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Introduction : Management of clinically negative neck (cN0) in patients with parotid gland cancer is controversial. Treatment options can include observation, elective neck dissection or elective radiotherapy. Areas covered : We addressed the treatment options for cN0 patients with parotid gland cancer. A literature review was undertaken to determine the optimal management of this group of patients. Expert opinion : Patients with parotid carcinoma and clinically negative neck have various options for their management. The analysis of tumor stage, histology and grade is essential to better define patients at risk for occult lymph node metastasis. These patients can be managed by surgery, radiotherapy or their combination, depending on the presence of risk factors, the moment at which such risk factors are detected, patient-related clinical conditions, medical provider expertise and institutional facilities.

When macrophage-like J-774 cells are subjected to limited oxidative stress, such as exposure to hydrogen peroxide in a moderate bolus dose, some of their lysosomes rupture-as here assayed by the acridine orange relocalization test-secondary to intralysosomal, iron-catalysed, oxidative reactions. The resultant leakage into the cytosol of hydrolytic enzymes, such as cathepsin-D (as shown here), may initiate a slow degradation/fragmentation process of an apoptotic type within cells still having intact plasma membranes. In contrast, severe oxidative stress also results in extensive lysosomal rupture but leads to necrosis. The chelation of (normally occurring) intralysosomal low-molecular weight iron, by endocytotic uptake of desferrioxamine, largely prevents oxidative stress-induced apoptosis whereas lysosomal iron-loading, by endocytotic uptake of complexed ferric iron, considerably enhances the process. We conclude that oxidant-mediated and iron-catalysed lysosomal rupture leads to decompartmentalization of lysosomal enzymes which in turn may initiate and promote the apoptotic process.

Interleukins 6 (IL-6) and 12 (IL-12), and the chemoattractant chemokine RANTES were studied in ethmoidal mucosa, using reverse transcriptase polymerase chain reaction. The 49 patients had chronic sinusitis or nasal/paranasal polyposis, and some also allergy. To the best of our knowledge, this is the first study that demonstrates RANTES and IL-12 on mRNA level in human sinonasal mucosa in situ. mRNA for IL-6, IL-12 and RANTES were detected in 2, 8 and 6 patients with chronic sinusitis, respectively, and in mucosa from patients with polyposis a positive expression was observed in 4, 14 and 10 cases. There were no statistically significant differences. Analysing the entire group of 49 patients, disregarding type of mucosal disease, the number of patients with positive RANTES was significantly higher than that for IL-6. Similarly, IL-12 positivity was more frequently expressed than IL-6. mRNA for IL-6 was expressed in only 2 of the allergic patients. The cytokine production studied thus seems to be unrelated to the clinically defined entities. There is thus a local production in human diseased sinonasal mucosa of RANTES, as well as of IL-6 and IL-12. The local production of RANTES is an important prerequisite for recruitment and migration of inflammatory cells into the tissue. IL-12 is a co-stimulator of antigen-specific responses of established T helper 1 (Th1) clones, and regulates the responsiveness of the clones to a number of T cell growth factors. The study supports a shift towards Th1 cells in these disease entities.

The presence of epidermal growth factor receptor (EGFR) was studied in laryngeal biopsy specimens from 14 patients, all with severe dysplasia or carcinoma in situ. All 14 cases showed positive immunoreaction for EGFR. In 5 of the specimens there were also areas with moderate dysplasia, 3 of which showed scattered EGFR positive cells, whilst 2 were negative. In 8 biopsy specimens there were areas with mild dysplasia, but none of them showed any positive immunoreaction for EGFR. Thus EGFR is present in laryngeal severe dysplasia and carcinoma in situ, indicating the potential malignant neoplastic nature of these lesions. The immunostaining for EGFR may be used as an aid to differentiate between severe dysplasia and carcinoma in situ (Group III lesions), moderate (Group II lesions) and mild dysplasia (Group I lesions).

The immunoreactivity of epidermal growth factor receptor (EGFR) was studied in laryngeal biopsy specimens from 24 patients. The study comprised 5 cases of normal laryngeal mucosa, 5 cases of dysplasia, 7 cases of well differentiated squamous cell carcinoma, and 7 cases of poorly to moderately differentiated squamous cell carcinoma. EGFR was in general not expressed in normal and dysplastic epithelia, whilst all carcinomas showed a rather strong positive immunoreactivity. There was no significant difference in staining patterns between the well and poorly to moderately differentiated carcinomas. The results suggest that EGFR constitutes a component of neoplastic, but probably not preneoplastic, laryngeal disease. The study failed to reveal any difference in staining pattern between different types of laryngeal squamous cell carcinoma.

The vocal cord fine surface structure was examined by scanning electron microscopy (SEM), and the observations related to the light-microscopical (LM) findings after embedding and cutting. The SEM micrographs were assessed using a rating system based on 7 parameters. The proportion of "normal" and "abnormal" SEM areas varied within the respective histologic groups. There was, however, a significant difference between the SEM ratings in the group with hyperplasia-keratosis, with or without mild dysplasia, compared to the groups with severe dysplasia-carcinoma in situ and invasive squamous cell carcinoma. In the small number of cases with moderate dysplasia and juvenile laryngeal papilloma, the SEM ratings displayed pronounced disparity.

In the nasal mucosa of rodents, both formaldehyde and wood dust have proved to be carcinogenic. Wood dust is also a well-known nasal carcinogen in man. The effects of long-term exposure of humans to formaldehyde, however, are more obscure. In this investigation two groups of workers with well-defined exposure to formaldehyde and to formaldehyde and wood dust, respectively, were compared with a control group regarding histological changes in nasal specimens from the middle turbinate. Significant changes were found in the formaldehyde group but not in the group exposed to both formaldehyde and wood dust. No correlation was found between histological changes and duration of exposure, doses of exposure or smoking habits.

Amyloidosis of the larynx is a rare disease, accounting for less than 1% of all benign laryngeal 'tumours'. Three cases of this type of lesion are reported--one of the vocal cord, one of the false vocal cord and one of the subglottis and trachea. In 2 of the patients the amyloidosis was localized, while the third was later found also to have an epipharyngeal solitary plasmacytoma with amyloid deposits and in addition amyloidosis of the nasal cavity. However, the amyloidosis in this patient may still be regarded as being localized, as the clinical examination and laboratory tests afforded no evidence of generalized disease. Amyloidosis of the larynx may be manifested as a localized tumour or as a diffuse infiltration. The symptoms and signs will, of course, depend on the site of the amyloid deposit. When the vocal cords are involved hoarseness may result, and this was the most prominent sign in the present cases. The treatment of laryngeal amyloidosis is primarily by endoscopic excision. Amyloid substance has specific staining properties. The Congo red reaction with a green birefringence in polarized light and Phorwhite BBU using fluorescence microscopy are regarded as the most reliable staining reactions. Electron microscopy has revealed a typical fibrillar structure of amyloid.

Exposure to oil mist used in metal work sometimes gives symptoms from skin and airways. This study was performed to evaluate histological and functional respiratory tract disorders. Six male lathe workers aged 31-64 years exposed to oil mist for 4-29 years were examined and compared with matched controls. The investigation included case history, ENT examination, nasal mucociliary function, routine blood tests, IgE, RAST, X-ray of sinus and lungs and biopsy of the nasal mucosa. The mucociliary test showed no difference between the groups. However, all 6 exposed workers had pathological histology findings in the nasal mucosa including lack of cilia, basal cell hyperplasia, goblet cell hyperplasia, squamous metaplasia and subepithelial hyalinization. The biopsies from the controls were mainly normal. The remainder of the investigations revealed no pathology. The study shows that exposure to oil mist--even below the permitted threshold limit--may cause airway symptoms and histological signs comparable to a premature ageing.

Photometric examination of vocal cord epithelia disclosed no difference in the nuclear DNA content or nuclear area of normal and keratotic laryngeal epithelia. For 2 out of 3 epithelia displaying hyperplasia the values were slightly elevated. There seem to be no morphologic or photometric grounds for considering either hyperplasia or keratosis to be premalignant. Eight patients with moderate dysplasia were selected; 3 with and 5 without subsequent development of severe dysplasia or carcinoma in situ. In all 8 cases the DNA values were not increased, but in 6 there was an increased variation about the mean. There were no morphologic or photometric differences between the epithelia subsequently developing severe dysplasia or carcinoma in situ and those that did not. The 3 patients developing severe dysplasia or carcinoma in situ were then followed for 112, 27 and 106 months and showed no evidence of invasive carcinoma. The other 5 patients with moderate dysplasia were followed for 48 to 123 months without any sign of recurrent disease. There are no photometric grounds for considering moderate dysplasia as a precancerous lesion. Long-term investigation is required to ascertain the risk that carcinoma in situ or invasive carcinoma will develop in patients with laryngeal hyperplasia, keratosis and moderate dysplasia.

Industrial workers more and more frequently seek medical advice for nasal and sinus symptoms that they attribute to occupational exposure. The present study comprised 10 paint-sprayers exposed to solvents (primarily toluene and isobutylacetate) and dust. The working environment was checked by an industrial hygienist and a careful clinical examination including biopsies from the nasal mucosa was carried out. The results revealed prominent nasal symptoms in 3 patients and 4 suffered from cough. The histological examination showed in no case a normal nasal mucosa. The histological grading showed a significantly higher score in the exposed group compared to a matched control group. However, no conclusive connection between the duration of exposure and the clinical symptoms and morphological changes was possible to make, which will necessitate an extended study to evaluate the exact importance of the duration of exposure. The study indicates the possibilities of an early presymptomatic detection of nasal mucosal disturbances and arises the question whether the existing TLVs are adequate in preventing damage to the nasal mucosa and adherent clinical symptoms.

The histological study of the non-tumours nasal mucosa in 22 wood-workers with ethmoidal adenocarcinoma was carried out and special attention was paid to the presence of cuboidal metaplasia with or without dysplasia. The workers had been exposed to wood dust for an average of 38 years (range 18 to 55 years). In 19 cases cuboidal metaplasia was found and 16 of these also had dysplasia. In 10 cases there was a transitional zone with dysplastic cuboidal epithelium in continuity with the tumour. In 5 cases there was squamous metaplasia. The results indicate cuboidal metaplasia with dysplasia being a possible precursor to nasal adenocarcinoma in workers exposed to wood dust, similar to the findings of squamous metaplasia and squamous cell carcinoma in nickel workers.

The aim of the present study was to obtain a more objective evaluation of nuclear hyperchromasia and polymorphism in laryngeal epithelium. The method is based on a photometric assay of nuclear size and DNA content in Feulgen stained slides. The DNA content of hyperchromatic nuclei should exceed the mean for nuclei of normal epithelium by more than twice the standard deviation. In comparison with lymphocytes (2N) the DNA content in hyperchromatic nuclei corresponds to 3.3 N. The mean DNA contents of normal, dysplastic and carcinomatous laryngeal nuclei were 69, 71 and 118 A.U. The mean nuclear area for normal, dysplastic and carcinomatous epithelial cells were 48, 41 and 73 micrometer2. The higher the degree of atypia displayed by the cells the greater was the variability of the DNA content and the nuclear size. The investigation shows that the method may provide a more objective basis for evaluating hyperchromasia and polymorphism.

Wood dust is a well known nasal carcinogen in man, as formaldehyde is in rats. In certain occupational environments, combined exposure to wood dust and formaldehyde is common. Little is known about the effects of this combination. A pilot study was performed on four groups of Sprague-Dawley rats: one exposed to wood dust (25 mg/m3), another to formaldehyde (12.4 ppm) and a third to both wood dust and formaldehyde; the fourth group served a control group. After 104 weeks of exposure the nose and lungs were examined histologically. One well differentiated squamous cell carcinoma was found in the formaldehyde group. Squamous cell metaplasia was found significantly more often among the formaldehyde-exposed rats. Squamous cell metaplasia with dysplasia was most frequently observed, however, in the group exposed to both formaldehyde and wood dust. There were also significantly more rats with pulmonary emphysema in the groups exposed to wood dust than in the other groups.