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Background
This rare soft tissue tumor was first described in the jaws of newborn infants. Although the first name for this tumor was a congenital melanocarcinoma, it is now clear that it is a tumor derived from neural crest origin.
OUTLINE
EPIDEMIOLOGY CHARACTERIZATION SYNONYMS MNTI
Pigmented ameloblastoma
Retinal anlage tumor
Melanotic progonoma
Melanotic epithelial odontoma
Pigmented teratoma
Atypical melanoblastoma
Melanotic adamantinoma
Pigmented epulis
Retinal choristoma
Melanoameloblastoma
Retinoblastic teratoma.INCIDENCE AGE RANGE-MEDIAN 90% in first year of life, usually from age 1-6 months.
Mean age 4.3 months
Rare adult cases
Equal
DISEASE ASSOCIATIONS CHARACTERIZATION FETAL HYDANTOIN SYNDROME Melanotic neuroectodermal tumor of infancy and fetal hydantoin syndrome.
Jimenez JF, Seibert RW, Char F, Brown RE, Seibert JJ.
Am J Pediatr Hematol Oncol 1981 Spring;3(1):9-15 Abstract quote
Fetal hydantoin syndrome (FHS), a characteristic pattern of altered growth and development, has been well described in recent years in offsprings of epileptic mothers taking phenytoin or other hydantoin anticonvulsants during the gestational period. Recent reports of neuroblastoma in three patients with the FHS further raise the questions of the "oncogenic effect " of hydantoin compounds.
A case of melanotic neuroectodermal tumor of infancy (MNTI) has been studied clinically and pathologically including light microscopy, histochemistry, and electron microscopy. This case strengthens the evidence for the teratogenic and oncogenic effects of hydantoin compounds and we believe that it represents the first reported case of FHS associated with MNTI. It would be most important from a clinical standpoint to carefully scrutinize individuals with the FHS for neoplasias.
Furthermore, detailed gestational drug history in children with neuroblastoma and other neoplasias should be carefully searched for, with the hope of clarifying the definitive oncogenic effect of hydantoin compounds.
TRAUMA Melanotic neuroectodermal tumor of infancy discovered after head trauma.
Paueksakon P, Parker JR, Fan X, Miles G, Ruiz H, Wushensky C, Johnson MD.
Department of Pathology, Vanderbilt University Medical Center, Nashville, Tenn., USA.
Pediatr Neurosurg 2002 Jan;36(1):33-6 Abstract quote
Melanotic neuroectodermal tumor of infancy (MNTI) is a rare neoplasm that generally arises in the maxilla during the first year of life. Involvement of bones of the cranial vault or brain is extremely rare.
We describe a 7-month-old black female who presented after falling out of bed onto a concrete floor. Subsequently, she developed an anterior frontal mass that enlarged over several days. Radiographs of the skull at her local hospital showed a depressed right frontal skull fracture. However, computerized tomography of the head (reviewed at our institution) revealed a slightly hyperdense extra-axial mass which crossed the anterior frontal midline, widening the metopic suture and extending into the anterior subgaleal scalp. Hyperostosis of the adjacent frontal calvarium was also present. A craniotomy revealed a dark, 1.5-cm calcified epidural lesion with some features of an unusual hematoma. Microscopic evaluation revealed a chronic hematoma and MNTI. The tumor recurred within a year.
MNTI should be included in the differential diagnosis of epidural and skull lesions in infants.
PATHOGENESIS CHARACTERIZATION DYSONDONTOGENESIS OF NEURAL CREST TISSUE Melanotic neuroectodermal tumor of the neurocranium in infancy.
Walsh JW, Strand RD
Childs Brain 1982 Sep-Oct;9(5):329-46 Abstract quote
Melanotic neuroectodermal tumors of the neurocranium are a rare but life-threatening disorder of infancy. 11 previously reported cases are reviewed in terms of clinical presentation, radiological diagnosis, and management. A twelfth case, a 4-month-old infant who developed three discrete sites of tumor unilaterally in the neurocranium is presented. Several hypotheses for the mechanism of formation of these tumors are reviewed.
The authors propose that the mechanism of formation involves a dysontogenesis of neural crest tissue and that these tumors form, at least in part, from fragments of melanin-containing arachnoid villi which are displaced during embryonic development.
LABORATORY/RADIOLOGIC/
OTHER TESTSCHARACTERIZATION RADIOLOGIC Three-dimensional reconstruction of melanotic neuroectodermal tumor of infancy involving the occipital bone and dura.
Raila FA, Parent AD, Ward BA, Fratkin JD.
Department of Radiology, University of Mississippi Medical Center, Jackson 39216-4505, USA.
J Neuroimaging 1997 Apr;7(2):123-6 Abstract quote
A rare case of melanotic neuroectodermal tumor of infancy involving the right occipital bone in an 11-month-old infant is described. The bone tumor and its dural extension were surgically removed.
Three-dimensional reconstruction of the tumor and brain from neuroimaging data added worthwhile information for preoperative planning.
Microscopic examination revealed melanotic and neuroblastic tissue in a fibrillary matrix involving the expanded bone and superficial dura. A focal osteoblastic cranial mass in an infant should alert the clinician to consider this tumor.
GROSS APPEARANCE/
CLINICAL VARIANTSCHARACTERIZATION GENERAL Melanotic neuroectodermal neurocranial tumor of infancy of extra-intra-and subdural right temporal location: CT examination, surgical treatment, literature review.
Parizek J, Nemecek S, Cernoch Z, Heger L, Nozicka Z, Spacek J.
Neuropediatrics 1986 Aug;17(3):115-23 Abstract quote
A melanotic neuroectodermal neurocranial tumor of infancy of extra-intra-subdural right temporal location, examined by CT and successfully operated in a 33-month-old boy is reported in context with the literature.
Out of 30 cases (including our case) of melanotic neuroectodermal neurocranial and intracranial tumors (MNNIT) 18 were located in the neurocranium (MNNT) and 12 intracranially, i.e. in the brain and cerebellum (MNIT). 23 tumors were located medially (11 at the anterior fontanel, one at the posterior fontanel, one in the 3rd ventricle, one in the sella turcica, one in the pineal region, 8 in the cerebellar vermis) and 7 laterally (five involved the temporal bone, one of which with intracranial propagation (our case), one in the temporal lobe of the brain, one in the skull posterior to the mastoid process). Twenty-eight cases were children (16 boys, 8 girls, four not stated), two adults.
The location is important in respect to biology and surgery: MNNIT can be grouped as to its relation to the arachnoid barrier layer into malignant and benign. MNIT localised medially subarachnoidally are malignant. MNNT of small dimensions localised medially and laterally extraarachnoidally are benign. MNNT of extreme dimensions localised medially extra-intradurally are also benign, but difficult to treat. In the MNNT when diagnosed early and operated radically, the mortality can be lowered.
Our case, presented on CT (1978) as first case of combined extra-intra-subdural location, represents the 173rd MNT and the 18th related to neurocranium.
Melanotic neuroectodermal tumor of infancy. A review of seven cases
Johnson RE, Scheithauer BW, Dahlin DC.
Cancer 1983 Aug 15;52(4):661-6 Abstract quote
The melanotic neuroectodermal tumor of infancy (MNTI) is a rare, usually benign, pigmented neuroectodermal tumor which most often involves the maxilla.
The authors reviewed seven cases of MNTI, with patient ages of our patients ranged from nine weeks to 18 months; six of the seven were less than six months old at initial diagnosis. Four patients were males, and all were white. One tumor each was located in the femur, the temporal bone, and the epididymis; the remaining lesions occurred in the maxilla. Three of the four maxillary tumors recurred locally; the epididymal and femoral tumors metastasized. Two of these cases had unique clinical or pathologic features.
The case of the femoral tumor is remarkable in that it is the first reported one of MNTI presenting in a long bone. This tumor was aggressively malignant; within two months after its discovery, a large mass of similar tumor was formed in the pelvis, and the tumor resulted in the patient's death.
To the authors' knowledge, the case of the temporal bone tumor is the first one of MNTI in which neuronal differentiation of the neuroblastic cells is convincingly demonstrated. This finding provides additional evidence in support of the neuroectodermal theory of origin of these neoplasms.
VARIANTS EPIDIDYMIS Melanotic neuroectodermal tumor of infancy (MNTI) in the epididymis. A case report with immunohistological studies and special consideration of malignant features.
Jurincic-Winkler C, Metz KA, Klippel KF.
Department of Urology, General Hospital Celle, Germany.
Zentralbl Pathol 1994 Jul;140(2):181-5 Abstract quote
Melanotic neuroectodermal tumors of infancy (MNTI) are uncommon, usually benign neoplasms, most frequently found in the maxilla. These tumors are extremely rare in the epididymis. Only 18 cases with this site of origin are documented.
We report on the third epididymal MNTI with some morphological characteristics of malignancy but favorable clinical outcome. The 2 cm large tumor of a 6-month-old male infant showed large epitheloid cells in the center and small neuroblastoma-like cells at the periphery. Despite invasion of lymphatics there is no evidence of relapse or metastases during 4 years of follow-up.
Immunohistochemically, the large tumor cells were distinctly positive for cytokeratin, vimentin, GFAP, the melanoma marker NKI-C3, NSE, and S100. The small tumor cells were only slightly positive for GFAP, NKI-C3, NSE, and S100 but they were negative for cytokeratin and vimentin. Neurofilament and chromogranin could not be proved in the tumor.
FEMUR Melanotic neuroectodermal tumor of infancy: a malignant tumor of the femur.
Johnson RE, Scheithauer BW, Dahlin DC.
Mayo Clin Proc 1982 Nov;57(11):719-22 Abstract quote
An 18-month-old white girl had a malignant melanotic neuroectodermal tumor of infancy of the left femur. Light microscopic findings of a biopsy specimen of the femoral lesion demonstrated the characteristic histologic features, that is, nests of small cells with hyperchromatic nuclei and scant cytoplasm lying within cleftlike spaces lined by cuboidal, melanin-producing cells.
Electron microscopy confirmed both neuroblastic and melanocytic differentiation. Despite radiation and chemotherapy, an extensive pelvic tumor developed, which prompted laparotomy 20 months after the femoral biopsy, The apparently metastatic tumor was largely necrotic, but viable nests of undifferentiated small cells and rare individual melanin-containing cells were identified. The patient died 4 months later, at 3 years of age.
This case is of particular importance because it is the first example of this tumor found in a long bone. No similar lesions were seen in 17,000 primary tumors of bone treated and seen in consultation at this institution.
Its aggressively malignant clinical course is also unusual; only 6 of the 159 cases of melanotic neuroectodermal tumor of infancy reported to date have expressed malignant behavior.
MANDIBLE Melanotic neuroectodermal tumor of infancy in the mandible: report of a case.
Hoshina Y, Hamamoto Y, Suzuki I, Nakajima T, Ida-Yonemochi H, Saku T.
Niigata University, First Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Niigata University, Japan.
Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2000 May;89(5):594-9 Abstract quote
A case of melanotic neuroectodermal tumor of infancy occurring in the mandible is described. The patient was a 1-month-old boy with a rapidly growing tumor of the mandible. Computed tomography showed 2 well-defined osteolytic lesions in the right mandible.
Histopathologic diagnosis of a biopsy specimen was melanotic neuroectodermal tumor of infancy. The tumor was excised with removal of the surrounding bone, but 1(1/2) months later it recurred, and segmental mandibulectomy and reconstruction of the defect with a titanium miniplate was performed. Retrospectively, evidence of recurrence was noted on computed tomography taken on the tenth postoperative day. The recurrence was caused by incomplete removal of the tumor. Histopathologically, the tumor cells of the recurrent lesion were dispersed extensively in the bone marrow, and bone remodeling was active.
The surgical procedure may have stimulated tumor cell proliferation and reactive bone formation. The patient was followed for 2 years with no evidence of recurrence or metastasis.
PINEAL GLAND Malignant melanotic neuroectodermal tumor arising from the pineal body.
Ogata A, Fujioka Y, Nagashima K, Tashiro K, Aida T, Abe H.
Department of Pathology, Hokkaido University School of Medicine, Sapporo, Japan.
Acta Neuropathol (Berl) 1989;77(6):654-8 Abstract quote
A case of a melanotic neuroectodermal tumor arising from pineal region of a 4-year-old girl is presented. The tumor had spread diffusely to the meninges, consistent with malignant behavior.
Histologically, the tumor consisted primarily of epithelial elements arranged in tubules, cords and nests separated by fibrous vascular tissue in addition to a small neuroblastomatous focus. Melanin pigment was frequently observed in the epithelial tumor cells, and melanin-laden macrophages were also often observed. No teratoid elements were found. Immunohistochemically, tumor cells were positive for neuron-specific enolase but were nonreactive for S-100 protein, epithelial membrane antigen, glial fibrillary acidic protein, vimentin, alpha-fetoprotein and human chorionic gonadotrophin.
Ultrastructurally, the epithelial nature of the tumor cells could be easily demonstrated. In addition, melanosomes in various stages in maturation were observed, indicating melanogenesis of the tumor.
On the basis of the tumor location and the histological similarities previously observed for the fetal pineal body, it is very likely that this melanotic epithelial tumor could have originated from the fetal pineal gland.
HISTOLOGICAL TYPES CHARACTERIZATION GENERAL Malignant melanotic neuroectodermal tumor: light and electron microscopic study.
Navas Palacios JJ.
Cancer 1980 Aug 1;46(3):529-36 Abstract quote
An 11-year-old white boy had a melanotic neuroectodermal tumor of infancy (MNTI) in his right mandible. Gross-examination showed that the tumor had originated in the right lower dental nerve, destroyed the right mandible, infiltrated the surrounding soft tissues, and metastasized to several lymph nodes.
The typical alveolar pattern was observed in most of the tumor mass; however, solid areas with neuroblastic features were present in the infiltrating and metastasizing portions of the tumor. Ultrastructural study demonstrated unequivocal neuroblastic and melanocytic differentiation.
A clinicopathologic and immunohistochemical analysis of melanotic neuroectodermal tumor of infancy.Barrett AW, Morgan M, Ramsay AD, Farthing PM, Newman L, Speight PM.
University College, Queen Mary College, and Great Ormond Street Hospital for Children.
Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2002 Jun;93(6):688-98 Abstract quote Objective. The purpose of this study was to review the features of 8 cases of melanotic neuroectodermal tumor of infancy (MNTI) of the jaws with respect to the expression of NB84, CD99, PGP 9.5, specific cytokeratins, and Ki-67, markers not previously reported in this entity.
Study Design. A clinicopathologic and immunohistochemical analysis of MNTIs in 8 children was undertaken.
Results. Patients were aged 2(1/2) months to 14 months. Seven were males. Seven lesions affected the maxilla. Microscopically, collections of larger, melanocyte-like cells were admixed with smaller, neuroblast-like cells. All MNTIs contained melanin; although most showed cellular atypia, mitoses were infrequent (<2 per 10 high-power fields). However, in one lesion in which the melanocyte-like cells appeared less differentiated, 7 mitoses per 10 high-power fields were counted. The larger cells expressed cytokeratins 7 (4/8), 8 (8/8), 18 (6/8), and 19 (3/8); PGP 9.5; neuron-specific enolase (6/8); S100; HMB45; and chromogranin A (2/8). The small cells expressed CD56 (7/8), neuron-specific enolase (7/8), synaptophysin (3/8), PGP 9.5 (3/8), and chromogranin A (2/8). No MNTIs expressed NB84. The most mitotically active tumor was the only one to show membrane expression of CD99 (by both cell populations), have a detectable Ki-67-positive fraction (25% in both the large- and small-cell components), behave aggressively, and require bilateral maxillectomy. All other MNTIs responded to local excision, and none metastasized.
Conclusions. Most MNTIs are benign and respond to conservative excision. Histology is an unreliable means of predicting clinical behavior, but this study has identified some morphologic and phenotypic features that may indicate a more aggressive lesion.
VARIANTS GANGLIONIC DIFFERENTIATION Melanotic neuroectodermal tumor of infancy: report of a case with ganglionic differentiation.
Shah RV, Jambhekar NA, Rana DN, Raje NS, Albuqurque KV, Mistry RC, Desai PB, Advani SH.
Department of Medical Oncology, Tata Memorial Hospital, Bombay, India.
J Surg Oncol 1994 Jan;55(1):65-8 Abstract quote
Melanotic neuroectodermal tumor of infancy (MNTI) is a rare but well-documented lesion of neuroectodermal derivation. Maturation of the neural elements has been reported only occasionally.
We report a case of MNTI of the maxilla showing maturation of neural elements to ganglionic cells.
SPECIAL STAINS/IMMUNOPEROXIDASE/
OTHERCHARACTERIZATION SPECIAL STAINS IMMUNOPEROXIDASE Pigmented neuroectodermal tumour of infancy: an immunohistochemical study.
Stirling RW, Powell G, Fletcher CD.
Department of Histopathology, St Thomas's Hospital Medical School, London, UK.
Histopathology 1988 Apr;12(4):425-35 Abstract quote
The pigmented neuroectodermal tumour of infancy is a rare neoplasm of uncertain histogenesis which, in the majority of cases, arises in the maxilla and pursues a benign course. Currently, it would be classified in the group of peripheral primitive neuroectodermal tumours.
Histologically it is composed of two principal cell types: neuroblast-like and melanocyte-like. Three typical cases are presented herein, which appear to be the first examined with a panel of antibodies. The neuroblast-like cells labelled positively for neurone-specific enolase but were negative for S-100, neurofilaments, glial fibrillary acidic protein, vimentin, cytokeratin, epithelial membrane antigen (EMA) and carcinoembryonic antigen (CEA). The melanocyte-like cells stained positively for neurone-specific enolase, vimentin and cytokeratin but were negative for S-100, neurofilaments, glial fibrillary acidic protein, EMA and CEA.
The significance of these findings is discussed in the light of previous suggestions about the differentiation that these tumours show.
Pigmented neuroectodermal tumor of infancy. A light microscopic and immunohistochemical study.
Argenyi ZB, Schelper RL, Balogh K.
Department of Pathology, University of Iowa, Iowa City.
J Cutan Pathol 1991 Feb;18(1):40-5 Abstract quote
We studied two cases of pigmented neuroectodermal tumor of infancy (PNTI) by routine light microscopy and immunohistochemistry on formalin fixed, paraffin embedded tissues using antibodies to HMB-45 "melanoma associated" antigen, S-100 protein, neuron specific enolase (NSE), Leu-7 antigen, chromogranin, epithelial membrane antigen, collagen Type IV, alpha-fetoprotein and muscle-specific actin and to the intermediate filaments cytokeratin (CK), vimentin, desmin and neural filaments.
We found that the large epithelioid cells, many of which contained melanin pigment, were strongly positive for CK and HMB-45, and less intensively positive for vimentin and NSE. The small neuroblast-like cells revealed only focal, weak NSE positivity. Both cell types were negative for S-100 protein and for the other antigens examined.
Our results suggest that: (1) the large and small cell populations in PNTI have different immunophenotypes; (2) the expression of CK and HMB-45, together with the S-100 negativity, appears unique for the pigmented cells; and (3) this profile may be helpful in the exclusion of melanoma and peripheral neuroblastoma from the differential diagnosis.
Melanotic neuroectodermal tumor of infancy. A reexamination of a histogenetic problem based on immunohistochemical, flow cytometric, and ultrastructural study of 10 cases.
Pettinato G, Manivel JC, d'Amore ES, Jaszcz W, Gorlin RJ.
Department of Pathology, 2nd Medical School, University of Naples, Italy.
Am J Surg Pathol 1991 Mar;15(3):233-45 Abstract quote
Ten cases of melanotic neuroectodermal tumor of infancy (MNTI) were studied. There were nine males and one female ranging in age from 2 weeks to 10 months; one patient was 8 years old. Sites of origin were the maxilla (five), epididymis (two), mandible (one), skull (one), and soft tissues of the cheek (one).
Six tumors recurred from 1 to 18 months after diagnosis. One patient had widespread dissemination. Electron microscopic study of four cases showed cells with melanosomes at various stages of maturation, and cells with neuroblastic features, including neurosecretory granules and cytoplasmic processes.
Nine cases of MNTI were studied immunohistochemically. Small neuroblastic cells and large cells in all cases were reactive for neuron-specific enolase (NSE), synaptophysin, HMB45, and dopamine-beta-hydroxylase, large cells in all cases and few small cells were reactive for cytokeratin (CK) and vimentin (VIM). Epithelial membrane antigen was observed in large cells in three cases, four cases expressed Leu 7 antigen, three were focally positive for glial fibrillary acidic protein, one for desmin, and one for chromogranin. All cases were nonreactive for retinol-binding proteiELEn, neurofilaments, alpha-fetoprotein, S-100 protein, and carcinoembryonic antigen. Five normal adult retinas were studied similarly; the pigmented epithelium of the retina was reactive for CK, VIM, HMB45, NSE, and S-100. DNA study, performed in eight tumors, revealed aneuploidy in two (DNA index = 1.7 and 1.8); these cases recurred within 1 month. No differences were observed according to site or behavior.
MNTI is a primitive neuroectodermal tumor with polyphenotypic expression of neural and epithelial markers, melanin production, occasional glial, and rhabdomyoblastic differentiation, and no photoreceptor differentiation. It probably represents a dysembryogenetic neoplasm that recapitulates the retina at 5 weeks of gestation.
ELECTRON MICROSCOPY Melanotic neuroectodermal tumor of infancy: an ultrastructural study, literature review, and reevaluation.
Cutler LS, Chaudhry AP, Topazian R.
Cancer 1981 Jul 15;48(2):257-70 Abstract quote
Two cases of melanotic neuroectodermal tumor of infancy were examined by electron microscopy and an extensive review of the literature was performed. Ultrastructural examination revealed several features not previously described for this lesion.
Three different types of melanin granule formation were observed, many cells had a single cilium, and cell junctions of the "close" or "modified-tight" type were seen, but no desmosomes were found. The morphologic data were consistent with the concept that the tumor arises from neural crest cells.
The review of the literature indicated that there have been 158 reported cases of this lesion, including the two reported here. There were five cases of malignant tumor reported for a rate of 3.2%. This rate of malignancy is very high in view of the fact that the tumor has been described as universally benign. The significance of this finding is discussed with regard to melanin-producing lesions of the oral cavity.
Melanotic neuroectodermal tumor of infancy occurring in the left thigh of a 6-month-old female infant.
Scheck O, Ruck P, Harms D, Kaiserling E.
Institute of Pathology, Eberhard-Karls University, Tubingen, Federal Republic of Germany.
Ultrastruct Pathol 1989 Jan-Feb;13(1):23-33 Abstract quote
We report an exceptional case of melanotic neuroectodermal tumor of infancy (MNTI) occurring in the soft tissue of the left thigh of a 6-month-old female infant.
The tumor consisted mainly of small round cells (neuroblasts) arranged in cords and nests that were separated by broad fibrovascular areas. In addition, there were a few medium-sized tumor cells containing melanin pigment (melanocytic cells) that in electron microscopy contained melanosomes as well as tonofilaments.
Both tumor cell types immunostained for neuron-specific enolase (NSE) and vimentin, and the melanocytic cells reacted additionally with the antikeratin antibody KL1. Within the tumor stroma, neurofilament- and S-100-protein-positive neural cells and vimentin- and desmin-positive myofibroblasts were seen. Although dense-core granules were demonstrated ultrastructurally in some neuroblasts, no immunostaining for chromogranin A, Leu-7, serotonin, or regulatory peptides was found. MNTI located in an extremity can be confused with malignant small round and blue cell tumors of childhood. The distinction between MNTI and these tumors is of clinical significance because MNTI, in most cases, is a benign tumor that, in contrast to the latter, can be cured by complete excision.
The presence of a biphasic cell population with neuroblasts and melanocytic cells must be considered the main diagnostic feature of MNTI.
DIFFERENTIAL DIAGNOSIS KEY DIFFERENTIATING FEATURES PIGMENTED PNET Primitive neuroectodermal tumors of the cerebrum: a histological and immunohistochemical study of 10 cases.
Grant JW, Steart PV, Gallagher PJ.
Department of Pathology, Southampton University General Hospital.
Clin Neuropathol 1988 Sep-Oct;7(5):228-33 Abstract quote
Four males and 6 females, 5-66 (mean 27) years, with supratentorial primitive neuroectodermal tumors (PNETs) have been treated in one center in a 5-year period. Symptoms and signs had been present from 4 days to 8 years and were highly variable.
The frontal hemisphere was involved in 6 cases. Seven patients have died but with a combination of surgery and radiotherapy 3 patients have survived 20 months or longer. All tumors were composed of rounded, hyperchromatic undifferentiated cells but there were focal areas of astrocytic (5 cases), mesenchymal (4 cases) or neuronal differentiation (1 case). In 9 of the 10 cases a proportion of the undifferentiated round cells stained with antibodies to GFAP. Seven of these also showed nuclear staining for S100 protein and 6 of these, plus the tumor that did not stain for GFAP, had cytoplasmic staining for neuron specific enolase. Six tumors stained with antibodies to vimentin but there was no staining for common leukocyte antibody, cytokeratin or myoglobin.
These results, in particular those with GFAP, indicate that PNETs undergo differentiation even in areas of apparent morphological uniformity. Furthermore, immunohistochemistry is useful in distinguishing PNETs from other "small blue cell tumors" such as malignant lymphoma and undifferentiated secondary carcinoma.
PROGNOSIS AND TREATMENT CHARACTERIZATION PROGNOSTIC FACTORS Melanotic neuroectodermal tumor of infancy. Clinicopathological, immunohistochemical, and flow cytometric study.
Kapadia SB, Frisman DM, Hitchcock CL, Ellis GL, Popek EJ.
Department of Otolaryngic Pathology, Armed Forces Institute of Pathology, Washington, D.C.
Am J Surg Pathol 1993 Jun;17(6):566-73 Abstract quote
Twenty cases of melanotic neuroectodermal tumor of infancy (MNTI) are reported. The patients (13 females, seven males), whose ages ranged from 1 to 9 months (mean, 5 months), typically presented with a rapidly growing mass.
Tumor sites included the maxilla (13 cases), mandible (three cases), dura (two cases), brain (one case), and skull/orbit (one case). The mean tumor size was 3.5 cm (range, 1.0-10.0 cm). Follow-up was obtained on 12 cases. Five tumors (45%) recurred within 4 months of diagnosis, but none metastasized. One surgical death occurred.
Histologic appearance was distinctive, with tubular or alveolar formations of large melanin-containing cells around nests of smaller neuroblastic cells possessing scant or fibrillar cytoplasm.
Twelve tumors were studied immunohistochemically; tumor was positive for cytokeratin in 12 of 12, for HMB 45 in 12 of 12, for vimentin in seven of eight, and for epithelial membrane antigen (EMA) in four of nine tumors, mainly in the large cells. Neuron-specific enolase (NSE) (seven of 12) and Leu 7 (nine of 12) were positive in small and large cells; some tumors also expressed synaptophysin (four of 12), glial fibrillary acidic protein (GFAP, three of 12 tumors), or S-100 protein (two of 12 tumors). No staining was found for chromogranin, desmin, or carcinoembryonic antigen (CEA). Eight of 10 tumors studied had interpretable results on flow cytometry (FCM) (four DNA diploid, three DNA aneuploid, and one DNA diploid with a prominent shoulder). Tumor recurred locally in two of five cases with follow-up, and we were unable to demonstrate the usefulness of FCM in predicting recurrences.
Further studies are necessary to define better the potential usefulness of FCM in predicting aggressive behavior. Distinctive morphology and multiphenotypic (epithelial, neural, melanocytic) expression distinguish MNTI from melanoma and metastatic neuroblastoma.
RECURRENCE Average recurrence rate is 15-20%
TREATMENT Surgical excision
SURGERY Subtotal maxillectomy for melanotic neuroectodermal tumor of infancy.
Mast BA, Kapadia SB, Yunis E, Bentz M.
Department of Pathology of the University of Pittsburgh Medical Center, and Children's Hospital of Pittsburgh, PA, USA.
Plast Reconstr Surg 1999 Jun;103(7):1961-3 Abstract quote
Melanotic neuroectodermal tumor of infancy is a rare pigmented neoplasm occurring in infants before 1 year of age. It is a rapidly growing tumor that most frequently affects the craniofacial skeleton. Although melanotic neuroectodermal tumor of infancy is benign in the vast majority of cases, inadequate excision, occasional multicentricity, and a small malignant potential result in a fairly high recurrence rate.
On the basis of data obtained from the literature and our clinical experience, we advocate an aggressive surgical approach consisting of complete surgical excision when vital structures are not involved.
Histopathologic confirmation of complete excision is mandatory to minimize the risk of recurrence and provide the patient with curative treatment and minimal morbidity.
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