Cell kinetic markers in cutaneous squamous and basal cell carcinoma of the head and neck

IntroductionProliferation markers play a significant role in the biologic behavior of tumors. Geminin is a known inhibitor of the cell cycle and DNA replication and has not been previously reported in cutaneous basal and squamous cell carcinomas of the head and neck.ObjectivesWe aimed to investigate proliferation markers ki67, MCM2, and geminin in head and neck cutaneous basal and squamous cell carcinomas.MethodsForty cases of each tumor were immuostained with ki67, MCM2, and geminin followed by assessment of labeling indices (LIs). MCM2/ki67- and geminin/ki67-ratios were also determined; t-test was used for statistical analysis (p < 0.05).ResultsThere was no significant difference in ki67 (p = 0.06) and MCM2 (p = 0.46) between cutaneous basal and squamous cell carcinomas; however, geminin LI was significantly higher in squamous cell carcinomas compared to cutaneous basal cell carcinomas (p < 0.001). Only geminin/ki67 showed a significant difference between the two tumors with the ratio showing significantly higher numbers in squamous cell carcinomas (p = 0.015).ConclusionsGeminin could be regarded as an effective factor in the pathogenesis of head and neck cutaneous cutaneous basal cell carcinomas and squamous cell carcinomas and may be one of the responsible elements in the difference between the biologic behavior of these tumors.     

The clinical value of serum squamous cell carcinoma antigens 1 and 2 in head and neck squamous cell carcinoma

Objective

The usefulness of pretreatment measurement of SCC antigen in patients with head and neck SCC is still controversial. Our aim of this study was to evaluate the clinical usefulness of serum SCC antigen, SCCA1 and SCCA2 in the management of patients with head and neck SCC.

Value of the supraomohyoid neck dissection with frozen section analysis as a staging procedure in the clinically negative neck in squamous cell carcinoma of the oral cavity

Summary A retrospective analysis was performed to evaluate with the efficacy of elective supraomohyoid neck dissection (SOND) with frozen section (FS) analysis in 57 newly diagnosed patients (62 SONDs) with squamous cell carinoma of the oral cavity. The protocol included sampling of both the most suspect and largest node in the jugulodigastric region (if present) and the most distal jugulo-omohyoid lymph node (if present). These nodes were then studied with FS histological examination. In the absence of evident nodes for FS analysis during surgery, histological examination uncovered occult metastatic disease in 3 of 11 SOND specimens. Among the remaining patients FS analysis revealed occult metastatic disease in 10 of the 51 samples (19.6%). In these latter cases surgery was continued using standard or modified radical neck dissection en bloc with the primary tumor. In 1 specimen only a single metastasis was found outside the original extent of the SOND. Among 41 FS analysis reports stating the absence of metastatic disease, histological examination of the SOND specimens demonstrated occult nodal disease in 7 (17%). All of the cervical metastases appeared in the ipsilateral side of the neck. False FS reports did not occur. In the histologically proven absence of metastatic disease in the SOND specimens, disease recurrence in the neck occurred only in 3 cases (7%), all in the presence of local failure: once in the previous SOND area, once in the ipsilateral supraclavicular region and once on the contralateral side. The results of our analyses support the conclusion that elective SOND with FS can be a valid staging procedure and a valuable approach to the management of the clinically negative neck in patients with squamous cell carcinoma of the oral cavity. Offprint requests to: J. J. Manni     

Prevalence and localization of nodal metastases in squamous cell carcinoma of the oral cavity: role and extension of neck dissection

Lymph node (LN) metastases represent the most important negative prognostic factor in squamous cell carcinoma (SCC) of the oral cavity, even though controversies still exist regarding their management. The aim of this study was to retrospectively analyze our experience in surgical management of SCC of the oral cavity with particular focus on the prevalence and localization of lymph nodal metastases and recurrences. The clinical records of 89 consecutive patients treated from 1983 to 2002 by concomitant surgery on both the T and N sites, excluding those undergoing salvage surgery, were reviewed. A total of 119 neck dissections (ND) were performed. Survival outcomes were calculated by the Kaplan–Meier method, while univariate comparisons by the log-rank and non-parametric tests were performed between different groups of patients. Five-year overall and determinate survivals were 50 and 57%, respectively. LN metastases were observed in 52% (56% of these showing extracapsular spread) and their presence strongly correlated with determinate survival (p < 0.0001). The prevalence of clinical and occult nodal disease was not related to the pT status. Neck levels II (59%) and I (56%) were most frequently involved. Metastases to level IV accounted for 15% of positive LN, even though 28% of them turned out to be skip metastases. Five neck recurrences were observed, only one of which was salvaged by surgery. The high prevalence of clinical and occult LN metastases in this setting suggests that ND should be performed on a nearly routine basis, even for lesions with a low-T category and a cN0 neck. Moreover, ND should always encompass level IV due to the possibility of skip metastases, particularly in tumors involving the oral tongue. In patients with a cN+ neck, levels from I to V should be addressed, particularly in the presence of metastases at levels III and IV.     

Results of selective neck dissection in the primary management of head and neck squamous cell carcinoma

Selective neck dissection (SND) is known to be a valid procedure to stage the clinically N0 neck but its reliability to control metastatic neck disease remains controversial. This study analysed if selective neck dissection is a reliable procedure to prevent regional metastatic disease in head and neck squamous cell carcinoma (HNSCC). We retrospectively analysed the medical records of 163 previously untreated patients with squamous cell carcinoma of the oral cavity, oropharynx, larynx and hypopharynx treated initially in our departement from January 1990 to December 2002. All patients had unilateral or bilateral SND, in combination with surgical resection of the primary tumour. SND was performed in 281 necks. Finally, 146 patients who underwent 249 SND (39 I–III, I–IV, 210 II–IV, II–V) had adequate follow-up and were assessed for the regional control. The median follow-up was 37 months (1–180 months). The end points of the study were neck control following SND and overall survival. Twenty-five percent (30/119) of patients staged cN0 had lymph node (LN) metastasis. Overall, regional recurrence was observed in 2.8% of the necks (7/249): 1.6% (4/249) in dissected field and 1.2% (3/249) in undissected field. Seventy-eight percent (194/249) of the necks were staged pN0 with a subsequent failure rate of 1.5% (3/194); 16% (39/249) were staged pN1 and postoperative radiotherapy (PORT) was proposed in 21 of these patients. The failure rate with PORT was 9.5% and 5.5% without PORT. Six percent (16/249) of the necks were staged pN2b and all had PORT with one subsequent recurrence. Extracapsular spread (ECS) was reported in 16.5% of positive SND specimens (9/55); all by one were treated by PORT with a subsequent failure rate of 22% (2/9). At 3 years, overall survival for the whole population was 70% and statistically highly correlated with pN stage (p<0.001). These results support the reliability of SND to stage the clinically N0 neck. SND is a definitive operation not only in pN0 but also in most pN1 and pN2b necks. PORT is not justified in pN1 neck without ECS. In pN2b necks, the low rate of recurrence supports adjuvant PORT. The presence of ECS, despite adjuvant PORT, remains associated with a higher risk of recurrence.     

Synchronous laryngeal squamous cell carcinoma and Hodgkin lymphoma of the head and neck region

During the pathologic examination of neck dissection specimens, unexpected findings may occasionally be encountered. Such findings include the presence of a second primary tumor or a chronic infectious or inflammatory disease. We report a case of a 65-year-old man who underwent a supracricoid partial laryngectomy and bilateral neck dissection for squamous cell carcinoma of the larynx. Histopathologic examination of the larynx revealed well-differentiated squamous cell carcinoma, but examination of the neck dissection specimen revealed a mixed cellularity subtype of classical Hodgkin lymphoma.     

The role of tonsillectomy in the initial diagnostic work-up of head and neck squamous cell carcinoma of unknown primary

ObjectiveThe aim of the present study was to determine the value of tonsillectomy in the initial diagnostic work-up of head and neck squamous cell carcinoma of unknown primary (HNSCCUP).Material and methodsA single-center retrospective study (1999–2012) included 45 patients. All cases underwent physical examination, panendoscopy and contrast-enhanced neck and chest CT scan; 27 (60%) also underwent 18-FDG PET scan. Imaging was systematically performed before panendoscopy. In 34 cases (75%), histologic tonsil samples ipsilateral to the HNSCCUP were collected (28 tonsillectomies and 6 biopsies) during panendoscopy. Categoric variables were compared on Chi-square test.ResultsClinical examination and CT did not identify any primary tumor. In 13 cases (38%), invasive squamous cell carcinoma (SCC) was diagnosed on histological samples (12 tonsillectomies, 1 biopsy). For these 13 cases, lymph nodes were located in the upper or middle jugular group, and in 3 cases lymph nodes were cystic on CT scan. In 7 cases (26%), there was an abnormal tonsillar 18-FDG uptake ipsilateral to the cervical lymphadenopathy; tonsillectomy was performed, and SCC was found in 5 of these cases: i.e., 18-FDG PET showed sensitivity and specificity of respectively 55.5 and 88.8%.ConclusionTonsillectomy has a role in the initial diagnostic work-up of HNSCCUP. It is especially useful when lymph nodes are located in the upper and/or middle jugular group with a cystic aspect on CT.     

A systematic review and Number Needed to Treat analysis to guide the management of the neck in patients with squamous cell carcinoma of the head and neck

Objectives

To systematically review the literature to identify studies from which it is possible to perform a Number Needed to Treat (NNT) analysis to identify, in a more clinically intuitive manner, neck node levels for which treatment is essential in the N0 and N+ neck with respect to the primary site of tumour.

Methods

Systematic literature review using a defined search strategy; data extraction from studies meeting the inclusion criteria; calculation of NNT for individual neck node levels with respect to primary site.

Results

A total of 6169 articles were identified from searches of Embase, Medline, The Cochrane library of randomised control trials, conference proceedings and the bibliographies of retrieved papers. Titles and abstracts were screened; from these, 219 studies were retrieved for detailed review. One hundred and ninety six papers were excluded and 23 studies were included in the final analysis. Following review of the data from these studies, and accepting a NNT cut-off of 5 we confirmed that the following lymph node levels should be treated:

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  N0 neck: oral cavity levels II; larynx levels VI; oropharynx levels IIA; hypopharynx levels VI.

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  N+ neck: oral cavity insufficient data; larynx levels IIA − IV + VI; oropharynx levels IIA − III; hypopharynx levels IIA, IIB − IV + VI.

Conclusions

NNT is a clinically intuitive parameter to guide appropriate lymph node level treatment in patients presenting with squamous cell carcinoma of the head and neck.     

头颈部鳞癌及癌旁组织端粒酶活性检测

目的：研究原发头颈部鳞癌及相关癌旁组织中端粒酶活性表达,探讨春作为头颈部鳞癌分子生物学标志物的可能性。方法：采用ＴＲＡＰ－ＰＣＲ－ＥＬＩＳＡ,对３２例原发头颈部鳞癌及１５例癌旁组织进行端粒酶活性检测。结果：３２例原发头颈部鳞癌中,２７例端粒酶活化,阳性率为８４．４％;１５例癌旁组织中５例端粒酶活化,阳性率为３３．３％。有淋巴结累及者端粒酶阳性率（８６．７％）高于无淋巴结累及者（８２．４％）,低分化     

Free flap reconstruction for early stage tongue squamous cell carcinoma: surgical margin and recurrence

Abstract

Background: To identify the difference of surgical margin and recurrence status of early stage tongue carcinoma via wide excision in a single institution with and without free flap reconstruction.

Objective: Survey whether the reconstruction methods for early tongue cancer affects disease control, survival outcomes.

Methods: This was a retrospective study and patients with early tongue cancer underwent surgery via tumor ablation with (group 1?=?56) or without free flap reconstruction (group 2?=?291).

Results: The percentage of patients with free margin less than 5?mm was higher in the group 2 than in group 1 (49.48% vs. 19.64%, p?<?.001), as the mean free margin was significantly larger in group 1 than in group 2 (7.88?mm vs. 5.68?mm; p?<?.001). Despite higher number of T2 stage patients in group 1 (89.29%), the group 1 resulted in a significant lower recurrence rate (p?=?.024).

Conclusions: The utilization of free flap reconstruction for early stage tongue cancer achieved a large pathologic free margin and had relative lower recurrence and good survival rates.     

Proteolytic patterns of head and neck squamous cell carcinoma

The significance of plasminogen activators and matrix metalloproteases for clinical outcome, growth and metastatic behavior of head and neck squamous cell carcinoma (SCC) is still controversial. The majority of studies has been based on either immunohistological stainings, which provide only limited quantitative information, or in vitro experiments. We analyzed 44 head and neck SCC and 11 mucosa tissue samples for the expression of gelatinolytic or fibrinolytic proteases by quantitative zymographic analysis and compared lytic activities to clinical and histopathological data. We calculated activation ratios for matrix metalloproteinases-2 and –9 (MMP-2 and MMP-9) by separate evaluations of inactive and activated MMP forms. Increased gelatinolytic and fibrinolytic activity was found in head and neck SCC when compared to mucosa. Increased values were caused by MMP-9 and urokinase type plasminogen activator, respectively. No statistically significant correlations of either protease lytic activity or activation ratio could be related to T-stage, metastasis, tissue necrosis or the differentiation stage of tumors. The data recorded are compared with previously published reports. Received: 27 August 1998 / Accepted: 6 January 1999     

头颈部鳞癌端粒酶活性的定量检测

目的：了解头颈部鳞癌及其颈淋巴结转移癌端粒酶的表达情况,探讨粒酶活性定量分析在头颈鳞癌诊断中的价值。方法：采用端粒重复序列液体闪烁计数法检测端粒酶活性。共检测取自２５例头颈部鳞癌患者的组织样本５５份,其中７例患者同时取有原发癌及其颈淋巴结转移癌两份样本,以２３份正常组织为对照。结果：①３２份原发鳞癌组织中端粒酶活性（ｃｐｍ值）在１０００以上的２８份,除２份外,均明显高于正常组织;２３份正常组织的端     

Tumour-associated macrophages secrete IL-6 and MCP-1 in head and neck squamous cell carcinoma tissue

Conclusion. Tumour-associated macrophages (TAMs) in head and neck squamous cell carcinomas (HNSCCs) secrete interleukin 6 (IL-6) and monocyte chemotactic protein (MCP-1) that can be down-regulated by L-leucine-methylester (LLME); however, there is no qualitative difference between function of TAMs and tissue macrophages in mucosa as measured by IL-6 and MCP-1 secretion. Objectives. TAMs play an important role in the interaction with tumour cells in malignant tumours. The cells in the tumours that are the main sources of the various signal substances need to be further elucidated. The aim of this investigation was to reveal whether TAMs in HNSCCs secrete IL-6 and MCP-1. These cytokines influence tumour cell growth and macrophage influx in tumours, respectively. Materials and methods. In order to inhibit macrophage function in F-spheroids, in some experiments the tissue fragments were initially incubated with LLME, a substance that selectively inhibits function of phagocytes. IL-6 and MCP-1 secretion from untreated F-spheroids was compared to cytokine secretion from LLME-treated F-spheroids as measured by ELISA. Results. LLME did not affect the viability of F-spheroids and reduced IL-6 and MCP-1 secretion from monocyte-derived macrophages in vitro. F-spheroids from LLME-treated tissue fragments showed lower IL-6 and MCP-1 secretion compared with F-spheroids from tissue fragment untreated with LLME.     

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.     

Synchronous squamous cell carcinoma and malignant lymphoma in the head and neck region

Synchronous malignancy of squamous cell carcinoma (SCC) and malignant lymphoma (ML) in the head and neck region is extremely rare. Here, we report the case of a 57-year-old man with a right-sided neck mass; he was referred to our hospital in September 2001. A series of staging work-ups revealed that he was simultaneously affected by oropharyngeal SCC and nasopharyngeal ML. He underwent conventional radiotherapy, and both the primary tumors showed complete remission. The metastatic lymph nodes showed poor response to the radiotherapy, and the patient was surgically salvaged by modified radical neck dissection. Although systemic chemotherapy against ML was scheduled, he refused the treatment and died of disseminated ML. It is essential to determine the lesion that should be given priority treatment in case of double primary malignancies; this can be facilitated by determining the prognosis of each malignancy.