Gingival squamous cell carcinoma mimicking periodontal disease.

Gingival squamous cell carcinoma (GSCC) is relatively rare, representing less than 10% of oral cavity squamous cell carcinomas. Because of its proximity to the teeth and periodontium, the tumor can mimic tooth-related benign inflammatory conditions. In this article, a case of GSCC with clinical features very similar to those of periodontal disease in an 86-year-old nonsmoking woman is presented. Consequently, clinicians should be aware of this pathology to play an important role in the early detection of gingival cancer.

Preservation of the internal jugular vein in the radical treatment of node-positive neck--is it safe?

BACKGROUND: The aim of this study was to evaluate risk factors of neck recurrence in patients with pN+ necks submitted to a modified or a classic radical neck dissection and the safety of preserving the internal jugular vein in the treatment of a subgroup of these patients. METHODS: The medical records of 311 untreated patients with squamous cell carcinoma of the oral cavity (106 cases), oropharynx (95 cases), larynx (49 cases), and hypopharynx (61 cases) were reviewed. Their clinical stages (CS) were CS II in 1%, CS III in 19.9%, CS IVA in 76.2%, and CS IVB in 19.6% of the cases. All patients were pN+. RESULTS: Ipsilateral neck recurrence occurred in 18 cases (5.8%), 14 cases (4.5%) where the internal jugular vein was resected, and 4 cases (1.3%) where the internal jugular vein was preserved. Neck recurrence did not have significant correlation with tumor site (P = .852), T stage (P = .369), N stage (P = .963), adjuvant radiotherapy (P = .701), number of positive lymph nodes (P = .886), jugular vein preservation (P = .240), and extracapsular spread (P = .670). There was significant correlation between neck recurrence and the lymph node size (.040). CONCLUSIONS: Modified radical neck dissection with internal jugular vein preservation can be performed in selected patients with lymph node metastases, with no significant increase in the risk of neck recurrence.

Giant pleomorphic adenoma of the parotid gland.

Pleomorphic adenoma is the most common type of all benign and malignant salivary gland tumors, involving more frequently the parotid gland. It is a benign tumor with a slow and continuous growth that without treatment can reach an enormous size. We present a case of a giant pleomorphic adenoma in a 78-year-old man with a history of more than 30 years of a growing lesion in the parotid gland. Clinical examination revealed a giant mass on the right side of the face, however without any sign of facial nerve damage. The tumor was completely resected by total parotidectomy and preservation of the facial nerve. Macroscopically, the tumor measured 28 cm and weighed 4.0 Kg. On the histological examination there was a predominance of epithelial and myoepithelial cells in a hyaline and myxoid stroma. It was not found any area of malignant transformation. In the post-operatory the aesthetic and functional results were excellent.

Multiple cutaneous metastases from a parotid adenoid cystic carcinoma.

Cutaneous metastasis from salivary gland adenoid cystic carcinoma is extremely rare. We report a case of a 39-year-old man that presented multiple cutaneous metastases from a parotid salivary gland adenoid cystic carcinoma. The clinical, histopathological and immunohistochemical features are described and discussed. This case shows the importance of a detailed and periodical skin examination in patients treated for salivary gland adenoid cystic carcinoma.

Factors that influence treatment decision in older patients with resectable head and neck cancer.

OBJECTIVES: To find clinical factors related to administration of substandard treatment in older patients with head and neck cancer. STUDY DESIGN: Historic cohort. METHODS: Patients of 70 years of age of older with diagnosis of resectable head and neck cancer were included. Treatment offered to patients was classified as standard or substandard by experienced surgeons. Relation of age, clinical stage, comorbidities, performance status, and treatment with substandard treatment was explored. The effect of substandard treatment on survival was assessed. RESULTS: Three hundred twelve patients were included. Substandard treatment was offered to 19.9% of patients. Associated factors related to selection of substandard treatment were higher age, oro/hypopharynx tumor site, severe comorbidity, advanced clinical stage, and low Karnofsky Index. Patients submitted to substandard treatment had lower overall and cancer-specific survival (45.9% vs. 19.9% and 63.0% vs. 33.1%, respectively). CONCLUSION: Selection of substandard treatment decreases overall and cancer-specific survival. Selecting substandard treatment for reasons such as chronologic age, tumor site, or moderate or mild comorbidities worsen patient prognosis.

Shorter CAG repeat length in the AR gene is associated with poor outcome in head and neck cancer.

OBJECTIVE: Alterations in the size of the [CAG](n) repeats of the AR gene have been described in several types tumors. The purpose of this study was to evaluate if there is an association between the AR [CAG](n) repeat alleles and the relative risk for head and neck cancer and to analyse microsatellite instability (MSI) and loss of heterozygosity (LOH) in these tumors. DESIGN: Matched samples of blood and head and neck tumors were evaluated using two methodologies, silver-stained gels to perform the analyses of MSI and LOH, and automated analysis to confirm these results and for genotyping of the AR [CAG](n) repeat length. Sixty-nine individuals without cancer were used as a control group for both procedures. The Log-rank test was used to compare overall survival and disease-free survival curves. The Cox proportional hazards regression models were performed to determine the [CAG](n) repeats as an independent prognostic factor. RESULTS: Patients with alleles

H19-DMR allele-specific methylation analysis reveals epigenetic heterogeneity of CTCF binding site 6 but not of site 5 in head-and-neck carcinomas: a pilot case-control analysis.

Aberrant methylation of seven potential binding sites of the CTCF factor in the differentially methylated region upstream of the H19 gene (H19-DMR) has been suggested as critical for the regulation of IGF2 and H19 imprinted genes. In this study, we analyzed the allele-specific methylation pattern of CTCF binding sites 5 and 6 using methylation-sensitive restriction enzyme PCR followed by RFLP analysis in matched tumoral and lymphocyte DNA from head-and-neck squamous cell carcinoma (HNSCC) patients, as well as in lymphocyte DNA from control individuals who were cancer-free. The monoallelic methylation pattern was maintained in CTCF binding site 5 in 22 heterozygous out of 91 samples analyzed. Nevertheless, a biallelic methylation pattern was detected in CTCF binding site 6 in a subgroup of HNSCC patients as a somatic acquired feature of tumor cells. An atypical biallelic methylation was also observed in both tumor and lymphocyte DNA from two patients, and at a high frequency in the control group (29 out of 64 informative controls). Additionally, we found that the C/T transition detected by HhaI RFLP suppressed one dinucleotide CpG in critical CTCF binding site 6, of a mutation showing polymorphic frequencies. Although a heterogeneous methylation pattern was observed after DNA sequencing modified by sodium bisulfite, the biallelic methylation pattern was confirmed in 9 out of 10 HNSCCs. These findings are likely to be relevant in the epigenetic regulation of the DMR, especially in pathological conditions in which the imprinting of IGF2 and H19 genes is disrupted.

Classic and molecular cytogenetic analyses reveal chromosomal gains and losses correlated with survival in head and neck cancer patients.

PURPOSE: Genetic biomarkers of head and neck tumors could be useful for distinguishing among patients with similar clinical and histopathologic characteristics but having differential probabilities of survival. The purpose of this study was to investigate chromosomal alterations in head and neck carcinomas and to correlate the results with clinical and epidemiologic variables. EXPERIMENTAL DESIGN: Cytogenetic analysis of short-term cultures from 64 primary untreated head and neck squamous cell carcinomas was used to determine the overall pattern of chromosome aberrations. A representative subset of tumors was analyzed in detail by spectral karyotyping and/or confirmatory fluorescence in situ hybridization analysis. RESULTS: Recurrent losses of chromosomes Y (26 cases) and 19 (14 cases), and gains of chromosomes 22 (23 cases), 8 and 20 (11 cases each) were observed. The most frequent structural aberration was del(22)(q13.1) followed by rearrangements involving 6q and 12p. The presence of specific cytogenetic aberrations was found to correlate significantly with an unfavorable outcome. There was a significant association between survival and gains in chromosomes 10 (P = 0.008) and 20 (P = 0.002) and losses of chromosomes 15 (P = 0.005) and 22 (P = 0.021). Univariate analysis indicated that acquisition of monosomy 17 was a significant (P = 0.0012) factor for patients with a previous family history of cancer. CONCLUSIONS: The significant associations found in this study emphasize that alterations of distinct regions of the genome may be genetic biomarkers for a poor prognosis. Losses of chromosomes 17 and 22 can be associated with a family history of cancer.

Predictive factors for distant metastasis from oral and oropharyngeal squamous cell carcinoma.

The presence of distant metastasis after the initial treatment of head and neck squamous cell carcinoma is not considered a common event and is associated with a poor outcome. The objective of this study was to investigate the prevalence and risk factors associated with the diagnosis of distant metastasis in oral and oropharyngeal carcinoma patients. The medical charts of 2327 patients treated from 1954 to 1997 were reviewed. They were 1703 patients (73.2%) with oral cavity and 624 (26.8%), oropharyngeal tumours. Regarding the primary treatment: 637 patients (27.4%) underwent surgery alone; 1147 (49.3%), radiotherapy alone and 543 (23.3%), combined treatment (surgery and radiotherapy). During the follow-up period after the initial treatment, 89 patients (3.8%) were diagnosed with distant metastasis. The variables associated with the distant metastasis-free survival were: tumour site (p=0.008); T stage (p<0.001); N stage (p<0.001); treatment performed (p<0.001) and decade of admission at the institution (p<0.001). The multivariate analysis (Cox regression) showed that the clinical stage (p=0.007); treatment performed (p=0.012) and decade of admission at the institution (p=0.004) were independent predictive factors for distant metastasis. Distant metastasis has been diagnosed more frequently in the latter decade and the significant predictors associated with its presence were the advanced clinical stage and patients who had undergone combined treatment.

Trends of oral and oropharyngeal cancer survival over five decades in 3267 patients treated in a single institution.

The objective of this study was to analyze the influence of changes in the treatment on the prognosis of patients treated over 44 years in a single institution. The 5-decade trends in treatment approach and 5-year survival of 3267 patients treated between 1953 and 1997 were analyzed. An increase was observed in primary surgical treatment and its association with radiotherapy. In the 1950s, 29.1% of the patients were treated by surgery, 54.5% by radiotherapy and 16.4% by combined treatment; in the 1990s, these proportions were 39.7, 9.7 and 50.6%, respectively (P<0.001). There was a significant increase in the 5-year survival rates from 28.7% for patients treated in the 1950s to 43.2% in the 1990s (P<0.001). The changes in treatment approach for oral and oropharyngeal cancer over the last 5 decades, with an increase of surgical treatment and its combination with radiotherapy significantly improved the survival rates.

Predictive factors and distribution of lymph node metastasis in lip cancer patients and their implications on the treatment of the neck.

The frequency of neck metastasis in lip cancer patients is low, however if present, it decreases survival rates, which reinforce the neck treatment as an important step in the management of these patients. This study evaluates the predictive factors, the distribution of lymph node metastasis and their implications on the neck treatment. A retrospective analysis of lip cancer patients treated in our institution from 1969 to 1999 was performed. A total of 617 patients were analysed. One hundred and seven patients (17.3%) were submitted to a neck dissection. T3/T4 tumours and commissure involvement were significantly associated with the risk of neck metastasis (P<0.001 and P=0.004, respectively). No cases had levels IV and V involved with node metastasis, either clinically or pathologically. The results suggest that supraomohyoid neck dissection could be the option for the elective treatment in T3/T4 tumours and those with commissure involvement, and the therapeutic option for patients with clinically positive necks.

Postoperative complications after en bloc salvage surgery for head and neck cancer.

OBJECTIVE: To analyze the frequency of and risk factors for postoperative complications after en bloc salvage surgery for head and neck cancer. DESIGN: Retrospective cohort study. SETTING: Patients were evaluated from February 7, 1990, to November 17, 1999, in a tertiary cancer center hospital. PATIENTS: Consecutive sample of 124 patients from the hospital database. Only patients with recurrent head and neck squamous cell carcinoma undergoing en bloc salvage resection were eligible for the study. MAIN OUTCOME MEASURES: We analyzed the frequency of and risk factors for complications after salvage surgery. RESULTS: The tumor location was the lip in 6 patients, oral cavity in 55, oropharynx in 31, larynx in 24, and hypopharynx in 8. Previous treatment was surgery alone in 20 patients, radiotherapy alone in 68, surgery and radiotherapy in 21, and radiotherapy and chemotherapy in 14. An additional patient received chemotherapy alone before salvage surgery. The clinical stage of the recurrent tumor was I or II in 23 patients and III or IV in 101 patients. Postoperative complications occurred in 66 patients (53.2%). Fifty-three patients (42.7%) had minor complications, and 23 patients (18.5%) had major ones. There were 4 postoperative deaths (3.2%). The major factor associated with the overall occurrence of postoperative complications was the clinical stage of the recurrent tumor (P =.02). The occurrence of minor complications correlated with the previously treated site, with complications occurring more often in patients undergoing locoregional vs local treatment (P =.04). Major complications were associated with the time between initial treatment and salvage surgery (P =.05). CONCLUSIONS: Salvage surgery can be performed with acceptable rates of postoperative complications. The clinical stage of the recurrent tumor and the previous site treated were the 2 major factors associated with the occurrence of postoperative complications.

Total glossectomy in the organ preservation era.

PURPOSE OF REVIEW: Total or subtotal glossectomy is considered a highly morbid procedure. However, in some institutions and in selected cases of unsuccessful chemoradiation regimens, it is performed with acceptable oncological and functional outcomes. RECENT FINDINGS: Chemoradiation for advanced oral and oropharyngeal cancers is also highly morbid and some authors reported reasonable functional results after major glossectomies. Also, there is a lack of prospective trials comparing the long-term outcome between chemoradiation and major glossectomies. SUMMARY: Total and/or subtotal glossectomies with immediate reconstruction can be performed in highly selected patients with advanced oral or base of the tongue carcinomas, as a primary or salvage procedure, with acceptable outcomes.

Validation of the Washington University Head and Neck Comorbidity Index in a cohort of older patients.

OBJECTIVES: To validate the prognostic ability of the Washington University Head and Neck Comorbidity Index (WUHNCI) relative to 5-year survival in a cohort of older patients with head and neck cancer and to compare it with that of the Adult Comorbidity Evaluation 27 (ACE-27). DESIGN: Validation study. SETTING: Academic research. PATIENTS: Three hundred twenty-one patients older than 70 years with head and neck cancer in a tertiary cancer center. Comorbidity was measured using the ACE-27, WUHNCI, and National Cancer Institute (NCI) comorbidity index. MAIN OUTCOME MEASURE: Five-year overall survival. RESULTS: Five-year overall and cancer-specific survival, respectively, were as follows: Using the WUHNCI, 52.2% and 62.9% for a score of 0; 25.1% and 41.7% for a score of 1; 39.3% and 64.9% for a score of 2; and 19.5% and 45.0% for a score of 3 or higher. Using the ACE-27, 54.4% and 61.7% for a score of 0 (no comorbidity); 46.8% and 61.7% for a score of 1 (mild comorbidity); 31.7% and 51.6% for a score of 2 (moderate comorbidity); and 13.8% and 43.7% for a score of 3 (severe comorbidity). The C statistics were 0.641 for the NCI comorbidity index, 0.656 for the ACE-27, and 0.686 for the WUHNCI. CONCLUSIONS: The WUHNCI did not demonstrate good discriminative power compared with the ACE-27 in a cohort of older patients. To be widely used, instruments developed to measure comorbidities must be reliable in any population. We believe that the ACE-27 is still the best index to assess comorbidities and that it should be used in studies evaluating the prognostic effect of comorbidities.

Predictive factors for complications in elderly patients who underwent head and neck oncologic surgery.

BACKGROUND: Postoperative complications are relevant outcomes in patients with head and neck tumor who have undergone surgery. Few trials have assessed predictive factors in older patients. We assessed the predictive effect of preoperative clinical factors on postoperative complications. METHODS: We conducted a cohort study with 242 patients older than 70 years with head and neck cancer who underwent surgery. Logistic regression identified predictive factors for postoperative complications. Significant variables were used to build a predictive index. RESULTS: Comorbidities were present in 87.6% of patients, and 56.6% had some type of complication (44.6% local and 28.5% systemic). Male sex, bilateral neck dissection, presence of 2 or more comorbidities, reconstruction, and clinical stage IV were associated with postoperative complications. The predictive index showed a receiver operating characteristics curve (ROC) area of 0.69. CONCLUSION: It is possible to predict postoperative complications in older patients with head and neck tumors who underwent oncologic surgery using clinical preoperative variables.

Internal jugular vein preservation in neck dissection for pN1-N2c oral and oropharyngeal carcinoma.

PURPOSE: The aim of this study is to evaluate risk factors of neck recurrence in patients with pN1-N2 neck stage, submitted to a modified radical neck dissection with preservation of the internal jugular vein. MATERIALS AND METHODS: We reviewed the medical records of 72 patients with squamous cell carcinoma of the oral cavity (43 cases) and oropharynx (29 cases). The clinical stage of the neck was N1 in 23 cases and N2a-c in 49. RESULTS: Neck recurrences occurred in 6 cases at the side in which the internal jugular vein was preserved. Neck recurrence did not have significant correlation with tumor site (P = .391), T stage (P = .999), N stage (P = .203), adjuvant radiotherapy (P = .999), number of positive lymph nodes (P = .180), lymph nodes size (P = .429), and extracapsular spread (P = .400). CONCLUSIONS: Modified radical neck dissection with internal jugular vein preservation can be performed in selected patients with lymph node metastases, with no significant increase on the risk of neck recurrence.

Comorbidity is a prognostic factor in elderly patients with head and neck cancer.

BACKGROUND: The number of aged patients with head and neck cancer is increasing. Comorbidities are common in this population. It is necessary to evaluate the effect of comorbidities as measured with the ACE-27 index on recurrence and survival of elderly patients with head and neck cancer, adjusting by other prognostic factors as age, clinical stage and functional status index. PATIENTS: Three hundred and ten patients greater than 70 years of age with head and neck cancer in a referral cancer center were studied. Comorbidity measured with the ACE-27 index was the main independent variable. The outcomes were recurrence and survival. RESULTS: Comorbidities were present in 75% of patients. Five-year disease-free survival, overall survival and cancer-specific survival were 63.1, 42.8 and 55.8%, respectively. Advanced clinical stage and Karnofsky index < or =70 were associated with recurrence. Age >80 years, male gender, Karnofsky index < or =80, advanced clinical stage, and ACE value > or =2 were independently associated with overall survival. The ACE-27 value was not associated with cancer-specific survival. The Karnofsky performance index was associated with overall survival and mortality and acted as a confounding factor on multivariable analysis on overall and cancer-specific survival. CONCLUSIONS: Comorbidity measured with ACE-27 was a prognostic factor for overall survival in patients older than 70 years with head and neck cancer. The Karnofsky performance index could be included in multivariable analysis of survival for older patients with head and neck cancer.

Is galectin-3 a good method for the detection of malignancy in patients with thyroid nodules and a cytologic diagnosis of "follicular neoplasm"? A critical appraisal of the evidence.

BACKGROUND: Thyroid nodules are the most common surgical disease of the thyroid. Fine-needle aspiration biopsy (FNAB) is the most commonly employed tool for establishing a diagnosis. However, 15% to 25% of FNAB reports yield inconclusive results. Immunostaining of cytological smears from FNAB with galectin-3 has been proposed as a tool for differentiating between benign and malignant nodules. We performed a systematic review to evaluate the utility of galectin-3. METHODS: Prospective studies of nodules with FNAB reports of "follicular neoplasm" and with a definitive diagnosis confirmed by histopathology were selected. Calculations of individual sensitivity, specificity, and positive and negative likelihood ratios were made. RESULTS: The articles selected were those with the best methodological quality. CONCLUSION: Galectin-3 could be a good tool to guide therapeutic decision in patients with thyroid nodules and FNAB results of follicular neoplasm, but available information has methodological flaws that precludes a definitive answer about galectin-3 utility in the clinical setting.

Prognostic factors in salvage surgery for recurrent oral and oropharyngeal cancer.

BACKGROUND: Therapeutic decisions in recurrent oral and oropharyngeal squamous carcinoma (SCC) remain controversial. METHODS: Two hundred forty-six consecutive patients who underwent salvage surgery for recurrent squamous cell carcinoma (SCC) of the oral cavity and oropharynx were studied. The tumor sites were lip, 33 cases; oral cavity, 143; oropharynx, 70. The previous treatment was surgery in 73 patients, radiotherapy in 96, combined surgery and radiotherapy in 76, and chemotherapy in one. The clinical stage of recurrence was I/II in 51 cases and III/IV in 195 cases. The disease-free interval (DFI) was less than 1 year in 156 cases and greater than 1 year in 90 cases. RESULTS: The rate of recurrence was 54.9%, and the overall 5-year actuarial survival rate was 32.3%. The significant prognostic factors in multivariate analysis were restage (p = .049) and DFI (p = .045). CONCLUSION: Patients with recurrent oral and oropharyngeal SCC at initial clinical stages (rCS I and II) and with a DFI greater than 1 year had a favorable prognosis.

DNA methylation in the CTCF-binding site I and the expression pattern of the H19 gene: does positive expression predict poor prognosis in early stage head and neck carcinomas?

Loss of allele-specific expression by the imprinted genes IGF2 and H19 has been correlated with a differentially methylated region (DMR) upstream to the H19 gene. The H19-DMR contains seven potential CCCTC-binding factor (CTCF) binding sites. CTCF is a chromatin insulator and a multifunctional transcription factor whose binding to the H19-DMR is suppressed by DNA methylation. Our study included a group of 41 head and neck squamous cell carcinoma (HNSCC) samples. The imprinting status of the H19 gene was analyzed in 11 out of 35 positive cases for H19 gene expression, and only 1 of them showed loss of imprinting. We detected a significant correlation (P = 0.041, Fisher's exact test) between H19 expression and tumor recurrence. Among H19 positive cases, six were T2, in which five developed recurrence and/or metastasis. Inversely, in the group of tumors that showed no H19 gene expression, 5 out of 24 were T2 and only 1 presented regional recurrence. These data support the hypothesis that H19 expression could be used as a prognostic marker to indicate recurrence in early stage tumors. We also examined the methylation of the CTCF binding site 1 in a subgroup of these samples. The H19 gene silencing and loss of imprinting were not correlated with the methylation pattern of the CTCF binding site 1. However, the significant correlation between H19 expression and tumor recurrence suggest that this transcript could be a marker for the progression of HNSCC.