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Glycoproteins were isolated from the particulate fraction of four nasal polyps and three nasal papillomas by affinity chromatography on lectins conjugated with agarose (Concanavalin A [Con A], wheat germ agglutinin [WGA], Ricinus communis agglutinin [RCA], peanut agglutinin [PNA], and Dolichos biflorus agglutinin [DBA]). The glycoprotein mixtures so isolated were then analyzed by sodium dodecyl sulfate gel electrophoresis. Glycoprotein profiles of nasal polyps were similar to each other, but were distinctively different from those of nasal papillomas. Binding sites for Con A, WGA, and RCA isolated from nasal papillomas contained intense bands with a molecular weight less than 15,000 daltons, which were absent in nasal polyps. The major component of PNA-binding sites of nasal polyps is of a molecular weight of 65,000 daltons, which was not detected in nasal papillomas.

Presentation of a 48-y old woman who developed a neuroendocrine tumor of the nasal cavities. This lesion progressed rapidly despite an extensive resection and repeated chemotherapy. The patient refused radiotherapy. Before her death, 28 months later, she exhibited a paraneoplastic Cushing-like syndrome. At autopsy, restricted to the brain, there was a 5 cm diameter tumor invading the frontal area without alteration of the hypothalamus or the pituitary gland. Routine histology and electron microscopy confirmed the neuroendocrine nature of the tumor. Immunohistochemistry revealed the tumor to be positive only for neurone specific enolase, negative for S-100 protein, neurofilament and ACTH. The pituitary gland was positive for most usual hormones (GH, PRL, TSH, LH, FSH) but only few cells were slightly positive for ACTH. Many Crooke cells were observed. These findings suggest that the tumor secreted an ACTH-like substance (not detected actually by immunochemistry) that stimulated the activity of the adrenal cortex but inhibited normal production of ACTH at the pituitary gland level.

Histamine, norepinephrine and serotonin were assayed and localized by fluorescence histochemistry in normal mucosa and nasal polyps because of their possible role in the development of inflammation and edema. Histamine was present in greater concentration in nasal polyps than in normal mucosa. Norepinephrine was present primarily in the base of nasal polyps and in greater concentration than in normal mucosa. Patients with aspirin sensitivity and asthma had much lower histamine concentrations in their nasal polyps than all other patients with nasal polyps. A proposal for a possible mechanism of formation of nasal polyps based on vascular and inflammatory mechanisms and incorporative roles for histamine and norepinephrine is presented.

A series of 19 inverted papillomas (transitional type or Schneiderian papillomas) of the nose were examined using an immunogold-silver (IGS) technique and an indirect immunoperoxidase technique. We demonstrated beta-HCG production in all 19 specimens with both methods. The staining demonstrated by the IGS technique was of a greater intensity and in a larger number of cells than that observed by the indirect immunoperoxidase method.

Using the Sternberger method (Immunoluk Histoset KIT) GFAP (glial fibrillary acidic protein) was demonstrated immunohistochemically in 4 nasal gliomas. In these histologically complex tumour-like lesions mesenchymal, epithelial, and neuroglial tissues as well as small groups of scattered glial elements could be differentiated specifically by the highly sensitive GFAP immunoperoxidase technique. GFAP was present in astrocytes and astrocyte-like differentiations. The reactivity of cell processes was essentially lower. The GFAP immunostain does not always correlate with Mallory's phosphotungstic acid hematoxylin (PTAH) stain and Gallyas' silver impregnation method for astrocytes. Additionally the immunohistochemical investigation of semithin sections prepared by the so-called pop off technique after Bretschneider et al. (1981) allows the correct localization of GFAP in astrocytes and their modulations. Furthermore, in this study, the intimate connection of epithelium and glial cells as well as astrocytes containing hemosiderin granules could be demonstrated. The latter findings suggest a possible phagocytotic activity of astrocytes. Our results show that the demonstration of GFAP by the Sternberger method is a valuable aid in establishing astrocytic glial differentiations and modulations in complex tumour-like lesions such as nasal gliomas.

Tumorous amyloid deposits in the nasal mucosa of two horses differed from generalized AA-amyloidosis with respect to clinical features, organ distribution, and resistance to KMnO4 treatment. Using a panel of antibodies directed against different human amyloid fibril proteins and employing the peroxidase-anti-peroxidase (PAP) technique, we showed the described equine amyloid to be A lambda-type, as demonstrated by immunohistochemical cross-reactivity. Consequently, we identified a second amyloid class in horses and showed that immunoglobulin light-chain-derived amyloid may also be present in animals.

The data obtained with the use of microspectrophotometric studies of nuclear DNA in the process of induction and development of epithelial tumours of nasal cavity and paranasal sinuses in albino mongrel rats are analyzed. Exponential increase of the DNA accumulation index in the process of neoplasm induction is observed. A jump-like increase of the DNA accumulation index with relatively uniform values is established in the normal tissues, then in the metaplastic and dysplastic epithelia and in benign tumours as well as in the malignant tumours.

3000 IgE serum concentrations were determine d radioimmunologically in a large group of 1616 tumor patients and a group of 308 controls. Because of a wide scattering the individual IgE levels do not give a diagnostic indication. On the other hand we have found a highly significant difference (p less than 0.001) between the IgE levels of male and female tumor patient-groups, which does not exist among the controls. Female patients tend to lower, male patients to higher levels. In patients with carcinoma of the testis three times higher IgE levels were found. Their relation to a coincidence with high HCG levels is discussed. Furthermore IgE follow up-studies are described. They correlate close by with the clinical picture. Consequently IgE follow up-studies are applicable to tumor prognosis and possibly to tumor therapy.

Many works have shown a high frequency of increased nuclear DNA contents in various precancerous lesions. The true nuclear sizes, which are known to be well correlated with DNA values, may be stereologically estimated from nuclear profile data on tissue sections. Therefore, karyometry, which may be effected very efficiently by automated image analysis, offers an attractive choice when studying sections, in which photometric DNA evaluations are often unreliable. Prerequisites are Feulgen-stained slides and a stringent standardization of all histological procedures. Very few karyometric studies have been done on precancerous lesions. Automated image analysis has seldom been used for nuclear profile data gathering on sections. Suitable stereological models are necessary. The best-known are those for spherical nuclei, which allow an estimation of the size-distribution ('unfolding'). A specific model for parallel-oriented spheroids is particularly suitable for epithelial nuclei. It yields many stereological parameter estimations but does not yet allow a size-shape unfolding. We have used the model for parallel spheroids on nasal epithelial biopsies from nickel workers. The nuclear dimensions are usually clearly increased in metaplasia and dysplasia. Some rare dysplastic zones, however, present a major contribution of normal-sized nuclei, and this may have a prognostic significance. Our model may be applied to other epithelia. A new sphere unfolding model has been used on liver sections from Farber-protocol-treated rats. Compared to normal livers, where tetraploid nuclei predominate over diploid ones, transitional cell zones show an overwhelming predominance of diploid nuclei, and hyperplastic precancerous nodules have various degrees of non-modal and high-value ploidies. Karyometry may help to determine which lesions should be considered as possible premalignancies.

A 39-year-old bus driver had been suffering for 2 years from a malignant polypoid mucosal proliferation of the upper nasal concha-ethmoid region, resembling a highly differentiated, villous-glandular adenocarcinoma of enteric type. There were numerous mono- and amphicrine cells and a massive quantity of oxyphilic, frequently Paneth-like goblet cells in the tumor. Immune-histochemically, a number of gastrin- and fewer glucagon-positive cells were identified. The somatostatin level in the serum was clearly increased. Electron-microscopically, 7 different endocrine cell types were identifiable, in order of decreasing frequency: A-like- and G-cells, both types of 5-HT-cells, A-cells, EG- and K-cell-like elements. Particularly impressive were the muco-argyrophilic amphicrine cells, containing A-granules. The unusual enteric character of the carcinoma seems to result from boundary movements and tissue displacements in an ecto-entodermal embryonic border region. There was no history of occupational wood dust inhalation.

Olfactory neuroblastoma (OLF NB) is an uncommon neurogenic tumor arising in the nasal cavity. To identify the immunohistochemical reactivity of OLF NB, we examined specimens from ten patients for the presence of neuron-specific enolase (NSE), S-100 protein (S-100) and glial fibrillary acidic protein (GFAP). Formalin-fixed paraffin sections were treated with rabbit antisera using the peroxidase-antiperoxidase (PAP) and avidin-biotin immunofluorescence methods. Results were compared with those observed in four neuroblastomas (two central and two peripheral sites), 17 medulloblastomas, four pheochromocytomas and five paragangliomas. All OLF NB were positive for NSE and S-100. NSE was uniformly distributed throughout clusters of tumor cells within tumor nodules. The S-100 reactivity was distributed in neoplastic cell nuclei and long cytoplasmic processes of cells which interconnected to form a network at the periphery of tumor cell nests. GFAP was observed only in astrocyte-like cells in one tumor. Although the S-100-positive cells in OLF NB resembled S-100-positive sustentacular cells of paraganglioma and pheochromocytoma, the network pattern was distinctive in OLF NB. The immunodiagnostic pattern of OLF NB includes the following: (a) NSE present in irregular clusters of tumor cells, (b) S-100 present in peripheral cells which form a marginal network, (c) and GFAP rarely present.

A 73-year-old male was admitted because of a localized tumor in the nasal cavity, which was suspected to be malignant lymphoma by biopsy specimens. Laboratory findings were within normal limits except for small amounts of M protein (IgG-lambda) in the serum. The patient was successfully treated by radiotherapy, with the disappearance of both the tumor and M protein. Two years after the onset, however, a solid tumor was observed in the soft tissue, followed by rapid systemic dissemination. An increase in M protein was obvious, and the biopsy specimens disclosed plasmacytoma. The patient died three months after admission, and post-mortem examinations revealed a diffuse infiltration of plasmacytes predominantly in the soft tissues.

In a case of olfactory neuroblastoma, originally misdiagnosed as an undifferentiated carcinoma, cytologic examination of material scraped from the superior nasal vault revealed tumor cells suggestive of neuroblastoma. The most significant cytodiagnostic feature was the presence of a fibrillary cytoplasm with ill-defined borders. Also noteworthy were the smudged hyperchromatic nuclei and structures resembling rosettes or pseudorosettes. The diagnosis was confirmed by electron microscopy, which revealed the presence of dense-core neurosecretory granules, clear vesicles, neurotubules and neurofilaments, and by immunohistochemistry, which showed positive staining for neuron-specific enolase but negative staining for keratin and glial fibrillary acidic protein. Since olfactory neuroblastoma has a relatively good prognosis and aggressive surgical resection may be curative, it is important that this tumor be distinguished from other small cell malignancies arising in the nasal cavity. The present case shows that the diagnosis can be made by the cytologic examination of scrapings from the tumor.

Neuroendocrine (Merkel cell) carcinomas of the skin have been recognized as such for several years. Given the reported wide variability in the morphology and clinical evolution of these tumors, the notion that may they comprise several variants rather than a single type has been advocated. Electron microscopy has played a key role in the early recognition of these tumors while immunohistochemical studies for various neuroendocrine markers have facilitated their subsequent diagnosis and improved our understanding as to their complexity by the demonstration of immunoreactivity for NSE (neuron specific enolase) and a number of neuropeptides. There has also been considerable interest in the study of the cytoskeletal intermediate filament complement of neuroendocrine neoplasms in general and of those of the skin in particular. Early reports indicated that neuroendocrine skin carcinomas had neurofilaments while subsequent investigations determined that they had cytokeratin. However, more recent studies have indicated that at least some neuroendocrine skin carcinomas could in fact coexpress both aforementioned classes of intermediate filament proteins. This brief report is presented to confirm the latter investigations.

Nasal mucosal biopsy specimens encompassing normal and pathological epithelia were obtained from nickel workers, a population with an increased incidence of carcinomas of the respiratory tract. The immunohistochemical detection of keratins was carried out using monoclonal antibodies AE1 and AE3. The antibody AE1 stained only the basal cells of normal mucociliary epithelium. Regular metaplasias showed an increased stain with AE3; all layers of the surface epithelium were stained. The dysplastic and neoplastic lesions exhibited an extraordinary increase in the staining patterns with AE3 and to a lesser extent with AE1. Involucrin, which was absent from the normal pseudostratified epithelium, appeared in all metaplastic-dysplastic lesions and in keratinized areas of carcinomas. The combined detection of keratins and involucrin proved useful in detecting the degree of maturity and differentiation of preneoplastic and neoplastic lesions of the nasal mucosa.

A primary adenocarcinoma of the nasal cavity with light microscopic, electron microscopic, and immunocytochemical features of an enteric-type carcinoma is presented. The carcinoma contained a variety of dense-core granules similar to those seen in enterochromaffin cells of different functional types. Some granules demonstrated an immunoreactivity with serotonin, cholecystokinin, gastrin, somatostatin and leu-enkephalin antibodies. It is suggested that the endocrine cells in the neoplasm belong to the non-neuroectodermal paraneurone system.

To assess the suggested etiological role of human papillomavirus (HPV), biopsies from 14 patients operated on for an inverted papilloma (11 cases) and squamous cell carcinoma (3 cases) of the nasal cavity and paranasal sinuses were analysed for light microscopical evidence of HPV, by indirect immunoperoxidase (IP-PAP) to demonstrate HPV structural proteins, and using in situ DNA-hybridization to disclose the DNA of HPV types 6, 11 and 16. The majority of the inverted papillomas contained areas of metaplastic squamous cells, including koilocytes as well as dysplastic changes consistent with intra-epithelial neoplasia as described in uterine cervix. In 3 patients, frankly invasive squamous cell carcinomas were found, originating from dysplastic squamous epithelium. Of the 14 lesions, 7 (50%) expressed HPV antigens, usually confined to only a few cells close to the surface of the epithelium. None of the malignant lesions expressed HPV antigens. In situ DNA-hybridization disclosed HPV 11 DNA alone in 5 lesions, but none of the lesions contained HPV 6 DNA. HPV 16 DNA was found in 2 lesions as a single HPV type, and in 3 other lesions concomitant with HPV 11. All three carcinomas contained HPV 16 DNA. The HPV DNA distribution proved to be different from that found in the genital tract HPV lesions; HPV DNA was less abundant in the nasal papillomas, and it was also found in the basal and suprabasal cells.(ABSTRACT TRUNCATED AT 250 WORDS)

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.