Patterns of mandibular invasion by gingival squamous cell carcinoma.

PURPOSE: This study examined patterns of invasion of lower gingiva cancer into the mandible. Our goal was to clarify the most common routes for gingival squamous cell carcinoma to enter and spread within the mandible. PATIENTS AND METHODS: The subjects were 176 patients with lower gingival squamous cell carcinoma who underwent mandibulectomy; all tumors were examined histopathologically. The method of mandibulectomy was decided on the basis of conventional plain radiographic and computed tomographic findings. RESULTS: The tumor extended to the periosteum in 33%, to the cortical bone in 23%, and to the bone marrow in 9% of the patients who underwent mandibular resection. The remaining 35% of our patients had no evidence of mandibular invasion. CONCLUSION: The area of bone resorption on preoperative clinical and radiographic examinations often disagreed with the extent of mandibular invasion on histopathologic examination.     

A study of osteoclast-related cytokines in mandibular invasion by squamous cell carcinoma

The purpose of this study was to analyze the mechanism of bone invasion in carcinoma of the mandibular gingiva. We investigated 38 specimens of lower gingival carcinoma and histopathologically classified them into an invasion group (23 cases) and a non-invasion group (15 cases) on the basis of light microscopy evidence. These specimens were examined using immunohistochemical techniques involving antibodies of parathyroid hormone-related protein (PTHrP), tumor necrosis factor (TNF)-alpha, interleukin (IL)-1alpha, -1beta, -6, -11, -18 and transforming growth factor (TGF)-beta. The invasion group showed a high level of expression of PTHrP, TNF-alpha, IL-6 and IL-11 positive cells (P<0.01 versus non-invasion group). The difference in the levels of expression of IL-1alpha, -1beta, -18 and TGF-beta positive cells was not significant between these two groups. Our results suggest that various cancer-derived cytokines, such as PTHrP, TNF-alpha, IL-6 and IL-11, play an important role in the mechanism of bone invasion associated with lower gingival squamous cell carcinoma.     

The cellular and molecular mechanisms of bone invasion by oral squamous cell carcinoma

Oral squamous cell carcinomas (SCCs) are malignant tumours that frequently invade the mandibular bone and bone invasion is a common clinical problem. Recent studies have revealed that bone resorption by osteoclasts is an important step in the process of bone invasion by oral SCCs. However, the cellular and molecular mechanisms of bone invasion by oral SCCs remain unclear. Oral SCCs invade the mandibular bone through an erosive, mixed or infiltrative pattern that correlates with clinical behaviours. The expressions of interleukin (IL)-6, IL-11, tumour necrosis factor (TNF) α and parathyroid hormone-related protein (PTHrP) were higher in the infiltrative pattern than in the erosive pattern. These cytokines lead to receptor activator of NF-κB ligand (RANKL) expression or osteoprotegerin (OPG) suppression not only in oral SCC cells but also in cancer stromal cells to induce osteoclastogenesis. Taken together, oral SCCs provide a suitable microenvironment for osteoclastogenesis to regulate the balance of RANKL and OPG. In this review, we introduce recent advances in the knowledge of the cellular and molecular mechanisms, by which oral SCC invades mandibular bone based on the recent findings of our lab and others.     

Mandibular invasion by oral squamous cell carcinoma

Forty-five specimens consisting of mandibular bone and adjacent squamous cell carcinoma were histologically investigated. In 23 of them, there was no involvement of the mandibular bone: a continuous periosteal layer separated the tumour from the bone. Tumour spread through periosteal lymphatics was not observed in any of these cases and therefore there is no reason to sacrifice bone when the tumour is not fixed to the jaw. Twenty-two specimens exhibited bony involvement. In 10 of them, the bone was eroded by an advancing tumour front. None of these cases exhibited tumour invasion into cancellous spaces, dental canal or periodontal ligament space. Tumours with this type of bony involvement are amenable to mandible-sparing surgical treatment. The other 12 exhibited diffuse growth into cancellous bone, dental canal and, if present, periodontal ligament space. Cases like these are to be operated on by removing the entire thickness of the involved mandibular part. Tumours involving bone were slightly larger than those leaving bone uninvolved. The tumours eroding bone were of a smaller size than those infiltrating bone. The differences, however, are too small to have a predictive value in treatment planning. Attention is drawn to the presence of dental epithelial rests that should not be mistaken for invading tumour nests.     

Analysis of cell proliferation and pattern of invasion in oral squamous cell carcinoma

Cell proliferation markers play an important role in the biological behavior of neoplasms. This study investigated the immunohistochemical expression of PCNA, Ki-67 and Cyclin B1 proteins based on the pattern of cell invasion in oral squamous cell carcinoma (OSCC). A total of 39 OSCC specimens and 13 samples of normal oral mucosa (control) were immunohistochemically analyzed. Protein expression was evaluated according to World Health Organization - Histological Malignancy Grading (WHO-HMG) and a specific grading system for invasion, graded from 1 to 4, varying from a consistently well-defined "pushing" border to diffuse infiltration and cellular dissociation, and was then correlated with clinical features. We found higher expression of Ki-67 and Cyclin B1 in OSCC when compared with the control group. High Ki-67 expression levels were more commonly seen in the floor of the mouth than in the tongue (P = 0.009). Cyclin B1 showed a positive correlation with histological grade, according to WHO-HMG criteria (P = 0.01). Our results suggest that Cyclin B1 is a reliable proliferation marker for indicating degree of tumor proliferation. Correlations between PCNA, Ki-67, Cyclin B1 and invasive tumor front with overall survival were not observed. Further studies are needed in order to elucidate whether cell proliferation activity at the tumor invasion front is related to prognosis.     

Mandibular invasion by oral squamous cell carcinoma. Clinical aspects

In this paper we have tried to correlate the clinical and radiological aspects to the histological findings in squamous cell carcinomas of the oral cavity, in relation to bone involvement in the mandible. 52 patients were analyzed and we conclude that there is a positive indication for mandible sparing surgery, even if there is fixation to the jaw or radiologically visible bone involvement.     

Correlation between invasion mode and the histologic risk assessment model in oral squamous cell carcinoma

Purpose

The histologic risk assessment (HRA) model was proposed to assess clinical outcome of oral squamous cell carcinomas (SCCs), and its prognostic value has been confirmed in several studies, but its underlying molecular mechanisms has not been fully investigated. The objective of this study was to evaluate the association between immunohistochemical invasion mode of head and neck SCC and the HRA grading system.

Methods

The HRA model consisting of risk scores (RSs), based on perineural invasion (PI), lymphocytic infiltration (LI), and worst pattern of invasion (WPOI), was used for grading 80 samples of head and neck SCC, followed by immunohistochemical staining with antibodies against E-cadherin, N-cadherin, and podoplanin. The two major invasion modes were considered as epithelial-mesenchymal-transition (EMT) and collective cell invasion (CCI) with profiles of E-cadherin^?/N-cadherin+/podoplanin^? and E-cadherin+/N-cadherin^?/podoplanin⁺, respectively. All other immunohistochemical profiles were classified as partial/incomplete EMT. Statistical analysis was performed by Kruskal-Wallis and Mann-Whitney U tests (P?<?0.05).

Results

Invasion pattern was significantly different among the three RSs (P?=?0.01) and across the different scores of LI (P?=?0.03) but not perineural invasion (PNI) (P?=?0.07) and WPOI (P?=?0.70).

Conclusions

Based on our results, it seems that there is a difference in EMT, CCI, and partial/incomplete EMT among the variables of the HRA model which might help clarify its functioning system.

     

Evaluation of cortical mandibular bone in patients with oral squamous cell carcinoma

Clinical Oral Investigations - The aim of the study was to evaluate the mandible cortical bone changes in patients with oral squamous cell carcinoma (OSCC). Twenty patients who underwent some...     

Bone scanning for evaluating mandibular bone extension of oral squamous cell carcinoma

Inability to control the primary tumor in oral cancer, leading to local recurrence, results in low survival rates. The extent of bone involvement is therefore a critical factor in planning treatment. To evaluate whether uptake of 99mTc-DPC (dicarboxypropane-diphosphate) was reliable in demonstrating the extent of mandibular involvement, 13 consecutive patients with squamous cell carcinoma of the mandibular gingiva, floor of the mouth, and lower buccal sulcus were studied. Bone involvement, as judged from preoperative radiographs and bone scans, was compared with that determined through careful analysis of histologic sections of jaw specimens. The bone scan findings corresponded well with the histologic findings in 10 cases. In contrast to earlier studies, there were no false-positive findings. False-negative bone scans were seen in three cases in which there was infiltration of the upper cortex of the mandible. A negative bone scan, therefore, cannot guarantee absence of bone involvement. Nevertheless, bone scanning seems to provide valuable information for preoperative evaluation of evident tumor infiltration of bone.     

CT和SPECT对下牙龈癌侵犯下颌骨诊断价值的比较

目的:评价CT和SPECT在检测下颌牙龈鳞状细胞癌侵犯下颌骨中的价值.方法:收集2002年2月-2006年10月间青岛大学医学院附属医院21例下颌牙龈鳞状细胞癌住院患者,以组织病理学检查结果为对照,对CT、SPECT资料进行比较,评价CT和SPECT的诊断价值.结果:21例患者中,SPECT的灵敏度、准确度、阴性预测值、正确指数分别为100.00%、95.24%、100.OO%、1.00,CT的灵敏度、准确度、阴性预测值、正确指数分别为80.00%、80.95%、20.00%、0.80,CT有80.00%(4/5)的假阴性,而SPECT无假阴性.结论:与CT相比,SPECT的诊断效能高,故可作为牙龈癌侵犯下颌骨的筛查方法.     

Cone-beam CT in the assessment of mandibular invasion by oral squamous cell carcinoma: results of the preliminary study

This preliminary retrospective study evaluates the diagnostic value of cone-beam computed tomography (CBCT), as a potential standard preoperative procedure, in assessing mandibular invasion by oral squamous cell carcinoma (OSCC) compared with conventional preoperative panoramic radiography (PR), magnetic resonance imaging (MRI) and histological examination of the resection specimen (the golden standard). Between September 2006 and September 2009, 23 patients with histology proven primary OSCC, adjacent to or fixed to the mandible were included. The tumours were classified into four groups, ranging from no bone invasion to evident bone invasion. Sensitivity and specificity for PR were 55% (95% CI [0.350;0.619]) and 92% (95% CI 0.737;0.984]), respectively, both were significantly lower than the 91% (95% CI [0.740;0.909]) and 100% (95% CI [0.845;1]), respectively, for CBCT. MRI showed 82% sensitivity (95% CI [0.608;0.941]) and 67% specificity (95% CI [0.474;0.779]). CBCT has the potential to become a new diagnostic tool in the OSCC screening procedure to predict mandibular invasion or erosion, but its value may be limited by its relatively low sensitivity. A prospective study will start on 64 patients (α = 0.05; power 0.8; effect size 0.5) to improve these results statistically.     

The correlation of histologic features with a panoramic radiography pattern and a computed tomography pattern of bone destruction in carcinoma of the mandibular gingiva

OBJECTIVE: We sought to clarify the correlation among a computed tomography (CT) or a panoramic radiography (PR) pattern of bone destruction, a histologic pattern of bone destruction, and a mode of invasion in carcinoma of the mandibular gingiva. STUDY DESIGN: CT images, panoramic radiographs, and decalcified, hematoxylin-eosin-stained preparations of the excised mandibular bone of 62 patients with carcinoma of the mandibular gingiva were retrospectively evaluated. Each computed tomograph, panoramic radiograph, and the histologic pattern of bone destruction was classified as 1 of 5 types: erosive, erosive and partly mixed, mixed, mixed and partly invasive, or invasive. The mode of invasion of the tumor was also assessed with a hematoxylin-eosin-stained preparation of the initial biopsy specimen. The relationships among the CT pattern, the PR pattern, the histologic pattern of bone destruction, and the mode of invasion of the tumor were statistically analyzed by using the Spearman rank correlation test. RESULTS: The CT pattern (P =.005) and the PR pattern (P =.003) were significantly correlated with the histologic pattern with respect to the bone destruction. The CT pattern (P =.996), the PR pattern (P =.997), and the histologic pattern (P =.521) of bone destruction were not correlated with the mode of invasion seen in the biopsy specimen. CONCLUSION: The CT pattern and the PR pattern of bone destruction reflect the histologic pattern of bone destruction caused by carcinoma of the mandibular gingiva but are not associated with the mode of invasion of the tumor.     

Assessment of mandibular invasion of squamous cell carcinoma by various modes of imaging: constructing a diagnostic algorithm

The aim of this study was to determine the optimal combination of preoperative examination methods to predict mandibular invasion by squamous cell carcinoma of the oral cavity. Data were gathered prospectively but evaluated retrospectively. The preoperative results of clinical examination, conventional radiography, bone single photon emission computed tomography (SPECT), computed tomography and magnetic resonance imaging were compared to the histological results of resection specimens from 67 patients with tumours, adjacent or fixed to the mandible, histologically confirmed as squamous cell carcinoma. The examination methods with acceptable sensitivity and specificity were selected and diagnostic algorithms were constructed using all possible combinations. The preferred diagnostic algorithm was found to be either computed tomography or magnetic resonance imaging, followed by a bone SPECT in cases where the first scan is negative. A negative bone SPECT rules out mandibular invasion (100% sensitivity). This algorithm accurately predicted mandibular invasion in 85% of the patients, without yielding false negative results. In this study group, application of such an algorithm would have resulted in a reduction of the number of unnecessary mandibular resections by 50%. The suggested, preferred, diagnostic algorithm shortens the preoperative screening process, avoiding unnecessary costs, as well as considerably reducing the number of unnecessary mandibular resections.     

The prediction of mandibular invasion by squamous cell carcinomas with the expression of osteoclast-related cytokines in biopsy specimens

Destruction of bone by tumour is caused by osteoclasts rather than by tumour cells directly. Tumour cells of invasive oral squamous cell carcinomas (SCC) release osteoclast-related cytokines and cytokines activate osteoclasts. The purpose of this study was to investigate the possibility of predicting mandibular invasion by SCC by analysis of the expression of osteoclast-related cytokines in biopsy specimens of SCC, adjacent or fixed to the mandible. Thirty-five biopsy specimens from the pathology archives were examined from patients who had been treated for SCC, adjacent or fixed to the mandible. The patients were divided into those with and without medullary invasion. The expression of tumour necrosis factor (TNF)–α, interleukin (IL)-6 and IL-11 was studied by immunohistochemical analysis. No significant differences were found in expression of TNF–α, IL-6 and IL-11 between biopsy specimens with or without medullary invasion. Quantification of the density of tumour-infiltrating lymphocytes was not reproducible. In conclusion, the expression of TNF–α, IL-6 and IL-11 in biopsy specimens of SCC, adjacent or fixed to the mandible, is not an appropriate method for predicting the presence of medullary invasion of the mandible.     

Primary intraosseous squamous cell carcinoma arising in a mandibular keratocyst.

Primary intraosseous carcinoma (P1OC) of the jaws is rare. They either arise de novo or as a consequence of malignant transformation of a benign cyst or tumor. A 56-year-old patient with a P1OC of the mandible arising from an odontogenic keratocyst is described.     

舌癌浸润方式与淋巴结包膜外侵犯的关系及临床意义

目的 :探讨舌癌不同浸润方式与颈淋巴结转移癌包膜外侵犯间的关系及其临床意义。方法 :分析行根治性颈清扫术的 2 0例连续性舌癌病例 ,按Anneroth等描述的肿瘤浸润方式评估舌癌的恶性程度 ,以常规HE及免疫组化染色法观察淋巴结转移癌包膜外侵犯情况。结果 :舌癌淋巴结包膜外侵犯多见于浸润方式为III、IV型的舌癌 ,包膜外侵犯在整个淋巴结被肿瘤取代或仅部分被肿瘤浸润时均可发生 ,癌细胞常成簇或以单个细胞形式浸润至淋巴结周围之脂肪间隙或淋巴结间 ,并可扩散至胸锁乳突肌。结论 :肿瘤浸润方式对评估舌癌的恶性程度有重要意义 ,对浸润方式为III、IV型的舌癌应采取根治性颈淋巴结清扫术。     

Factors influencing the patterns of invasion of the mandible by oral squamous cell carcinoma

The pattern of tumour invasion of the mandible depends on the extent of invasion. Both the width (P=0.02) and depth (P=0.01) in patients with an invasive or infiltrative pattern of disease were greater than in tumours showing the less aggressive erosive pattern in which the tumour mass is separated from the resorbing bone by a connective-tissue layer. Evidence in this study suggests that the erosive pattern develops through a mixed pattern to the invasive pattern of disease as the tumour progresses through the bone. The invasive pattern of disease was evident at a much shallower depth in the molar region of the mandible (mean 9 mm), with a decreased ratio of alveolar to basal bone, than in the premolar and parasymphyseal region (mean 25 mm) (P=0.02). The hypothesis to explain this phenomenon is that the more superficial alveolar bone responds by resorbing in advance of the tumour, but the basal bone is unable to respond in the same way and becomes widely infiltrated. The attached mucosa with its firm collagen attachment to bone is proposed as the main route of tumour entry into the mandible in both dentate and edentulous mandibles.