Is human papillomavirus involved in laryngeal neuroendocrine carcinoma?

The purpose of this study was to detect human papillomavirus (HPV) infection in laryngeal neuroendocrine carcinoma (LNEC) and to explore the possible relationship between HPV-induced malignant transformation and prognosis in LNEC. Ten cases of LNEC from a tertiary referral hospital were retrospectively analyzed. Clinical data were subtracted from patients’ files. Pretreatment biopsy material was tested for the presence of HPV6, 11, 16, and 18 using a PCR-based detection method. Immunohistochemical staining was performed for Ki-67, p16^INK4A, and p53 expression. All cases were negative for the low-risk HPV types HPV6 and HPV11 that are associated with laryngeal papillomatosis. High-risk HPV was detected in two cases; an atypical carcinoid was positive for HPV16 and a large-cell neuroendocrine carcinoma for HPV18. Both HPV-positive tumors had a high Ki-67 labeling index. Two of the four cases with a good response to therapy were hrHPV-positive (both HPV DNA positive) compared with none of the five poor responders. Our findings show that HPV may play a role in the pathogenesis of LNEC. The relationship between HPV, improved prognosis and good response to therapy for squamous cell carcinoma of the head and neck may also be true for a subset of LNEC.     

Is Ki67 a marker for the transformation of laryngeal dysplasia to carcinoma?

CONCLUSION: Ki67 is not a reliable marker of malignant transformation in laryngeal dysplasia. OBJECTIVES: No reliable means of predicting which cases of laryngeal dysplasia will undergo malignant transformation currently exists. Our aim was to evaluate Ki67, a marker of cell proliferation, as a potential marker for the transformation of laryngeal dysplasia to squamous cell carcinoma. PATIENTS AND METHODS: Eighty consecutive cases of previously untreated patients with a histological diagnosis of laryngeal dysplasia from 1987 to 1993 were identified from the pathological archives. Standard immunohistochemical techniques were used to identify Ki67-positive cells and activity was scored on a scale of 0-4 using defined criteria. RESULTS: Of the 80 cases there were 24 females and 56 males with a mean age of 56 years (range 29-80 years). Twenty cases subsequently transformed to a squamous cell carcinoma. For each Ki67 score (0-4), the rate of malignant transformation was: 0, 1 of 6 patients (17%); 1, 7 of 33 patients (21%); 2, 5 of 22 patients (23%); 3, 4 of 13 patients (31%); and 4, 3 of 6 patients (50%). A higher Ki67 score seemed to correlate with a higher likelihood of malignant transformation but this did not reach statistical significance (p=0.17, Pearson chi(2) test). Considering a score of 3 or 4 as positive for predicting malignant transformation produced a test of relatively high specificity (80%) but poor sensitivity (35%).     

The cadherin–catenin complex in laryngeal squamous cell carcinoma

Abnormal Wnt signaling and impaired cell–cell adhesion due to abnormal E-cadherin and β-catenin function have been implicated in many cancers, but have not been fully explored in laryngeal squamous cell carcinoma. In this study, β-catenin cellular location and E-cadherin expression levels were analyzed in 16 laryngeal squamous cell carcinomas (LSCCs) (9 glottic and 7 supraglottic) and 11 samples of non-tumoral inflammatory larynx tissue, using immunohistochemical methods. All non-tumoral tissues showed equally strong membranous expression of β-catenin, while cytoplasmic expression was found in only 3 of the 11 samples. By contrast, whereas 8/9 glottic LSCCs exhibited only membranous expression of β-catenin, 6/7 supraglottic LSCCs displayed both membranous and cytoplasmic expression (p = 0.003). Strong E-cadherin staining was observed in 9/11 non-tumoral tissues and 7/9 glottic LSCCs, whereas 4/7 supraglottic LSCCs exhibited weak expression. Reduced membrane expression of E-cadherin and cytoplasmic retention of β-catenin in supraglottic LSCC seems to be related with more aggressive biological behavior which has been described in clinical studies. Further research is required to clarify the involvement of β-catenin in the mechanism associated with malignant transformation in laryngeal tissues.     

Differential β-catenin expression between glottic and supraglottic laryngeal carcinoma

Glottic carcinomas present with a favorable prognosis comparing to supraglottic. This fact is mainly attributed to differences in anatomical, histological and embryological aspects. It is possible that differential molecular anatomy between the two distinct anatomical entities contributes to this clinical observation as well. The current study intended to evaluate, by immunohistochemistry in paraffin-embedded tissue samples from 97 invasive squamous laryngeal carcinomas, the possible differential expression of crucial molecules for malignant cell’s function such as integrin-linked kinase, phosphorylated Akt, E-cadherin, β-catenin, androgen receptor, estrogen receptor-β and vimentin between glottic and supraglottic laryngeal carcinomas. We documented a correlation of supraglottic laryngeal carcinomas with high grade (p = 0.001) and enhanced tumor TNM stage (p < 0.001). The supraglottic location was correlated with the abolishment of β-catenin from the membrane (p = 0.025). However, the diverse anatomical locations are not characterized by statistically significant differential expression of ILK, p-Akt, AR, ER-β, E-cadherin and vimentin. Our results show that it is possible that molecular factors, such as β-catenin, are differently expressed in glottic and supraglottic carcinomas, leading to the distinct clinical behavior of those tumors.     

Does CT help in predicting preepiglottic space invasion in laryngeal carcinoma?

Objective

Evaluating preepiglottic space involvement in laryngeal cancer by CT may lead misinterpretation. We sought to understand the causes of misinterpretation in evaluating the preepiglottic space by CT and assessed the effects of misinterpretation in treatment plans of patients with laryngeal squamous cell carcinomas.

Is syndecan-1 an independent prognostic factor in patients with laryngeal carcinoma?

Syndecan-1 is a member of the syndecan family of cell membrane heparan sulphate proteoglicans. The aim of this study was the evaluation of prognostic value of syndecan-1 expression in laryngeal cancer. The findings were correlated with the clinico-pathological parameters of the tumours, as well as with patient survival rate. Paraffin-embedded samples from 99 patients with laryngeal cancer selected from the files of the ENT-Dept. of Medical Academy in Lublin were immunostained with anti-syndecan-1 monoclonal antibody. The patients' mean age was 57 years and the over 5-year survival rate was 53.2%. Syndecan-1 immunoreactivity was observed in 99 (100%) of carcinomas. In our study, a statisti- cally significant correlation between syndecan-1 expression and patient survival rate was observed (chi2 = 9631; p = 0.008) as well as between syndecan-1 expression and various clinical stages of disease (chi2 = 6771; p = 0.034). The significant difference in the presence of syndecan-1 expression among the patients with various stage of histological differentiation of carcinoma (chi2 = 14.9; p = 0.001), and among the patients with present and absent metastatic changes in regional lymph nodes (chi2 = 16.698; p = 0.001) was observed. In a Coxs multivariate analysis syndecan-1 had an independent prognostic value (p = 0.014). Our results indicate that syndecan-1 could be used as a prognostic marker in laryngeal cancer.     

Does waiting time for radiotherapy affect local control of T1N0M0 glottic laryngeal carcinoma?

This is a retrospective study of 362 patients with a T1N0M0 glottic laryngeal carcinoma treated by radiotherapy. Waiting time was defined as time from the day of histopathological diagnosis to the first day of radiotherapy. The Cox regression model was used to analyse the influence of waiting time for radiotherapy on the incidence of recurrence. The median follow‐up time was 4.4 years. The median waiting time for radiotherapy was 43 days. Local recurrences were found in 58 patients. There was no significant correlation (P = 0.88) between waiting time and the outcome of early glottic cancer as analysed by Cox regression. This retrospective study did not demonstrate an effect of waiting time for radiotherapy on the outcome of early glottic laryngeal cancer.     

Does waiting time for radiotherapy affect local control of T1N0M0 glottic laryngeal carcinoma?

This is a retrospective study of 362 patients with a T1N0M0 glottic laryngeal carcinoma treated by radiotherapy. Waiting time was defined as time from the day of histopathological diagnosis to the first day of radiotherapy. The Cox regression model was used to analyse the influence of waiting time for radiotherapy on the incidence of recurrence. The median follow-up time was 4.4 years. The median waiting time for radiotherapy was 43 days. Local recurrences were found in 58 patients. There was no significant correlation (P= 0.88) between waiting time and the outcome of early glottic cancer as analysed by Cox regression. This retrospective study did not demonstrate an effect of waiting time for radiotherapy on the outcome of early glottic laryngeal cancer.     

Polypoid type of laryngeal sarcoidosis – case report and review of the literature

A 45-year-old mentally retarded woman was discovered to produce a stridor upon inhalation. Fiberoptic laryngoscopic study revealed a smooth-surfaced, wide, and pedunculated tumor on the right arytenoid and the right aryepiglottic fold. Histopathological study revealed that the tumor was characterized by granulomatous inflammation. The condition was diagnosed as laryngeal sarcoidosis. The tumor was resected surgically. Surgical resection of the tumor and injection of corticosteroid should be performed for polypoid-type laryngeal sarcoidosis. The case is discussed in detail, along with a review of the literature pertaining to sarcoidosis of the larynx. Received: 13 December 1999 / Accepted: 6 April 2000     

Tracheal and laryngeal rupture in neonates: complication of delivery or of intubation?

Neonatal tracheal or laryngeal rupture is a rare but life-threatening condition that is attributable to traumatic endotracheal intubation or traumatic delivery. We present a review of the literature and 6 new cases of laryngeal or tracheal rupture following complicated delivery. High-risk groups were identified as 1) low-birth weight neonates, for intubation trauma, and 2) extremely high-birth weight neonates with shoulder dystocia, for trauma due to delivery. Two specific types of ruptures can be distinguished. The less-rare type involves a partial anterior rupture in the subglottic area, which can occur after traumatic intubation or traumatic delivery. The rarer type involves a distal circumferential tracheal rupture that gives rise to ventilatory problems, usually after a delay of several days. This type of rupture was only observed following traumatic delivery. Early diagnosis, optically guided orotracheal intubation, and timely treatment can reduce the risks of mortality and morbidity.     

Supraglottic activity: evidence of vocal hyperfunction or laryngeal articulation?

False vocal fold (FVF) adduction and compression of the arytenoid cartilages to the petiole of the epiglottis in an anterior to posterior (A-P) direction have been thought to characterize voice disorders with abnormally increased muscle tension or effort, often termed hyperfunctional voice disorders. To further evaluate the association between hyperfunctional voice disorders and supraglottic activity, we compared the incidence of static and dynamic supraglottic activity in individuals with normal laryngeal mucosa, normal voice quality, and no voice complaints to two populations: subjects with vocal fold nodules and subjects with complaints of dysphonia without visible vocal fold lesions, glottal incompetence, or impairment of arytenoid cartilage motion ("hyperfunctional" group). Thirty-two subjects were assigned to one of these three groups (10 control, 12 nodule, and 10 hyperfunctional). Laryngeal movements were recorded using flexible videoendoscopy while a subject was performing speech tasks such as sustained phonation, syllable repetitions, sentence imitations, and conversation. Samples were randomized by subject and task and rated for presence or absence of A-P and FVF compression. Statistically significant group differences were found for FVF compression across speech tasks (chi-square, p<0.001). The control group had the smallest incidence (45%), nodule patients the next larger incidence (68%), and hyperfunctional patients the largest incidence (80%). Statistically significant group differences were found for A-P compression across speech tasks (chi-square, p<.05). The control group had the smallest incidence (74%), nodule patients the next larger incidence (78%), and hyperfunctional patients the largest incidence (92%). Statistically significant task differences were found for the presence of FVF compression in control subjects (chi-square, p<.005), hyperfunctional patients (chi-square, p<.025), and nodule patients (chi-square, p<.001), but not for A-P compression for any of the groups. A higher incidence of FVF compression was present for the speech tasks that included glottal stops. This context-specific variation in supraglottic activity suggested a dynamic component to FVF compression and also explained the high proportion of FVF compression in the control group. Each video sample was also rated for consistency of FVF or A-P compression to explore the static and dynamic nature of supraglottic activity. For samples on which raters agreed, A-P compression was typically present consistently, suggesting a static component, and FVF compression inconsistently, suggesting a dynamic component, for all three groups (chi-square, p<.001). These findings do not support previous suggestions that supraglottic activity may be a precursor to developing vocal fold nodules, as the nodule patients did not exhibit a higher incidence or consistency of A-P or FVF compression than patients with hyperfunctional voicing patterns in this study. Subjects in the hyperfunctional voice group were found to have static components of FVF and A-P compression. The presence of FVF compression in speech tasks that included glottal stops in the control group suggests an articulatory function at the laryngeal level.