婴儿色素性神经外胚瘤临床病理观察

目的：探讨色素性神经外胚瘤的病理形态、免疫组化及诊断和鉴别要点。对5例色素性神经外胚瘤病例进行临床病理、免疫组化及电镜观察。结果：色素性神经外胚瘤好发于1岁以内的婴儿，3例肿瘤发生在上颌骨，2例发生在附皋。镜下由两种细胞构成，即上皮样瘤细胞和小圆形似成神经细胞样瘤细胞。免疫组化示上皮样瘤细胞CK、HMB45阳性，小圆形瘤细胞NSE阳性，超微结构显示肿瘤细胞内分别可见前黑色素小体、黑色素小体和神经内分泌颗粒。结论：色素性神经外胚瘤是一种少见的原始性神经外胚层肿瘤，生物学行为属于潜在恶性或低度恶性肿瘤。     

Melanotic neuroectodermal tumor of infancy. A review of seven cases

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.     

Malignant melanotic neuroectodermal tumor: light and electron microscopic study

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.     

Malignant neoplasm of mixed mesenchymal and neuroepithelial origin (ectomesenchymoma) of thigh

A 49-year-old man had a malignant soft tissue tumor of the right thigh with metastasis to the femoral region and lower quadrant of the anterior abdominal wall on the right side and the left supraclavicular lymph nodes. The neoplasm showed features of chondrosarcoma and primitive neuroectodermal tumor (combined neuroblastoma, ependymoma, astrocytoma, and oligodendroglioma). The gliomatous part of the mixed tumor was confirmed by identification of the glial fibrillary acidic protein (GFAP). The diverse cellular population suggests a tumor origin from the ectomesenchymal remnant of the neural crest. The mesenchymal component of the neural crest would differentiate into the chondrosarcoma and the neuroectodermal component into the primitive neuroectodermal neoplasm. These various neoplastic elements, then, would form a neoplasm of mixed mesenchymal and neuroepithelial origin or an ectomesenchymoma.     

Tropism of the in situ growth from biopsies of childhood neuroectodermal tumors following transplantation into experimental teratoma

Experimental teratoma induced from human pluripotent stem cells with normal karyotype can be described as a failed embryonic process and includes besides advanced organoid development also large elements of tissue with a prolonged occurrence of immature neural components. Such immature components, although benign, exhibit strong morphological resemblance with tumors of embryonic neuroectodermal origin. Here, we demonstrate that biopsy material from childhood tumors of neural embryonic origin transplanted to mature experimental teratoma can show an exclusive preference for matching tissue. Tumor specimens from five children with; Supratentorial primitive neuroectodermal tumor (sPNET); Pilocytic astrocytoma of the brainstem; Classic medulloblastoma; peripheral primitive neuroectodermal tumor (pPNET) or neuroblastoma (NB), respectively, were transplanted. Analysis of up to 120 sections of each tumor revealed an engraftment for three of the transplanted tumors: pPNET, sPNET, and NB, with a protruding growth from the latter two that were selected for detailed examination. The histology revealed a strict tropism with a non‐random integration into what morphologically appeared as matched embryonic microenvironment recuperating the patient tumor histology. The findings suggest specific advantages over xenotransplantation and lead us to propose that transplantation to the human embryonic microenvironment in experimental teratoma can be a well‐needed complement for preclinical in vivo studies of childhood neuroectodermal tumors.     

Simultaneous occurrence of melanotic neuroectodermal tumor and brain heterotopia in the oropharynx.

A case is described of heterotopic brain tissue with simultaneous occurrence of melanotic neuroectodermal tumor in the oropharynx of a 6-week-old infant. The melanotic neuroectodermal tumor was embedded within the heterotopic glial tissue. This coexistence leads us to speculate that a defect causing a pinching-off of both neural crest cap and medullary epithelium of neural tube might have taken place at, or before, the 25-30 somite stage. The displaced embryonic structures subsequently differentiated into glial tissue, choroid plexus, and melanotic neuroectodermal tumor. This observation may be interpreted as further support in favor of a neural crest origin of juvenile melanotic neuroectodermal tumor.     

Ewing's sarcoma and primitive neuroectodermal family of tumors

Ewing's sarcoma (ES) initially was believed to be of perivascular endothelial origin. The Ewing's sarcoma family of tumors (EFT) includes ES of bone (ESB), extraosseous ES (EES), peripheral primitive neuroectodermal tumor of bone (pPNET), and malignant small-cell tumor of the thoracopulmonary region, or Askin's tumor, all of which are now known to be neoplasms of neuroectodermal origin. The degree of neuronal differentiation has been used for histopathologic subclassification of the EFT as classical ES (ESB or EES), which is characterized by minimal evidence of neural differentiation, and pPNET, which displays evidence of neural differentiation by standard microscopy, electron microscopy, or immunohistochemistry. Because the behavior, prognosis, and treatment appear to be similar for all subsets of EFT, this histopathologic subclassification may not be clinically significant, though some debate remains whether neural differentiation predicts for inferior outcome.     

Melanotic primitive neuroectodermal (neuroepithelial) tumor of medulla

A 69-year-old man had a melanotic primitive neuroectodermal tumor of the medulla displaying various neuroepithelial elements including undifferentiated neuroepithelial cells forming Homer Wright's rosettes as well as neoplastic neuroglia resembling those seen in medulloblastoma. The neuroglial tumor cells were verified by demonstrating glial fibrillary acidic protein (GFAP) in the cells. These findings support the concept that the primitive neuroectodermal tumor and medulloblastoma are similar neoplasms. They have been described by such diverse names as melanotic medulloblastomas and progonomas. Review of 18 reported cases of intracranial melanotic primitive neuroectodermal tumors, including the present one, reveals that they have common pathologic features, are most frequent in the cerebellum and fourth ventricle, often metastasize widely within the neuraxis or even systemically, occur more frequently in children than adults, and strike males more often than females.     

Biology of pediatric peripheral neuroectodermal tumors

The pediatric peripheral neuroectodermal tumors which include neuroblastoma, peripheral neuroepithelioma and Ewing's sarcoma may correspond to distinct neural crest cell lineages or tumors arrested at different stages of neural crest development. Besides a brief commentary on the salient clinical features of these tumors, this review examines how cell and molecular biological studies have contributed to a re-classification of these tumors. The differentiation of these tumors is reviewed with a particular emphasis on retinoic acid induced differentiation of neuroblastoma as a model to identify genes important in controlling cell growth, suppression of tumorigenicity and induction of differentiation.     

Malignant peripheral primitive neuroectodermal tumor of the uterus

Peripheral primitive neuroectodermal tumor (PPNET) is rare, occurring most often in young adults. Approximately 50 cases have been reported, with only four cases involving the female genital tract. We report the fifth patient. The term "PPNET" should be used only for tumors with neuroectodermal elements exclusively that occur at sites outside the central and sympathetic nervous system. The pathologic differential diagnoses include rhabdomyosarcoma, immature malignant teratoma, small cell carcinoma of the cervix, and ganglioneuroma. Therapy for this tumor has varied, and no effective regimen has been established.     

Prognostic value of clinicopathologic characteristics including neuroectodermal differentiation in osseous Ewing's sarcoma family of tumors in children.

AIMS AND BACKGROUND: The aim of the present study was to determine the relationship between clinico-pathologic parameters, including neuroectodermal differentiation, and their impact on survival in a series of pediatric patients with osseous tumors of the Ewing's sarcoma family admitted to the Pediatric Department of the Istituto Nazionale Tumori of Milan. METHODS: Seventy-three patients were enrolled. The variables analyzed were sex, age, site of primary tumor, serum lactate dehydrogenase (LDH) level at diagnosis, involvement of periosseous soft tissues by primary tumor, presence of metastatic disease, status of disease after the treatment plan, as well as the presence of mitoses, morphologic and immunocytochemical neural markers, and neuroendocrine markers in the primary tumor. RESULTS: Neural and neuroendocrine markers were not significantly associated with any of the other parameters. In the univariate analysis, significant risk factors related to unfavorable outcome were elevated LDH, metastatic disease, lack of complete remission after treatment, presence of mitoses and of morphological neural markers; immunocytochemical neural and neuroendocrine markers lacked prognostic value. In the multivariate analysis, only LDH levels and the status of disease following the treatment were retained. CONCLUSIONS: LDH level at diagnosis might be a useful marker to identify different risk levels; neuroectodermal differentiation might have no clear-cut impact on the clinical management of osseous Ewing's sarcoma family of tumors.     

N-myc amplification and neuronal differentiation in human primitive neuroectodermal tumors of the central nervous system

Despite the phenotypic similarities between primitive neuroectodermal tumors of the central nervous system, childhood neuroblastoma, and peripheral neuroepithelioma, a histogenetic relationship among these neoplasms has not been shown. High levels of N-myc expression occur selectively in developing brain and in some embryonic tumors of neural origin. N-myc amplification and high levels of N-myc expression in childhood neuroblastoma have been correlated with disease stage and prognosis. To determine whether the copy number of the N-myc gene in primitive neuroectodermal tumors of the central nervous system is altered, we examined 20 primitive neuroectodermal tumors by Southern and/or slot blot hybridization to a 1-kilobase N-myc genomic DNA sequence and a 492-base pair N-myc-specific subclone as well as to a 1.1-kilobase albumin complementary DNA sequence as a control for gene copy number. Amplification of the N-myc gene was detected in two cerebellar tumors both of which exhibited neuronal differentiation by light microscopy. These tumors had not been treated previously. Of the remaining 18 tumors, eight were undifferentiated, three showed early neuroblastic, and seven focal glial differentiation. These findings suggest a possible relationship between N-myc amplification and neuronal differentiation.     

Neural characteristics of Ewing's sarcoma and related tumors: Ultrastructural study with immunohistochemical analysis

Background. Recent immunocytochemical and cytogenic studies have shown that Ewing's sarcoma and peripheral primitive neuroectodermal tumor (PNET) are probably related neoplasms of common neuroectodermal origin. The purpose of this study was to investigate the morphological characteristics of neural differentiation in these tumors. Methods. We investigated the ultrastructure of 17 cases of Ewing's sarcoma and related tumors in the specimens of 17 patients, and carried out immunohistochemical analysis. Results. Ultrastructurally, the cell process and basal laminae were frequently observed in all cases of an unclassified small round-cell type of malignant peripheral nerve sheath tumor (MPNST-related tumor). In contrast, a poorly developed cell process and fragmented basal lamina were rarely observed in Ewing's sarcoma or in PNET. Cytoplasmic neurosecretory granule-like particles were found in two specimens of Ewing's sarcoma and two of PNET, and were abundant in one MPNST-related tumor specimen. These ultrastructural neural features were not common in Ewing's sarcoma, and were occasionally present in PNET. There was a discrepancy between positivity for immuno-neural markers and ultrastructural neural features. Conclusion. The differential diagnosis between Ewing's sarcoma and PNET was based on the degree of their morphological neural differentiation. Thus, we consider that the diagnosis of PNET should be made on the basis of ultrastructural neural features, taking into account immunohistochemical and histological considerations.     

A case of primary cerebral neuroblastoma in adolescence

Primary cerebral neuroblastoma is one of a group of highly malignant undifferentiated primitive neuroectodermal tumours arising from germinal matrix cells of the embryonic neural tube. They occur primarily in young children and are extremely rare in adults. They may be multicentric and have often spread throughout the central nervous system at the time of diagnosis. A case of a 16‐year‐old man is described, and the recent literature is reviewed.     

Electron microscopic findings in primitive neuroectodermal tumors of the cerebrum.

The fine structure of 3 primitive neuroectodermal neoplasms of the cerebral hemispheres was studied. The predominant tumor cells were undifferentiated cells with prominent nuclei and scanty cytoplasm containing few organelles. Ultrastructural evidence suggesting differentiation into ependymal, neuronal and possibly astrocytic elements was also present. This study suggests that the cell of origin of this tumor is a primitive multipotential cell of the cerebrum.     

Preferential expression of alpha B-crystallin in astrocytic elements of neuroectodermal tumors.

Recently the authors have identified a major component of Rosenthal fibers as alpha B-crystallin, a major lens protein. In the current study the authors investigated the expression of alpha B-crystallin in four cultured glioma cell lines and in 115 human neuroectodermal tumors. alpha B-crystallin was expressed differentially by those glioma cell lines, but not by neuroblastoma cell lines. Northern blot analysis revealed two distinct messages for alpha B-crystallin in C-6, whereas only a single message in U-373MG and G26-24. In human surgical specimens positive immunostaining was frequently observed in the following brain tumors: pilocytic astrocytoma of the juvenile type, anaplastic astrocytoma, glioblastoma multiforme, and subependymal giant cell astrocytoma. The astrocytic elements of mixed oligoastrocytomas, glioblastomas with sarcomatous components, and gangliogliomas were likewise strongly stained. In contrast, little immunoreactivity was observed in ependymal and choroid plexus tumors. Thus, alpha B-crystallin is mainly expressed by astrocytic tumors among neuroectodermal neoplasms, without regard to the presence of Rosenthal fibers.     

Schwannoma of maxillary sinus

Schwannoma, also known as neurilemmoma, is a solitary, encapsulated peripheral tumour of neuroectodermal derivation that originates from schwann cells of neural sheath of motor/ sensory peripheral nerves or sympathetic nerves. About one- third of all schwannomas occur in head and neck region but nose and paranasal sinuses, are rare sites. We report a case of schwannoma arising from the maxillary sinus and eroding the orbital floor. To the best of our knowledge, this is the sixth; case of schwannoma solely arising in the maxillary sinus, reported in the literature.     

Immunohistochemical staining for ganglioside GD1b as a diagnostic and prognostic marker for primary human brain tumors

Immunohistochemical staining intensity for ganglioside GD1b was determined for 108 human neuroectodermal tumors. Most of the tissue elements that immunostained were tumor cells; only a few axons and occasional neurons reacted in some specimens. All pilocytic astrocytomas stained very positively, whereas none of the ependymomas and only 11% of primitive neuroectodermal tumors, 20% of glioblastomas, and 28% of anaplastic astrocytomas showed more than faint staining. A similar association between grade and immunostaining was seen in tumors containing an oligodendrogliomatous component, but reactivity was not as strong as in astrocytic tumors or primitive neuroectodermal tumors. Results of Cox regression showed significant associations between immunostaining intensity and survival for all cases taken together (P = 0.007); for the group consisting of astrocytomas, oligoastrocytomas, and oligodendrogliomas (P = 0.002); and for astrocytomas alone (P = 0.04). Results were also significant using a proportional hazards model controlling for patient age (all cases P = 0.005; astrocytomas only P = 0.02), but not when controlling for tumor grade. Our results indicate that immunohistochemical staining for GD1b is correlated with tumor grade and that it may be of prognostic utility in some primary human brain tumors, especially astrocytomas.