The topography of cervical lymph node metastases revisited: the histological findings in 526 sides of neck dissection from 439 previously untreated patients

The pathological reports, minimum datasets and topographical plots of the neck dissections from 439 cases of oral and oropharyngeal cancer reported by a single pathologist following a standard protocol were analysed. Metastasis was evident in 47% of patients including bilateral metastases in 6%, extracapsular spread in 29% and matting in 7%. The extent of metastasis (both volume and distribution) was greatest in tumours of the oropharynx followed by lateral tongue, ventral tongue and floor of mouth. The typical 'inverted-cone pattern' was seen in 67% of patients with metastasis. A single micrometastasis was seen in 14%, skip lesions in 10% and involvement of 'other' nodal groups in 4%. Contralateral neck metastases (0.4%), peppering (2%), flushing of lymph node sinuses (1%) and all nodes positive (0.4%) accounted for the remaining 'aberrant' patterns. Skip lesions were seen in tumours at all sites other than retromolar.     

cN0舌癌患者颈淋巴结转移的区域分析

目的探讨cN0舌癌患者颈淋巴结转移的区域分布情况,为cN0舌癌患者颈淋巴清扫的术式选择提供参考。方法取61例cN0舌癌患者根治性颈淋巴清扫术后标本,收集各平面区域的淋巴结进行病理切片,分析其淋巴结转移情况及各区域的分布。结果 20例患者发现淋巴结转移,转移率32.8%,811颗淋巴结中62颗证实有转移,占7.6%。其中平面Ⅰ为11.0%（26/237）,平面Ⅱ为8.2%（20/243）,平面Ⅲ为6.0%（13/218）,平面Ⅳ为3.5%（3/85）,平面Ⅴ无淋巴结转移。结论 cN0舌癌患者仍有较高的颈淋巴结转移率,转移淋巴结主要分布于平面Ⅰ、Ⅱ和Ⅲ,少部分转移至平面Ⅳ,选用肩胛舌骨上颈淋巴清扫术最好扩展至平面Ⅳ。     

T2 carcinoma of the tongue: the histopathologist's perspective.

The histological characteristics and extent of tumour spread at the primary site and in the neck are described in a series of 50 patients with a T2 squamous cell carcinoma of the oral tongue. The likely site of origin was lateral tongue in 29 cases and ventral tongue in 21 cases. Simultaneous tumours were evident in four resections and multifocal dysplasia in a further 13. Lymph node metastasis was diagnosed histologically in 27 cases, including one case with bilateral metastases. Comparison of the groups, with and without metastasis, showed significant differences in tumour thickness, tumour diameter, multifactorial histological malignancy grade, vessel invasion and nerve invasion. The number of positive lymph nodes per patient ranged from 1 to 16 (mean 3), and 17 dissections showed spread beyond the nodal capsule. Postoperative follow-up ranged from 1 to 6 years and, at the time of analysis, 18 patients had died of or with disease. Loco-regional failure was related to 'high-risk' features at the primary site and extracapsular spread in the neck.     

舌根恶性多形性腺瘤双颈淋巴结转移（附病例报告）

目的：研究舌根恶性多形性腺瘤（MPA）双侧颈淋巴结内癌转移的临床表现、诊断、治疗及预后。方法：对舌根恶性多形性腺瘤双侧颈淋巴结内癌转移病例,分析其临床表现、影像学表现、诊疗过程及组织病理学特征,并进行文献回顾。结果：本文病例为老年男性,首诊症状为颈侧上部无痛肿物,鼻咽镜检查发现舌根无痛性肿物,钳取活检为中分化鳞状细胞癌,行舌根肿瘤扩大切除及双侧改良根治性颈淋巴清扫术,术后病理为舌根恶性多形性腺瘤,恶性成分为鳞状细胞癌,可见淋巴管内瘤栓,双侧Ⅰ、Ⅱ、Ⅲ区颈淋巴结内癌转移（18/42）。术后放疗50Gy,随访1年,未见肿瘤复发与转移。结论：舌根MPA极罕见,双侧颈淋巴结内癌转移病例,经文献检索未见报告。手术彻底广泛切除原发灶并行颈清扫术,辅以放疗,预后良好。     

Pathology of the N0 neck.

The incidence, extent and distribution of nodal metastasis is described in 152 neck dissections from patients with an NO neck undergoing surgery for an intraoral/oropharyngeal squamous cell carcinoma. The preoperative N stage had been determined by palpation under general anaesthesia and magnetic resonance imaging. Metastasis was detected histologically in 32 (21%) of the 152 NO necks. The number of positive nodes per NO neck ranged from 1 to 6. In total, 52 positive nodes were found and 29 (56%) measured 10 mm or less in maximum dimension. Twenty-one dissections (66%) contained a single positive node and 24 (75%) showed a single positive anatomical level. Three cases showed 'skipping' of levels within the neck and one case showed 'peppering'. Seventeen (53%) of the 32 positive NO necks and 31 (60%) of the 52 positive nodes contained only 'micrometastases' (deposits < 3 mm). Microscopic extracapsular spread was evident in five NO necks including one case with extracapsular spread at multiple levels. The study concludes that preoperative staging by palpation and routine magnetic resonance imaging cannot be relied upon to detect early cervical metastatic disease, and the topographic distribution of positive nodes indicates that modified neck dissections should include level IV when the primary tumour involves the tongue.     

Incidence of metastasis to level V lymph nodes in clinically positive necks among Sri Lankan patients with oral squamous cell carcinoma

Oral squamous cell carcinoma (OSCC) remains the most common cancer among males in Sri Lanka. Metastasis to neck is a crucial prognostic factor. A modified radical/radical neck dissection including levels I –V, was performed in patients with OSCC who had a clinically positive neck (cN+). Currently, evidence suggests that sparing level V in a cN+ may be justified due to less chance of metastasis in early stages of the disease. To the best of our knowledge, the incidence of metastasis to level V in patients with cN+s has not been previously investigated in a Sri Lankan context. We aimed to determine level V lymph node metastasis and related clinicopathological indicators in cN+s in patients with OSCC. A multicentre retrospective study investigated postoperative biopsy reports of 187 patients for five years. OSCC patients with cN+s who underwent neck dissections of levels I-V were included. Only 6.4% of patients had histopathologically positive level V lymph nodes. A total of 127 lymph nodes were harvested from level V of those who showed level V positivity and out of them 68 were positive with a third of cases showing extranodal extension (ENE). The buccal mucosa (n=4) and lateral aspect of the anterior two thirds of the tongue (n=4) were the common primary sites for level V metastasis. In patients who showed positivity in levels III and IV, a considerably higher probability of level V nodes being positive was seen, which was statistically significant (p = 0.0001). We have concluded that the routine performance of a modified radical/radical neck dissection for cN+s should be stopped, as the incidence of Level V positivity is significantly low. Assessing the cN+ for N stage, status of levels III and IV, pattern of invasion, differentiation, and the site may be used instead as predictors for level V positivity.     

Elective management of the neck in oral cavity squamous carcinoma: current concepts supported by prospective studies

The incidence of occult cervical metastasis in oral cavity cancer, even in early stages, is significant, necessitating elective treatment of the neck in a majority of cases. There is no method of imaging or other examination that will detect microscopic foci of metastatic disease in cervical lymph nodes. Immunohistochemical and molecular analysis of neck specimens reveals the incidence of occult metastases to be higher than revealed by light microscopy with ordinary hematoxylin and eosin staining. The neck may be treated electively by surgery or irradiation. Surgery has the advantage of permitting pathological staging of the neck, avoiding unnecessary radiation treatment and indicating cases where adjuvant therapy should be employed. As oral cavity cancer rarely metastasizes to level V, a radical or modified radical neck dissection of all five node levels is not necessary. Selective dissection of levels I–III (“supraomohyoid neck dissection”) is the usual procedure of choice for elective dissection of the neck. Most of the relatively small number of isolated metastasis to level IV are from primary tumours of the tongue, which are known to produce “skip” metastases. Thus an “extended supraomohyoid neck dissection” of levels I–IV is recommended by some authors for elective treatment of the neck in tongue cancer. A number of recent prospective multi-institutional studies have demonstrated that sublevel IIB is rarely involved with isolated metastasis from oral cavity primary tumours, except from some tongue cancers. Thus it is justifiable to omit dissection of sublevel IIB in elective treatment of most cases of oral cavity cancer. Bilateral neck dissection should be performed in elective treatment of tumours involving midline structures, and in patients with ipsilateral neck metastasis.     

Effects of incision and irradiation on regional lymph node metastasis in carcinoma of the hamster tongue

The effects of incision and irradiation on regional lymph node metastasis in DMBA-induced squamous cell carcinomas of the hamster tongue are reported. Metastasis to the submandibular lymph nodes was confirmed histologically in 48.0% of the animals. The incidence of lymph node metastasis was significantly increased (65.9%) after repeated incisions of tongue carcinomas. Three gray whole-body irradiation also increased the rate of metastasis from 31.0% to 46.3%. Higher incidences of lymphatic vessel invasion after incision and concomitant lymph node metastasis in the lymphatic invasion-positive group indicated a stepwise relationship leading to an increase in lymph node metastasis after incision. Because of the high incidence of metastases and close resemblance to human carcinomas in the tumor cell deposition and establishment of metastatic foci, DMBA-induced tongue carcinoma with invasion may serve as an experimental model of human oral carcinomas.     

Immunoexpression of matrix metalloproteinase-2 and matrix metalloproteinase-9 in the metastasis of squamous cell carcinoma of the human tongue

Background: Squamous cell carcinoma of the tongue has frequent lymph node metastases and poor prognosis. Matrix metalloproteinase‐2 (MMP‐2) and matrix metalloproteinase‐9 (MMP‐9) are reported to degrade basement membrane, facilitating invasion and metastasis. This study determined the expression of MMP‐2/MMP‐9 in primary tongue cancer with or without cervical metastases and analysed the significance of such expression in relation to the presence or absence of metastases. Methods: Expressions of MMP‐2/MMP‐9 were detected by immunohistochemistry in 10 specimens of normal oral mucosa, 20 lymph node‐negative tongue cancers, 41 lymph node‐positive tongue cancers and their metastasized tumours in cervical lymph nodes. Results: MMP‐2/MMP‐9 expression was seldom found in normal epithelium. In lymph node‐negative tongue cancer, 45% and 40% of these primary tumours were positively stained for MMP‐2/MMP‐9, respectively. Importantly, in lymph node‐positive tongue cancer, 71% and 79% of these primary tumours were positive for MMP‐2/MMP‐9, respectively. Overexpression of MMP‐2/MMP‐9 was present in the metastatic lymph nodes. Conclusions: Our results imply that MMP‐2 and/or MMP‐9 play an important role in invasion and metastasis in tongue cancer, and that analysis of MMP expression and/or activity in primary tumours may have a predictive value for the actual or potential presence of cervical metastases.     

cN0舌鳞癌颈部Ⅲ区、Ⅳ区淋巴结的微小转移分析

目的 分析临床颈部阴性（cN0）舌鳞癌患者的颈部Ⅲ区、Ⅳ区淋巴结微小转移情况。方法 采用角蛋白免疫组化染色结合半连续切片技术,对25例cN0舌鳞癌颈部Ⅲ区、Ⅳ区的471个淋巴结进行复查。结果 常规病理检查证实有转移的11个位于Ⅲ区的阳性淋巴结,角蛋白免疫组化染色均能检出;在常规病理检查为阴性的460个淋巴结中,角蛋白免疫组化染色结合半连续切片技术,仅在1个Ⅲ区淋巴结中检出一个2.0 mm×1.5 mm的微转移灶,在Ⅳ区淋巴结中未检出微转移灶。结论 cN0舌鳞癌Ⅳ区淋巴结转移率很低,对所有的cN0舌鳞癌患者均清扫Ⅳ区似无必要。     

兔舌不同部位VX-2鳞癌与颈淋巴结转移模型的生物学特性

目的:制作兔舌不同部位VX-2鳞癌和颈淋巴结转移模型,并对其生物学特性进行研究,为舌癌多学科治疗提供研究平台。方法:将新西兰白兔20只,随机分为4组,每组5只,分别植入VX-2鳞癌瘤块。观察瘤块植入后肿瘤生长、体积变化、成瘤率、颈淋巴结转移率、转移的部位、数目以及兔生存期等指标。数据采用SPSS11.5软件包进行游程检验、独立样本t检验和χ2检验。结果:总成瘤率75%,其中舌缘80%,舌中线区70%,颈淋巴结转移率均70%,舌缘转移至同侧颈淋巴结,舌中线区转移至双侧颈淋巴结。平均生存期为舌缘(33.25±6.20)d,舌中线区(39.00±3.74)d。各区间无统计学意义(P>0.05),舌癌和颈部转移淋巴结均为低分化鳞癌。结论:瘤块移植法能成功制作不同部位兔舌VX-2鳞癌模型,成瘤率和转移率均较高,生存期为4～6周。其生物学特性与人舌癌基本一致,生长迅速,容易转移,是研究舌癌较理想的动物模型。     

Patients with unilateral squamous cell carcinoma of the tongue and ipsilateral lymph node metastasis do not profit from bilateral neck dissection

Objectives

The purpose of this study was to evaluate the necessity of elective bilateral neck dissection for treating strict unilateral squamous cell carcinoma (SCC) of the tongue.

Methods

A cohort of 169 patients with unilateral non-midline crossing SCCs of the tongue treated by local resection and neck dissection was investigated. Study endpoints were nodal relapse and overall survival. The mean follow-up was 7.4 years.

Results

A total of 146 (88.1%) patients were treated by neck dissection. Lymph node metastases were diagnosed in 50 (34.2%) patients. Only two (1.1%) had contralateral lymph node metastases. Risk factors for developing a primary lymph node metastasis were size of tumor (T2/T3, p =?0.03; OR?=?2.2), lymphangiosis (p =?0.003; OR?=?4.7), and higher-grade differentiation (p =?0.051; OR?=?2.43). Metachronous lymph node metastases were detected in 23 (13.6%) patients (19 ipsilateral, one contralateral and three bilateral). The main risk factor for developing a metachronous lymph node metastasis was the presence of a primary lymph node metastasis (p =?0.004; HR?=?4.65). Patients with initial neck dissection came up with lower 5-year recurrence rates (13.6%) compared to patients without neck dissection (27.3%; p =?0.014). Bilateral neck dissection showed no advantage regarding nodal relapse free and overall survival (p =?0.606) compared to unilateral neck dissection irrespective of initial N or T stage.

Conclusion

Patients with unilateral SCC of the tongue benefit from an ipsilateral neck dissection regarding nodal relapse. The value of elective bilateral neck dissection as standard treatment seems questionable even if positive lymph nodes were diagnosed ipsilateral at primary therapy.

     

原发性舌鳞状细胞癌颈淋巴结低位转移规律的临床研究

目的 研究分析原发性舌鳞状细胞癌颈部淋巴结低位（Ⅳ区和Ⅴ区）转移的临床规律,为舌癌颈部淋巴结低位区域的清扫决策提供参考依据。方法 选取2010年1月—2015年12月上海交通大学医学院附属第九人民医院收治的原发性舌鳞状细胞癌同期或二期行全颈（Ⅰ～Ⅴ区）淋巴结清扫患者203例,收集其临床病理资料及随访信息,分析原发舌鳞状细胞癌颈部低位淋巴结转移的临床病理影响因素和预后。结果 在203例患者中,Ⅳ区和Ⅴ区转移率分别为14.78%和4.93%,男性较女性更易出现Ⅳ区转移（P=0.04）,不吸烟较吸烟更易出现V区转移（P=0.046）;Ⅲ区和Ⅳ区的淋巴结状态与Ⅴ区转移风险明显相关（P=0.001）;Ⅲ区包膜外侵犯患者发生Ⅳ区（P=0.014）和V区（P=0.026）转移的风险明显增加;发生低位淋巴结（Ⅳ/Ⅴ）转移的患者5年生存率仅为14.70%,是原发性舌鳞状细胞癌患者的独立不良预后因素（P<0.000 1）。结论 原发性舌鳞状细胞癌绝大部分转移发生于Ⅰ～Ⅲ区,低位淋巴结转移比率较低,对于cN0患者和Ⅰ～Ⅱ区淋巴结转移但无包膜外侵犯的cN+患者,Ⅴ区淋巴结可以选择观察。     

Recurrent nodal metastases in the posterior triangle: implications for treatment of the atypical tumour

We studied the incidence of recurrent nodal metastases in level V (posterior triangle) in patients who had previously had a staging or therapeutic dissection of the neck, with or without postoperative radiotherapy. Of 160 patients studied (177 neck dissections), 41 (26%) developed recurrent metastases in the neck. Four patients (3%) developed ipsilateral recurrent disease in level V. In these four patients, level III or IV lymph nodes were shown histologically to have extracapsular spread at the time of the original dissection. All four metastases were located at or just beyond the anatomical boundaries of the posterior triangle. None of the metastases at level V were from oral or oropharyngeal primary tumours.     

cN0口腔鳞癌颈部Ⅱb区淋巴结转移的临床分析

目的 :探讨cN0口腔鳞癌患者颈部Ⅱb区淋巴结的转移情况。方法 :对2008-01—2011-03期间就诊的,94例c N0口腔鳞癌患者资料进行了统计分析,所有患者均在原发灶切除同期行颈淋巴结清扫术,术后单独分离Ⅱb区淋巴结并进行常规病理检查。结果:在94例患者的102侧颈清标本中,22例患者的22侧颈部发生了转移。仅有1例舌癌患者的颈部淋巴结转移灶累及Ⅱb区,Ⅱb区淋巴结转移率为4.5%,该患者还伴有颈部Ⅰ、Ⅱa区转移。结论:cN0口腔鳞癌颈部Ⅱb区淋巴结转移率较低,建议cN0患者行择区性淋巴结清扫术时,可酌情保留颈部Ⅱb区淋巴组织。     

Salivary gland adenoid cystic carcinoma with cervical lymph node metastasis: a preliminary study of 62 cases

Adenoid cystic carcinoma (ACC) is an infrequent malignant neoplasm that originates most commonly in the major and minor salivary glands of the head and neck region. This study provides new information on head and neck ACC with cervical lymph node metastasis. Of 616 patients who underwent primary tumour resection from 1995 to 2008 in the authors' hospital, 62 cases with cervical lymph node metastasis were analyzed. The general incidence of cervical lymph node metastasis in ACC was approximately 10%. The base of tongue, mobile tongue and mouth floor were the most frequent sites of lymph nodes metastasis, with incidences of 19.2%, 17.6% and 15.3%, respectively. Most cases occurred via a classic 'tunnel-style' metastasis and the level Ib and II regions were the most frequently involved. Primary site and lymphovascular invasion were significantly associated with lymph node metastasis. High patient mortality was significantly correlated with lymph node positive cases. The tongue-mouth floor complex has a high propensity for cervical lymph node metastasis, which occurs through a classic 'tunnel-style' metastasis. Peritumoral lymphovascular invasion could be taken as strong predictor for lymph node metastasis, which ultimately leads to poor prognosis of ACC patient. Selective neck dissection should be considered in such cases.     

Development of a new invasion and metastasis model of human oral squamous cell carcinomas

A new model was devised in order to establish an in vivo model for oral carcinoma that exhibits significant local invasion and metastasis. One hundred and fifty-two nude mice had tumour cells from one of two established oral squamous cell carcinoma (SCC) cell lines (OSC-19 and OSC-20) implanted into the tongue or the oral floor via an intra-oral route and, as a control, the subcutaneous tissue of the back. The back tumours showed an expansive growth pattern, lacking significant invasion of surrounding tissues. In contrast, the tumours implanted into the tongue or the oral floor exhibited invasive growth and the histological appearance was similar to that of the original tumours. Moreover, regional neck lymph node and pulmonary metastases were observed in this model. Regional neck lymph node metastases were detected in 81.0% of mice implanted with OSC-19 cells and in 13.6% of mice implanted with OSC-20 cells. OSC-19 and OSC-20 cells showed pulmonary metastases in 9.5 and 9.1% of mice, respectively. These results suggest that this intra-oral implantation model is valuable in the study of the mechanism of invasion and metastasis of oral SCC.     

Application of fuzzy inference to European patients to predict cervical lymph node metastasis in carcinoma of the tongue

In head and neck cancers, the presence of cervical lymph node metastasis is an important determinant of outcome. Many attempts have been made to predict cervical lymph node metastasis, but the accuracy of currently available techniques remains inadequate. We used fuzzy inference to predict cervical lymph node metastasis retrospectively in 75 patients with squamous cell carcinoma of the tongue and prospectively in 23 patients. Our model was based on three variables: tumor size, keratinization, and mode of invasion. The accuracy of fuzzy inference for the prediction of cervical lymph node metastasis in the 75 patients studied retrospectively was 86.7%, the sensitivity was 70.8%, and the specificity was 94.1%. In the 23 patients studied prospectively, the accuracy was 91.3%, the sensitivity was 50.0%, and the specificity was 95.2%. The accuracy obtained in this European series of patients was similar to that previously obtained in Japanese patients. We conclude that fuzzy inference may be a useful method for predicting cervical lymph node metastasis. Its high specificity is likely to reduce the number of unnecessary neck dissections. However, the current level sensitivity is inadequate for routine clinical use. Therefore, other predictors of lymph node metastasis should be identified to refine the current model.     

Regional lymph node metastasis in carcinoma of the hamster tongue

The incidence of regional lymph node metastasis in the hamster tongue carcinoma induced by DMBA was studied. Metastasis to the regional lymph node was confirmed by histologic examination in 25 (22.1%) of the 113 experimental animals. Of a total of 238 lymph nodes examined, metastatic deposits were found in 35 (14.6%) lymph nodes. Systemic administration of cortisone increased the rate of metastasis from 16.7% to 26.1%, but the difference was not statistically significant. The necessity of extending the tumor-bearing period and the addition of mechanical trauma to the primary carcinoma to increase the rate of metastasis are stressed.