bromochloroacetic-acid and Neuroectodermal-Tumors--Primitive--Peripheral

Topics: Antibodies, Monoclonal; Carcinoma, Small Cell; Cell Line; Desmosomes; Humans; Intermediate Filament Proteins; Keratins; Lung Neoplasms; Neoplasms; Neuroectodermal Tumors, Primitive, Peripheral; Rhabdomyosarcoma

Ewing sarcoma family tumors (EFTs) of the head and neck are rare and may be difficult to diagnose, as they display significant histologic overlap with other more common undifferentiated small blue round cell malignancies. Occasionally, EFTs may exhibit overt epithelial differentiation in the form of diffuse cytokeratin immunoexpression or squamous pearls, resembling the so-called adamantinoma-like EFTs and being challenging to distinguish from bona fide carcinomas. Furthermore, the presence of EWSR1 gene rearrangement correlated with strong keratin expression may suggest a myoepithelial carcinoma. Herein, we analyze a series of 7 adamantinoma-like EFTs of the head and neck, most of them being initially misdiagnosed as carcinomas because of their anatomic location and strong cytokeratin immunoexpression, and subsequently reclassified as EFT by molecular techniques. The tumors arose in the sinonasal tract (n=2), parotid gland (n=2), thyroid gland (n=2), and orbit (n=1), in patients ranging in age from 7 to 56 years (mean, 31 y). Microscopically, they departed from the typical EFT morphology by growing as nests with peripheral nuclear palisading and prominent interlobular fibrosis, imparting a distinctly basaloid appearance. Moreover, 2 cases exhibited overt keratinization in the form of squamous pearls, and 1 sinonasal tumor demonstrated areas of intraepithelial growth. All cases were positive for CD99, pancytokeratin, and p40. A subset of cases showed synaptophysin, S100 protein, and/or p16 reactivity, further confounding the diagnosis. Fluorescence in situ hybridization assays showed EWSR1 and FLI1 rearrangements in all cases. Our results reinforce that a subset of head and neck EFTs may show strong cytokeratin expression or focal keratinization, and are therefore histologically indistinguishable from more common true epithelial neoplasms. Thus, CD99 should be included in the immunopanel of a round cell malignancy regardless of strong cytokeratin expression or anatomic location, and a strong and diffuse CD99 positivity should prompt molecular testing for the presence of EWSR1 gene rearrangements.

Topics: 12E7 Antigen; Adamantinoma; Adolescent; Adult; Antigens, CD; Biomarkers, Tumor; Biopsy; Bone Neoplasms; Calmodulin-Binding Proteins; Cell Adhesion Molecules; Cell Differentiation; Child; Diagnosis, Differential; Female; Gene Rearrangement; Head and Neck Neoplasms; Humans; Immunohistochemistry; In Situ Hybridization, Fluorescence; Keratins; Male; Middle Aged; Myoepithelioma; Neuroectodermal Tumors, Primitive, Peripheral; Predictive Value of Tests; Proto-Oncogene Protein c-fli-1; RNA-Binding Protein EWS; RNA-Binding Proteins; Sarcoma, Ewing; Tissue Array Analysis; Young Adult

Ewing's sarcoma/primitive neuroectodermal tumor (EWS/PNET) is an aggressive neoplasm of bone and soft tissue. Histologically, it is characterized by the presence of small round blue cells, which usually express MIC-2 and FLI-1 immunohistochemically. The most specific feature for diagnosis, however, is cytogenetic or molecular evidence of a consistent abnormality, the t(11;22)(q24;q12), or variants thereof. The immunohistochemical expression of keratins in a significant proportion of these cases has been highlighted in several recent studies. The ultrastructural features of these keratin-positive tumors have not, however, been characterized in detail. In this study we analyzed the ultrastructural features of 12 well-documented EWS/PNETs that stained strongly for pankeratin by immunohistochemistry. Ultrastructurally, the tumor cells contained a few organelles, which included a small number of mitochondria, poorly developed Golgi complexes, free ribosomes, and inconspicuous rough-endoplasmic reticulum. Rudimentary cell junctions were seen in 2 tumors while prominent junctions were observed in the remaining 10. Five tumors contained intracytoplasmic filaments, and definite tonofibrils were identified in 2. Well-developed basal lamina around tumor cells were also demonstrated in 2 tumors. Follow-up information was available for all cases. Seven patients died of disease, 2 are alive with disease, and 3 have no current evidence of disease. The cohort includes 5 patients with a type-1 translocation, which has been associated with a better prognosis in some studies; 4 of these patients have died of their disease, and 1 is alive with recurrent disease. This study shows that keratin-positive EWS/PNETs have evidence of epithelial differentiation ultrastructurally, and may possibly represent a more aggressive subset of the EWS/PNET group of tumors.

Topics: Adolescent; Adult; Biomarkers, Tumor; Bone Neoplasms; Child; Fatal Outcome; Female; Humans; Immunohistochemistry; Keratins; Male; Microscopy, Electron, Transmission; Neuroectodermal Tumors, Primitive, Peripheral; Oncogene Proteins, Fusion; Proto-Oncogene Protein c-fli-1; Reverse Transcriptase Polymerase Chain Reaction; RNA-Binding Protein EWS; RNA, Neoplasm; Sarcoma, Ewing; Soft Tissue Neoplasms; Transcription Factors

A case of olfactory neuroepithelioma was investigated electron microscopically and immunohistochemically. The tumor mass was found in the nasal cavities of a 10-year-old female dog, which showed epistaxis, nasal discharge and facial swelling. The tumor tissue consisted of tubular structure of cuboidal to columnar cells and compactly arranged nests of small cells surrounded by a fibrovascular stroma. Mitotic figures were frequently observed. Immunohistochemically, the tumor cells frequently showed positive for neurofilament protein, synaptophysin and/or carnosine in addition to keratin. Ultrastructurally, tight junction was observed between the tumor cells. No dense-cored secretory granules were shown in the tumor cells. These findings indicated that the present tumor had neuronal and epithelial features probably originating from the olfactory epithelium.

Topics: Animals; Carnosine; Dog Diseases; Dogs; Fatal Outcome; Female; Immunohistochemistry; Keratins; Microscopy, Electron; Nasal Cavity; Neuroectodermal Tumors, Primitive, Peripheral; Neurofilament Proteins; Nose Neoplasms; Synaptophysin

Small cell carcinomas (SCCs) and peripheral neuroectodermal tumors (PNETs) are two distinct neoplasms that show considerable histologic, immunohistochemical, and clinical overlap, but differ in their therapies and prognoses. In an attempt to further diagnostically distinguish the two, 33 SSCs were analyzed from both pulmonary and extrapulmonary sites for the MIC2 gene product, a cell surface antigen strongly and reliably expressed in PNETs and Ewing's sarcoma (ES). Two of the 33 SCCs stained positively, but the staining was less intense than that seen with PNET and ES. The remaining 31 tumors did not stain. These data indicate that, in combination with a panel of immunohistochemical stains, analysis of neuroendocrine tumors for MIC2 expression may be useful in distinguishing between small cell carcinomas of both pulmonary and extrapulmonary origins and soft tissue PNETs.

Topics: 12E7 Antigen; Antibodies, Monoclonal; Antigens, CD; Carcinoma, Small Cell; Cell Adhesion Molecules; Female; Humans; Immunohistochemistry; Keratins; Male; Membrane Glycoproteins; Middle Aged; Neuroectodermal Tumors, Primitive, Peripheral; Paraffin Embedding

Forty-two cases of peripheral neuroepithelioma (PN) retrieved from the files of the National Cancer Institute (Bethesda, MD) and the Pathology Department of Padua University, Italy, were reviewed. No sex predilection was observed (25M/17F) and ages ranged from 7 to 54 yr (median 22 yr). Roughly a third of the tumors were thoracopulmonary ("Askin tumor"), a third were axial, and a third were in extremities. A lobular pattern with rosettes or pseudo-rosettes characterized PN. Seventeen cases showed a strong diastase-sensitive PAS positivity. Transitional areas with an Ewing's-like appearance and, in one case, transition to malignant nerve sheath tumor have been documented. The presence of neuron specific enolase (NSE), S-100 protein, HNK-1, neurofilaments, vimentin, keratin (AE1-AE3), beta 2-microglobulin, chromogranin A, and synaptophysin was investigated using the avidin-biotin technique. Immunocytochemically, NSE (95% of cases), beta 2-microglobulin (77.5%), synaptophysin (73.3%), and S-100 protein (67.5%) were the most consistently positive markers. Ultrastructurally, PN is characterized by a primitive appearance, although it was routinely possible to recognize neural features such as primitive neuritic extensions and dense core granules, either in the cytoplasm or in the cellular processes. In our experience, a light microscopic picture of a primitive round cell tumor with a lobular pattern, and particularly with rosettes when present, with NSE and beta 2-microglobulin positivity by immunocytochemistry, ideally with positive synaptophysin, along with supportive electron microscopy, is required for the diagnosis of PN. Conversely, no one feature alone is generally sufficient for diagnosis, but does allow distinction from extraosseous Ewing's, which (like osseous Ewing's) lacks features of neural differentiation.

Topics: Adolescent; Adult; beta 2-Microglobulin; Child; Child, Preschool; Chromogranin A; Chromogranins; Cytoskeleton; Desmin; Female; Humans; Immunohistochemistry; Keratins; Male; Microscopy, Electron; Middle Aged; Neuroectodermal Tumors, Primitive, Peripheral; Peripheral Nervous System Neoplasms; Phosphopyruvate Hydratase; S100 Proteins; Vimentin

To determine the possible histogenesis of the intracranial variant of olfactory neuroblastoma.. Four specimens from three cases of intracranial olfactory neuroblastoma were studied by light microscopy and immuno-histochemistry, and electron microscopy in two cases.. Light microscopical examination showed small cell tumour with additional features of epithelioid cells in one case and ganglion cells in another. Olfactory and Homer-Wright rosettes were present. All the specimens showed a uniform positive reaction to neurone specific enolase, S-100, and cytokeratin antibodies. Glial fibrillary acidic protein was absent. The salient electron microscopic features were the presence of cell junctions, cytoplasmic intermediate filaments, basal bodies and cytolasmic processes. Dense cored vesicles were absent.. The results strongly support the view that intracranial olfactory neuroblastomas are of olfactory epithelial origin and differ from conventional neuroblastomas.

Topics: Adult; Brain Neoplasms; Cranial Fossa, Posterior; Humans; Immunoenzyme Techniques; Keratins; Male; Neuroectodermal Tumors, Primitive, Peripheral; Phosphopyruvate Hydratase; S100 Proteins

A panel of 12 antibodies was used to further characterize the immunohistochemical staining profile of olfactory neuroblastoma. The following results were obtained for the 11 neoplasms that were immunostained: neuron-specific enolase 11/11(+), S-100 protein 8/11(+), microtubule-associated protein-2 8/11(+), class III beta-tubulin isotype 9/11(+), neurofilament 200 kD 8/11(+), synaptophysin 7/11(+), glial fibrillary acidic protein 1/11(+), chromogranin A 1/11(+), vimentin 1/11(+), keratin (CAM 5.2) 4/11(+), keratin (AEI/AE3) 0/11(+), and epithelial membrane antigen 0/11(+). Expression of two intermediate filaments was found in 4 of the 11 tumors. The authors' data showing that 72% of olfactory neuroblastomas were S-100 protein positive and only one was immunoreactive for glial fibrillary acidic protein agree with other published immunohistochemical studies. With only a single exception, each of the 11 neoplasms was labeled with one or more antibodies that detect neuronal cytoskeletal proteins (class III beta-tubulin isotype, microtubule-associated protein-2, neurofilament 200 kD). These immunohistochemical results are complementary to the reported electron microscopic findings of intermediate filaments and microtubules in olfactory neuroblastomas.

Topics: Adult; Aged; Chromogranin A; Chromogranins; Female; Glial Fibrillary Acidic Protein; Humans; Immunohistochemistry; Keratins; Male; Membrane Glycoproteins; Membrane Proteins; Microtubule-Associated Proteins; Middle Aged; Mucin-1; Nasopharyngeal Neoplasms; Neuroectodermal Tumors, Primitive, Peripheral; Phosphopyruvate Hydratase; S100 Proteins; Synaptophysin; Tubulin; Vimentin

Two cases of olfactory neuroblastoma which presented clinically as intracranial lesions are described. Prominent features of epithelial differentiation were present, which led to initial diagnoses of poorly differentiated carcinoma. The true nature of the lesions was only established subsequently by careful histological examination, immunohistochemistry and electron microscopy. The potential towards epithelial differentiation in such tumours was emphasized and certain new histological features were described, including a biphasic epithelial and stromal pattern, papillae formation and positive staining for cytokeratin. These two cases underline the importance of exhaustive examination of poorly differentiated epithelial-like lesions of the frontal lobes by conventional histology, immunohistochemistry and electron microscopy.

Topics: Brain Neoplasms; Cell Differentiation; Diagnosis, Differential; Epithelium; Humans; Immunohistochemistry; Keratins; Male; Microscopy, Electron; Middle Aged; Neoplasm Metastasis; Neuroectodermal Tumors, Primitive, Peripheral

We report anatomoclinical and immunohistochemical analysis of sixteen cases of esthesioneuroblastomas. Microscopic study confirm difficulty of diagnostic for this tumors. Results of S 100 protein reaction for Schwann cells identification, NSE and HNK1 reaction for nervous cells and KL1 reaction for epithelial cells drawn from olfactory mucosa, allow definition of immunologic ENO profile. Pattern immunologic criteria are defined by S 100, NSE or/and HNK1, and eventually KL1 positive reactions permit differential diagnosis with other nervous tumors or undifferentiated carcinomas of nasal fossa. Histo-prognostic patterns are defined by S 100 reactivity distributed in neoplastic cells and cytoplasmic process of cells, to form a continuous network in well differentiated ENO and discontinuous network in undifferentiated forms of ENBO. These results confirm histogenesis of this tumor derived from olfactory mucosa and emphasized only two distinct types: neuro epithelial tumors corresponding to ENEO and cases of ENBO and nervous tumors grouping ENCO and any cases of ENBO.

Topics: Antibodies, Monoclonal; Antibodies, Neoplasm; Glial Fibrillary Acidic Protein; Humans; Immunologic Techniques; Keratins; Nasal Cavity; Neoplasm Proteins; Neuroectodermal Tumors, Primitive, Peripheral; Nose Neoplasms; Olfactory Mucosa; Phosphopyruvate Hydratase; Prognosis; S100 Proteins; Schwann Cells

Morphological features and immunoreactivity for cytokeratin (CK), glial fibrillary acidic protein (GFAP) and neuron-specific enolase (NSE) of three canine neuroepitheliomas and three canine ependymomas were investigated. Neuroepitheliomas were in three German shepherds as intradural-extramedullary solitary masses, with spinal cord displacement between T10 and L2. Histologically, they contained tubules and acini, lined by epithelial cells with focal squamous metaplasia, rosette-like structures, and polygonal to spindle-shaped cells between tubules. Acini were empty or filled with a homogeneous, eosinophilic periodic acid-Schiff (PAS)-positive material. Mitotic indices varied from low to moderate. Ependymomas occurred in the third (two cases) and fourth ventricle in adult boxers. Histologically, they were composed of cells with an ill-defined, scant amphophilic cytoplasm, with a central round euchromatic nucleus; cells formed pseudorosettes, with a central fibro-vascular stroma. Neuroepitheliomas stained for CK, but ependymomas did not. Both failed to stain for GFAP, NSE, or phosphotungstic acid hematoxylin (PTAH). Thus, antibodies to cytokeratin are useful to distinguish neuroepitheliomas from ependymomas.

Topics: Animals; Cross Reactions; Diagnosis, Differential; Dog Diseases; Dogs; Ependymoma; Glial Fibrillary Acidic Protein; Immunoenzyme Techniques; Immunohistochemistry; Intermediate Filaments; Keratins; Neuroectodermal Tumors, Primitive, Peripheral; Phosphopyruvate Hydratase; Spinal Cord Neoplasms

N-Nitrosopiperidine (CAS: 100-75-4) and 2,6-dimethylnitrosomorpholine induced tumors of the olfactory epithelium in white Wistar rats. Some tumors were serially transplanted to NMRI nude mice (nu/nu) and passaged up to 16 times in a 1-year period. Tumor tissues from rats and mice were analyzed by conventional pathological stains, by electron microscopy, and by immunofluorescence microscopy with the use of antibodies specific for different intermediate filaments. Both carcinogens induced tumors built of undifferentiated small, round cells in which neuroblastic (Homer-Wright) rosettes and ependymal (Flexner) rosettes were visible. In some tumors areas of squamous cell metaplasia could be observed, which sometimes differentiated toward squamous cell carcinoma. Electron microscopy showed neurosecretory granules in some tumor cells, and biochemical studies of plasma showed in some instances elevated ACTH and calcitonin levels. Intermediate filament typing showed that in general the undifferentiated tumor cells lack intermediate filaments, although in 6 of 29 tumors a few cells that stained positively for neurofilaments were found. Flexner rosettes, the areas showing squamous cell differentiation, and occasional single tumor cells were positive with keratin antibodies. Neurofilament expression was observed in a minor population of tumor cells placed in tissue culture. These findings are used to argue that the chemically induced rat tumors are a model for human esthesioneuroepithelioma and furthermore that the light basal cells of the epithelium may be the stem cells of the rat tumors as well as of its rare counterparts in humans.

Topics: Adrenocorticotropic Hormone; Animals; Antibodies; Calcitonin; Disease Models, Animal; Fluorescent Antibody Technique; Humans; Intermediate Filaments; Keratins; Microscopy, Electron; Neuroectodermal Tumors, Primitive, Peripheral; Nitrosamines; Nose Neoplasms; Olfactory Mucosa; Rats; Rats, Inbred Strains

Eight cases of a highly aggressive undifferentiated carcinoma of the nasal cavity and paranasal sinuses are described. The patients, who ranged in age from 30-77 years, had multiple sinonasal symptoms, and each had involvement of the nasal cavity, maxillary antrum, and ethmoid sinus. Six tumors extended into the orbital bones, and five penetrated the cranial cavity. Five patients died of disease from 1 to 41 months after diagnosis (median: 4 months), and three are alive with tumor less than 1 year following diagnosis. Microscopically, the neoplasms formed nests, trabeculae, and sheets containing medium-sized cells with small to moderate amounts of eosinophilic cytoplasm. A high mitotic rate, tumor necrosis, and prominent vascular permeation were characteristic. Seven neoplasms were immunoreactive for cytokeratin, five for epithelial membrane antigen, and four for neuron-specific enolase. Ultrastructurally, occasional small desmosomes and rare membrane-bound, dense-core granules were observed. Sinonasal undifferentiated carcinoma is a distinctive clinicopathologic entity that must be distinguished from other, less aggressive sinonasal neoplasms.

Topics: Adult; Aged; Carcinoma; Combined Modality Therapy; Ethmoid Sinus; Female; Follow-Up Studies; Humans; Keratins; Male; Maxillary Sinus Neoplasms; Membrane Proteins; Middle Aged; Mucin-1; Nasal Cavity; Neuroectodermal Tumors, Primitive, Peripheral; Nose Neoplasms; Orbital Neoplasms; Paranasal Sinus Neoplasms; Phosphopyruvate Hydratase