA levels after the surgical excision of the tumor.[22] However, the diagnosis of MNTI is not necessarily correlated with the increase in the serum levels of VMA. A significant number of cases of MNTI have been reported with normal levels of VMA.

Dehner et al. in 1979 described various stages of melanocytes and neuroblast like cells within the tumor, suggesting its neuroectodermal origin. Immuno-histochemical markers in different studies suggest that MNTI is a primitive neuroectodermal tumor with polyphenotypic expression of neural and epithelial markers, melanin production, occasional rhabdomyoblastic, glial,[23] ganglionic[24] and osseous[25] differentiation and no photoreceptor differentiation. It probably represents a dysembryogenetic neoplasm that recapitulates the retina at 5 weeks of gestation.[23]

Differential diagnosis of MNTI includes various pediatric small round cell neoplasms such as neuroblastoma, Ewing's sarcoma, peripheral neuroepithelioma, rhabdomyosarcoma, peripheral primitive neuroectodermal tumor, desmoplastic small round cell tumor, malignant melanoma and lymphoma.[26]

Post-operatively the present case was followed-up for 6 months, which revealed no evidence of recurrence and the child was healthy [Figure 7]. Although the prognosis of benign MNTI is excellent after complete surgical excision, long-term follow-up is mandatory as the course of the disease cannot be predicted by morphological findings.[27]

Figure 7

Post-operative extra-oral view