Melanotic Neuroectodermal Tumor of Infancy: a Clinicopathological Case Report.

Melanotic neuroectodermal tumor of infancy (MNTI) is a rare neoplasm that affects mainly children under 1 year of age. A 4-month-old boy was referred for evaluation of a lesion with 1 month of evolution. Intra-oral examination detected a firm upon palpation submucosal nodular mass, measuring 1.5 cm in diameter, affecting the anterior maxillary alveolar ridge and covered by a slightly blue mucosa with evident telangiectasia. The patient underwent an incisional biopsy and histological and immunohistochemical analyses revealed nests of AE1/AE3 positive epithelioid cells with abundant melanin pigmentation. Other cell types, resembling neuroblasts, were also present and positive for CD56, synaptophysin and enolase. The diagnosis of MNTI was established and the patient was referred for treatment. Conservative surgical resection was performed along with 3 adjacent teeth under general anesthesia. The patient is in follow-up for 1,5 year without recurrence. Conservative surgical management of MNTI may be an alternative to maxillectomy, contributing to the patient´s quality of life.

Melanotic neuroectodermal tumor of infancy: a clinicopathological case report

Abstract Melanotic neuroectodermal tumor of infancy (MNTI) is a rare neoplasm that affects mainly children under 1 year of age. A 4-month-old boy was referred for evaluation of a lesion with 1 month of evolution. Intra-oral examination detected a firm upon palpation submucosal nodular mass, measuring 1.5 cm in diameter, affecting the anterior maxillary alveolar ridge and covered by a slightly blue mucosa with evident telangiectasia. The patient underwent an incisional biopsy and histological and immunohistochemical analyses revealed nests of AE1/AE3 positive epithelioid cells with abundant melanin pigmentation. Other cell types, resembling neuroblasts, were also present and positive for CD56, synaptophysin and enolase. The diagnosis of MNTI was established and the patient was referred for treatment. Conservative surgical resection was performed along with 3 adjacent teeth under general anesthesia. The patient is in follow-up for 1,5 year without recurrence. Conservative surgical management of MNTI may be an alternative to maxillectomy, contributing to the patient´s quality of life.

Resumo Tumor neuroectodérmico melanótico da infância (TNMI) é um neoplasma raro que afeta principalmente crianças com idade abaixo de 1 ano. Um menino de 4 meses foi referenciado para avaliação de uma lesão com 1 mês de evolução. O exame intra-oral detectou uma massa nodular submucosa firme à palpação, medindo 1,5 cm de diâmetro, afetando rebordo alveolar anterior da maxila e recoberta por mucosa de coloração levemente azulada com telangiectasia evidente. O paciente foi submetido à biopsia incisional e as análises histológica e imunohistoquímica revelaram ninhos compostos por células com abundante pigmento de melanina, positivas para AE1/AE3. Outro tipo celular, semelhante à neuroblastos, também estava presente e foram positivas para CD56, sinaptofisina e enolase. O diagnóstico de TNMI foi estabelecido e o paciente encaminhado para tratamento. Ressecção cirúrgica conservadora sob anestesia geral ao longo de 3 dentes adjacentes foi realizada. O paciente está em acompanhamento há 1 ano e meio sem sinais de recorrência. O tratamento cirúrgico conservador do TNMI pode ser uma alternativa à maxilectomia, contribuindo para a qualidade de vida do paciente.

Clinicopathological features of melanotic neuroectodermal tumor of infancy: Report of two cases.

Melanotic neuroectodermal tumor of infancy (MNTI) is an extremely rare, pigmented neoplastic entity of neural crest origin. Histological and immunohistochemical profiles indicate the presence of two components, small rounded neuroblast-like cellular areas and areas with large melanin-containing cells which consist of combination of neural, melanocytic, and epithelial cell types. Here we present two interesting cases of infants with MNTI which have different clinicopathological features. The first case is a 3-month-old female with rapidly growing MNTI involving the lacrimal sac and inferior wall of the orbital cavity, treated with total maxillectomy without orbital exenteration followed by chemotherapy. The second case is a 7-month-old male with slow-growing maxillary MNTI treated with complete surgical excision. In the female patient, histological findings revealed a predominance of neuroblast-like cellular areas and a high Ki67 index indicating rapid cellular proliferation. In the male patient however, large melanin-containing cells were dominant in this slow-growing tumor. These findings support the presence of two different types of MNTI, rapid-growing and slow-growing types, determined by the component of neuroblast-like cellular areas.

BRAFV600E Mutation in Melanotic Neuroectodermal Tumor of Infancy: Toward Personalized Medicine?

The melanotic neuroectodermal tumor of infancy (MNTI) is a rare neoplasm that primarily affects the maxilla of infants during their first year of life. Complete resection is the conventional treatment and recurrence rates vary from 10% to 60%. The recurrent tumors grow more aggressively and can invade other anatomic structures, such as the nasal cavity, the orbit, and the skull base. The aggressive behavior of MNTIs may require radical resection, which may not be possible in some cases because of its rapid and invading growth together with invasion of vital structures. In these situations, adjunct radiotherapy or chemotherapy has been used. However, as there are no conclusive data regarding the molecular profile of this tumor, currently there is no targeted therapy that may be used in the treatment of selected aggressive cases. On the basis of MNTI similarities with melanomas, such as derivation from the neural crest cells and presence of large melanin-containing cells, we hypothesized that MNTIs also may harbor the BRAFV600E oncogenic mutation. We show for the first time that this important pediatric tumor may harbor the oncogenic BRAFV600E mutation, providing the first insights to their personalized treatment.

Embryonal tumor with abundant neuropil and true rosettes with melanotic (retinal) differentiation.

Embryonal tumor with abundant neuropil and true rosettes (ETANTR) is a rare variant of central nervous system primitive neuroectodermal tumor occurring exclusively in the pediatric population. We report a unique case of a 6-month male child presenting with a large intraventricular lesion. Histological examination revealed a tumor composed of primitive neuroectodermal cells in dense aggregates, interspersed by hypocellular areas containing small round cells widely dispersed in neuropil-like material. Few ependymal and occasional ependymoblastic rosettes were appreciated. Focal melanotic neuroepithelium recapitulating retinal differentiation was also seen. Documentation of such cases may expand the neuroectodermal differentiation spectrum of ETANTR.

Melanotic neuroectodermal tumor of infancy: a case report.

Melanotic neuroectodermal tumor of infancy (MNTI) is a rare pigmented tumor generally occurring in the head and neck region in children 12 months of age or younger. Approximately 380 instances of this tumor are reported in the medical literature. We presented a case of MNTI that occurred in the left temporal bone of a 2-month old female infant. And, the clinical assessment, histologic diagnosis, and management is reviewed.

Melanotic neuroectodermal tumor of infancy: report of a case with myogenic differentiation.

An 8-month-old boy presented with a 6-week history of a skull mass of the anterior fontanelle. The mass was excised, and the histopathologic features were diagnostic for melanotic neuroectodermal tumor of infancy. The tumor showed focal myogenin positivity, which has not been previously reported in this tumor. The patient has no evidence of recurrent tumor 10 months after the excision. No adjuvant therapy was given. In addition, we stained a case of melanotic neuroectodermal tumor of infancy obtained from Columbus Children's Hospital; focal myogenin positivity was present.

Establishment and characterization of new cell lines derived from melanotic neuroectodermal tumor of infancy arising in the mandible.

Three cell systems (MINT1/2/3) derived from a melanotic neuroectodermal tumor of infancy (MNTI) arising in the mandible of a 1-month-old newborn boy have been established, and their cytological natures have been characterized. The cells had immunopositivities for pan-keratin, vimentin, neuron-specific enolase, S-100 protein and melanoma-associated antigen (HMB-45). These immunohistochemical phenotypes were basically the same as those observed in tissue sections, in which, synaptophysin, myelin basic protein, c-myc gene products, carcinoembryonic antigen, and epithelial membrane antigen were also immunolocalized in tumor cells. Karyotyping analyzes revealed that the chromosome numbers of the three cell systems ranged from 60 to 67 with 3n ploidies, and that there were many structural aberrations, such as del(11)(q13), del(22)(q13), add(2)(p11), add(7)(q22), extra copies for chromosomes 1, 2, 3, 5, 7, 9, 10, 11, 12, 16, 20, and 22, der(9)t(9;13)(p13;q12)add(9)(q34), and der(13;21)(q10;q10), which were shared by the three cell systems, while der(19)t(11;19)(q13;p13) was found in MINT1 and MINT3. When stimulated by endothelin-3 and vitamin D(3), the cells had spinous cell shapes with immunopositivities for HMB-45, neurofilament protein and glial fibrillary acidic protein, which indicated more neural differentiation. The established cell systems will be useful for further investigation on the molecular and genetic basis of MNTI to understand its pathogenesis, which is largely unknown.

December 2004: one-year-old girl with aggressive skull tumor.

December 2004. Twelve-month old girl presented with recurrent subcutaneous lesion in the left parietal region, one year after excision of a "benign" tumor. An MRI demonstrated left temporo-parietal skull tumor infiltrating the soft tissue, surrounding craniotomy flap, and extending to the brain parenchyma. Biopsy revealed biphasic neoplasm displaying nests of poorly differentiated neuroblastic cells positive for synaptophysin and pigmented cuboidal epithelioid cell positive for keratins, epithelial membrane antigen and MHB-45. In addition, some neoplastic cells were immunoreactive for synaptophysin as well as HMB-45 and epithelial markers, suggestive of their origin from a common progenitor. Interestingly, cell with the neuroblastic immunophenotype displayed 80% nuclear MIB-1 reactivity indicating that the aggressiveness of the neoplasm was confined mostly to this pattern of differentiation. The overall histological features are consistent with a rare malignant variant of a melanotic neuroectodermal tumor of infancy.

Melanotic neuroectodermal tumor of infancy in the soft tissues of the arm: fine needle aspiration biopsy and histologic correlation-a case report.

A case of melanotic neuroectodermal tumor of infancy (MNTI) presenting as a soft tissue mass in the right arm of a 6-mo female child is discussed. The mass was diagnosed by fine-needle aspiration biopsy (FNAB) and confirmed by histological examination. This communication emphasizes the characteristic cytology of MNTI and discusses its significance in the context of this tumor occurring in the soft tissues. The cytology smears were distinctive in showing a dual population of small, rounded, undifferentiated cells and larger melanin-containing epithelial-like cells. It is the identification of the latter cells in the smears which differentiates this tumor from other round cell tumors of infancy and helps in the correct diagnosis by FNAB.

Biological functions of the ISWI chromatin remodeling complex NURF.

The nucleosome remodeling factor (NURF) is one of several ISWI-containing protein complexes that catalyze ATP-dependent nucleosome sliding and facilitate transcription of chromatin in vitro. To establish the physiological requirements of NURF, and to distinguish NURF genetically from other ISWI-containing complexes, we isolated mutations in the gene encoding the large NURF subunit, nurf301. We confirm that NURF is required for transcription activation in vivo. In animals lacking NURF301, heat-shock transcription factor binding to and transcription of the hsp70 and hsp26 genes are impaired. Additionally, we show that NURF is required for homeotic gene expression. Consistent with this, nurf301 mutants recapitulate the phenotypes of Enhancer of bithorax, a positive regulator of the Bithorax-Complex previously localized to the same genetic interval. Finally, mutants in NURF subunits exhibit neoplastic transformation of larval blood cells that causes melanotic tumors to form.

Cell cycle-associated proteins in melanotic neuroectodermal tumor of infancy.

OBJECTIVE: The purpose of the present study was to compare the immunohistochemical expression of cell cycle-associated proteins in neuroblastic and melanocytic cell populations of melanotic neuroectodermal tumor of infancy. STUDY DESIGN: Three cases of melanotic neuroectodermal tumor of infancy were selected. The immunohistochemical expression of MDM-2, p53, proliferating cell nuclear antigen, cyclin D1, and cyclin A was assessed through use of the streptavidin-biotin-peroxidase complex technique. RESULTS: Positive immunostaining for MDM-2, proliferating cell nuclear antigen, cyclin D1, and cyclin A was occasionally observed in the large melanin-containing epithelioid cells. CONCLUSIONS: These data suggest that MDM-2 expression may be important for the development of melanotic neuroectodermal tumor of infancy and that the melanocytic cell population, not the neuroblastic one, is the proliferative component of the tumor.

Regulation by retinoic acid of insulin-degrading enzyme and of a related endoprotease in human neuroblastoma cell lines.

Physiologically, the action of insulin-like growth factors (IGFs) is controlled at different levels, from its transcription start by tissue-specific and development-specific transcriptional factors to its degradation by peptidases such as insulin-degrading enzyme (IDE). Since IGF-II is the major autocrine/paracrine growth factor for neuroblastoma cells, we studied the expression and the role of IDE in this system. Here, we show that (a) IDE is expressed in several human neuroectodermal tumor cell lines, including neuroblastoma cell lines; (b) in a neuroblastoma cell line, IDE expression is up-regulated by retinoic acid, a well-known inducer of neuronal differentiation and/or programmed cell death; (c) IDE is probably not the only IGF-degrading enzyme present in these cells, since the activity of a novel thermolysin-like metalloendopeptidase, clearly distinct from IDE, is also detected. The TME activity is inhibited by IGF-I, Des-IGF-I, and IGF-II, and it is down-regulated by retinoic acid. Since retinoic acid plays a relevant role in controlling the growth of these cells and affects the expression of IDE, we have also: (a) identified the retinoic acid receptors (RARs) and retinoid X receptors (RXRs) expressed in these cell lines and (b) by means of synthetic retinoid analogues identified the RAR/RXR isoforms whose activation may be sufficient to induce the expression of the IDE gene. These results provide evidence that complex posttranslational molecular mechanisms participate in the autocrine/paracrine growth control of the IGF-II loop in neuroblastomas involving proteolytic systems.