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Melanotic neuroectodermal tumor of infancy: review of literature and case report
Journal of Pediatric Surgery (2008) 43, E25–E29
www.elsevier.com/locate/jpedsurg
Melanotic neuroectodermal tumor of infancy: review of literature and case report Heba Selim a , Shagufta Shaheen b , Khaled Barakat c , Abdulhafez A. Selim d,⁎ a
Department of Oral and Maxillofacial Surgery, Ain Shams University School of Dentistry, Cairo 11381, Egypt Department of Internal Medicine, Saint Joseph Hospital, Chicago, IL 60657, USA c Oral and Maxillofacial Surgery, Faculty of Dentistry, El-Menia University, Cairo 61111, Egypt d Biomedical Technology Group, College of Science, KFUPM, PO Box: 1774, Dhahran 31261, Saudi Arabia b
Received 29 December 2007; revised 20 February 2008; accepted 22 February 2008
Key words: Melanotic neuroectodermal tumor of infancy; Anterior maxillary region tumors; Surgical excision; Tumors recurrence; HMB-45; Intra-oral mass
Abstract Melanotic neuroectodermal tumor of infancy (MNTI) is an uncommon, fast-growing, pigmented neoplasm of neural crest origin. It primarily affects the maxilla of the infants during the first year of life. Approximately, a few hundred of these tumors have been reported in medical literature. We present a case of a newborn with MNTI involving the anterior maxillary region. The treatment included surgical excision of the lesion with safe margins, using an intraoral approach and removal of associated developing tooth buds. We made no attempt at immediate bone grafting. The patient had no recurrence at 1 year postoperatively. The diagnostic features and management alternatives of MNTI are discussed. © 2008 Elsevier Inc. All rights reserved.
Melanotic neuroectodermal tumor of infancy (MNTI), first described by Krompecker in 1918, is a relatively uncommon benign osteolytic neoplasm of neural crest origin, affecting newborns and infants [1]. The lesion was reported under variety of names that reflects great controversy about the cell of origin and pathophysiology of the lesion. Some of the terms applied to this lesion included pigmented ameloblastoma, melanotic prognoma, retinal anlage tumor, melanotic epithelial odontoma, pigmented teratoma, atypical ameloblastoma, melanotic adamantinoma, pigmented epulis, melanoameloblastoma, and retinal ameloblastoma [2]. In spite of the controversy in the nomenclature of the lesion, it has a typical clinical picture and histopathologic description. This in turn facilitates early definitive diagnosis. Although MNTI is classified as a benign lesion, it is often clinically worrisome because of its rapid onset and alarming local growth rate. The typical MNTI begins on the anterior aspect of the maxilla and rapidly expands to form a swelling ⁎ Corresponding author. Tel.: +966 38607316. E-mail address: [email protected] (A.A. Selim). 0022-3468/$ – see front matter © 2008 Elsevier Inc. All rights reserved. doi:10.1016/j.jpedsurg.2008.02.068
or a tumescence that is cosmetically obvious to the parents of the infant [3,4]. Clinical differential diagnosis of the lesion includes those lesions that can present early in life and involve anterior maxilla. The main line of treatment of MNTI is surgical excision [5]. This treatment offers high success rate; however, local recurrence is reported in literature (10%-15%).
1. Case report A 6-month-old boy was referred to the outpatient clinic of Department of Oral and Maxillofacial Surgery, Ain-Shams University Faculty of Dentistry (Cairo, Egypt) in August 2006 because of rapidly growing swelling in anterior maxillary region. The first sign of swelling was noticed by the parents 2 months ago at the time of eruption of deciduous tooth. His mother reported interference with breast-feeding for the last 1 month when the lesion started growing rapidly. Clinical examination revealed healthy male infant (weighing
E26
H. Selim et al.
Fig. 1 A, Extraoral examination showing swelling in the right anterior maxillary region displacing upper lip. B, Intraoral examination revealed ill-defined firm sessile bluish mass occupying the anterior maxillary region, extending about 4 cm anteroposteriorly and 2.5 cm superioinferiorily.
8.5 kg) with swelling in the right anterior maxillary region displacing upper lip and swelling adjacent to his mouth (Fig. 1). Intraoral examination revealed an ill-defined firm sessile bluish mass occupying the anterior maxillary region, extending about 4 cm anteroposteriorly and 2.5 cm superioinferiorily. The mass was in the right maxilla starting in the
alveolar ridge and displacing the maxillary sinus superiorly and lateral nasal wall medially with expansion of both buccal and palatal plates of bone. The erupted deciduous canine tooth was involved and displaced by the tumor mass. Overlying mucosa was stretched, bluish in color with central defect (Fig. 2).
Fig. 2 A, Exposure and dissection of the tumor mass from an intraoral approach. Transmucosal approach was used. A 2-line pyramidal flap design was used. We used a chevron incision extending from the left canine region to the right maxillary tuberosity with an oblique incision in the left side to facilitate flap reflection. A mucoperiosteal flap was reflected apically exposing the full extent of the lesion that was approximating the nasal floor and displacing the primitive maxillary sinus. Palatal mucoperiosteum was reflected to expose the palatal extension of the lesion that reached to the midpalatal region. B, Bone defect after complete excision of the tumor mass. The lesion was well demarcated from surrounding bony margins and easily separated from surrounding tissues. Lesion dissection started anteriorly then reflected laterally to separate the lesion from palatal and nasal mucosa medially. C, Tumor mass was totally excised with involved teeth buds. The excised tumor mass was fibrous in consistency (4.5 × 2.5 cm), well demarcated, and bluish in color with developing deciduous incisors embedded within the mass. D, Primary closure of intraoral incision. Wound was carefully inspected and debrided. There was no attempt to graft the residual bony defect, and the wound was closed using interrupted sutures.
Melatonic neuroectodermal tumor of infancy
E27
Fig. 3 Histologic examination of biopsy specimen (H&E) showing a biphasic proliferation of small rounded neuroblast-like cells and larger epitheliod cells with eosinophilic cytoplasm containing variable amounts of melanin.
Radiographic examination (intraoral periapical radiograph) showed an ill-defined homogeneous radiolucent lesion in the anterior maxilla, measuring 4 × 3 cm, related to teeth germ of developing deciduous central and lateral incisors. The previously described clinical and radiographic picture was suggestive of provisional diagnosis of MNTI. Results of routine laboratory investigations were within normal limits. The urine levels of vanillylmandelic acid (VMA) were within normal range. Incisional biopsy was done under general anesthesia. Tissue specimen was harvested from the center of the tumor mass (Fig. 3). Microscopic examination of the incisional specimens of the tumor showed a biphasic proliferation of small rounded neuroblast-like cells and larger epitheliod cells with eosinophilic cytoplasm containing variable amounts of melanin (Fig. 3). The treatment included surgical excision of the lesion with safe margins from an intraoral approach and removal of associated developing teeth buds. We had no attempt for immediate bone grafting. The patient was followed up for 1 year to rule out recurrence of the lesion and to evaluate spontaneous bone healing.
2. Discussion Most of the lesions present during the first year of life (N90%), usually in the first 6 months. Males were more affected than females (7:6) [3]. More than 90% of reported cases involve the head and neck region; other reported sites include epididymis, brain, shoulder, skin, femur, and mediastinum. The most commonly affected site is the anterior aspect of the maxilla (about 60% of cases). The lesion usually presents as painless sessile lightly pigmented (blue or black) solitary nontender, nonulcerated firm
swelling. Intraoral lesions are usually covered by stretched intact mucosa with bluish discoloration, often reaching 2 to 5 cm at the time of diagnosis. In many cases, it involves erupted or developing deciduous anterior teeth. No thrill or pulsation can be elicited in MNTI [3]. Clinical differential diagnosis of the lesion include those lesions that can present early in life and involve anterior maxilla such as congenital epulis of a newborn, central giant cell granuloma, ossifying fibroma, fibrous dysplasia, hemangioma, arteriovenous malformations, craniopharyngioma, Langerhans cell histiocytosis, rhabdomyosarcoma, Ewing's sarcoma, and lymphoma [3,4]. Plain dental radiography, computed tomographic (CT) scanning, and magnetic resonance imaging have been used to evaluate the content and the extent of MNTI. The radiographic appearance of MNTI within bone is a wellcircumscribed radiolucency, although diffused and illdefined examples have also been reported. The bone is destroyed as the tumor advances, suggesting a malignant process [6]. The CT scanning with intravenous contrast is often used to delineate the margins of osseous involvement. In addition, magnetic resonance imaging with gadolinium contrast can be used to evaluate the bony extent of the lesion [6]. Once provisional diagnosis is established with the aid of clinical and radiographic findings, definitive diagnosis can be done by histologic evaluation of the biopsy specimen. The histologic appearance of MNTI is unique and characteristic with biphasic cell pattern and moderately vascular fibrous tissue background. One portion of the lesion contains large polygonal cells arranged into sheets. These cells have pale abundant cytoplasm, pale nuclei with finely dispersed chromatin, in addition to melanin pigment that gives MNTI its characteristic blue-black appearance. The second cell type is lymphocyte-like or neuroblast-like cells, located in the center of the cell nests. Throughout the lesion mitosis is rare,
E28 but when present, is normal in appearance. Reported malignant cases have the same histologic description with increased mitosis, hypercellularity, and focal necrosis [7]. Metastatic lesions have been described in the lymph nodes, the liver, the adrenal gland, the spinal cord, and a variety of other sites [7,8]. Immunohistochemistry is of assistance in cases that are more difficult to diagnose. The cuboidal cells express cytokeratin as well as melanoma-associated antigen (HMB45), but they are usually negative for S-100 [8]. Although MNTI can be easily diagnosed under light microscope, other diagnostic modalities can be done using electron microscopy. Electron microscopic examination demonstrates ultrastructural evidence of neural, epithelial, and melanocytic features. Fine, delicate cytoplasmic fibers are suggestive of neurofibrils, reminiscent of glial tissue. Melanosomes are noted in many of the cuboidal cells [9]. The polygonal cells noted for their melanin production have been cultured in vitro. These cells developed long dendritic processes suggestive of their neural crest origin. In addition, melanotransferrin expression has been noted with DNA analysis of these cells [10]. Typically, the hematologic laboratory values as well as the blood chemistry values are within the reference range. Several patients with MNTI have demonstrated a high urinary excretion of VMA. This finding adds credence to a neural crest origin because elevated VMA has been reported in neuroblastoma, ganglioneuroblastoma, pheochromocytoma, and other neural crest tumors. However, the presence of urinary VMA is not diagnostic for MNTI [1,3]. As is the case for these lesions, the urinary level of VMA returns to the reference range after surgical removal of MNTI that has caused elevated VMA. In addition, no correlation between the presence of elevated VMA and more aggressive or malignant clinical behavior has been shown [3]. The treatment of choice for MNTI is surgical excision, and it is usually curative. This treatment can usually be accomplished with a partial maxillectomy, by using a WeberFergusson incision and a facial degloving approach. Teeth, developing teeth, and the adjacent bone must be injured when they lie near the borders of MNTI because many clinicians advocate that a 5-mm margin of healthy tissue be included with the surgical specimen [11,12]. Permanent reconstruction of the maxillary alveolus and missing dentition may have to be delayed until after growth is completed, often in the teenaged years. The skills of an orthodontist, prosthodontist, oral surgeon, and/or dentist may be required, based on the extent of the missing structures to correct any functional and cosmetic deformity [13,14]. In the case presented, we made no attempt to graft the residual bony defect. The possibility of local recurrence is a problem that has been documented. Overall, the average recurrence rate is 15% to 20%. The recurrent lesions, possibly secondary to
H. Selim et al. inadequate excision or multicentricity, usually become apparent within the first year after surgery. One should address the recurrence in the postoperative care by monitoring the patient with physical and radiographic examination at monthly intervals for the first postoperative year [3,13]. In the case presented, the patient had no recurrence at 1 year postoperatively. In instances of inoperable recurrence or where clear margins are impossible to obtain, radiation therapy and/or chemotherapy have been used, but very few examples exist for preferences to be established [14]. The rapid clinical growth rate could lead to the possibility of diagnosing MNTI as a malignant lesion with subsequent over treatment. Care must be taken to obtain a complete workup of the patient and to evaluate the histopathologic condition to prevent this misdiagnosis [15]. On the other hand, approximately 1% of MNTI tumors are malignant, with only rare tumors producing metastases [3]. Metastatic spread of MNTI occurs infrequently, in less than 5% of malignant cases. Few, if any, parameters exist either clinically or histologically to predict the development of metastatic lesions. Management of these rare cases is different [3,15].
3. Conclusion Melanotic neuroectodermal tumor of infancy is an uncommon, fast-growing, pigmented neoplasm of neural crest origin. Most of the patients with the lesion present in their first year of life. The definitive diagnosis should be carried out with histopathologic and immunohistochemical examination. Surgical resection should preserve the function of vital structures and organs. Recurrence usually occurs in the first year after surgery. Infants younger than 3 months who have tumors in the maxilla should be followed closely because of the high risk of recurrence.
References [1] Borello ED, Gorlin RJ. Melanotic neuroectodermal tumor of infancy— a neoplasm of neural crest origin. Report of a case associated with high urinary excretion of vanillylmandelic acid. Cancer 1966;19(2): 196-206. [2] Fletcher C. Melanotic neuroectodermal tumor of infancy. Clinic pathological, immunohistochemical and flow cytometry study. Am J Surg Pathol 1995;17:566-73. [3] Kruse-Lösler B, Gaertner C, Bürger H, et al. 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(2):204-16. [4] Oruckaptan HH, Soylemezoglu F, Kutluk T, et al. Benign melanocytic tumor in infancy: discussion on a rare case and review of the literature. Pediatr Neurosurg 2000;32(5):240-7. [5] Retna Kumari N, Sreedharan S, Balachandran D. Melanotic neuroectodermal tumour of infancy: a case report. J Indian Soc Pedod Prev Dent 2007;25(3):148-51.
Melatonic neuroectodermal tumor of infancy [6] Suzuki C, Maeda M, Matsushima N, et al. Melanotic neuroectodermal tumor of infancy in the skull: CT and MRI features. J Neuroradiol 2007;34(3):212-3. [7] Kapadia SB, Frisman DM, Hitchcock CL, et al. Melanotic neuroectodermal tumor of infancy. Clinicopathological, immunohistochemical, and flow cytometric study. Am J Surg Pathol 1993;17(6):566-73. [8] Nelson ZL, Newman L, Loukota RA, et al. Melanotic euroectodermal tumour of infancy: an immunohistochemical and ultrastructural study. Br J Oral Maxillofac Surg 1995;33(6):375-80. [9] Min KW. Usefulness of electron microscopy in the diagnosis of “small” round cell tumors of the sinonasal region. Ultrastruct Pathol 1995;19(5):347-63. [10] Metwaly H, Cheng J, Maruyama S, et al. Establishment and characterization of new cell lines derived from melanotic neuroectodermal tumor of infancy arising in the mandible. Pathol Int 2005;55 (6):331-42.
E29 [11] Dashti SR, Cohen ML, Cohen AR. Role of radical surgery for intracranial melanotic neuroectodermal tumor of infancy: case report. Neurosurgery 1999;45(1):175-8. [12] Eckardt A, Swennen G, Barth EL, et al. Long-term results after mandibular continuity resection in infancy: the role of autogenous rib grafts for mandibular restoration. J Craniofac Surg 2006;17(2): 255-60. [13] Latham K, Podda S, Wolfe SA. Melanocytic neuroectodermal tumor of infancy: excision and primary palatal repair at 7 months of age. J Craniofac Surg 2007;18(2):450-4. [14] Kumari TP, Venugopal M, Mathews A, et al. Effectiveness of chemotherapy in melanotic neurectodermal tumor of infancy. Pediatr Hematol Oncol 2005;22(3):199-206. [15] McGuire TP, Gomes PP, Forte V, et al. Rapidly growing intraoral swelling involving the maxilla of an infant. J Oral Maxillofac Surg 2007;65(8):1595-9.
www.elsevier.com/locate/jpedsurg
Melanotic neuroectodermal tumor of infancy: review of literature and case report Heba Selim a , Shagufta Shaheen b , Khaled Barakat c , Abdulhafez A. Selim d,⁎ a
Department of Oral and Maxillofacial Surgery, Ain Shams University School of Dentistry, Cairo 11381, Egypt Department of Internal Medicine, Saint Joseph Hospital, Chicago, IL 60657, USA c Oral and Maxillofacial Surgery, Faculty of Dentistry, El-Menia University, Cairo 61111, Egypt d Biomedical Technology Group, College of Science, KFUPM, PO Box: 1774, Dhahran 31261, Saudi Arabia b
Received 29 December 2007; revised 20 February 2008; accepted 22 February 2008
Key words: Melanotic neuroectodermal tumor of infancy; Anterior maxillary region tumors; Surgical excision; Tumors recurrence; HMB-45; Intra-oral mass
Abstract Melanotic neuroectodermal tumor of infancy (MNTI) is an uncommon, fast-growing, pigmented neoplasm of neural crest origin. It primarily affects the maxilla of the infants during the first year of life. Approximately, a few hundred of these tumors have been reported in medical literature. We present a case of a newborn with MNTI involving the anterior maxillary region. The treatment included surgical excision of the lesion with safe margins, using an intraoral approach and removal of associated developing tooth buds. We made no attempt at immediate bone grafting. The patient had no recurrence at 1 year postoperatively. The diagnostic features and management alternatives of MNTI are discussed. © 2008 Elsevier Inc. All rights reserved.
Melanotic neuroectodermal tumor of infancy (MNTI), first described by Krompecker in 1918, is a relatively uncommon benign osteolytic neoplasm of neural crest origin, affecting newborns and infants [1]. The lesion was reported under variety of names that reflects great controversy about the cell of origin and pathophysiology of the lesion. Some of the terms applied to this lesion included pigmented ameloblastoma, melanotic prognoma, retinal anlage tumor, melanotic epithelial odontoma, pigmented teratoma, atypical ameloblastoma, melanotic adamantinoma, pigmented epulis, melanoameloblastoma, and retinal ameloblastoma [2]. In spite of the controversy in the nomenclature of the lesion, it has a typical clinical picture and histopathologic description. This in turn facilitates early definitive diagnosis. Although MNTI is classified as a benign lesion, it is often clinically worrisome because of its rapid onset and alarming local growth rate. The typical MNTI begins on the anterior aspect of the maxilla and rapidly expands to form a swelling ⁎ Corresponding author. Tel.: +966 38607316. E-mail address: [email protected] (A.A. Selim). 0022-3468/$ – see front matter © 2008 Elsevier Inc. All rights reserved. doi:10.1016/j.jpedsurg.2008.02.068
or a tumescence that is cosmetically obvious to the parents of the infant [3,4]. Clinical differential diagnosis of the lesion includes those lesions that can present early in life and involve anterior maxilla. The main line of treatment of MNTI is surgical excision [5]. This treatment offers high success rate; however, local recurrence is reported in literature (10%-15%).
1. Case report A 6-month-old boy was referred to the outpatient clinic of Department of Oral and Maxillofacial Surgery, Ain-Shams University Faculty of Dentistry (Cairo, Egypt) in August 2006 because of rapidly growing swelling in anterior maxillary region. The first sign of swelling was noticed by the parents 2 months ago at the time of eruption of deciduous tooth. His mother reported interference with breast-feeding for the last 1 month when the lesion started growing rapidly. Clinical examination revealed healthy male infant (weighing
E26
H. Selim et al.
Fig. 1 A, Extraoral examination showing swelling in the right anterior maxillary region displacing upper lip. B, Intraoral examination revealed ill-defined firm sessile bluish mass occupying the anterior maxillary region, extending about 4 cm anteroposteriorly and 2.5 cm superioinferiorily.
8.5 kg) with swelling in the right anterior maxillary region displacing upper lip and swelling adjacent to his mouth (Fig. 1). Intraoral examination revealed an ill-defined firm sessile bluish mass occupying the anterior maxillary region, extending about 4 cm anteroposteriorly and 2.5 cm superioinferiorily. The mass was in the right maxilla starting in the
alveolar ridge and displacing the maxillary sinus superiorly and lateral nasal wall medially with expansion of both buccal and palatal plates of bone. The erupted deciduous canine tooth was involved and displaced by the tumor mass. Overlying mucosa was stretched, bluish in color with central defect (Fig. 2).
Fig. 2 A, Exposure and dissection of the tumor mass from an intraoral approach. Transmucosal approach was used. A 2-line pyramidal flap design was used. We used a chevron incision extending from the left canine region to the right maxillary tuberosity with an oblique incision in the left side to facilitate flap reflection. A mucoperiosteal flap was reflected apically exposing the full extent of the lesion that was approximating the nasal floor and displacing the primitive maxillary sinus. Palatal mucoperiosteum was reflected to expose the palatal extension of the lesion that reached to the midpalatal region. B, Bone defect after complete excision of the tumor mass. The lesion was well demarcated from surrounding bony margins and easily separated from surrounding tissues. Lesion dissection started anteriorly then reflected laterally to separate the lesion from palatal and nasal mucosa medially. C, Tumor mass was totally excised with involved teeth buds. The excised tumor mass was fibrous in consistency (4.5 × 2.5 cm), well demarcated, and bluish in color with developing deciduous incisors embedded within the mass. D, Primary closure of intraoral incision. Wound was carefully inspected and debrided. There was no attempt to graft the residual bony defect, and the wound was closed using interrupted sutures.
Melatonic neuroectodermal tumor of infancy
E27
Fig. 3 Histologic examination of biopsy specimen (H&E) showing a biphasic proliferation of small rounded neuroblast-like cells and larger epitheliod cells with eosinophilic cytoplasm containing variable amounts of melanin.
Radiographic examination (intraoral periapical radiograph) showed an ill-defined homogeneous radiolucent lesion in the anterior maxilla, measuring 4 × 3 cm, related to teeth germ of developing deciduous central and lateral incisors. The previously described clinical and radiographic picture was suggestive of provisional diagnosis of MNTI. Results of routine laboratory investigations were within normal limits. The urine levels of vanillylmandelic acid (VMA) were within normal range. Incisional biopsy was done under general anesthesia. Tissue specimen was harvested from the center of the tumor mass (Fig. 3). Microscopic examination of the incisional specimens of the tumor showed a biphasic proliferation of small rounded neuroblast-like cells and larger epitheliod cells with eosinophilic cytoplasm containing variable amounts of melanin (Fig. 3). The treatment included surgical excision of the lesion with safe margins from an intraoral approach and removal of associated developing teeth buds. We had no attempt for immediate bone grafting. The patient was followed up for 1 year to rule out recurrence of the lesion and to evaluate spontaneous bone healing.
2. Discussion Most of the lesions present during the first year of life (N90%), usually in the first 6 months. Males were more affected than females (7:6) [3]. More than 90% of reported cases involve the head and neck region; other reported sites include epididymis, brain, shoulder, skin, femur, and mediastinum. The most commonly affected site is the anterior aspect of the maxilla (about 60% of cases). The lesion usually presents as painless sessile lightly pigmented (blue or black) solitary nontender, nonulcerated firm
swelling. Intraoral lesions are usually covered by stretched intact mucosa with bluish discoloration, often reaching 2 to 5 cm at the time of diagnosis. In many cases, it involves erupted or developing deciduous anterior teeth. No thrill or pulsation can be elicited in MNTI [3]. Clinical differential diagnosis of the lesion include those lesions that can present early in life and involve anterior maxilla such as congenital epulis of a newborn, central giant cell granuloma, ossifying fibroma, fibrous dysplasia, hemangioma, arteriovenous malformations, craniopharyngioma, Langerhans cell histiocytosis, rhabdomyosarcoma, Ewing's sarcoma, and lymphoma [3,4]. Plain dental radiography, computed tomographic (CT) scanning, and magnetic resonance imaging have been used to evaluate the content and the extent of MNTI. The radiographic appearance of MNTI within bone is a wellcircumscribed radiolucency, although diffused and illdefined examples have also been reported. The bone is destroyed as the tumor advances, suggesting a malignant process [6]. The CT scanning with intravenous contrast is often used to delineate the margins of osseous involvement. In addition, magnetic resonance imaging with gadolinium contrast can be used to evaluate the bony extent of the lesion [6]. Once provisional diagnosis is established with the aid of clinical and radiographic findings, definitive diagnosis can be done by histologic evaluation of the biopsy specimen. The histologic appearance of MNTI is unique and characteristic with biphasic cell pattern and moderately vascular fibrous tissue background. One portion of the lesion contains large polygonal cells arranged into sheets. These cells have pale abundant cytoplasm, pale nuclei with finely dispersed chromatin, in addition to melanin pigment that gives MNTI its characteristic blue-black appearance. The second cell type is lymphocyte-like or neuroblast-like cells, located in the center of the cell nests. Throughout the lesion mitosis is rare,
E28 but when present, is normal in appearance. Reported malignant cases have the same histologic description with increased mitosis, hypercellularity, and focal necrosis [7]. Metastatic lesions have been described in the lymph nodes, the liver, the adrenal gland, the spinal cord, and a variety of other sites [7,8]. Immunohistochemistry is of assistance in cases that are more difficult to diagnose. The cuboidal cells express cytokeratin as well as melanoma-associated antigen (HMB45), but they are usually negative for S-100 [8]. Although MNTI can be easily diagnosed under light microscope, other diagnostic modalities can be done using electron microscopy. Electron microscopic examination demonstrates ultrastructural evidence of neural, epithelial, and melanocytic features. Fine, delicate cytoplasmic fibers are suggestive of neurofibrils, reminiscent of glial tissue. Melanosomes are noted in many of the cuboidal cells [9]. The polygonal cells noted for their melanin production have been cultured in vitro. These cells developed long dendritic processes suggestive of their neural crest origin. In addition, melanotransferrin expression has been noted with DNA analysis of these cells [10]. Typically, the hematologic laboratory values as well as the blood chemistry values are within the reference range. Several patients with MNTI have demonstrated a high urinary excretion of VMA. This finding adds credence to a neural crest origin because elevated VMA has been reported in neuroblastoma, ganglioneuroblastoma, pheochromocytoma, and other neural crest tumors. However, the presence of urinary VMA is not diagnostic for MNTI [1,3]. As is the case for these lesions, the urinary level of VMA returns to the reference range after surgical removal of MNTI that has caused elevated VMA. In addition, no correlation between the presence of elevated VMA and more aggressive or malignant clinical behavior has been shown [3]. The treatment of choice for MNTI is surgical excision, and it is usually curative. This treatment can usually be accomplished with a partial maxillectomy, by using a WeberFergusson incision and a facial degloving approach. Teeth, developing teeth, and the adjacent bone must be injured when they lie near the borders of MNTI because many clinicians advocate that a 5-mm margin of healthy tissue be included with the surgical specimen [11,12]. Permanent reconstruction of the maxillary alveolus and missing dentition may have to be delayed until after growth is completed, often in the teenaged years. The skills of an orthodontist, prosthodontist, oral surgeon, and/or dentist may be required, based on the extent of the missing structures to correct any functional and cosmetic deformity [13,14]. In the case presented, we made no attempt to graft the residual bony defect. The possibility of local recurrence is a problem that has been documented. Overall, the average recurrence rate is 15% to 20%. The recurrent lesions, possibly secondary to
H. Selim et al. inadequate excision or multicentricity, usually become apparent within the first year after surgery. One should address the recurrence in the postoperative care by monitoring the patient with physical and radiographic examination at monthly intervals for the first postoperative year [3,13]. In the case presented, the patient had no recurrence at 1 year postoperatively. In instances of inoperable recurrence or where clear margins are impossible to obtain, radiation therapy and/or chemotherapy have been used, but very few examples exist for preferences to be established [14]. The rapid clinical growth rate could lead to the possibility of diagnosing MNTI as a malignant lesion with subsequent over treatment. Care must be taken to obtain a complete workup of the patient and to evaluate the histopathologic condition to prevent this misdiagnosis [15]. On the other hand, approximately 1% of MNTI tumors are malignant, with only rare tumors producing metastases [3]. Metastatic spread of MNTI occurs infrequently, in less than 5% of malignant cases. Few, if any, parameters exist either clinically or histologically to predict the development of metastatic lesions. Management of these rare cases is different [3,15].
3. Conclusion Melanotic neuroectodermal tumor of infancy is an uncommon, fast-growing, pigmented neoplasm of neural crest origin. Most of the patients with the lesion present in their first year of life. The definitive diagnosis should be carried out with histopathologic and immunohistochemical examination. Surgical resection should preserve the function of vital structures and organs. Recurrence usually occurs in the first year after surgery. Infants younger than 3 months who have tumors in the maxilla should be followed closely because of the high risk of recurrence.
References [1] Borello ED, Gorlin RJ. Melanotic neuroectodermal tumor of infancy— a neoplasm of neural crest origin. Report of a case associated with high urinary excretion of vanillylmandelic acid. Cancer 1966;19(2): 196-206. [2] Fletcher C. Melanotic neuroectodermal tumor of infancy. Clinic pathological, immunohistochemical and flow cytometry study. Am J Surg Pathol 1995;17:566-73. [3] Kruse-Lösler B, Gaertner C, Bürger H, et al. 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(2):204-16. [4] Oruckaptan HH, Soylemezoglu F, Kutluk T, et al. Benign melanocytic tumor in infancy: discussion on a rare case and review of the literature. Pediatr Neurosurg 2000;32(5):240-7. [5] Retna Kumari N, Sreedharan S, Balachandran D. Melanotic neuroectodermal tumour of infancy: a case report. J Indian Soc Pedod Prev Dent 2007;25(3):148-51.
Melatonic neuroectodermal tumor of infancy [6] Suzuki C, Maeda M, Matsushima N, et al. Melanotic neuroectodermal tumor of infancy in the skull: CT and MRI features. J Neuroradiol 2007;34(3):212-3. [7] Kapadia SB, Frisman DM, Hitchcock CL, et al. Melanotic neuroectodermal tumor of infancy. Clinicopathological, immunohistochemical, and flow cytometric study. Am J Surg Pathol 1993;17(6):566-73. [8] Nelson ZL, Newman L, Loukota RA, et al. Melanotic euroectodermal tumour of infancy: an immunohistochemical and ultrastructural study. Br J Oral Maxillofac Surg 1995;33(6):375-80. [9] Min KW. Usefulness of electron microscopy in the diagnosis of “small” round cell tumors of the sinonasal region. Ultrastruct Pathol 1995;19(5):347-63. [10] Metwaly H, Cheng J, Maruyama S, et al. Establishment and characterization of new cell lines derived from melanotic neuroectodermal tumor of infancy arising in the mandible. Pathol Int 2005;55 (6):331-42.
E29 [11] Dashti SR, Cohen ML, Cohen AR. Role of radical surgery for intracranial melanotic neuroectodermal tumor of infancy: case report. Neurosurgery 1999;45(1):175-8. [12] Eckardt A, Swennen G, Barth EL, et al. Long-term results after mandibular continuity resection in infancy: the role of autogenous rib grafts for mandibular restoration. J Craniofac Surg 2006;17(2): 255-60. [13] Latham K, Podda S, Wolfe SA. Melanocytic neuroectodermal tumor of infancy: excision and primary palatal repair at 7 months of age. J Craniofac Surg 2007;18(2):450-4. [14] Kumari TP, Venugopal M, Mathews A, et al. Effectiveness of chemotherapy in melanotic neurectodermal tumor of infancy. Pediatr Hematol Oncol 2005;22(3):199-206. [15] McGuire TP, Gomes PP, Forte V, et al. Rapidly growing intraoral swelling involving the maxilla of an infant. J Oral Maxillofac Surg 2007;65(8):1595-9.