Prognostic significance of lymph node reactivity in patients with laryngeal carcinoma

Apart from the presence or absence of metastases in patients with laryngeal carcinoma, there are changes of reactivity in cervical lymph nodes that are seen histologically as nonspecific reactive lymphadenitis. These changes are morphological manifestations of the regional lymphatic system reactivity in relation to tumor, and their presence may be of prognostic value. To test this hypothesis, 45 patients with laryngeal carcinoma were examined for the evidence of node reactivity. The classification applied by Tsakraklides et al. was used, defining patterns of lymphocyte predominance, germinal center appearance (indicating lymph node stimulation) and whether or not lymphocyte depletion had occurred. The presence of node reactivity was compared with long-term (5-year) survivals in the group of patients studied. By applying statistical analysis it was found that lymph node stimulation was a favorable prognostic factor, while its absence worsened prognosis.     

Prognostic importance of harvested lymph node number,metastatic lymph node number,and lymph node ratio in surgically managed laryngeal squamous cell carcinoma

IntroductionLymph node metastasis is a well-known prognostic factor for laryngeal carcinoma. However, current nodal staging systems provide limited information regarding prognosis. Additional parameters should be considered to improve prognostic capacity.ObjectivesTo assess the prognostic values of metastatic lymph node number, ipsilateral/contralateral harvested lymph nodes, and lymph node ratio in patients undergoing surgical treatment of laryngeal squamous cell carcinoma.MethodsSeventy-four patients diagnosed with laryngeal squamous cell carcinoma primarily managed surgically were included in this study. The patients’ pathological and survival data were obtained from their medical records. The effects of harvested lymph nodes and lymph node ratio on disease-free survival, disease-specific survival, and overall survival were analyzed.ResultsIpsilateral, contralateral, and bilateral evaluations of harvested lymph nodes showed no significant associations with prognosis. Lymph node ratio was significantly associated with overall survival when evaluated bilaterally. Metastatic lymph node number showed more suitable stratification than TNM classification.ConclusionsMetastatic lymph node number and bilateral lymph node ratio parameters should be taken into consideration to improve the prognostic capacity of TNM.     

Prognostic significance of lymph node histology in patients with squamous cell carcinoma of the larynx,pharynx, or oral cavity

In a double-blind retrospective analysis, sections of lymph nodes regional to head and neck squamous cell carcinomas were microscopically examined to assess morphologically the immunologic pattern of response. Patients whose nodes showed evidence of immunologic stimulation had five-year survival rates significantly higher than those whose nodes showed no evidence of immunologic stimulation. None of the patients whose nodes showed the lymphocyte depletion pattern survived five years. The stage or histologic grade of the tumors did not influence these correlations. Metastases occurred much more frequently in patients whose nodes showed immunologic activity than in those whose did not. The data support the concept that immunologic capacities are important host defense mechanisms against malignancy. Histologic assessment of immunologic activity in regional nodes seems to be an important parameter for predicting survival.     

Prognostic value of lymph node density in buccal squamous cell carcinoma

Purpose

Lymph node density(LND) has been shown to be a better prognosticator than conventional nodal classification to predict prognosis for squamous cell carcinoma(SCC) of the oral cavity. However, studies focusing on subsites of oral cancer are meager. The role of LND for buccal SCC was evaluated in this study.

临床颈淋巴结转移阴性喉及喉咽癌前哨淋巴结检测

目的前瞻性研究喉及喉咽鳞癌患者前哨淋巴结(sentinel Iymph node,SLN)的存在、位置、数量、阳性率及制定颈部治疗计划。方法30例术前未曾经过任何治疗的喉及喉咽鳞癌患者,临床颈部触诊及影像学检查均属于NO,均在原发灶周围黏膜下注射2毫升亚甲蓝液,在20-30分钟后于颈部检查染色淋巴结。其中5例在手术前日于相同部位注射1毫居里99m锝-右旋糖苷(1mci 99m Tc-Dx),分别于注射后30分、1小时和2小时应用发射型计算机断层扫描连续静态显像观察。6例在手术当中对SLN进行了冰冻活检。30例的前哨淋巴结、颈清标本及原发病灶,均行常规组织病理学检查。结果30例注射亚甲蓝患者中28例(占93.3%)发现染色的SLN。注射99m锝-右旋糖苷的5例患者,则100%在发射型计算机断层扫描连续静态显像中观察到SLN的核素图像。共查得前哨淋巴结49枚,平均每例1.6枚。其大多数位于Ⅱ或Ⅲ区,其中有5例共有6枚SLN被确定有转移,占全部病例的16.7%(5/30),5例中有3例在颈部其他部位同时发现转移淋巴结。结论喉及喉咽鳞癌SLN检出是一个有前途的预测方法,对于制定颈部治疗方针有指导意义,但尚需进一步研究和完善。     

Reliability of sentinel lymph node biopsy for regional staging of head and neck Merkel cell carcinoma

OBJECTIVE: To determine (1) the reliability of sentinel lymph node (SLN) biopsy and (2) the need for cytokeratin 20 (CK-20) immunostaining in the staging of head and neck Merkel cell carcinoma (MCC). DESIGN: Retrospective cohort study (median follow-up of 34.5 months). SETTING: Tertiary care center. PATIENTS: Ten patients with head and neck MCC who underwent regional staging with SLN biopsy (SLNB) and CK-20 immunostaining. INTERVENTIONS: Sentinel lymph nodes were identified using preoperative lymphoscintigraphy, intraoperative gamma probe, and isosulfan blue dye. The SLNs were evaluated with hematoxylin-eosin and CK-20 immunostaining. Patients with negative SLNB results were followed up clinically. MAIN OUTCOME MEASURES: Percentage of positive SLNs, regional recurrence in the setting of a negative finding from SLNB, and percentage of positive SLNs requiring CK-20 immunostaining for diagnosis of micrometastatic MCC. RESULTS: At least 1 SLN was identified in every patient. Of 24 nodes, 19 (79%) were from the neck region and 5 (21%) were from the parotid basin. Two of the 24 SLNs, in 2 (20%) of 10 patients, were positive for metastatic disease. Both positive SLNs appeared negative on hematoxylin-eosin-stained sections, but small foci of micrometastatic MCC were identified with CK-20 immunostaining. No cranial nerve complications occurred. Regional failure in the setting of a negative finding on SLNB was observed in 1 (12%) of 8 patients. CONCLUSIONS: Biopsy of SLNs represents a safe and reliable technique for regional staging of MCC of the head and neck. It provides pathologists with a limited number of SLNs for focused analysis, which is imperative because hematoxylin-eosin immunostaining is often insufficient for identifying micrometastatic MCC. The use of anti-CK-20 antibody allows accurate identification of micrometastatic MCC.     

Prognostic value of lymph node density for major salivary gland carcinoma without clinical lymph node metastasis

Background and objectiveThis study aimed to investigate whether lymph node density (LND) was correlated with overall survival (OS) in major salivary gland carcinoma without clinical lymph node metastasis.MethodsSixty patients who were diagnosed with major salivary gland carcinoma without clinical lymph node metastasis were enrolled. Of these, 50 patients underwent neck dissection. LND was defined as the ratio of the number of positive lymph nodes to the total number of resected lymph nodes.ResultsAn LND of ≥0.1 was significantly associated with a short OS (p < 0.05). Multivariate analysis with adjustment for pathological N classification and positive surgical margin showed that an LND of ≥0.1 is a predictor of OS.ConclusionResults demonstrated that lymph node density functions as a predictor of outcomes for major salivary gland carcinoma without clinical lymph node metastasis.     

Prognostic significance of sinus histiocytosis and lymphocyte predominance in lymph nodes of patients with laryngeal carcinoma

The prognostic value of morphological parameters such as sinus histiocytosis and nonspecific lymphocyte predominance in removed neck lymph nodes in patients with squamous cell carcinoma of the larynx was presented. Long term results of the treatment in group of 179 patients have shown that regional lymph node reactivity (sinus histiocytosis and reactive lymphadenitis) is a good prognostic factor, while lack of stimulation is a factor of bad prognosis.     

Determination of lymph node micrometastases in patients with supraglottic carcinoma

CONCLUSIONS: The frequency of loss of heterozygosity (LOH) at D9S 171 microsatellite locus on 9p21 may serve as an available method to evaluate occult micrometastases in laryngeal squamous cell carcinoma. High frequency of LOH was associated with a decreased probability of survival time. OBJECTIVE: To explore an available and sensitive method to detect cervical lymph node micrometastases in patients with laryngeal squamous cell carcinoma, the frequency of LOH at D9S171 microsatellite locus on 9p21 was studied. PATIENTS AND METHODS: Twenty samples from supraglottic cancer and 182 lymph nodes from neck dissections were examined by LOH comparing immunohistochemical (IHC) staining using cytokeratin 19 (CK19), and hematoxylin and eosin (H&E) staining. The frequency of lymph node metastasis and the clinical relevance were analysed. RESULTS: The frequency of LOH was 37.4% of lymph nodes and all of the primary tumors. Occult micrometastases were present in 9 of 20 cases; 23.6% of lymph nodes were positive for CK19 by IHC; 16.5% of lymph nodes were positive by H&E. There was a highly significant difference among the three methods. The highest rate of positive lymph nodes was at level II of the neck. There was a highly significant difference between overall survival time and lymph node metastasis with LOH and CK19 analysis.     

Significance of extracapsular lymph node metastases in patients with head and neck squamous cell carcinoma

The presence of cervical lymph node metastasis remains the most significant prognostic indicator of survival and disease recurrence in patients with squamous cell carcinoma of the head and neck. An approximately 50% reduction in 5-year survival rate is seen with the development of lymph node metastasis in patients with squamous cell carcinoma of the head and neck. A further precipitous and significant decline in survival and an unacceptably high rate of local-regional and distant failure occurs when extracapsular spread of lymph node metastasis is present. Extracapsular spread is noted in a majority of the lymph nodes larger than 3 cm and in a significant number of nodes less than 2 cm. Extracapsular spread has even been demonstrated in lymph nodes measuring less than 1 cm. Extracapsular spread, thus, is the most important predictor of survival, local-regional recurrence, and distant metastasis. The spread of metastatic disease beyond the lymph node capsule demands aggressive therapy directed toward local-regional disease and addressing the high incidence of distant metastases.     

Prognostic significance of nodal ratio in cutaneous squamous cell carcinoma of the head and neck

The TNM classification is not specific for head and neck skin cancer and makes no allowance for disease extent. Studies have shown that the relative number of metastatic-to-examined lymph nodes, termed the Nodal ratio, is a reliable independent prognosticator in several types of cancer. The study was designed as a retrospective analysis in a university affiliated tertiary care center setting. The files of all patients (n = 71) with cutaneous head and neck squamous cell carcinoma and regional lymph node metastasis who attended a tertiary medical center between 1990 and 2008 were reviewed for clinical variables and outcome, and Nodal ratio was calculated. Data were analyzed for impact on survival. On multivariate analysis Nodal ratio and age were found to be significant predictors of overall survival. The N-ratio was the only significant predictor of disease-specific survival. Age, type of treatment (selective/modified neck dissection), pathologic N stage, and radiotherapy had no effect. The Nodal ratio is a potentially valuable prognostic index in cutaneous squamous cell carcinoma. The minimal number of nodes that need to be excised has to be determined.     

声门上型喉癌颈淋巴结微转移的检测及其预后分析

目的:探索检测喉癌颈淋巴结微转移的敏感而可行的方法。方法:对20例声门上型喉癌患者原发部位及其182个颈淋巴结,按颈淋巴结清扫各区分别进行研究。检测手段包括:常规苏木精-伊红染色,角蛋白CK19免疫组化分析。对患者进行3~5年随访,对比其阳性率对患者颈淋巴结转移及预后的相关关系及总体生存率的比较。结果:发现喉鳞状细胞癌原发组织CK19阳性率100%;CK19颈淋巴结阳性率23.6%,常规苏木精-伊红颈淋巴结阳性率16.9%;苏木精-伊红检测在Ⅱ、Ⅲ区分别发现颈淋巴结转移为86.7%,13.3%,CK19在Ⅱ、Ⅲ、Ⅳ区发现颈淋巴结转移为88.4%,9.3%及2.3%。统计学分析,两者阳性率有显著差异,各区颈清扫淋巴结组织阳性率有显著差异,以颈淋巴结清扫Ⅱ区阳性率最高。总体生存时间与2种检测手段分析(LogRank检测),CK19检测的颈淋巴结转移与生存时间的下降有密切相关性,P<0.01,而苏木精-伊红检测无相关性。结论:角蛋白CK19免疫组化分析可认为是声门上型喉癌颈淋巴结微转移的有效检测手段,且较高的检出率与患者的生存时间的下降有密切相关性。     

Prognostic significance of presentation-to-diagnosis interval in patients with oropharyngeal carcinoma

OBJECTIVE: To evaluate the prognostic impact of presentation-to-diagnosis interval (PDI) and its association with other clinical factors in patients with oropharyngeal squamous cell carcinoma (OpSCC). DESIGN: Retrospective cohort study. SETTING: Otolaryngology clinic of an academic medical center. PATIENTS: Eighty-seven patients with OpSCC referred to the otolaryngology service at the Johns Hopkins Medical Institutions from March 1994 to August 2001 were included in the study. Selection criteria included confirmed pathological diagnosis of OpSCC, availability of referral record for PDI determination, and no past history of oropharyngeal cancer. MAIN OUTCOME MEASURES: The PDI is defined as the time between the patient's first presentation to a medical professional for tumor-related symptoms and the time when the diagnosis of OpSCC was made. The prognostic impact of PDI and its association with other clinical factors were assessed using univariate and multivariate analyses. RESULTS: Forty percent of patients (35/87) had a PDI of 3 months or longer. Referred otalgia, active smoking status at the time of diagnosis, stage IV disease, and advanced T stage were associated with a poor prognosis. Prolonged PDI itself was not associated with a significant decrease in survival in univariate analysis (hazard ratio, 1.27; P =.52). Furthermore, no significant correlation was found between PDI and N stage, T stage, young age at presentation (<45 years), or tobacco use. CONCLUSIONS: Difficulty in making the diagnosis of OpSCC is evident by the high proportion of patients with PDI of 3 months or longer. The PDI does not appear to have an impact on survival. Referred otalgia, widely recognized as a strong indicator of invasive head and neck cancer, portends a poor prognosis.     

Merkel cell carcinoma

PURPOSE: To determine the natural history and treatment outcomes for patients with Merkel cell carcinoma. METHODS: Review of the literature. RESULTS: The probability of regional node involvement at presentation exceeds 50%; few patients present with distant metastases. Comprehensive treatment of the primary site and regional lymphatics with surgery or radiotherapy results in the highest likelihood of cure. The role of adjuvant chemotherapy remains investigational. CONCLUSION: The probability of regional dissemination at diagnosis is high. The optimal treatment is resection of the primary tumor and treatment of the regional lymphatics. Resection of all gross tumor should be accomplished followed by local-regional radiotherapy in most patients.     

Prognostic significance of serum squamous cell carcinoma antigen in patients with head and neck cancer

Conclusions: Serum squamous cell carcinoma antigen (SCC-Ag) level was an independent prognostic factor for survival in patients with head and neck squamous cell carcinoma (HNSCC), and the prognostic value depended on the carcinoma site. Objectives: To assess the value of SCC-Ag as a prognostic indicator in patients with HNSCC and to determine the effect of primary tumor site on prognosis. Methods: We reviewed 493 patients with HNSCC between 2004 and 2012. The chi-squared test was used to assess associations between SCC-Ag levels and TNM classification. A Cox proportional hazard model was used to assess the hazard ratio of SCC-Ag at different sites for death, and it was analyzed as a continuous variable. Results: The median serum level of SCC-Ag was 1.1 ng/ml (range 0–20). SCC-Ag was significantly higher in patients with advanced T and N classification tumors. Primary sites in the oral cavity, in the hypopharynx, advanced T and N classification, distant metastasis, and SCC-Ag were negatively associated with survival in univariate analysis. Multivariate analysis revealed that SCC-Ag was a significant risk factor for overall survival in cancers of the oral cavity, hypopharynx, and larynx, but not in oropharyngeal cancer.     

Feasibility of sentinel lymph node radiolocalization in neck node-negative oral squamous cell carcinoma patients

We examined the reliability of the use of lymphoscintigraphy (LS) and a hand-held gamma probe (GP) to identify the sentinel lymph node (SLN), and sequentially determined the feasibility of SLN radiolocalization in clinical neck node-negative oral squamous cell carcinoma (SCC) patients. A radiolabel with the unfiltered (99m)Tc tin colloid was injected submucosally around the primary site followed by LS at 2-hour intervals. Preoperative localization was performed with GP. After en bloc removal of the regional lymphatics, histopathologic results for the nodes were compared with the SLN radiolocalization. The LS and GP counts were well correlated, and there was concordance between SLN and neck node status in 7 of 8 cases (87.5%). We thus considered that our concept in this study was valid in determining the necessity for neck dissection for those node-negative oral SCC patients.     

Level IIb lymph node metastasis in laryngeal squamous cell carcinoma

OBJECTIVES: Selective neck dissection, despite preservation of the spinal accessory nerve, can lead to some degree of postoperative shoulder dysfunction as a result of removal of level IIb lymph nodes. The aim of this study was to determine whether level IIb lymph nodes can be preserved in elective or therapeutic neck dissection as a treatment for patients with laryngeal squamous cell carcinoma (SCC). STUDY DESIGN: This was a prospective analysis of a case series. METHODS: A prospective analysis of 65 patients with laryngeal SCC who underwent surgical treatment of the primary lesion with simultaneous neck dissection from January 1999 to December 2002 was performed. During the neck dissection, the contents of the level IIb lymph nodes were dissected, labeled, and processed separately from the remainder of level II nodes and the main neck dissection specimen. The incidence of pathologic metastasis to level IIb lymph nodes and the regional recurrence within this area were evaluated. In addition, several potential risk factors for metastatic disease in the level IIb lymph nodes such as sex, age, cT stage, cN stage, and the presence of other positive lymph nodes were also evaluated. RESULTS: A total of 125 neck dissections were performed in this series. Of these dissections, 102 (82%) were elective and 23 (18%) were therapeutic. The prevalence of metastases in the level IIb lymph nodes was 1% (one of 46) and 0% (zero of 56) in clinically node-negative (N0) ipsilateral and contralateral necks, respectively, and 37% (seven of 19) and 0% (zero of four) in clinically node-positive ipsilateral and contralateral necks, respectively. There was a statistically significant association between level IIb metastases and clinically positive N stage (P<.001). The presence of other positive lymph nodes was also shown to have a statistically significant association with metastasis in the level IIb lymph nodes (P=.001). Only two of 46 patients (4%) with clinically N0 necks developed a regional recurrence. However, three of eight cases (38%) with positive pathologic level IIb lymph nodes developed regional recurrence. CONCLUSION: Level IIb lymph node pads may be preserved in elective neck dissection in patients with laryngeal SCC. However, this area should be removed thoroughly during therapeutic neck dissection in the treatment of clinically node-positive necks.     

Prognostic significance of p53/bcl-2 co-expression in patients with laryngeal squamous cell carcinoma

OBJECTIVE: The p53, bcl-2, and bax genes are known to be involved in control of cell cycle progression and regulation of apoptotic cell death. Although they are frequently altered in laryngeal squamous cell carcinoma, their clinical relevance is not yet fully understood. In the present study, individual and combined expressions of these genes were related with patient survival as well as with proliferative and apoptotic activity. DESIGN: Retrospective study. METHODS: Paraffin-embedded tissue sections of 88 laryngeal squamous cell carcinomas that were diagnosed and treated between 1986 and 1996 were investigated for p53, bcl-2, and bax protein expression by immunohistochemistry. Apoptotic cells were visualized using the nick end labeling method. To assess proliferative activity of tumors, mitotic indices were determined. RESULTS: Age of patients, advanced disease (stages HI and IV), high mitotic activity, positive bcl-2 expression, high level of p53 expression, and p53/bcl-2 co-expression were significantly associated with shortened overall survival in univariate analysis. In multivariate analysis, only age and p53/bcl-2 co-expression had independent prognostic value. Other combinations of genes, i.e., bcl-2-to-bax and p53-to-bax ratios, were not associated with patient outcome. A significant positive correlation was found between apoptotic and mitotic activity. However, protein levels of p53, bcl-2, and bax were unrelated to proliferation and apoptosis of tumor cells. CONCLUSIONS: The co-expression of p53/bcl-2 was an independent predictor of patient outcome and had a prognostic value superior to both parameters considered separately. The rate of apoptosis mainly counterbalanced proliferative activity but appeared not to be significantly influenced by p53, bcl-2, and bax.