Two anomalous localizations of mucocele: clinical presentation and retrospective review.

Two Caucasian males (57 and 70 years old) were referred to our attention with parasinus mucoceles, maxillary and frontal mucocele, respectively, that had eroded the orbital rim and caused swelling of the eyelids and brow. Invasion of the orbital space caused several ophthalmic symptoms such as diplopia, proptosis, ptosis, and the formation of a palpable mass. Ophthalmic involvement was the first sign of the mucocele. The mucoceles were completely excised through a skin incision and the diseased mucosa of the sinuses was removed: endonasal fibre optic surgery and the Caldwell-Luc procedure were used in the patient with maxillary mucocele. The cases are described with retrospective review.

Oncological outcome after CO2 laser cordectomy for early-stage glottic carcinoma.

This study aims to define indications for micro-endoscopic laser surgery in early glottic carcinoma (Tis, T1a and T1b), to examine patterns of local recurrences and related retreatment methods. A cohort of 79 patients with previously untreated early glottic carcinoma, subjected to endoscopic CO2 laser excision between January 1993 and October 2000, was retrospectively examined. Patients included in data analysis had a mean follow-up of 39 months. Depth and extension of excisions were graded according to European Laryngological Society Classification, and included 5 types of cordectomy. Actuarial overall survival, determinate survival, disease-free survival, ultimate local control, and laryngeal preservation rates, at 3 years, were 97.5%, 98.7%, 89.9%, 92.4%, and 97.4%, respectively. Survival curves for overall and disease-free survival were calculated from the date of diagnosis using the KaplanMeier method. Of the 8 patients with local recurrences, 5 were managed with larynx-sparing treatment: a second endoscopic CO, laser cordectomy was performed in 2 patients, a supracricoid laryngectomy in 2 patients, and one patient was treated with radiotherapy. The remaining 3 patients were submitted to total laryngectomy, one of whom died due to neck metastases. One patient died from other causes. All other patients were alive and disease-free at the last follow-up. Understanding the diffusion pathways and timing of laryngeal glottic cancer is important both for treatment and prognosis. Correct knowledge of the subsites of the larynx and the routine use of pre-operative and intra-operative diagnostic assessment is useful in the selection of the appropriate type of resection. Microendoscopic laser surgery is efficacious for early glottic carcinoma, with oncological results comparable to those observed following radiotherapy or conventional partial laryngectomy, however, in this case, local recurrences have a greater range of re-treatment options.

Iatrogenic Horner's syndrome.

PURPOSE: To report two cases of Horner's syndrome. One presented after the ablation of a schwannoma of the cervical sympathetic chain, the second after upper thorascopic sympathectomy for primary palmar hyperhidrosis. METHODS: A 42-year-old man underwent excision of a left neck mass found during routine physical examination. A 20-year-old girl with axillary and palmar hyperhidrosis was treated with cervical sympathectomy. RESULTS: In the early postoperative days, miosis, ptosis, anhidrosis, and enophthalmos were observed. CONCLUSIONS: In the ablation of a schwannoma, postoperative Horner's syndrome is associated with the relationship between nerves and the tumor mass, which makes it impossible to separate them surgically in most cases. In thorascopic sympathectomy, patients should be warned of this complication.

Grisel's syndrome: a rare complication following adenoidectomy.

Grisel's syndrome, defined as subluxation of the atlanto-axial joint, not associated with trauma or bone disease, is found primarily in children. There are few references to this syndrome in the ENT literature but it may occur in association with any condition that results in hyperaemia and pathological relaxation of the transverse ligament of the atlanto-axial joint. Several common otolaryngeal conditions have been associated with the syndrome: pharyngitis, adenotonsillitis, tonsillar abscess, cervical abscess, and otitis media. Moreover, the syndrome has been observed after numerous otolaryngologic procedures such as tonsillectomy, adenoidectomy and mastoidectomy. Non-traumatic subluxation of the atlanto-axial joint should be suspected in cases of persistent neck pain and stiffness. X-rays and computed tomography scans of the cervical spine can confirm the diagnosis. Early management, consisting of cervical immobilization and medical treatment, is considered the key factor for a satisfactory outcome. Inappropriate treatment may result in a permanent and painful neck deformity that may even require surgical fusion. Neurological complications have been reported in the literature, with outcome ranging from mild paresthesia, clonus, to quadriplegia or acute respiratory failure and death. The case is described of an 8-year-old boy who developed Grisel's syndrome following adenoidectomy. The pathogenesis, classification, diagnosis, and treatment of this condition are discussed.

Schwannoma of cervical sympathetic chain: assessment and management.

Schwannoma arising from the cervical sympathetic chain is an uncommon benign nerve tumour. This tumour most often presents as an asymptomatic solitary neck mass, with slow-growing and rare malignant degeneration. Definitive pre-operative diagnosis may be difficult and investigations are not usually helpful. The carotid artery and internal jugular vein may be displaced anterior-laterally. Diagnosis relies on clinical suspicion and confirmation is often obtained by means of surgical pathology. Surgical excision is the treatment of choice for this tumour, with recurrence being rare. Homer's syndrome is a common post-operative neurological consequence, but does not appear to cause problems to the patient. The case is described of a 42-year-old male who presented an asymptomatic left neck mass. Diagnostic studies included computed tomography, magnetic resonance imaging, and ultrasound which confirmed a circumscribed mass in the upper left portion of the neck next to the thyroid gland. The mass was excised through a transverse left cervical skin incision. Post-operatively the patient showed clinical findings of Horner's syndrome. The pathologic and radiological evaluations, treatment and postoperative complications of this neoplasm are discussed.

Nasal polyposis: microsurgical ethmoidectomy and interruption of autonomic innervation vs conventional surgery.

Nasal polyposis is an invalidating disease which develops through chronic inflammation which leads to tissue oedema and eventually polyps. Treatment is aimed at eliminating polyps, resolving rhinitis symptoms, re-establishing nasal breathing and olfaction and preventing recurrence. The pathogenesis can be explained, in part, by degranulation of mast cells and release of mediators attracting eosinophils which, in turn, can cause tissue damage and oedema. Neurovascular reflexes and factors related to the complex anatomy of ethmoidal labyrinth may be responsible for the onset and persistence of oedema. This would offer a rationale to treatments modifying ethmoid anatomy and blocking neurovascular reflexes in the management of nasal polyposis. The advent of microsurgery and of diagnostic and operative endoscopy has led, over the last twenty years, to earlier detection and to less traumatic and more precise surgical treatment of nasal polyps. With these techniques resection of parasympathetic innervation is also possible, which is in keeping with the proposed rationale and cannot be easily achieved by conventional surgery. To evaluate the impact of this resection on the management of nasal polyposis a review of data has been made in a series of patients with diagnosis of nasal polyposis established by clinical examination, resistant to pharmacological therapy and treated between 1983 and 1998 at the Oto-Neuro-Ophthalmology Department of Florence University (Italy). Patients were treated by conventional surgery (386 cases), by microsurgery without resection of the parasympathetic component of the vidian nerve (97 cases), or by microsurgery with resection of this latter component (94 cases). The rate of recurrence and of major post-operative complications, respectively, were: 39.9% and 4.4% for patients treated by conventional surgery; 37.1% and 6.2% with microsurgery without resection of parasympathetic innervation; and 25.5% and 2.1% with resection of this innervation. The difference in recurrence rate between the three groups was significant (p < 0.05). The average disease-free interval was 45.7 months with conventional surgery and 53.5 months with microsurgery (regardless of resection of innervation). Results show that microsurgery for nasal polyposis together with resection of parasympathetic innervation improves results compared to those with conventional surgery and does not cause an increase in post-operative complications.

Microsatellite instability as biomarker for risk of multiple primary malignancies of the upper aerodigestive tract.

Head and neck cancer (HNC) patients are at high risk of developing second primary tumors of the upper aerodigestive tract and this is a chief cause of death. Genomic instability reflecting the propensity and the susceptibility of the genome to acquire multiple alterations is considered a driving force behind multiple carcinogenesis and the alterations of the length of single repetitive genomic sequences or microsatellite instability (MI), implicating impaired DNA repair mechanisms, and could be a sensitive marker for assessing genomic instability in multiple HNC. To investigate whether a genetic defect(s) involving the mismatch repair system constitutes a risk factor in patients with multiple head and neck cancer, we examined replication errors (RER) at 10 microsatellite loci in 21 primary and 5 second primary cancers in 21 patients with multiple malignancies of the upper aerodigestive tract, in comparison with match-paired primary HNC from patients without multiple malignancies. A RER+ phenotype (alterations at > or =2 loci) was observed at 10 microsatellite alterations on chromosomes 2, 3, 11, 17 in at least one tumor from 15 out of 21 (71.5%) patients with multiple primary cancers but only in 11 tumors from 40 (27.5%) HNC patients with single cancer (P=0.001). A RER+ phenotype was also associated with a positive familial cancer history (P=0.046). Our results suggest that a genetic instability may play an important role in the pathogenesis of multiple primary cancers and that testing for MI in a primary HNC may be useful in detecting patients with high risk for developing multiple malignancies of the upper aerodigestive tract.

Cumulative prognostic value of p53 mutations and bcl-2 protein expression in head-and-neck cancer treated by radiotherapy.

We investigated the prognostic significance of p53-gene mutation (exon 5-9) and bcl-2-protein expression in primary squamous-cell carcinoma of the head and neck (HNSCC) treated by curative radiotherapy (RT). Primary squamous-cell carcinomas for analysis were obtained from 85 consecutive head-and-neck-cancer patients, with complete follow-up data. We detected bcl-2 protein in 24% (20/85) of HNSCC studied; 38 (45%) of the 85 tumours had cells bearing p53 mutations. A strong association was observed between tobacco exposure and bcl-2-protein expression (p = 0.003), an association also evident in those patients who had a p53-mutated carcinoma (p = 0.049). Moreover, we found that most of the bcl-2-positive cancers (70%) were also mutated in the p53 gene (p = 0.010). In univariate and in multivariate analyses, the simultaneous detection of bcl-2 expression and a p53-gene mutation in a tumour biopsy specimen was associated with greater risk of locoregional failure (p = 0.002 and 0.001 respectively) and worse survival (p = 0. 045 and 0.033) within 5 years in HNSCC patients treated by RT. The present study shows a cumulative prognostic value of simultaneous detection of bcl-2 over-expression and p53-gene aberration in some primary HNSCC treated with conventional RT, and provides further evidence for cross-talk between p53 and bcl-2, suggesting that these genes are important determinants of radiation-induced apoptosis, thereby modulating resistance to RT. Int. J. Cancer (Pred. Oncol.) 84:573-579, 1999.

Multiple primary tumors of the upper aerodigestive tract: is there a role for constitutional mutations in the p53 gene?

Head-and-neck cancer (HNC) patients have a high risk of developing second primary tumors of the upper aerodigestive tract, the main cause of death. Although the roles of tobacco and diet in multiple head-and-neck carcinogenesis have been thoroughly investigated, little is known about individual genetic susceptibility factors involved in this process. Genomic instability, reflecting the propensity and the susceptibility of the genome to acquire multiple alterations, could be considered a driving force behind multiple carcinogenesis. Mutation of the p53 tumor-suppressor gene has been proposed to play an important role in this process. Therefore, we evaluated the incidence of inherited p53 germ-line alteration(s) in a population of 24 consecutive HNC patients and their first-degree relatives affected by multiple malignancies as well as the occurrence of p53 somatic acquired mutation(s) in 16 cancers, including first and second primaries from 5 HNCs of the same group. Mutations in exons 4-11 of the p53 gene were investigated using SSCP-PCR analysis and DNA sequencing. Analysis was extended to the peripheral blood and cancer biopsies available from first-degree relatives of cancer-prone families with p53 germ-line mutations. p53 germ-line mutations were identified in the peripheral blood and corresponding cancers of 3 HNC patients who had multiple malignancies. The only missense mutation detected was mapped in exon 6; it is a GTG to GAG substitution with an amino acid change from Val to Glu at codon 197. The remaining 2 p53 germ-line mutations were single-nucleotide substitutions without amino acid change in exon 6 (codon 213, CGA to CGG) and in exon 8 (codon 295, CCT to CCC), respectively. These mutations were found in HNC patients with a family history of cancer. Abnormal expression of wild-type p53 protein in normal and pathological tissues from patients with the same sense single-nucleotide substitutions was detected by immuno-histochemistry.

Reduced E-cadherin expression correlates with unfavorable prognosis in adenoid cystic carcinoma of salivary glands of the oral cavity.

Reduced expression of E-cadherin (E-cad), a transmembrane glycoprotein, is associated with loss of differentiation, acquisition of an invasive phenotype, and an unfavorable prognosis in carcinomas from several sites. We used immunohistochemistry to study the expression of E-cad in 50 adenoid cystic carcinomas (ACCs) in salivary glands to evaluate correlations with clinicopathologic parameters and patient survival. Absent or low E-cad expression was observed more frequently in solid than in cribriform or tubular carcinomas. E-cad expression also was significantly correlated with histologic grade and the growth pattern. In addition, ACCs showing low or absent E-cad expression were more frequently larger than 4 cm in diameter, and distant metastases developed more frequently. Reduced expression correlated with shorter disease-free intervals and actuarial survival rates. Univariate and multivariate analysis identified tumor stage and E-cad expression as the only 2 parameters predictive of the disease-free interval. E-cad expression and tumor stage, grade, and type of growth were significant prognostic factors for survival in univariate analysis, while tumor stage, type of growth, and E-cad expression were the only significant covariates in multivariate analysis. These findings indicate that the loss of E-cad has an important role in the natural history of ACC, as it is associated with loss of differentiation and development of metastases. We also provide evidence that E-cad expression is an independent indicator of clinical aggressiveness in patients with ACC, together with clinical stage and type of growth at the periphery of the tumor.

Warthin's tumour associated with autoimmune diseases and tobacco use.

To better clarify the possible role of immune mechanisms in the pathogenesis of Warthin's tumour (WT), we performed a retrospective study of patients with WT surgically treated at the Institute of Otolaryngology Head and Neck Surgery, University of Florence, during a 25-year period; looking for a possible association with autoimmune pathologies. The retrospective analysis of clinical records of 140 WT patients compared with those of 380 patients with pleomorphic adenoma revealed a higher incidence of autoimmune disorders, particularly organ-specific disease (i.e. insulin-dependent diabetes mellitus, Hashimoto's thyroiditis, autoimmune hyperthyroidism and hypothyroidism) in WT patients than in pleomorphic adenoma (PA) patients (23% vs 3%; R.R.: 8.69; p < 0.0001). Moreover, we demonstrate a positive smoking history in 87% of WT patients compared to only 38% of PA subjects (p < 0.001). Because of the well-known possible association among multiple immune disorders, our data support the hypothesis of an immune pathogenesis of WT and also suggest the possible role of tobacco smoke in facilitating such immune reactions responsible for the lympho-epithelial coexistence of WT.

Potential biomarkers in predicting progression of epithelial hyperplastic lesions of the larynx.

Factors contributing to malignant transformation of laryngeal pre-neoplastic lesions remain largely unknown. Potential etiologic factors may be related to a genetically controlled sensitivity to environmental carcinogens. In this study, we investigated bleomycin-induced chromosome fragility in 15 patients with laryngeal keratoses who experienced a malignant transformation of pre-neoplastic lesions during follow-up, as compared with chromosome fragility in 15 historical controls with no progression of laryngeal keratoses during a 10-year follow-up, in a match-paired analysis. Chromosomal analysis demonstrated a higher sensitivity to clastogens in patients with malignant progression of laryngeal pre-neoplastic lesions than that of control patients with no evolution of their original laryngeal keratoses (p < 0.01). Furthermore, in the attempt to identify possible prognostic markers we studied proliferative activity (MIB-1 expression) and p53 gene aberration in biopsy samples from non-invasive and invasive laryngeal lesions in both groups. p53 immunostaining was observed in 10/15 (66.7%) of pre-neoplastic lesions and in 11/15 (73.3%) of metachronous laryngeal cancers. No differences in terms of p53 expression were noted between transformed and not-transformed lesions. Mutations at p53 gene were observed in 3/15 (20%) of pre-invasive biopsies and in 4/5 (80%) of the laryngeal cancers analyzed. Our data suggest that p53 alteration is an early event in the genesis of a subset of laryngeal carcinomas and that there is no conclusive data about the possible clonal development of metachronous laryngeal carcinoma from a p53 mutated pre-invasive disease in the same patient. MIB-1 expression was found to progressively increase with degree of epithelial hyperplasia and dysplasia in both transformed (p = 0.007) and not-transformed (p < 0.1) lesions. Surprisingly, pre-invasive lesions with tumor evolution showed a lower proliferative activity when compared with laryngeal lesions without malignant transformation (p = 0.013). These data suggests that subjects with pre-neoplastic laryngeal lesion showing an increased susceptibility to carcinogens and with less proliferative disease could be at a higher risk for development of laryngeal carcinoma.