Squamous Cell Carcinoma Of Upper Aerodigestive Tract Research Articles

Differential gene expression and methylation of upper aerodigestive tract and lung squamous cell carcinoma between European ancestry (EA) and African ancestry (AA) patients.

e18031 Background: Pan-cancer analysis of cancer disparities revealed both head and neck and lung cancer are among the top cancers with significant disparities in overall survival outcomes between EA and AA patients. Analysis of The Cancer Genome Atlas (TCGA) for all cancer in EA and AA found genetic signatures associated with noted disparities, such as somatic copy number alterations, TP53 mutations, CCNE1 amplification, and overexpression of genes correlated with chromosomal instability. To inform whether epigenetic and transcriptomic factors could be driving the disparities seen in squamous cell carcinoma (SCC) of the upper aerodigestive tract (UADT) and lung, we sought to analyze genomic data to identify differentially methylated and expressed genes between EA and AA patients and determine whether these affected survival. Methods: TCGA was queried to extract data from self-identified EA and AA patients with head and neck, esophageal, and lung SCC. Literature suggests that SCC tumors share genetic and epigenetic signatures and can be analyzed as a group. Human papillomavirus positive patients were excluded. Patients were separated into EA and AA groups matched for age, stage, and smoking to account for clinical biases of biological analysis. DNA methylation (Epic array) and gene expression (RNA-Seq) profiles were compared between tumor tissue samples in EA patients, tumors in AA patients, and normal tissue. The genes that were identified to be differentially methylated were then analyzed to compare overall survival between hypomethylation and hypermethylation of each identified gene, with and without subgrouping by race. Differentially expressed genes were similarly analyzed between high and low expression. Overall survival was estimated by the Kaplan-Meier method and compared using the log-rank test. Results: A comparison of DNA methylation profiles found 79 genes that were differentially methylated when comparing EA tumor, AA tumor, and normal tissue samples. Survival analysis was performed on top 21 of the differentially methylated genes. Of these, 9 were found to have significant differences in overall survival when stratifying by race and methylation status. Differentially methylated genes included MAD1L1 (Mitotic Arrest Deficient 1 Like 1), which is known for its role in the spindle assembly checkpoint in mitosis and tumor suppression. Similar analysis revealed 404 genes that were differentially expressed comparing EA tumor, AA tumor, and normal tissue. Candidate genes based on expression level will be discussed. Conclusions: Differential DNA methylation and gene expression were noted between EA and AA groups with lung and UADT SCC. This difference may contribute to the disparity in overall survival seen between these groups that persists even when controlling for variables commonly associated with worse survival.

To study HPV and EBV in squamous cell carcinoma of upper aerodigestive tract by immunohistochemistry markers

Squamous cell carcinoma (SCC) in upper aerodigestive tract (UADT) is one of the predominant causes of mortality and morbidity in a developing nation like India. The major risk factors being tobacco usage and alcohol. Besides these there are certain viruses like high-risk Human Papilloma Virus (HPV) and Epstein Bar Virus (EBV). Which have a potential role in the etiology of SCC. More over these HPV positive tumors have better prognosis compared to HPV negative ones due their radiosensitivity. There are several methods employed in identification of these viruses of which IHC is cost effective, reliable with high sensitivity and specificity.In the present study, we identified 30 cases of SCC in UADT sent to Pathology department. Expression of p16 for HPV and LMP1 for EBV was performed on the tissue blocks manually.p16 was positive in around 17% (5/30 cases) whereas LMP1 showed 0% (0/30 cases) positivity. Majority of patients with p16 positivity in SCC of UADT are in the older age (above 50 years), showed moderately differentiated (Grade II) SCC, had nodal metastasis at the time of presentation. Some studies showed the association of HPV of SCC in UADT in younger population have better prognosis compared to HPV negative ones. In the current study HPV was identified (17%) in older population (above 55 years) and none of the cases showed positivity for LMP1(EBV).

A descriptive study of human papilloma virus in upper aero-digestive squamous cell carcinoma at Uganda cancer institute assessed by P16 immunohistochemistry

BackgroundCancer burden in sub-Saharan Africa is on the rise with one-third of cancers estimated to be caused by infectious agents. Head and neck squamous cell cancer (HNSCC) is the sixth most common malignancy in sub-Saharan Africa and includes tumors in the Upper Aero-digestive Tract (UADT). The established risk factors are tobacco and alcohol exposure with a recent recognition of the role of Human Papilloma Virus (HPV). The HPV related HNC is seen predominantly in the oropharynx, presents at a younger age and has a better prognosis. With a rapidly increasing incidence of these cancers in the developed world, it was important to study HPV in HNC in Uganda. The HPV can be detected using P16 immunohistochemistry as a surrogate marker thus making it suitable for screening. The study aimed at establishing the presence of HPV and the commonly affected sites in UADT squamous cell carcinoma (SCC) at Uganda Cancer Institute (UCI) using P16 immunohistochemistry.MethodologyThis was a cross sectional study in which 59 patients with histologically proven SCC from the oral cavity, oropharynx, larynx and hypopharynx were recruited. These patients’ demographics and clinical data were collected. Tissue sections from retrieved histology samples were stained by Haematoxylin and Eosin to reconfirm SCC. Subsequently, P16 expression was determined using P16 immunohistochemistry.ResultsSeventy-one patients were enrolled and 59 patients with confirmed SCC of the sites of interest were analyzed. The majority (79.7%) of the participants were male and over 50 years. 59.3% were tobacco smokers, 66.1% used alcohol, 52.2% used both. Only 27.1% used none of the substances. Only 27.1% of the participants were HIV positive. Most of the tumors were in the larynx (37.3%) and 64.4% were overall TNM stage 4. The overall prevalence of HPV in UADT SCC at UCI was 20.3, 95%CI 10.9–32.8. The oropharynx had the highest prevalence (30.8%).ConclusionThe prevalence of HPV in UADT SCC at UCI is significant at 20.3%. The most affected site, is the oropharynx. Vigilant HPV screening of these sites with confirmation where possible is recommended.

Comparison of Efficacy of Positron Emission Tomography/Computed Tomography with Contrast-Enhanced Computed Tomography in Pretreatment Evaluation of Head and Neck Cancers: An Institutional Experience

Abstract Introduction: Head and neck squamous cell carcinomas (SCCs) constitute 5.4% of all cancers worldwide, and 23% of all cancers in males and 6% of all cancers in females diagnosed in India. Lots of ambiguity exists in primary, nodal, and metastatic workup of these patients, especially in developing countries. Aim: The study was designed to compare the accuracy of whole-body positron emission tomography/computed tomography (WBPET/CT) scan with contrast-enhanced CT (CECT) face and neck as pretreatment evaluation for staging workup and management decision and to confirm the nodal findings on imaging with fine-needle aspiration cytology (FNAC). Design: It was a single-institute, prospective, observational, interventional study over a 2-year period. All cases of SCC of upper aerodigestive tract who were scheduled for definitive treatment concurrent chemoradiotherapy or radiotherapy were evaluated with routine investigations followed by imaging in the form of CECT face and neck and 18F-fluorodeoxyglucose (FDG) WBPET/CT. Results: In the 40 enrolled patients, all underwent CECT face and neck and WBPET/CT. During initial workup, biopsy was taken from primary site and FNAC was done from neck nodes for diagnosis and for staging. In 40 patients, CECT neck showed nodal metastasis in 39 patients; however, FNAC came positive in 38 cases. PET/CT showed nodal metastasis in 38 patients; however, FNAC came positive in 38 cases. Any node with Standardized uptake value (SUV) >2.5 was taken as suspicious lesion and FNAC was done. Sensitivity of CECT and PET/CT was 97.36% and 100%, respectively, while the specificity was 0% and 100%, respectively. Positive predictive value calculated for CECT and WBPET was 94.87% and 100%, respectively, while the negative predictive value for CECT and WBPET was 0% and 100%, respectively. Conclusion: In head and neck SCC, FDG-PET/CT is more accurate than CECT in staging of the neck.

Prognostic biomarkers of human papilloma virus (HPV)-positive neoplasia of the upper aerodigestive tract: a systematic review

Background: HPV-positivity in oropharyngeal cancer represents a distinct biological entity in terms of underlying genetics and clinical behaviour. Next-generation sequencing has enabled researchers to identify biomarkers associated with neoplasia that may aid in predicting tumour behaviour and offer potential treatment targets. This systematic review aims to evaluate the current known prognostic biomarkers of human papilloma virus (HPV)-positive upper aerodigestive tract (UADT) neoplasia. Methods: Data sources include Embase (1947–2015), Medline (1946–2015), Cochrane Central Register of Controlled Trials, Cochrane ENT Disorders Group Trials Register and mRCT. The above sources were searched on 19th December 2015 using a comprehensive strategy for studies evaluating clinical outcomes of known prognostic biomarkers of HPV-positive UADT. Articles were limited to English language and human subjects. All studies that provided original data on the clinical implications of biomarkers in HPV-positive neoplasia were included. Outcomes relating to malignant conversion, recurrence, regional and metastatic spread as well as response to treatment were evaluated. Results: The search returned 4,702 records with thirty-one case series included in the final qualitative synthesis. These encompassed studies evaluating overall survival (n=21), disease-specific survival (n=10), recurrence (n=23), response to treatment (n=2) and risk of metastasis (n=2) with some studies evaluating more than one outcome. Overexpression of p53 and EGFR were not found to be reliable indicators of prognosis with studies demonstrating mixed results. Conclusions: It is well established that HPV-positivity correlates with improved prognosis in most UADT squamous cell carcinoma (SCC). However, there are no reliable biomarkers that can predict which tumours may fall into the more aggressive subset in this group.

Second primary tumor in patients with upper aerodigestive tract cancer

SummaryIn the first three years after treatment of patients with squamous cell carcinoma of upper aerodigestive tract (UADT), there is a high incidence of recurrences. After the third year, the occurrence of second primary tumor (SPT) is an important cause of morbimortality.AimTo evaluate the incidence and the characteristics of the SPT in patients with squamous cell carcinoma of UADT, treated with curative intention.MethodsRetrospective study where the incidence, localization and treatment of SPT had been analyzed and survival rates were calculated.ResultsOf the 624 analyzed cases, 59 (9.4%) had SPT during follow-up (4 synchronous and 55 metachronous). The SPT free survival rate ranged from 2 to 191.3 months (median of 42.5 months). In 20 cases (33.9%) the SPT was diagnosed after the fifth year of follow-up. The most frequent site of STP was the UADT mucosa (49.1%), followed by the lungs (22.0%) and the esophagus (11.9%). The best survival after-SPT occurred in cases of UADT STP (32.2% in 5 years, median 16.2 months).ConclusionThe STP incidence was 9.4%. In 33.9% of the cases, the SPT was diagnosed after the fifth year of follow-up. The most frequent localization of STP was the UADT mucosa.

A rare truncating BRCA2 variant and genetic susceptibility to upper aerodigestive tract cancer.

Deleterious BRCA2 genetic variants markedly increase risk of developing breast cancer. A rare truncating BRCA2 genetic variant, rs11571833 (K3326X), has been associated with a 2.5-fold risk of lung squamous cell carcinoma but only a modest 26% increase in breast cancer risk. We analyzed the association between BRCA2 SNP rs11571833 and upper aerodigestive tract (UADT) cancer risk with multivariable unconditional logistic regression adjusted by sex and combinations of study and country for 5942 UADT squamous cell carcinoma case patients and 8086 control patients from nine different studies. All statistical tests were two-sided. rs11571833 was associated with UADT cancers (odds ratio = 2.53, 95% confidence interval = 1.89 to 3.38, P = 3x10-10) and was present in European, Latin American, and Indian populations but extremely rare in Japanese populations. The association appeared more apparent in smokers (current or former) compared with never smokers (P het = .026). A robust association between a truncating BRCA2 variant and UADT cancer risk suggests that treatment strategies orientated towards BRCA2 mutations may warrant further investigation in UADT tumors.

Tobacco smoking, NBS1 polymorphisms, and survival in lung and upper aerodigestive tract cancers with semi-Bayes adjustment for hazard ratio variation

Although single nucleotide polymorphisms (SNPs) of NBS1 have been associated with susceptibility to lung and upper aerodigestive tract (UADT) cancers, their relations to cancer survival and measures of effect are largely unknown. Using follow-up data from 611 lung cancer cases and 601 UADT cancer cases from a population-based case-control study in Los Angeles, we prospectively evaluated associations of tobacco smoking and 5 NBS1 SNPs with all-cause mortality. Mortality data were obtained from the Social Security Death Index. We used Cox regression to estimate adjusted hazard ratios (HR) for main effects and ratios of hazard ratios (RHR) derived from product terms to assess hazard ratio variations by each SNP. Bayesian methods were used to account for multiple comparisons. We observed 406 (66%) deaths in lung cancer cases and 247 (41%) deaths in UADT cancer cases with median survival of 1.43 and 1.72years, respectively. Ever tobacco smoking was positively associated with mortality for both cancers. We observed an upward dose-response association between smoking pack-years and mortality in UADT squamous cell carcinoma. The adjusted HR relating smoking to mortality in non-small cell lung cancer (NSCLC) was greater for cases with the GG genotype of NBS1 rs1061302 than for cases with AA/AG genotypes (semi-Bayes adjusted RHR=1.97; 95% limits=1.14, 3.41). A history of tobacco smoking at cancer diagnosis was associated with mortality among patients with lung cancer or UADT squamous cell carcinoma. The HR relating smoking to mortality appeared to vary with the NBS1 rs1061302 genotype among NSCLC cases.

Human papillomavirus‐related head and neck squamous cell carcinoma

Human papillomavirus‐related head and neck squamous cell carcinoma

Smoking addiction and the risk of upper-aerodigestive-tract cancer in a multicenter case-control study

Although previous studies on tobacco and alcohol and the risk of upper-aerodigestive-tract (UADT) cancers have clearly shown dose-response relations with the frequency and duration of tobacco and alcohol, studies on addiction to tobacco smoking itself as a risk factor for UADT cancer have not been published, to our knowledge. The aim of this report is to assess whether smoking addiction is an independent risk factor or a refinement to smoking variables (intensity and duration) for UADT squamous cell carcinoma (SCC) risk in the multicenter case-control study (ARCAGE) in Western Europe. The analyses included 1,586 ever smoking UADT SCC cases and 1,260 ever smoking controls. Addiction was measured by a modified Fagerström score (first cigarette after waking up, difficulty refraining from smoking in places where it is forbidden and cigarettes per day). Adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) for UADT cancers with addiction variables were estimated with unconditional logistic regression. Among current smokers, the participants who smoked their first cigarette within 5 min of waking up were two times more likely to develop UADT SCC than those who smoked 60 min after waking up. Greater tobacco smoking addiction was associated with an increased risk of UADT SCC among current smokers (OR = 3.83, 95% CI: 2.56-5.73 for score of 3-7 vs. 0) but not among former smokers. These results may be consistent with a residual effect of smoking that was not captured by the questionnaire responses (smoking intensity and smoking duration) alone, suggesting addiction a refinement to smoking variables.

Meat and Heme Iron Intake and Risk of Squamous Cell Carcinoma of the Upper Aero-Digestive Tract in the European Prospective Investigation into Cancer and Nutrition (EPIC)

Evidence from prospective studies on intake of meat and fish and risk of squamous cell carcinoma (SCC) of the upper aero-digestive tract (UADT) is scarce. We prospectively investigated the association of meat and fish intake with risk of SCC of the UADT and the possible mechanism via heme iron in the large multicenter European Prospective Investigation into Cancer and Nutrition (EPIC) study. Multivariable proportional hazards models were used to estimate relative risks (RR) of SCC of the UADT in relation to intake of total meat, as well as subtypes of meat, fish, and heme iron among 348,738 individuals from 7 European countries. During an average follow-up of 11.8 years, a total of 682 incident cases of UADT SCC were accrued. Intake of processed meat was positively associated with risk of SCC of the UADT in the total cohort [highest vs. lowest quintile: RR = 1.41; 95% confidence interval (CI) = 1.03-1.94], however, in stratified analyses, this association was confined to the group of current smokers (highest vs. lowest quintile: RR = 1.89; 95% CI = 1.22-2.93). Red meat, poultry, fish, and heme iron were not consistently related to UADT SCC. Higher intake of processed meat was positively associated with SCC of the UADT among smokers. Although this finding was stable in various sensitivity analyses, we cannot rule out residual confounding by smoking. Confirmation in future studies and identification of biologic mechanisms is warranted. Smokers may further increase their risk for SCC of the UADT if they additionally consume large amounts of processed meat.

The use of tobacco-free betel-quid in conjunction with alcohol/tobacco impacts early-onset age and carcinoma distribution for upper aerodigestive tract cancer

Recognition of how risk factors affect the age when cancers are first diagnosed may help to establish more appropriate cancer screening and preventive strategies. To investigate the independent and synergistic effects of alcohol, tobacco-free betel-quid (TF-BQ), and cigarette use on diagnosis age and dissemination of upper aerodigestive tract squamous cell carcinoma (UADT-SCC), we recruited pathology-proven 1522 patients with UADT-SCC for study. A 49-, 53-, 57-, and 62-year-old stepwise older median age at carcinoma diagnosis was, respectively, found among patients with oral, pharyngeal, esophageal, and laryngeal cancer. Oral cavity (53.2%) and larynx (11.6%) were separately the dominant and recessive sites where the UADT-SCC occurred. Although alcohol and tobacco bestowed increased risks of earlier tumor occurrence only for oral/pharyngeal and oral cancers, respectively, TF-BQ was consistently observed to confer elevated age-associated risks for each UADT-SCC [adjusted hazard ratio (aHR) = 1.6-2.3]. Alcohol and TF-BQ joint consumers experienced a stepwise increased cumulative risk (CR) of contracting carcinomas of the larynx (46.2%), esophagus (47.5%), pharynx (53.5%), and oral cavity (60.5-71.0%), with >68% of CRs found among drinkers who started chewing before age 20. Alcohol + Betel + Cigarette and Alcohol + Betel users exhibited earlier diagnosis ages than non-users: 10 years ahead for oral cancer, 7, 17, and 12 years earlier for pharyngeal, esophageal, and laryngeal cancers. Noticeably, higher cumulative cancer risks regarding earlier tumor occurrence were correspondingly identified for these users aged 43, 49, 43, and 44 upward. Tobacco-free betel-quid, in conjunction with alcohol and/or tobacco consumption, impacts early cancer occurrence for specific UADT-SCC and influences tumor site incidence pattern of these neoplasms.

Cetuximab concomitant with gemcitabine and radiotherapy in advanced squamous cell carcinomas of upper aerodigestive tract: a pilot study

To explore the response and toxicity of advanced non-metastatic squamous cell carcinomas of upper aerodigestive tract (SCC-UADT) to a combination of cetuximab concomitant with gemcitabine and radiotherapy. We managed patients with concomitant treatment of cetuximab (400 mg/m(2) as uploading dose, then 250 mg/m(2), IV) concomitant with gemcitabine (50 mg/m(2)) weekly for seven courses, and radiotherapy in classical fractionation until completion of 70 Gy. Primary endpoints were complete response (CR) to treatment and toxicity. We evaluated patients for toxicity on a weekly basis; evaluation of response included physical examination, endoscopy, computed tomography (CT) scan and biopsy when indicated, and was performed 6 weeks after completion of radiotherapy. Additional evaluations were done every 3 months to document disease status. Between November 2004 and November 2005, 20 patients were included. CR was 82.4%, overall response was 100%. Neck disease reached CR in 61.5% and partial in 38.5% of patients. The main toxicities were nausea, lymphopenia, neutropenia and mucositis. Grade 3 and 4 side effects were presented in 70.6% of patients, but mucositis, and lymphopenia without clinical repercussions, occurred in 88.2% of patients. Gastrostomy was required in 11.8% of patients to maintain nutrition. Radioepithelitis developed in 76.5%, but only three of these (23.1%) were grade III. Median overall survival was 53 months (range 6-55 months) and median progression-free survival has not yet been reached at the time of evaluation. Although toxicity is important, this approach has interesting activity and deserves further investigation.

Active and Involuntary Tobacco Smoking and Upper Aerodigestive Tract Cancer Risks in a Multicenter Case-Control Study

Several important issues for the established association between tobacco smoking and upper aerodigestive tract (UADT) cancer risks include the associations with smoking by cancer subsite, by type of tobacco, and among never alcohol drinkers and the associations with involuntary smoking among nonsmokers. Our aim was to examine these specific issues in a large-scale case-control study in Europe. Analysis was done on 2,103 UADT squamous cell carcinoma cases and 2,221 controls in the Alcohol-Related Cancers and Genetic Susceptibility in Europe project, a multicenter case-control study in 10 European countries. Unconditional logistic regression was done to obtain odds ratios (OR) and 95% confidence intervals (95% CI). Compared with never tobacco smoking, current smoking was associated with UADT cancer risks (OR, 6.72; 95% CI, 5.45-8.30 for overall; OR, 5.83; 95% CI, 4.50-7.54 for oral cavity and oropharynx; OR, 12.19; 95% CI, 8.29-17.92 for hypopharynx and larynx; and OR, 4.17; 95% CI, 2.45-7.10 for esophagus). Among never drinkers, dose-response relationships with tobacco smoking pack-years were observed for hypopharyngeal and laryngeal cancers (P(trend) = 0.010) but not for oral cavity and oropharyngeal cancers (P(trend) = 0.282). Among never smokers, ever exposure to involuntary smoking was associated with an increased risk of UADT cancers (OR, 1.60; 95% CI, 1.04-2.46). Our results corroborate that tobacco smoking may play a stronger role in the development of hypopharyngeal and laryngeal cancers than that of oral cavity and oropharyngeal cancers among never drinkers and that involuntary smoking is an important risk factor for UADT cancers. Public health interventions to reduce involuntary smoking exposure could help reduce UADT cancer incidence.

Carcinomes épidermoïdes simultanés de la cavité buccale et de l'oropharynx

Squamous cell carcinoma of the oral cavity is often a single localization, but the discovery of another or several associated lesions is not exceptional. The goal of our study was a retrospective analysis of patients having 2 simultaneous squamous cell carcinomas of the upper aerodigestive tract (UADT), i.e. diagnosed during the same panendoscopy by excluding the esophagus and the lung. Between 1995 and 2001, 1,129 patients were treated for squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, and larynx in the Bordeaux Maxillo-facial Surgery Unit. 1% of these patients presented 2 simultaneous squamous cell carcinomas of UADT. Our series was divided in 9 men (75%) and 3 women (25%) with an average age of 61.3 years (48-86). At the end of the study 2 patients were lost to follow-up, 3 patients were alive without recurrence, and 1 patient was alive with recurrence. The average follow-up time was 17.6 months. A review of the literature gave an incidence of simultaneous squamous cell carcinomas of UADT varying from 1.3 to 12.8% according to authors. Thus, any patient having squamous cell carcinoma of the UADT must be considered as having an important potential risk to present another simultaneous cancer and to benefit from a systematic panendoscopy. In spite of an early diagnosis, the prognostic of these lesions remains bad.

P166 Histopathological Analysis of Cystic Metastasis in Head and Neck Squamous Cell Carcinoma

Objective: Branchiogenic carcinoma is a controversial entity. Some authors believe that the reported cases reflect cystic degeneration of metastatic lymph nodes rather than a primary tumor arising from cyst epithelium. In a previous study, we found evidence of normal epithelium within malignant cysts in 2 cases of possible branchiogenic carcinoma. In contrast, in the setting of a known primary tumor where cystic metastases are present, there is histologically highly dysplastic epithelium lining these degenerative cysts. Our goal was to analyze lymph nodes from patients with head and neck squamous cell carcinoma (SCC), with a documented primary focus, for the presence of normal epithelium within lymph nodes taken during neck dissection. Design: Histologic review of neck dissection specimen slides for evidence of normal epithelium. Patients: Thirty-five patients with known upper aerodigestive tract (UADT) SCC. Interventions: Histopathologic slides from neck dissection specimens were reviewed for histologic evidence of normal squamous epithelium– or epithelial-lined cysts. Results: Fifty neck dissection specimens with 902 lymph nodes were evaluated. Ninety-six nodes were positive for metastatic disease; 15% had evidence of cystic degeneration. None of the lymph nodes evaluated had any evidence of normal epithelium. Conclusions: Cystic degeneration is a frequent phenomenon in metastatic lymph nodes in patients with UADT SCC, but in our study we found no evidence of normal epithelium in any of these cysts. Hence when combined with Martin’s other 3 criteria, the presence of SCC in a normal epithelium–lined cyst is suggestive of branchiogenic carcinoma.

P168 Parathyroidectomy in Patients With Primary Hyperparathyroidism and Negative Findings on Technetium Tc 99m Sestamibi Localization Scan

Objective: Branchiogenic carcinoma is a controversial entity. Some authors believe that the reported cases reflect cystic degeneration of metastatic lymph nodes rather than a primary tumor arising from cyst epithelium. In a previous study, we found evidence of normal epithelium within malignant cysts in 2 cases of possible branchiogenic carcinoma. In contrast, in the setting of a known primary tumor where cystic metastases are present, there is histologically highly dysplastic epithelium lining these degenerative cysts. Our goal was to analyze lymph nodes from patients with head and neck squamous cell carcinoma (SCC), with a documented primary focus, for the presence of normal epithelium within lymph nodes taken during neck dissection. Design: Histologic review of neck dissection specimen slides for evidence of normal epithelium. Patients: Thirty-five patients with known upper aerodigestive tract (UADT) SCC. Interventions: Histopathologic slides from neck dissection specimens were reviewed for histologic evidence of normal squamous epithelium– or epithelial-lined cysts. Results: Fifty neck dissection specimens with 902 lymph nodes were evaluated. Ninety-six nodes were positive for metastatic disease; 15% had evidence of cystic degeneration. None of the lymph nodes evaluated had any evidence of normal epithelium. Conclusions: Cystic degeneration is a frequent phenomenon in metastatic lymph nodes in patients with UADT SCC, but in our study we found no evidence of normal epithelium in any of these cysts. Hence when combined with Martin’s other 3 criteria, the presence of SCC in a normal epithelium–lined cyst is suggestive of branchiogenic carcinoma.

Widespread subcutaneous distant metastases from a head and neck squamous cell carcinoma

During the past 30 years, the incidence of squamous cell carcinoma (SCC) arising in the upper aerodigestive tract has generally increased worldwide.1 The development of SCC within the head and neck (HN) results from a series of genetic transformations producing a malignant phenotype.2 The essential nature of this malignant phenotype is its ability to act autonomously, initially invading local tissues and subsequently being capable of metastasizing to regional and distant sites. The cervical lymph nodes are the most common sites for regional metastases of oral and oropharyngeal SCC.3 The distribution of regional nodal deposits of metastatic SCC from various mucosal primary sites within the HN has been well documented in the literature.4,5 Distant metastases from primary cancers of the HN occur most commonly in the lungs, liver, and bone (Table 1). Other less common sites have been reported in the literature (Table 2). Historically the incidence of distant metastases (DMs) among patients with HN cancer has been very low. However, as local and regional control has improved, DMs may be seen as an increasingly important source of morbidity and mortality. There is a paucity of antemortem case reports of DM in the literature and none documenting subcutaneous deposits below the clavicles. In view of this, we report an unusual presentation of DM relating to widespread subcutaneous metastatic deposits. We also review the literature related to the presentation of DM arising from upper aerodigestive tract SCC.

MUC4 (sialomucin complex) expression in salivary gland tumors and squamous cell carcinoma of the upper aerodigestive tract

Objectives: This study investigates MUC4 expression in normal squamous epithelia and squamous cell carcinoma (SCC) of the upper aerodigestive tract (UADT), and in salivary gland neoplasms. Study design: MUC4 antigens in tumor and adjacent normal tissue are localized by immunocytochemical studies. Fresh frozen tissues from surgical resection specimens are further analyzed by Western blot. Results: MUC4 is identified by immunocytochemical staining throughout the normal UADT mucosa, in 34 of 40 primary UADT SCC, and in 11 of 12 metastatic cervical lymph nodes. A trend toward decreased MUC4 staining in moderately and poorly differentiated tumors is noted. Immunoblots show MUC4 in 4 of 5 SCC analyzed. Immunocytochemical staining of MUC4 in 13 major and minor salivary gland neoplasms reveal variable staining of normal and neoplastic tissue. MUC4 is demonstrated in immunoblots of normal parotid tissue and in the single parotid malignancy analyzed, but is not demonstrated in one minor salivary gland malignancy. These findings characterize normal UADT mucosal and salivary MUC4 expression, and MUC4 expression in SCC of the UADT and in salivary gland tumors. Significance: Correlation of MUC4 expression with clinical outcomes may establish MUC4 as a potential molecular prognostic marker for these tumors. (Otolaryngol Head Neck Surg 2001;124:127-41.)

Human papillomavirus and prognoses of patients with cancers of the upper aerodigestive tract.

Some studies have shown that human papillomavirus (HPV) infection may play not only an etiologic role in anogenital cancers but also a role in the clinical outcome. The objective of the current study was to determine whether detection of HPV DNA in primary squamous cell carcinomas of the upper aerodigestive tract (UADT) is a prognostic factor in patients with the disease. The authors analyzed archival specimens of UADT tumors from 101 randomly selected patients with evaluable samples for HPV DNA detection. HPV testing was performed using a general primer-mediated polymerase chain reaction. The overall detection rate was 16.8% (17 of 101 specimens). HPV DNA was detected at higher rates in specimens from younger patients and in well-differentiated tumors. Pharyngeal tumors were more likely to be HPV positive (30.0%) than buccal (10.3%) or laryngeal tumors (15.4%), but the differences were not significant. The detection rate was similar for T1-T2 tumors (17.4%) and T3-T4 tumors (15.6%). However, tumors without lymph node metastasis were more likely to be HPV positive (21.4%) than tumors with lymph node involvement (6.5%). Kaplan-Meier and Cox regression survival analyses did not show any difference in overall or disease free survival according to HPV detection. Although the HPV DNA detection rate was slightly higher in local than in regionally spread tumors, our results support the hypothesis that it is very unlikely that HPV detection plays any role in the prognoses of patients with UADT squamous cell carcinoma.