Mouth floor and mobile tongue epidermoid carcinomas thickness: prognostic value

INTRODUCTION: Most cancers of the oral cavity are epidermoid carcinomas. The prognosis is made on the patient's general health status and the tumoral stage. The UICC TNM staging classification system is one of the most important factors taken in consideration for the prognosis. But this classification in oral epidermoid carcinomas does not include the tumor thickness (except for T4 tumors). Several studies demonstrated that tumor thickness could influence the prognosis in epidermoid carcinoma and other types of cancers. The aim of our retrospective study was to assess the prognostic value of tumor thickness in oral epidermoid carcinoma. PATIENTS AND METHODS: The study included patients with mouth floor or mobile tongue epidermoid carcinoma classified T1N0, T2N0 and T3N0 between 1985 and 2005. All patients were treated with a curative intention. A pathologist analysed the tumor thickness and cervical lymph nodes. All the slides were examined to measure tumor thickness in millimetres. RESULTS: Three hundred and five patient files were reviewed and 124 patients were included, with 94 men (75.8%), and a mean age of 59.3 years (17-93). The mean and median tumor thickness were respectively 7.7 and 6.5 mm (0.4-30). The median tumor thickness was chosen for the study. There was a statistically significant link between the five-year probability of global survival and the initial tumor thickness and between neck node invasion and tumor thickness (p<0.05). DISCUSSION: This study suggests that tumor thickness should be taken in consideration in T1N0, T2N0 and T3N0 mouth floor and mobile tongue epidermoid carcinomas. In the future, the clinical evaluation of tumor thickness will help determine the therapeutic management.     

Management of contralateral N0 neck in tonsillar squamous cell carcinoma

OBJECTIVES: It is well established that tonsillar squamous cell carcinomas have a high probability of disseminating to the neck. An ipsilateral neck treatment is mandatory during initial treatment of stages II to IV tonsillar carcinomas. However, as of yet, no consensus exists whether to perform elective contralateral neck management. MATERIALS AND METHODS: A retrospective analysis of 43 N0-3 tonsillar cancer patients with contralateral clinically negative necks from 1992 to 2002 was performed. All patients had a contralateral elective neck dissection. Surgical treatment was followed by postoperative radiotherapy in 33 patients. The follow-up period ranged from 2 to 120 (mean 38) months. The Kaplan-Meier method and log-rank test were used to calculate the disease-specific survival rates and prognostic significance of contralateral occult lymph node metastasis. RESULTS: Clinically negative, but pathologically positive, contralateral lymph nodes occurred in 16% (7 of 43). Of the 33 cases with an ipsilateral node positive neck, contralateral occult lymph node metastases developed in 21% (7 of 33), in contrast with 0% in ipsilateral N0 necks. On the basis of the clinical staging of the tumor, 5% (1 of 22) of the cases showed lymph node metastases in T2 tumors, 36% (5 of 14) in T3, and 25% (1 of 4) in T4. None of the T1 tumors (3 cases) had pathologically positive lymph nodes (T1 + T2 vs. T3 + T4, P < .05). Patients with no evidence of contralateral nodal cancer had significantly improved disease-specific survival over patients with any pathologically positive nodes (5 year disease-specific survival rate 92% vs. 28%, P = < .05). CONCLUSION: The risk of contralateral occult neck involvement in above T3 staged tonsillar squamous cell carcinomas with unilateral metastases was high (approximately 21%), and patients who present with a contralateral metastatic neck have a worse prognosis than those who are staged as N0. Therefore, we advocate an elective contralateral neck treatment in tonsillar squamous cell carcinoma patients with ipsilateral node metastases.     

18F-FDG uptake on PET correlates with biological potential in early oral squamous cell carcinoma

Conclusion: The maximum standardized uptake value (SUVmax) of early oral squamous cell carcinoma (OSCC) may have a role as an imaging biomarker for assessment of malignant potential, including cell metabolism and angiogenesis. Objective: The usefulness of ¹⁸F-fluorodeoxyglucose positron emission tomography (FDG-PET) has been proven in various cancers, including OSCC. Moreover, in several carcinomas, the SUVmax of the tumor has been shown to correlate with the histological type, tumor stage, differentiation, and prognosis. Here, we investigated whether the SUVmax of early OSCC was associated with the biological features. Methods: Twenty-seven patients with newly diagnosed early OSCC who underwent preoperative FDG-PET and curative surgical resection were included in this study. Tumor sections were stained by immunohistochemistry for glucose transporter 1 (GLUT1), L-type amino acid transporter 1 (LAT1), CD98, microvessels (CD34), cell proliferation marker (Ki-67), and cell cycle regulator (p53). The correlation between SUVmax and clinicopathological findings or the expression level of these molecules was analyzed. Results: SUVmax of primary OSCC was significantly higher in patients with T2 stage. Moreover, patients whose tumors showed vascular invasion had a tendency to show higher SUVmax. A significant correlation was observed between SUVmax and the expression of LAT1 or microvessel density.     

Detection of the sentinal node in squamous-cell carcinoma of the oral cavity and oropharynx. Preliminary study

INTRODUCTION: The sentinel lymph node is defined as the first relay of the lymphatic drainage of the tumor. Isotopic detection of the sentinel lymph node and absence of its metastatic invasion should theoretically be predictive of total drainage of the tumor. The goal of this study was to evaluate sentinel lymph node detectability by lymphoscintigraphy in N0 and/or N1 squamous-cell carcinoma of oral cavity and oropharynx and to determine its negative predictive value. MATERIAL AND METHOD: Lymphoscintigraphy was used for sentinel lymph node detection. The procedure required peritumoral injection of technicium-labeled colloids to enable anatomical and cutaneous location of the sentinel lymph node. A one-way Tyco-Mallinckrodt probe was used for intraoperative detection of the sentinel lymph node. This prospective study included 21 patients with N0 or N1 squamous-cell carcinoma of the oral cavity and the oropharynx. The surgical attitude based on T and N was not modified in this prospective study without direct individual benefit for the patient. Neck dissection was achieved without difficulty. RESULTS: The sentinel lymph node was identified in 20 out of 21 subjects. The sentinel lymph node was not identified in one patient with recurrence T2N0M0 squamous-cell carcinoma of the oropharynx radiated 3 years earlier. The percentage of false-negatives was 12.5% (1 false-negative out of 8 positive patients), giving a sensibility of the detection method of 87.5% (IC (95%)=[47.35-99.68]). This false-negative patient had a T3N0M0 squamous-cell carcinoma of the oropharynx with a sentinel lymph node removed in territory III. Neck dissection revealed 1 N + R- in the sub-mandibular territory associated with 27 N-R-. The probability of not finding a metastatic node at neck dissection when the sentinel lymph node is not metastatic (negative predictive value) was 92.3% (12/13) (IC (95)=[63.97-99.81]). The specificity of the method was 100%, as was the positive predictive value, because no sentinel node was diagnosed positive wrongly on frozen sections among patients without true histological node metastasis. DISCUSSION: For routine care of patients with squamous-cell carcinoma of the oral cavity and the oropharynx detection of the sentinel lymph node is proposed primarily for patients with T1T2N0 staging. Larger tumors can modify the architecture and flow within the lymphatic ducts, and consequently even the concept of a sentinel lymph node. Systematic neck dissection is required or T3T4, even when N0. Our series of T1T2N0 tumors is too small to enable statistically significant conclusions. A low level of false-negative in a larger series would be necessary to propose this technique instead of convention neck dissection for T1T2 tumors of the oral cavity and oropharynx.     

Carcinoma of the external auditory canal and middle ear: therapeutic strategy and follow up

BACKGROUND: Carcinomas of the external auditory canal (EAC) and the middle ear are rare and considered to have a poor prognosis. The recommended therapeutic strategy consists of surgical excision and postoperative radiotherapy. However, there are different opinions about the extend of the primary operation. PATIENTS AND METHODS: A series of 21 patients with carcinoma of the EAC and middle ear were treated at the ENT-Department of the Hospital Fulda from 1985 to 2003. Their records and radiologic findings were reviewed retrospectively with particular reference to tumor type and size, its relation to surrounding tissues, surgical procedures and radiation techniques. The tumors were staged according to the modified Pittburgh staging system for temporal bone carcinomas. The average follow-up time was 6.2 years (range 0.2 - 18.75). RESULTS: 17 patients suffered from carcinoma of the EAC, 4 carcinomas were primarily located in the middle ear. There were 15 squamous cell carcinomas, 3 adenoidcystic carcinomas, 2 adenocarcinomas and one mucoepidermoid carcinoma. 12 patients came primarily to our institution and were staged as follows: pT1 (n = 2), pT3 (n = 2), pT4 (n = 8). 8 patients showed up with recurrent or residual tumors (all of T3 or T4 stage). One patient could not be classified. In 5 cases the tumor was inoperable. These patients underwent combined chemoradiation therapy. All other 16 patients were operated and most of them received adjuvant radiation therapy. In the group of patients who were primarily operated overall 5-year survival rate was 100 %. In contrast, patients who's recurrent or residual tumors were resected had a 5-year survival rate of only 33 %. Patients who received combined chemoradiation therapy showed a 2-year survival rate of 75 %. CONCLUSION: Carcinoma of the EAC and middle ear should be treated primarily by a lateral or subtotal temporal bone resection stage dependent combined with a parotidectomy as well as a neck dissection. Local resection of the EAC is not sufficient, not even in T1 tumors. As from stage T2, in cases of recurrent tumor removal and questionable free margins as well as in cases with lymph node metastases an adjuvant radiation therapy should be added. The most important survival factor is removal of the primary tumor with histologically clear margins.     

Magnetic resonance determination of tumor thickness as predictive factor of cervical metastasis in oral tongue carcinoma

OBJECTIVES: To establish an accurate and reproducible means of measuring tumor thickness as a preoperative prognostic factor for cervical metastasis in oral tongue carcinoma. STUDY DESIGN: Retrospective review. METHODS: Charts from 30 patients were reviewed, and the correlation between histopathological and magnetic resonance imaging (MRI) findings of actual tumor thickness or reconstructed tumor thickness measured between a reconstructed mucosal line and the deepest extent of the tumor was investigated. Magnetic resonance images were acquired on a 1.5 T-scanner with a T2-weighted sequence in the axial plane using 3-mm-thick sections and a 256 x 256 matrix. The correlation between N stage and tumor thickness acquired by histopathological scrutiny or MRI was also assessed. RESULTS: The correlation between histopathological and MRI examinations was more significant in terms of reconstructed than actual tumor thickness. No cervical metastasis was detected in patients with tumors of less than 6 mm of reconstructed thickness in the MRI examination. The difference in cervical metastasis between the two groups, namely, less than 6 or more than 6 mm, was statistically significant (P = .0051). CONCLUSIONS: Magnetic resonance imaging examination provides useful data for prognostic assessment and planning strategies with which to treat oral tongue carcinoma. The preoperative decision as to whether to attempt neck dissection could be based on a tumor thickness of 6 mm for patients with oral tongue carcinoma.     

Tumor biologic prognostic parameters in T1N0M0 squamous cell carcinoma of the oral cavity

BACKGROUND: Conventional prognostic factors in squamous cell carcinomas are tumor stage, tumor size, evidence of lymph node metastases, extracapsular spread of lymph node metastases, and Broder's grading. Unfortunately these parameters are only of limited value in predicting the biological behavior and ultimately the prognosis of a particular tumor. The present study was conducted for determining objective prognostic factors based on tumor biologic examinations in patients with squamous cell carcinomas of the oral cavity. These parameters were compared to the conventional prognostic factors. PATIENTS AND METHODS: Operative specimens of fourty-two patients who underwent surgery for a squamous cell carcinoma of the oral cavity with clinical TNM stage T1N0M0 were examined. All tumors were radically excised with histologic clear margins, which were confirmed by serial sections. The examinations included morphologic multifactorial tumor front grading, quantitative DNA analysis, and immunohistochemical assessment of proliferation markers (i.e. proliferating cell nuclear antigen [PCNA] and MIB1) and of oncogene products (i.e. p53; nm23). Prognostic significance of particular parameters was evaluated by univariate and multivariate Cox regression models. RESULTS: In clinical follow-up of 70 months on average, 6 patients developed local recurrences and 5 patients lymph node metastases. Three patients died of disease. Tumors which recurred had increased values for 2 c Deviation Index, 5 c Exceeding Rate along with high tumor front grading scores and proliferation scores. Using multivariate Cox regression analysis, parameters which were highly significant for prognosis were 5 c Exceeding Rate, tumor front grading score and PCNA score. None of the clinical parameters achieved statistical significance in the multivariate model. Tumors which recurred had also increased expression rates for p53 and nm23. Nevertheless this was statistically not significant. CONCLUSIONS: Tumor biologic examinations provide important informations about the clinical aggressiveness and ultimately about the prognosis of a particular tumor. Tumors with aggressive behavior can already be identified during initial diagnosis, which has consequences for the therapeutic management of the patients.     

Distribution pattern and pathologic analysis of metastatic sentinel and non-sentinel lymph nodes in lymphatic basin dissection for clinical T2/T3 oral cancer with clinical N0 status

ObjectiveThe localization pattern of metastatic sentinel lymph node (SN) and non-SNs and pathologic analysis of metastatic lymph nodes in SN lymphatic basin dissection (SLBD) were investigated in patients with cT2/T3cN0 oral squamous cell carcinoma (OSCC).MethodsThis prospective multicenter trial involved 10 institutions nationwide in Japan. A total of 57 patients were enrolled. The lateral neck was divided into 5 lymphatic basins. The lymphatic basin containing SNs was defined as the SN lymphatic basin.All patients underwent SLBD with backup selective neck dissection (I-III) combined with primary tumor removal. When SNs were found outside of levels I-III, including in the contralateral neck, SLBD was performed by removing the compartments containing SNs separately. SN metastasis was classified as isolated tumor cells (ITCs), micrometastasis, or macrometastasis. ITCs are defined as a lesion no larger than 0.2 mm in largest dimension and are classified as pN0.ResultsSN metastasis was observed in 22 cases. All metastatic lymph nodes, including false-negative cases, were detected in the SN lymphatic basin. Isolated tumor cells in the SNs did not affect prognosis, whereas micrometastasis tended to have poor prognosis.After adjusting for other risk factors, a positive SN remained a significant predictor of poor 5-year overall survival in pT2-4 OSCC.ConclusionSLBD for intraoperative SN biopsy is a sufficient therapeutic procedure and is valuable for determining pathologic nodal stage in OSCC. SN positivity was demonstrated to be an independent predictor of poor prognosis in patients with pT2-4 disease undergoing SLBD with backup selective neck dissection (I-III).     

Carcinoid tumor of the larynx: clinical analysis of 33 cases in Japan

CONCLUSION: In regard to the treatment of carcinoid tumor of the larynx, irradiation is not effective and tumor excision with a minimum surgical margin is associated with a high risk of local recurrence. Lymph node metastases to the neck are associated with worsening of the prognosis. To improve the survival rate, primary resection with a sufficient surgical margin (e.g. partial laryngectomy) and (elective) neck dissection is recommended, even for patients with early stage carcinoid tumors of the larynx. OBJECTIVE: The objective of this study was to clarify the prognostic factors, modalities of treatment for the primary lesions, and importance of neck dissection in the treatment of carcinoid tumors of the larynx. PATIENTS AND METHODS: The data of 33 cases of carcinoid of the larynx reported from Japan (including 2 of our cases) were analyzed. RESULTS: The distributions of the T and N classifications of the lesions were as follows T1, 50.0%; T2, 32.2%; T3, 14.3%; T4, 3.6%; N0, 57.1%; N1, 17.9%; N2, 25.0%; and N3, 0%. Fifteen patients underwent radiation therapy, of whom five underwent curative radiotherapy. While complete remission (CR) was maintained in one of these patients (T1N0), the remaining four patients developed recurrence. Five patients underwent preoperative radiation therapy. The response to the treatment was rated as no change in four patients and as progressive disease in the remaining one patient. Among the patients with N0 disease, seven patients (43.8%) developed lymph node metastases in the neck postoperatively. Distant metastases were the most frequent cause of death in the patients. The 3-year, 5-year, and 10-year survival rates of the patients were 58.5%, 36.5%, and 12.2%, respectively. Significant differences were recognized in the survival rates between patients with and without neck lymph node involvement at the first treatment (p=0.008), and between patients with and without postoperative lymph node recurrence in the neck (p=0.037).     

The prognostic impact of metastatic pattern of lymph nodes in patients with oral and oropharyngeal squamous cell carcinomas

In patients with squamous cell carcinomas of the oral cavity and the oropharynx the presence or absence of nodal metastases still is the most important predictive factor. The discriminative significance of extracapsular spread and the influence of features of the primary tumor—such as size and depth of invasion—on metastatic pattern, treatment failure and survival were evaluated. Five-year postoperative follow-ups of 115 consecutively treated patients were studied retrospectively concerning the incidence of distant metastases, local and regional recurrences and the 5-year survival rate. Maximum depth of invasion of the primary tumor and lymph node metastases were evaluated on the basis of histological patterns, and patients were grouped according to their histological diagnosis. The T4 category has a plain discriminative influence on the incidence of distant metastases, recurrent tumors and survival rate in contrast to the other T sizes. The classification N0, intranodal growth and extranodal growth of lymph node metastases resulted in a 5-year survival rate of 67, 59 and 31%. According to the classification, 84, 87 and 59% were without nodal recurrence after 5 years, and 79, 82 and 46% without distant metastases. Size and depth of invasion of the primary tumor are not connected significantly with the occurrence of extracapsular spread. The status of the lymph nodes in squamous cell carcinomas of the oral cavity and the oropharynx metastases and in particular the capsular rupture has the most significant prognostic influence. The histological feature of extracapsular spread could distinguish reproducibly high risk patients with squamous cell carcinomas of the oral cavity and the oropharynx.     

Distribution and impact of lymph node metastases in oropharyngeal cancer

CONCLUSIONS: In the treatment of oropharyngeal cancers, possible metastases to retropharyngeal lymph nodes (RPLNs) should be taken into account, especially in tumors arising in the lateral wall and/or posterior wall. Patients with multiple positive neck nodes must have intensified adjuvant therapy, especially when they have extracapsular spread (ECS). OBJECTIVE: To develop optimal treatment strategies for oropharyngeal cancers, we retrospectively analyzed the lymph node metastases of oropharyngeal squamous cell carcinoma. PATIENTS AND METHODS: Between 1988 and 2003, 77 patients with previously untreated oropharyngeal squamous cell carcinoma underwent neck dissections. RESULTS: Among the patients with tumor arising in the lateral wall or posterior wall, retropharyngeal nodes were involved in 29% (11/38), while RPLN metastasis was not observed in patients with tumors arising in the superior wall or anterior wall. The survival rate of patients with two or fewer positive lymph nodes was significantly better than that of patients with three or more positive lymph nodes (p < 0.05). The survival rate of the patients who had ECS was significantly worse than that of the patients who had lymph node metastases but not ECS (p < 0.05). There was no significant difference between the survival rates of the patients with and without RPLN metastases.     

Nachweis von TP53-Mutationen mittels Exfoliativzytologie (brush biopsy) oraler Leukoplakien

OBJECTIVE: The aim of this study was to determine the prevalence of mutations of the tumour suppressor gene TP53 in oral leukoplakias. MATERIAL AND METHOD: Brush biopsy specimens of 43 oral leukoplakias, 26 oral squamous cell carcinomas (OSCC) for reference, and the oral mucosa of 4 clinically normal volunteers were collected. DNA of the critical exons 5-8 was analysed by temperature gradient gel electrophoresis (TGGE). RESULTS: The prevalence of mutations was 57.7% in OSCC, 39.5% in leukoplakias and 0% in controls. The highest frequency of mutations was found in exon 5 (46.2%) in OSCC and in exon 6 (23.3%) in leukoplakia. More than one mutation was detected in 26.9% of OSCC and 7% of leukoplakia specimens. At least one mutation was found in 37.5% of T1 OSCC and 100% of T4 OSCC specimens and in 37.1% of the L1 leukoplakia and 100% of L3 leukoplakia specimens. CONCLUSIONS: TP53 mutations could be a useful prognostic indicator in precancerous oral lesions. Although the brush biopsy technique appears simple clinically, further investigations are necessary to specify the implications of genetic analysis.     

Patterns of chromosomal aberrations in metastasizing and nonmetastasizing squamous cell carcinomas of the oropharynx and hypopharynx

Although several cytogenetic events of the tumor progression cascade have been identified in the past, the specific types of chromosomal alterations that lead to the development of lymph node metastases are still unknown. Operative specimens of 20 patients (10 patients with metastasizing tumors, 10 patients with nonmetastasizing tumors) with squamous cell carcinomas of the oropharynx and hypopharynx, along with the corresponding lymph node metastases, were investigated by quantitative DNA measurements and comparative genomic hybridization (CGH). Nonmetastasizing tumors (N0) displayed overrepresentations on chromosomes 10q (8 cases); 5p (7 cases); 3q and 20q (6 cases each); 8q (5 cases); 1p and 21q (4 cases each); 7p and 20p (3 cases each); and 2p, 15q, and 19q (2 cases each). Loss of chromosomal material was found on 5q, 9p, and 14q (2 cases each). Metastasizing tumors (N+) demonstrated overrepresentations on chromosomes 5p, 15q, and 22q (6 cases each); 3q and 11q13 (5 cases each); 20p and 21q (4 cases each); and 10q (3 cases). In 2 cases, an overrepresentation of the chromosomal arm 3q was accompanied by a loss of chromosomal arm 3p. Less frequent overrepresentations were observed on chromosomes 1q and 17q. Deletions were found on chromosomes 18q (3 cases), 3p, 4q, 5q, and 19p (2 cases each); and sporadic deletions occurred on 2q, 6q, 8p, 9p, 10p, 13q, 14q, 15q, and 16q. Whereas overrepresentations on chromosomes 1p and 7p occurred exclusively in N0 tumors, overrepresentations on chromosomes 1q, 11q, and 22q, along with deletions on 18q, were only observed in N+ tumors. Quantitative DNA measurements revealed a significantly higher percentage of aneuploid cells and a higher degree of DNA entropy in the N+ tumors. Chromosomal overrepresentations on chromosomes 1q, 8q, 11q, 18q, and 19q occurred more frequently in the metastases than in the corresponding primary tumors. Pairwise analysis of chromosomal alterations in the primary tumors and associated lymph node metastases revealed a genetic relationship, although a greater number of chromosomes on average were affected in the lymph node metastases. Quantitative DNA measurements demonstrated greater aneuploid values in the metastases. Recurring patterns of chromosomal alterations in N0 and N+ tumors were demonstrated in this study. In general, metastasizing tumors are characterized by overrepresentations on chromosomes 11q13 and 22q, and deletions on 18q. These aberrations suggest an elevation along the tumor progression cascade.     

Survival and staging characteristics for non-squamous cell malignancies of the maxillary sinus

OBJECTIVE: To characterize the clinical behavior of non-squamous cell cancer of the maxillary sinus. METHODS: Cases of non-squamous cell maxillary sinus malignancy during 1988 through 1998 were extracted from the Surveillance, Epidemiology, and End Results database. Data for histologic type of tumor, tumor stage, and survival were analyzed using the Kaplan-Meier method to determine mean, median, and 5-year survival statistics for the overall cohort and for individual histologic types of tumor. The effect of tumor stage on overall survival was assessed. To determine relative survival, the non-squamous cell group was compared with a second group of patients with squamous cell carcinoma, matched according to age at diagnosis, year of diagnosis, and T stage. RESULTS: One hundred eighty-eight cases of non-squamous cell malignancy were identified. The mean patient age was 57.8 years, and 143 patients (76%) presented with T3 or T4 tumors. There were 31 adenocarcinomas, 64 adenoid cystic carcinomas, 15 mucoepidermoid carcinomas, 22 melanomas, 45 sarcomas, and 11 undifferentiated carcinomas. The overall mean survival was 63.4 months, and 5-year survival was 45.6%. Adenoid cystic carcinoma exhibited the best mean survival (79 months), whereas melanoma and undifferentiated carcinoma exhibited poor mean survivals (30.3 and 12.8 months, respectively). T stage did not statistically affect overall survival (P =.86). Survival for patients with non-squamous cell cancer was substantially better than survival for the matched group with squamous cell carcinomas (mean survival, 41.5 months; 5-year survival, 27.4%). CONCLUSIONS: Patients with non-squamous cell carcinoma of the maxillary sinus typically present with advanced T stage but have significantly better survival than patients with similar-stage squamous cell carcinoma of the maxillary sinus. T stage has less effect than histologic type of tumor on prognosis in non-squamous cell carcinoma of the maxillary sinus.     

Expression von Lektinbindungsstellen als prognostischer Parameter bei Mundschleimhautkarzinomen

BACKGROUND: Normal oral mucosa and invasive squamous cell carcinoma of the oral mucosa and the lips were examined immunoenzymatically for different lectin-binding sites and evaluated semiquantitatively. In 110 patients suffering from invasive squamous cell carcinoma of the oral mucosa or the lips, the course of the disease was examined retrospectively with regard to metastases, recurrence and survival time over a minimum of 60 months and was correlated with cell surface binding to lectins (PNA, WGA, UEA I) of the primary tumor. Normal oral mucosa shows intensive cell surface binding to the lectins PNA, WGA and UEA I, but in more than half of the cases the PNA-defined epitopes are blocked by sialic acid. RESULTS: The comparison of the cumulated survival rates showed a much better prognosis for primary tumors with lectin-binding sites than for those without. Strong and medium WGA-binding pT2 tumors showed significantly better survival rates than those pT2 tumors with poor WGA-binding sites. Carcinomas without lectin binding showed the highest recurrence risk in the course of the disease. In squamous cell carcinomas without WGA and UEA I bindings, the period of time before a relapse occurred was significantly shortened. Carcinomas expressing UEA I-binding sites showed a considerably lower metastasis rate than UEA I-negative tumors. Squamous cell carcinomas with complete sialic acid-blocked PNA-binding sites had the same lymph node metastasis rate as those without expression of PNA-specific disaccharides. A significantly lower metastasis rate than both these groups was exhibited by tumors without or with only partially blocked PNA-binding sites. DISCUSSION: In addition to aiding routine grading, the study of PNA-, WGA- and UEA I-binding patterns can therefore provide further information in cases of oral squamous cell carcinoma regarding the potential for metastasis and tumor prognosis.     

MRI-derived tumor thickness: an important predictor of outcome for T4a-staged tongue carcinoma

The objectives of this paper are to evaluate the heterogeneity of magnetic resonance imaging (MRI)-derived tumor thickness within tumors of the same T4a-staged tongue carcinoma and to elucidate the effects of tumor thickness on treatment outcomes. A sequential and prospectively maintained head and neck cancer database was retrospectively searched for newly diagnosed tongue carcinoma treated with surgery between 2003 and 2006. Fifty-eight patients with newly diagnosed T4a-staged tongue carcinoma were included in this study. Tumor thickness was obtained from preoperative magnetic resonance imaging. The mean MRI-derived tumor thickness was 22.29 mm. The patients with long tumor thickness (>26 mm) were associated with a significantly poor disease-specific survival (P = 0.015). The 2-year disease-specific survival rates were 72% in patients with short tumor thickness and only 27% in patients with long tumor thickness within the same T4a-staged disease. A substantial variation in MRI-derived tumor thickness was present within the same T4a-staged tongue carcinoma, and tumor thickness represented an important prognostic factor.     

Multiple primary carcinomas in patients with head and neck malignancies

BACKGROUND: Multiple primary tumors can lead to diagnostic and therapeutical problems. In this study we surveyed frequency, localisation, diagnostic, chronologic and therapeutic aspects of multiple primary carcinomas in patients with head and neck tumors. PATIENTS AND METHODS: The data of 843 patients from the tumor registry of the ENT-clinic Aachen were retrospectively studied. RESULTS: Larynx (41.87%) and oropharynx (12.57%) were the main localisation of the first primary neoplasma. In 65 patients (7.71%) multiple primary tumors were observed. 24.6% of these tumors occurred synchronously. Preferential localisation of a second tumor were lung (20%), oral cavity (15.3%) and larynx (13.8%). 28.57% of the metachronous tumors were observed after more than five years. In 46.15% clinical complaints led to the suspicion of a second tumor. Panendoscopy was the most reliable diagnostic procedure. The survival rate and time was significantly reduced in patients with synchronous tumors. 3-year survival rate was 15% compared to 81% in patients with metachronous tumor appearance (p < 0.0001). CONCLUSION: Patients with head and neck tumors have a high incidence of multiple primary malignomas varying from the region of the first presentation of a malignant tumor. Concepts comprising surgery provide the highest survival rates. Because of the high incidence of metachronous carcinomas after five years found in this study, the authors regard a prolonged follow-up period as necessary.     

Human papillomavirus co-infection and survival in oral and oropharyngeal squamous cell carcinoma: A study in 235 Brazilian patients

ObjectivesWhile unknown for oropharyngeal squamous cell carcinoma (OPSCC) and oral squamous cell carcinoma (OSCC), some studies assessing cervical carcinoma have shown that human papillomavirus (HPV) co-infection can be associated with its prognosis.MethodsThrough in situ hybridization (HPV and Epstein-Barr virus [EBV] probes) and immunohistochemistry (p16^INK4a, cyclin D1, p53, and Ki-67 antibodies), 126 OPSCC and 109 OSCC samples were assessed.ResultsAll patients were EBV-negative. OPSCC (25%) showed a significant association with HPV compared to OSCC (11%). Almost all HPV-associated cases were p16^INK4a-positive. Regarding OPSCC and OSCC, 23 and 7 cases were positive for high-risk HPV (HRHPV) only, 6 and 3 cases for low-risk HPV (LRHPV) only, and 3 and 2 cases for HRHPV/LRHPV, respectively. HPV-associated carcinomas showed a significantly higher proliferative index than HPV-unassociated carcinomas. Both carcinomas showed a similar overall survival rate, which was not affected by the HPV status. However, when comparing HPV-associated subgroups, patients with HRHPV/LRHPV-associated carcinomas showed worse survival.ConclusionLRHPV-associated and HRHPV/LRHPV-associated cases can also be detected when assessing OSCC and OPSCC. Further studies, especially in populations with a high prevalence of HPV-associated OPSCC, are necessary to understand the clinicopathological behavior of these neoplasm subgroups.     

Coexpression of VEGF and bFGF is associated with increased vascular density in head and neck carcinomas

BACKGROUND: Angiogenesis is crucial for tumor growth and metastasis. In several tumors, microvascular density has been shown to correlate with metastasis and aggressiveness. Vascular endothelial growth factor (VEGF) and basic Fibroblast Growth Factor (bFGF) are known to have potent angiogenic activity. Their expression has been identified in a wide variety of malignancies including head and neck squamous cell carcinoma (HNSCC). Aim of our study was to investigate the role of co-expression of VEGF and bFGF for angiogenesis in HNSCC. MATERIAL AND METHODS: Cryostat sections of 51 primary HNSCC were immunostained for VEGF and bFGF using a standard streptavidin-biotin complex procedure. To evaluate angiogenesis, endothelial cells were stained immunohistochemically using anti-vWF polyclonal antibody. Microvessels were quantified by counting vessels in a x200 field in the most vascular area of the tumor. RESULTS: 25/51 (49%) of the investigated carcinomas showed co-expression of both factors (VEGF+/bFGF+), while 6/51 (11.7%) carcinomas only expressed VEGF and 13/51 (25.5%) carcinomas expressed bFGF. 7/51 (13.7%) tumors showed no expression of these factors (VEGF-/bFGF-). Carcinomas with a co-expression of VEGF and bFGF showed a significantly increased mean microvessel density (88.3 +/- 24.4) compared to tumors expressing only VEGF (77 +/- 16.8) or bFGF (71.1 +/- 15.8) (p = 0.022) or tumors with no expression of both factors (51.1 +/- 13.4) (p < 0.001). The association of VEGF and bFGF expression level was not significant (p = 0.178). CONCLUSIONS: The positive correlation of the co-expression of angiogenic VEGF and bFGF with increased microvessel density underlines the importance of both factors for tumor angiogenesis in HNSCC. VEGF and bFGF might act cooperatively in the process of neovascularization in human head and neck cancer.     

Clinicopathological factors related to cervical lymph node metastasis in a patient with carcinoma of the oral floor

CONCLUSION: Tumors developing into the muscle layer and tumor thickness > or =5 mm are the most important risk factors associated with nodal metastasis. OBJECTIVE: It is necessary to identify the risk factors associated with cervical metastasis in patients with oral floor cancer to reveal the role of elective neck dissection for oral floor cancer. PATIENTS AND METHODS: Forty-eight patients with oral floor cancer were retrospectively analyzed for a correlation between clinicopathologic factors and cervical lymph node metastasis using Fisher's exact test and a logistic regression test. RESULTS: Univariate analysis showed significantly positive correlations for growth type, mitosis, perineural invasion, vascular invasion, lymphatic invasion, depth, thickness, and infiltration growth ratio. Multivariate analysis had a significantly positive correlation with nest formation and depth in all patients, and with thickness in patients with T1 or T2. In patients with bilateral cervical lymph node metastasis, lymph node metastasis was significantly positively correlated with perineural invasion.