Parotid gland carcinoma: 1987 and 1997 UICC T classifications compared for prognostic accuracy at 5 years.

In order to compare the correlation of 1987 and 1997 UICC T categories with the survival rate in parotid gland carcinoma, 134 patients attending the ENT clinics at the University of Ferrara (from 1970 and 1993) and Firenze (from 1970 to 1990) were analyzed by means of survival analyses (Kaplan-Meier and Cox algorithms). This study demonstrated that both systems showed a significant correlation with the survival rate, but T 1997 resulted in a more reliable prognostic value by means of a higher odds ratio. We conclude that the newer (1997) UICC T category better defines the prognosis for cancer of the parotid gland and should have a higher impact on the clinical evaluation of patients.

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.

[The N0 neck in patients treated by supraglottic laryngectomy: abstention, surgery or radiotherapy?]. / Le cou N0 chez les patients opérés de laryngectomie susglottique: abstention, chirurgie ou radiation?

The authors examined the therapeutical approach to the N0 neck in patients submitted to supraglottic laryngectomy (SL). In these patients the choice of the therapeutical protocol may consist of simple abstention, of neck dissection or of elective radiotherapy: every decision has to be taken considering all specific inconveniences of each option. In their report the authors examined the follow-up of the N0 necks of 421 patients submitted to SL from 1970 to 1991. The patients submitted to wait and see policy were 225 whereas 196 received uni- or bilateral neck dissection. After the cervical failure's salvage the final 3-years control of the neck was the same in the two groups (91.1% vs 91.4%). In a previous research on 1157 N0 necks of patients submitted to total laryngectomy they observed a 5-years cervical control of 88.8% after wait and see policy and of 92.3% after elective radiotherapy. The conclusions of the authors is that no one of the two protocols is preferable to the other one and that subsequently in many cases of supraglottic T1 and T2 cancers a wait and see policy may be justified in absence of consistent counter-indications.

Intraepithelial lymphocyte subpopulations and dendritic accessory cells in normal and hypertrophic adenoids.

The adenoids have been studied by immunocytochemistry and electron microscopy in children with and without adenoidal enlargement. Compared with normal adenoids, the enlarged ones showed a marked increase in the number of intraepithelial gamma-delta TCR+ lymphocytes and a slight increase in the number of intraepithelial CD8+ lymphocytes. This was accompanied by large amounts of dendritic human lymphocyte antigen (D related) (HLA-DR+) S-100+ accessory cells in the lymphoid tissue underlying the epithelium. By electron microscopy, dead epithelial cells apposed to intraepithelial lymphocytes, and clefts of the epithelial lamina, could be seen frequently in the enlarged adenoids, whereas, in the normal ones, they could not. Based on these findings, the hypothesis is drawn that imbalance of the system of the intraepithelial cytotoxic lymphocytes may lead to increased killing of epithelial cells and uncontrolled penetration of exogenous agents, and hence be involved in the pathogenesis of adenoidal hypertrophy.

Spontaneous in vitro differentiation of a myoepithelial cell line (PA 16/23) from a pleomorphic adenoma of the parotid gland is associated with reduced production of the autocrine growth factor interleukin 6.

A myoepithelial cell line (PA 16/23) was derived from a pleomorphic adenoma of the parotid gland. PA 16/23 cells have light microscopic, immunophenotypical and ultrastructural features of immature myoepithelial cells, i.e. they are of fusiform or stellate shape and show keratin and actin cytofilaments located mainly in the perinuclear cytoplasm, desmosomes and tracts of basal lamina. The PA 16/23 cells grew actively and expressed mRNA for and produced interleukin 6 (IL-6) which was released into the culture medium. This cytokine, in turn, acted as an autocrine growth factor on the cells. PA 16/23 cells also expressed high-affinity IL-6 receptors. In these cells, both IL-6 production and proliferation could be modulated by exogenous stimulants, such as IL-6 itself, IL-1, IL-4, tumour necrosis factor alpha, interferon gamma and lipopolysaccharide. From the 40th culture passage onwards, the PA 16/23 cells ceased to grow, either spontaneously or in response to exogenous stimulants. Moreover, they strongly reduced IL-6 production, and underwent morphological differentiation into more mature myoepithelial cells, with an increased amount and a different arrangement of the keratin and actin cytofilaments, which formed thick bundles in the peripheral cytoplasm. These findings suggest a role for IL-6 in modulating the proliferation and, possibly, the differentiation of the PA 16/23 cells.

Lack of detection of human papillomavirus (HPV) in transformed laryngeal keratoses by in situ hybridization (ISH) technique.

Laryngeal keratosis (LK) is a precancerous mucosal change with a variable possibility of malignant transformation. Recent studies evidencing HPV-DNA genomes in a large series of non-malignant and malignant laryngeal lesions suggest a role of HPV in the transformation of laryngeal lesions possibly in synergistic interaction with other carcinogens. In this study, we analyzed 115 biopsy specimens from benign laryngeal lesions to evaluate the risk of malignant transformation and its relationship to degree of dysplasia and to histological features of virus cell infection. The rate of transformation of LK was 8% (9/115). Our results indicate that the risk of transformation in laryngeal keratoses without dysplasia (LKWOD) is lower than that in laryngeal keratoses with dysplasia (2.2% vs 25%, respectively) (p < 0.05). An increased risk of malignant evolution in laryngeal keratoses with dysplasia (LKWD) was also related to the degree of dysplasia (rate of transformation of 12.5, 22.2 and 36% in mild, moderate and severe dysplasia, respectively). Histological features suggesting HPV infection (koilocytic-like atypia and epithelial papillary hyperplasia) were found in 6 LK only, no case subsequently developing cancer. In both benign and transformed LK, analyzed by ISH, we failed to detect HPV genomes, suggesting a major role of others carcinogens, such as tobacco and/or alcohol, in the transformation of LK.

Undifferentiated carcinoma of the nose and paranasal sinuses. An immunohistochemical and clinical study.

Among twenty-six "undifferentiated" tumors of the nasal cavity and paranasal sinuses treated from 1970 to 1990 at the Institute of Otolaryngology of Florence University, 13 were ultimately diagnosed as true undifferentiated sinusonasal carcinoma (SNUC) by conventional light microscopy and use of monoclonal antibodies to epithelial membrane antigen and cytokeratins. SNUC patients, who ranged in age from 20 to 82 years, often had multiple sinonasal symptoms due to very large tumors (nine of 13 tumors were staged as T3-T4) with short average delay of 4 months between onset of symptoms and diagnosis. Both data suggest the high growth capacity and aggressiveness of such a tumor. In our series, follow-up evidenced an overall crude 5-year survival rate of 15.5%. Worse prognostic factors are neck metastases and orbital invasion, according to the behavior of more common carcinomas of the nose and paranasal sinuses. We also found a better prognosis for SNUC primarily arisen in the nasal cavity than in paranasal sinuses (crude 5-year survival rate of 66% vs. 10%, respectively). The histopathological and clinical analysis of our series shows that SNUC is a highly aggressive, uncommon tumor of the nose paranasal sinuses, which should be recognized in advance for a more aggressive treatment by combined multiple therapy.

Does the epithelium play a central role in the immune function of rhinopharyngeal tonsils? An immunocytochemical and ultrastructural study.

Enlarged adenoids from 10 children with chronic rhinitis and otitis media with effusion have been studied immunocytochemically and ultrastructurally, to better define the possible role of the epithelium and the dendritic accessory cells in the immune activation of lymphoid cells, and provide further insight into the pathogenesis of the disease. The presence within the columnar epithelium of lymphocytes positive for CD8 antigen, and which electron microscopically have been found frequently apposed to degenerating epithelial cells suggests that the latter cells are targets for cytotoxic activity of intraepithelial lymphocytes, rather than being engaged in antigen presentation. Furthermore, the finding of typical dendritic accessory cells, recognized by their typical immunophenotypic and ultrastructural features, in the lamina propria, indicates that antigen presentation is more likely exerted by dendritic accessory cells. This is further supported by the fact that these cells express major histocompatibility (MHC) class II molecules, which are needed for antigen presentation, whereas epithelial cells do not. A possible relationship between epithelial damage and the pathogenesis of adenoidal enlargement is discussed.

Langerhans cells related to prognosis in patients with laryngeal carcinoma.

Intratumoral and peritumoral infiltration of T-zone histiocytes, mainly of mature Langerhans cells, was investigated in 88 patients with squamous cell carcinoma of the larynx by immunohistochemical methods using polyclonal antibodies against S100 protein and lysozyme. Granulocytic and lymphoid inflammatory infiltration and its relationship to the presence of Langerhans cells were also evaluated. Langerhans cells were present within the cancer tissues and showed a relationship with lymphoid infiltrate. No significant correlation was present among the density of Langerhans cells and the site of neoplastic growth (supraglottic or subglottic), granulocytic inflammatory infiltration, histological tumor grade, or clinical stage. Patients with high or intermediate density of Langerhans cells survived longer than those with low density (mean survival, 61%, 62%, and 0%, respectively). The number of Langerhans cells was relevant in patients with evident infiltration of lymphocytes and plasma cells, according to their ability to present antigens to sensitized T cells. Our results indicate that the presence of high or intermediate density of Langerhans cells and of marked lymphoid inflammation may be considered favorable prognostic factors for patients with squamous cell carcinoma of the larynx.

Glottic cancer involving anterior commissure: surgery vs radiotherapy.

A retrospective review of 182 patients with glottic cancer involving the anterior commissure (AC) is presented. Of these, 123 patients were first treated with conservative surgery and 59 underwent radiotherapy. Patients were staged according to the AJCC system and by the modality of neoplastic involvement of AC (pure AC cancer, glottic cancer involving AC up to the midline, and beyond the midline). Our results indicate a higher rate of local control and of specific-disease survival in the group of patients first treated with surgery than those treated with radiotherapy (86% vs 74% and 97.5% vs 84%, respectively) (p less than 0.05). For pure AC cancers, our results show better local control with primary radiotherapy than with conservation surgery (82% vs 76.5%), but surgical failures have been more successfully salvaged than have radiotherapy recurrences (ultimate local control, 97.5% vs 82%, respectively). These data suggest that the treatment of choice for AC cancers is conservation surgery, particularly frontolateral laryngectomy.

Labeling index in squamous cell carcinoma of the larynx.

Two cell kinetic parameters, the 3H-thymidine labeling index (TLI) and the mitotic index (MI), were studied in vitro on fragments of squamous cell carcinoma tissue of the larynx. They were evaluated to identify those elements able to characterize the growth of these solid tumors. The values of these parameters were analyzed as a function of the clinical stage and the involvement of the regional lymph nodes. Results showed a statistically significant increase in the TLI from stage T1 to T3. No statistically significant differences in the TLI values were observed between the patients with positive and negative lymph nodes.

Correlations between histopathological and biological findings in nasopharyngeal carcinoma and its prognostic significance.

Forty-five consecutive cases of nasopharyngeal carcinoma were morphologically and immunocytochemically studied using monoclonal (anti-B and anti-T cell) and polyclonal (anti-S100 protein and antilysozyme) antibodies with the peroxidase-anti-peroxidase method to identify infiltrating lymphocytes (T and B cell) and histiocytes (monocytic/macrophagic and dendritic cells) in nasopharyngeal carcinoma. A variable density of dendritic cells was found within the tumor nests in 22 (49%) of 45 nasopharyngeal carcinomas examined; infiltrating macrophages were demonstrated in 15 (33%) specimens and around the tumor in almost all cases. Cases with moderate or marked density of dendritic cells (S100+) survived longer than those without such infiltration (mean 5-year survival rates of 31%, 55%, or 64% in patients with absent, moderate, or marked densities, respectively; P less than 0.05). A significant relationship between monocytic/macrophagic cells (lysozyme+) within the tumor and survival was also found (mean 5-year survival rate of 27% or 61% in patients with absent, moderate, or marked densities, respectively). However, lymphocytic infiltration was not statistically related to a better survival. Analyzing lymphocytic infiltration, we found a large prevalence of T cells in the neoplastic tissue without any prognostic significance. These data were correlated to different histological subtypes according to the principal histological classifications of nasopharyngeal carcinomas (Micheau, et al.; World Health Organization; Cologne University) to individualize the scheme which correlates best with prognosis and biological features of nasopharyngeal carcinomas. Our data suggest that, considering dendritic cells and macrophages within cancer nests, nasopharyngeal carcinoma histiotypes can be correlated to patient prognosis.

[Histopathological parameters and lymphatic metastasis in supraglottic laryngeal carcinoma]. / Parametri istopatologici e metastatizzazione linfonodale nel carcinoma laringeo sopraglottico.

Histopathologic parameters in predicting lymph node metastasis of supraglottic laryngeal carcinoma. A systematic clinical-pathological study was performed on fifty-three resected cases of supraglottic laryngeal squamous cell carcinoma, followed up for at least 5 years. The aim of the research was to evaluate histopathologic parameters in predicting lymph node metastasis (N+) as expression of biological malignancy of the neoplasm. The following neoplastic microscopical features were studied: histopathologic and cytologic grading, pattern of growth, peritumoral inflammatory infiltrate, stromal reaction, tumoral necrosis. The results are as follows: stromal reaction and cytologic grading are not useful to identify N+ and N- cases. Cases with high and low degree of differentiation (Broder's grading) are significantly correlated respectively to low (14.3%) and high (70%) incidence of lymph node metastasis (p less than 0.03). A clear correlation is present between the pattern of growth "pushing" and lacking of node metastasis (84.6%). A favorable prognosis significance seems to be linked with the presence of peritumoral lymphoplasmocytic infiltrate, which results to be a marker of cases in which lymph node metastasis incidence is very low (5.5%; p less than 0.001). On the contrary lymph node metastasis incidence increase when tumoral necrosis is present (76.5%; p less than 0.001).

Interdigitating cells in the peritumoral infiltrate of laryngeal carcinomas: an immunocytochemical and ultrastructural study.

Interdigitating cells (IDCs) have been found in the peritumoral infiltrate of 18 patients with squamous cell carcinoma of the larynx. These cells have a dendritic shape and are characterized by the expression of S-100 protein and CD1a antigens. By electron microscopy, these cells are seen to establish intimate contacts with the apposed lymphocytes, which sometimes show signs of functional activation and proliferation. These findings indicate that IDCs may play a role in setting up a T-cell immune reaction against neoplastic cells, which may influence the biological behaviour and/or local growth of the tumour. Moreover, monocytes and cells with intermediate features between monocytes and IDCs are also found in the peritumoral infiltrate, thus suggesting that IDCs differentiate in situ from monocytic precursors, possibly under the influence of either tumour-derived factors or the local lymphoid microenvironment.

[Surgical treatment in 155 cases of hypopharyngeal carcinoma: analysis of results and causes of failure]. / Sul trattamento chirurgico di 155 carcinomi dell'ipofaringe: analisi dei risultati e delle cause di insuccesso.

A retrospective study has been performed on 155 cases of surgically treated hypopharyngeal carcinomas in order to bring to light what effect the type of surgery has on survival and the reasons for failure. The following operations were performed: 103 hemipharyngectomies with total laryngectomy (HPTL); 28 total circular pharyngectomies with total laryngectomy (CPTL); 16 hemipharyngectomies with partial laryngectomy (HPPL); 4 exereses in lateral pharyngectomy; 2 total laryngectomies and 2 hemipharyngectomies in lateral pharyngotomy. Analysis of the results is only performed on the three most numerous groups of patients. The overall neoplastic mortality rate at 5 years was 79% for the HPTL group while it was 50% and 61% in the CPTL and HPPL groups, respectively. The actuarial survival curves show a higher, statistically significant, cumulative 5-year survival rate for the CPTL group (55.9%) than for the HPTL group (30.5%). The authors conclude that, considering the particular submucosa spreading to which hypopharyngeal carcinoma is subject and the good functional recovery which can be obtained with modern reconstructive surgery of the alimentary tract, CPTL should be the treatment of choice, even in the less advanced cases, in order to significantly reduce the risk of local recurrences.

[Contralateral metastasis in patients with cancer of the larynx and the hypopharynx. Analysis and critical review of our caseload]. / Le metastasi controlaterali in pazienti con cancro laringeo ed ipofaringeo. Analisi e revisione critica della nostra casistica.

Cancers of the hypopharynx (pyriform fossa, post-cricoid area and posterior wall) and larynx show a high tendency to invade the cervical lymph nodes. Such nodal extension is a well known prognostic factor. In general, those lesions that are in well-lateralized primary sites (pyriform sinus, aryepiglottic fold...) tend to metastasize to the ipsilateral side of the neck. This concept, however, is fraught with exceptions; any lesion, especially with ipsilateral metastases, creates a risk for contralateral node involvement. The present study is based on a retrospective review of 450 clinical records of patients affected by well-lateralized laryngeal (301 pt.) and hypopharyngeal (149 pt.) carcinomas. The incidence of contralateral metastases was analyzed for this group; 25 out of 310 patients with laryngeal cancer (8.3%) and 20 out of 149 with hypopharyngeal cancer (13.4%) showed metastatic involvement of the contralateral neck. In patients with laterally oriented primary lesions, the initial appearance of cervical adenopathy is rarely contralateral since contralaterality is almost a manifestation of bilaterality of metastases. A contralateral disease is rarely possible even if the homolateral neck has been surgically treated. This is because of shunted lymph flow through the submental and submandibular lymphatics. Isolated contralateral disease was only found in 4 patients (1.3%): such data do not suggest any systematic, elective treatment of the contralateral neck NO in patients with unilateral laryngeal and hypopharyngeal cancers.

Vidian nerve resection, histamine turnover and mucosal mast cell function in patients with chronic hypertrophic non-allergic rhinitis.

Parasympathetic innervation of the respiratory tract of nasal mucosa plays an important role in the pathogenesis of chronic hypertrophic non-allergic rhinitis (C.H.N.A.R.), the vidian nerve providing the main parasympathetic nerve supply to respiratory mucosa. The present study investigates the effect of vidian nerve resection in 22 patient with intractable C.H.N.A.R. on histamine content and formation and on the number of mast cells and their degranulation in the respiratory tract. Samples were taken from respiratory mucosa for histamine and histidine-decarboxylase assay, and for microscopic observations for mast cell density and degranulation index, before and 12-24 months after vidian nerve resection. Neurectomy of the vidian nerve completely cured the clinical symptomatology, evaluated by rhinoreomanometry, and also significantly decreased both the high histamine levels and histidine-decarboxylase activity in patients with C.H.N.A.R. The density and degranulation index of mast cells were also significantly lower after surgery. These data suggest a relationship between cholinergic activity and the secretory response of mast cells and indicates a correlation between the parasympathetic nerve supply and chronic hyperthrophic non-allergic rhinitis. The significant reduction in mast cell density, histamine levels and histidine-decarboxylase activity also lends support to the hypothesis that the parasympathetic nerve supply plays a role in the regulation of mast cell histamine.