53. Halpert B, Patzer R: Maxillary tumor of retinal anlage. Surgery 22837, 1947 54. Caldwell JB, Ernst KF, Thompson HC: Retinal anlage tumor of the maxilla. Oral Surg 8:796, 1955 55. Misugi K: Mediastinal origin of a melanotic progonoma or retinal anlage tumor: Ultra-structural evidence for neural crest origin. Cancer 18477, 1956 56. Bore110ED, Gorlin RJ: Melanotic neuralectodermal tumor of infancy-a neoplasm of neural crest origin. Report of a case associated with high urinary excretion of vamillmandelic acid. Cancer 19:196, 1966 57. Nikai H, I_juhinN, Yamasaki A, et al: Ultrastructural evidence for neural crest origin of the melanotic neuroectodetmal tumor of infancy. J Oral Path01 6:22 I, 1977 58. Dehner LP, Sibley RK, Sank JJ, et al: Malignant melanotic neuroectodermal tumor of infancy. Cancer 43: 1389, 1979 59. Ashley OJB: Melanotic Adamantinoma of the skull. J Path01 Bacterial 87: 179. 1964
J Oral Maxillofac 50:994-998.
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60. Hahn JF, Sperber EE, Netsky MG: Melanotic neuroectodermal tumors of the brain and skull. J Neuropathol Exp Neural 35: 508, 1976 6 I. McCloskey JJ, Parker PC, Brooks WH, et al: Melanin as a component of cerebral gliomas: The rnelanotic cerebral ependymoma. Cancer 37:2373, 1976 62. Dehner LP: Peripheral and central neuroectodermal tumors. Arch Path01 Lab Med 110:997, 1986 63. Schulz DH: A malignant melanotic neoplasm of the uterus resembling the retinal anlage tumors. Am J Clin Path01 28524, 1957 64. Stirling RW, Powell G, Fletcher CDM: Pigmented neuroectodermal of infancy: An immunohistochemical study. Histopathology 12:425. 1988 65. Cohen BH, Handler MS, De Viro DC, et al: Central nervous system melanotic neuroectodermal tumor of infancy: Value of chemotherapy in management. Neurology 38: 163, 1988 66. Hupp JR, Topazian RG, Krutchkoff DJ: The melanotic neuroectodermal tumor of infancy. Int J Oral Surg 10:432. 198 1
Melanotic Neuroectodermal Tumor of Infancy: A Report of Two Cases PETER
DMD, MD,* THOMAS W. BRAUN, AND M.M. NAZIF, DDS, MDS*
Melanotic neuroectodermal tumor of infancy (MNTI) is a relatively rare tumor of the anterior maxilla in young infants. The lesion often has bluish areas of pigmentation and is characterized by displacement of involved tooth buds and localized aggressiveness.‘d Historically, several names for this lesion have been proposed in the literature, including pigmented congenital epulis, melanotic progonoma, retinal analage
* Associate Professor, Department of Oral/Maxillofacial Surgery, University of Pittsburgh Medical Center and Veterans Administration Medical Center, Pittsburgh, PA. t Chairman, Department Oral/Maxillofacial Surgery, University of Pittsburah Medical Center and Veterans Administration Medical Center, Pi&burgh, PA. $ Director of Dental Services, Children’s Hospital of Pittsburgh, Pittsburgh, PA. Address correspondence and reprint requests to Dr Braun: Department of Oral and Maxillofacial Surgery, University of Pittsburgh School of Dental Medicine, 350 1 Terrace St, Pittsburgh, PA 1526 1. 0 1992 American Association of Oral and Maxillofacial Surgeons 0278-2391/92/5008-0017$3.00/O
FIGURE 1. Preoperative appearance of the expanded left maxilla.
DEMAS. BRAUN, AND NAZlF
The specimen measured approximately 2 X 1.5 cm and was partially encapsulated. It was firm to palpation and had dark pigmented areas visible on the surface (Fig 3). Histologic study showed small, ovoid cells with hyperchromatic nuclei lining slitlike spaces or forming nests within a fibrous stroma, as well as numerous larger epithelioid cells containing melanin pigmentation (Figs 4, 5). A diagnosis of melanotic neuroectodermal tumor of infancy was made. There has been no recurrence after a 3-year follow-up.
FIGURE 2. Preoperative radiograph showing radiolucency and displaced teeth.
tumor, and melanotic epithelial odontoma. Occasionally, MNTI has been reported to occur in other anatomic locations distant from the premaxilla.“6 The lesion is of special significance because of its tendency to recur if inadequate excision is performed. Its aggressive behavior may give the impression of malignancy, which can result in overly aggressive treatment. The purpose of this article is to present two documented cases of MNTI that show the lesion’s variable clinical course.
A 3-week-old girl was referred by her pediatrician to a pediatric surgeon for the evaluation and treatment of a mass involving the left anterior maxillary alveolar ridge. The patient was admitted to Children’s Hospital of Pittsburgh, where clinical and radiographic examinations were obtained. A lcm mass involving the maxillary left alveolus, with dark pigmentation visible on the palatal aspect of the lesion was noted (Fig 6). All laboratory values were within normal limits. No urinary VMA test was done. The lesion was removed by enucleation and curettage under general anesthesia without complications. The partially encapsulated lesion was composed of two cell types, epithelioid cells containing melanin and irregularly ovoid cells with dark-staining nuclei. Residual tumor was noted at the margins (Figs 7. 8). A histologic diagnosis of melanotic neuroectodermal tumor of infancy was made. The patient was discharged and did well until 3 weeks later when the parent noted swelling in the area ofthe previous surgery. The family pediatrician referred the child to the pediatric surgeon who readmitted her to the hospital and requested oral surgical consultation. The tumor now extended toward the infraorbital region superiorly and into the tuberosity posteriorly, with signs of inflammation. All laboratory values and vital signs were within normal limits. No urinary VMA test was done. The
Report of Cases Case 1 A 6-month-old girl was referred by her family dentist for evaluation of an expanding mass in the anterior maxilla (Fig 1). The lesion was first noted 4 weeks earlier by her mother, who reported progressive enlargement. Examination showed a 2 X 2-cm, bluish, expansile mass of the left anterior maxilla with no apparent nasal extension. The mass was firm to palpation. Radiographic examination revealed a diffuse radiolucency, with tooth displacement and a “floating” unerupted primary maxillary incisor (Fig 2). The patient’s medical history, physical examination, and admission laboratory values were within normal limits. A urinary vanilmandelic acid (VMA) test was not done. Under general anesthesia, the lesion was removed by enucleation and curettage following a negative aspiration test. An alveolar crestal incision was made and a mucoperiosteal flap was dissected free of the underlying mass and elevated. The lesion and the contained unerupted primary incisor were removed. Two well-developed primary tooth buds, adjacent to the surgical site, were left undisturbed. The incision was closed primarily. Blood loss was minimal.
Excised lesion showing extensive pigmentation.
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FIGURE 4. Photomicrograph showing small oval cells with hyperchromatic nuclei and larger epithelioid cells with melanin pigmentation lining cleftlike spaces within a fibrous stroma.
(hematoxylin-eosin stain, original magnification X66).
diagnosis was acute inflammation of a recurrent tumor. Intravenous penicillin therapy was initiated and the patient was subsequently taken to the operating room. A partial left maxillectomy was performed, removing the left alveolus but leaving the left palatal shelf, lateral nasal wall, infraorbital rim, and infraorbital nerve intact. The defect was closed partially by mucosa and the remainder by packing. The surgical specimen measured 3 X 1.6 X 1.1 cm, with the central region containing a deeply pigmented l-cm nodule. Also identified were an incompletely formed primary incisor and molar. The tumor blended imperceptively with
the cancellous bone. The histologic findings were identical to those in the initial specimen and reconfirmed the diagnosis of MNTI. The pathology report noted residual tumor remaining at the margins, The postoperative course was uneventful and there has been no recurrence during 12 years of follow-up.
Discussion Melanotic neuroectodermal tumor of infancy (MNTI) is classified as a tumor of neural crest origin.
FIGURE 5. Photomicrograph showing ovoid cells with hyperchromatic nuclei and larger epithelioid cells containing melanin pigmentation in clusters and lining cleftlike spaces (hematoxylineosin stain, original magnification X 132).
DEMAS. BRAUN, AND NAZIF
Preoperative appearance of expanded maxilla.
This classification is based on histologic analysis of cells that resemble neuroblasts, electron microscopic studies finding neurosecretory granules, cell enzyme analysis, and the finding of elevated levels of urinary excretion of VMA. Elevated VMA levels have been associated with other neural crest tumors, such as neuroblastoma and pheochromocytoma.“4 MNTI most commonly occurs in the anterior maxilla (70%). The reason for this predilection to the maxilla is unknown. Other sites of occurrence include the skull (1 Oslo),mandible (6% to 9%), and brain (1% to 4%). MNTI rarely may occur in the skin, epididymis, uterus, ovary and mediastinum.“4 Males and females are equally affected, with 82% of cases found at less than 6 months of age and 95% of cases within 1 year of birth.‘-4 The lesion is usually not present at birth. MNTI has been reported in older adults, but some of these cases were questionable on review. ’ Clinically, MNTI appears as a rapidly expanding, nonulcerated mass. The tumor appears to arise in the maxilla and may have an exophytic component on the alveolus. Although it contains melanin, this pigmentation may not always be clinically evident.lm6 MNTI usually presents as a single lesion; however, multiple lesions have been reported.5,7 A computed tomography scan or magnetic resonance imaging may be helpful in localizing possible multiple sites.
897 When demctable,.the elevated levels of urinary VMA reported with MNTI return to normal after tumor remov~.‘.s,9,‘2 Unfortunately, the presence of measurable levels of urinary VMA is relatively uncommon. A review of urinary VMA testing in 195 cases of MNTI found the test positive in only 5 (2.5%) of cases.13 Usually, urinary assays for catecholamine metabolites, such as VMA, are accomplished with 24-hour samples. No urinary studies were performed on the two cases reported. MNTI is generally classified as benign despite rapid local growth potential. The local recurrence rate after conservative excision is 10% to 15%, but higher rates have been reported. ’ 6~‘4~‘5Recurrence is caused by residual tumor, as may have occurred in case 2. Malignancy occurs in approximately 2% of the cases, although some studies suggest a higher rate.lM6I5916 Metastasis has been noted to involve lymph nodes, liver, and bone. No significant histologic differences have been observed between malignant and benign lesions.‘*2,‘o-‘2,‘5 Death subsequent to disseminated MNTI has been reported.‘0-‘2 Histologically, this lesion is usually unencapsulated or partially encapsulated. The cells are arranged in clusters or line cleftlike spaces within a fibrous stroma. Two cell populations exist. One consists of small, ovoid cells with minimal cytoplasm and a hyperchromatic nucleus. The other consists of a larger epithelioid cell with more cytoplasm, which contains melanin pigmentation.‘-4.‘5 MNTI occasionally can also resemble other neural tumors, such as the pigmented papillary variant of a cerebellar medulloblastoma or the pigmented pineal gland (pineoblastic) neoplasm. Biopsy specimens of a patient with supraclavicular MNTI metastasis showed neuriticlike cells indistinguishable from a peripheral neuroblastoma.4 Electron microscopic studies of MNTI have been done.“-” Tissue from the second patient showed two
FIGURE 7. Photomicrograph showing dark-staining, melanincontaining cells and smaller ovoid cells (hematoxylin-eosin stain, original magnification X25).
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treatment involves conservative excision, enucleation, and curettage. ‘353’8 Recurrent cases may require a wider excision. Extensive resection is usually reserved for aggressive lesions.15 In a lesion that is not amenable to total resection, the remnants may not necessarily cause recurrence.6 As noted in the pathology report of patient 2, scattered residual tumor was evident at the margins subsequent to the partial maxillectomy and yet the child has had no recurrence over a 12-year period. This apparent success with incomplete removal should not reduce required follow-up assessment because the potential for an aggressive recurrence still remains.‘0-‘2~‘5 FIGURE 8. Photomicrograph showing dark-staining metanotic ceils interspersed with ovoid cells with hyperchromatic nuclei (hematoxylin-eosin stain, original magnification X200).
References I. Barnes L: Surgical Pathology of the Head and Neck, vol 1. New
cell types under scanning electron microscopy. The larger cell type contained melanosomes and the smaller cell type displayed neurotubules. Two separate cell lines have also been grown by tissue culture.4 Immunohistochemical studies involving cellular antigen-antibody reactions to identify various tissue markers also have been done on MNTI.‘4,15.‘7 These markers can be compared with known tissue markers to clarify the origin of MNTI.‘4*‘5,‘7 Presently, the studies indicate that MNTI is a primitive retinal analagelike neuroectodermal tumor with differentiation along neural, melanogenic, and epithelial lines. There are also occasional glial and myogenic features in MNTI, but no photoreceptor differentiation. I5One difficulty with immunohistochemical analysis is that neoplastic cells do not exactly reproduce all the immunochemical features of a mature normal cell type, therefore complicating specific tissue comparisons.” Another theory of MNTI origin considers the participation of neural crest cells in the formation of the dental papilla, which may account for the predominance of MNTI in the jaws.” MNTI tissue can also be analyzed by flow cytometry. This results in a cellular DNA analysis that quantitates whether cells within a tissue specimen are diploid or aneuploid.‘4,‘5 Diploid cells have twice the normal haploid number of chromosomes, while aneuploid cells deviate from an exact multiple of the haploid chromosome number. Although the studies are limited, they suggest that tumors with aneuploid cells may recur more often.‘4*‘S Tissues from the malignant MNTI cases have not been subjected to DNA analysis.” Despite its benign classification, this lesion’s potentially rapid growth requires prompt treatment to minimize adjacent tissue destruction. The recommended
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