Role of adjuvant chemotherapy in malignant mucosal melanoma of the head and neck.

The objective of this study was to analyze the role of adjuvant chemotherapy and prognostic factors in malignant mucosal melanoma of the head and neck (HNMM). Thirty-two patients with mucosal melanoma of the head and neck who received local treatment with or without adjuvant chemotherapy were reviewed. Clinicopathologic parameters including anatomic sites, gender, age (60 vs.>60years), stage, level of invasion, p53 and MDM2 [murine double minute 2] expressions, performance status, and adjuvant chemotherapy were evaluated. The patients' median age was 62years, and 16 (50%) received adjuvant chemotherapy. Expressions of p53 and MDM2 were demonstrated in six of 24 and three of 26 cases, respectively. Predictors of poor survival according to univariate analysis were level of invasion and anatomic location of the primary tumor. Patients who received adjuvant chemotherapy had prolonged survival (p=0.002), which was also shown in the multivariate Cox regression model (HR, 0.24; p=0.014). Our analysis suggests a significant role of adjuvant chemotherapy and different patterns of p53 and MDM2 expression in HNMM relative to cutaneous melanomas. However, since this study is retrospective and observational, with a small sample size, further studies are needed to confirm the definitive role of adjuvant chemotherapy in the treatment of malignant mucosal melanoma of the head and neck.

EGFR mutations and human papillomavirus in squamous cell carcinoma of tongue and tonsil.

This study was performed to determine the clinical significance of mutations in the EGFR (epidermal growth factor receptor) along with their association with human papillomavirus (HPV) infections in patients with squamous cell carcinoma of the head and neck (HNSCC). Exons 18-21 of the EGFR tyrosine kinase domain were sequenced and HPV typing was carried out using the HPV DNA chip in tissues obtained from patients with tongue and tonsil cancer. Univariate and multivariate analyses were used to identify the significant factors. One hundred and eight patients were enrolled. Ten patients (9%) were HPV positive and 17 (16%) had EGFR mutations. None of the patients with EGFR mutations were HPV positive. Gender, age (<60 years versus 60 years), and smoking history were not associated with EGFR mutations. A higher percentage of patients with tonsillar cancer were HPV positive than those with tongue cancer (26% and 0%, respectively; P<0.001). EGFR mutations were not a significant prognostic factor (P=0.746). HPV-positive patients had prolonged survival (P=0.025). Multivariate analysis revealed a longer overall survival in HPV-positive patients (P=0.007). EGFR mutations are not associated with the HPV-positive status, which may confer a better survival outcome. Clinical features of lung cancer patients with EGFR mutations were not observed in HNSCC. A further study will be needed to confirm these results.

A study of moderately differentiated neuroendocrine carcinomas of the larynx and an examination of non-neoplastic larynx tissue for neuroendocrine cells.

OBJECTIVES/HYPOTHESIS: To determine the most appropriate terminology for neuroendocrine carcinomas (NEC) of the larynx, successive clinicopathologic studies are encouraged. The typical location and immunophenotype of laryngeal NEC raise a question of whether any precursor cells exist. STUDY DESIGN: Six patients with laryngeal NEC were analyzed. Another 20 laryngectomy specimens were examined for the presence of non-neoplastic neuroendocrine cells. METHODS: Tumor morphology and patient outcome were determined, and tumor tissue underwent immunohistochemical examination to identify cytokeratin, neuroendocrine markers (chromogranin, synaptophysin, CD56, calcitonin), S-100 protein, and p53 protein. A neuroendocrine marker study was also performed on non-neoplastic regions of another 20 laryngectomy specimens to identify any neuroendocrine cells. RESULTS: Laryngeal NEC, all submucosal, exhibited various morphology with or without histologic evidences of neuroendocrine differentiation. The tumors showed frequent (67%) calcitonin expression, calcitonin secretion in one case, and common (50%) p53 over-expression. Three patients died within 3 years. In the non-neoplastic larynx specimens, Kulchitsky cell-like bipolar neuroendocrine cells were identified in the basal and middle layer of the respiratory epithelium of the ventricle and subglottis but none in the submucosal layer of the supraglottic region. The neuroendocrine cells did not express calcitonin. CONCLUSIONS: Moderately differentiated or large-cell NEC is a more favored term than atypical carcinoid until more refined classifications for upper respiratory tract NEC are agreed on. Despite the confirmed presence of neuroendocrine cells in the respiratory epithelium of the larynx, the origin of laryngeal NEC remains unknown. p53 mutation might be one of the major molecular steps in the pathogenesis of laryngeal NEC.

Epidemiologic survey of head and neck cancers in Korea.

Head and neck cancers have never been systematically studied for clinical purposes yet in Korea. This epidemiological survey on head and neck cancer patients was undertaken from January to December 2001 in 79 otorhinolaryngology resident-training hospitals nationwide. The number of head and neck cancer patients was 1,063 cases in the year. The largest proportion of cases arose in the larynx, as many as 488 cases, which accounted for 45.9%. It was followed by, in order of frequency, oral cavity (16.5%), oropharynx (10.0%), and hypopharynx (9.5%). The male:female ratio was 5:1, and the mean age was 60.3 yr. Surgery was the predominant treatment modality in head and neck cancers: 204 (21.5%) cases were treated with only surgery, 198 (20.8%) cases were treated with surgery and radiotherapy, 207 cases (21.8%) were treated with combined therapy of surgery, radiotherapy, and chemotherapy. Larynx and hypopharynx cancers had a stronger relationship with smoking and alcohol drinking than other primary site cancers. Of them, 21 cases were found to be metastasized at the time of diagnosis into the lung, gastrointestinal tract, bone, or brain. Coexisting second primary malignancies were found in 23 cases. At the time of diagnosis, a total of 354 cases had cervical lymph node metastasis accounting for 42.0%.

Cancers of the upper aerodigestive tract in Korea.

Cancers of the upper aerodigestive tract (UADT) constitute 3.5-4% of all malignancies. Since the majority of cases are squamous cell carcinomas which are related with epidemiologic factors, a different pattern of UADT cancer might be present between the Western and Asian populations. We performed a pathology based statistical study on UADT cancers in Korean patients. Cases from Korea Cancer Center Hospital, from January 1, 1988 through December 31, 1998, were subjected to the study. Among 2,842 cases, epithelial malignancies accounted for 87.8%, with squamous cell carcinoma as the major type (76.5%). The larynx was the most commonly affected site (26%), followed by the oral cavity (25.1%), oropharynx (13%), nasopharynx (9%), hypopharynx (8.4%), paranasal sinuses (6.4%), nasal cavity (6%) and salivary glands (6.1%). The percentage of squamous cell carcinoma was highest (98.7%) at the hypopharynx, and lowest at the nasal cavity (42.3%), which showed the most diverse tumor entities. Korean patients with UADT cancers presented with a higher incidence of non-epidermoid malignancy including sarcoma (1.5%) and malignant melanoma (1.4%), and a higher frequency of involvement of the sinonasal tract, compared with the Western patients.