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A case of Wegener’s granulomatosis (WG) presenting with hearing loss and right facial nerve palsy is reported. The definitive diagnosis was based upon clinical data and serum cANCA and AECA detection. Early assessment of WG prevented surgical facial nerve decompression to treat a chronic otitis media complication. Immunosuppressive therapy with steroids, cyclophosphamide and methotrexate was required for relief of clinical symptoms and cANCA negativity as an expression of disease remission. The effectiveness of co-trimoxazole for preventing relapses of WG is discussed.

Immunoscintigraphy with 111In-F(ab‘)2-anti-carcinoembryonic-antigen monoclonal antibody was performed in patients with primary head and neck tumours (n= 14), recurrences (n= 3) and suspected post-therapy lymph node metastases (n= 3). No false-positive but two false-negative results were obtained. Single photon emission tomography was performed 24 h after the intravenous administration of the radiopharmaceutical with a positive predictive value of 100 and a sensitivity of 90. Only two very small (< 1 mm diameter) and necrotic primary tumours escaped detection, while the recurrences and lymph node metastases were always correctly diagnosed, in contrast to computerized tomography and ultrasound. Even though highly selective patients only were considered in the present research, the results do suggest that immunoscintigraphy may be usefully applied in all routine protocols for the study of head and neck cancer.

The clinical findings, histopathology, management and outcome of 31 patients with verrucous squamous cell carcinoma of the larynx (VSCC) are discussed. Laryngeal VSCC is a rare, highly differentiated variant of SCC and has specific morphological features and clinical behavior. A close liaison between the laryngologist and pathologist is needed to formulate a correct diagnosis, because this tumor appears to be malignant clinically and histologically benign. A low-power magnification of multiple large specimens, including the deep margins of the lesion, is required in order to differentiate VSCC from keratosis, verruca vulgaris or SCC with verrucous appearance, and to detect underlying microscopic foci of invasive SCC within or adjacent to a verrucous carcinoma. Long-lasting hoarseness was the most common symptom as the glottic region was the most common site of VSCC. Presumed clinically positive N1 lymph nodes were observed in the necks of 7 patients, but none had metastatic disease on histopathological study. Surgery alone was the most effective form of treatment, as it allowed a good outcome of all treated patients. Surgery plus radiotherapy was associated with an early recurrence and a poor outcome in 2 of 7 patients treated. The generally “benign” behavior of VSCC allows for conservative surgery, with complete endoscopic resection using the carbon dioxide laser representing a more conservative surgical approach. Neck dissection is not indicated due to the non-metastatic behavior of this tumor.

We assayed methyl-p-hydroxyphenyllactate esterase (MeHPLAase) activity in 63 cases of primary laryngeal squamous cell carcinoma. MeHPLAase activity did not show any correlation with oestrogen, progesterone and epidermal growth factor (EGF) receptor levels. No significant relationship was found between MeHPLAase activity and age, sex, tumour site, T classification, stage of disease and EGFR status, whereas a significant inverse relationship was found between enzymatic activity and neck lymph node positivity at presentation. The median value of MeHPLAase activity tended to be higher in tumours with low histopathological grade than in those with high histopathological grade. During the follow-up period (median 50 months, range 2-90 months) locoregional recurrences were observed in 31 out of 63 (49%) cases. At the end of the study, 27 out of 63 (43%) patients had died of cancer. Cox univariate analysis using MeHPLAase activity as a continuous covariate showed that the levels of enzymatic activity were inversely associated with the risk of death and relapse. Assuming the mean value of enzymatic activity as the cut-off value, we found a statistically significant relationship between high MeHPLAase activity and longer relapse-free and overall survival. MeHPLAase activity status retained its prognostic significance also in the lymph node-negative subgroup of patients. On multivariate analysis, both EGFR and MeHPLAase activity proved to be independent factors for predicting a short relapse and the overall survival.

Epidermal growth factor receptor (EGFR) content was determined by a radioligand receptor assay in 140 primary laryngeal squamous cell carcinomas (median value of 8.4 fmol mg-1 protein, range 0-169.9 fmol mg-1 protein). Cox univariate regression analysis using EGFR as a continuous variable showed that EGFR levels are directly associated with the risk of death (chi 2 = 14.56, P-value = 0.0001) and relapse (chi 2 = 7.77, P-value = 0.0053). A significant relationship between EGFR status and survival was observed at the different arbitrary cut-off values chosen (8, 16 and 20 fmol mg-1 protein). The cut-off value of 20 fmol mg-1 protein was the best prognostic discriminator. In fact, the 5 year survival was 81% for patients with EGFR- tumours compared with 25% for patients with EGFR+ tumours (P < 0.0001). The 5 year relapse-free survival was 77% for patients with EGFR- tumours compared with 24% for patients with EGFR+ tumours (P < 0.010). When clinicopathological parameters and EGFR status were examined in the multivariate analysis, T classification and EGFR status retained an independent prognostic value. In this study we demonstrated that high EGFR levels single out patients with poor prognosis in laryngeal cancer.

Western blotting analysis of the p21 ras oncoprotein was performed in seven normal laryngeal mucosa specimens and 43 primary laryngeal cancers. Varying p21 levels, expressed as optical density (OD), were found in normal mucosa (median 1.94 OD, range 0.90-2.17 OD) and in primary laryngeal tumours (median 1.74 OD, range 0.30-6.37 OD). When p21 expression in laryngeal cancer was compared with the normal counterpart, higher levels were found in neoplastic than in normal laryngeal tissue (median 2.54 OD, range 1.76-6.37 OD, vs median 1.94 OD, range 0.90-2.17 OD) (P = 0.023). Immunohistochemical analysis demonstrated that most of the tumour cells (more than 70%) were immunostained while the stromal component was unreactive. No correlation between p21 expression and tumour location, stage and histopathological grade was observed. The correlation between ras p21 protein expression and epidermal growth factor receptor (EGFR) levels was also investigated. EGFR-positive cases did not show any difference in p21 expression with respect to EGFR-negative cases (median 1.52 OD, range 0.30-6.37 OD, vs median 1.84 OD, range 0.93-3.71 OD). Our findings suggest that overexpression of p21 protein is associated with a malignant phenotype in laryngeal cancer. Further studies should be undertaken to evaluate whether the assessment of p21 protein expression may have clinical significance in laryngeal cancer.

The gene dosage of cyclin D1 gene (CCND1) was examined in 51 primary laryngeal squamous cell carcinomas and amplification of the gene was found in 9 cases (17.6%). CCND1 amplification did not correlate with the clinico-pathological parameters. In a median follow-up period of 29 months the overall survival rate was 71.4% for patients affected with tumors displaying normal CCND1 dosage, and only 25% for patients with tumors carrying amplified CCND1. In multivariate analysis, only CCND1 and tumor size retained a statistically significant prognostic value (P=0.037, P=0.041). This is the first report in which CCND1 amplification is identified as a significant independent prognostic factor in laryngeal squamous cell carcinoma.