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.     

Tumor–stroma ratio is a crucial histological predictor of occult cervical lymph node metastasis and survival in early-stage (cT1/2N0) oral squamous cell carcinoma

Occult cervical lymph node metastasis is a significant prognostic factor in patients with early-stage (cT1/2N0) oral squamous cell carcinoma (OSCC). The aim of this study was to investigate the potential value of the tumor–stroma ratio (TSR) as a histological predictor of occult cervical metastasis and survival in early-stage OSCC. This retrospective study included 151 patients who underwent excision of the primary lesion and elective neck dissection from 2013 to 2017. The clinicopathological features of the tumor, risk factors associated with occult neck metastasis, and prognostic factors for overall survival (OS) and disease-free survival (DFS) were studied. A significant correlation of TSR (P = 0.009) was found with occult neck metastasis in the multivariate logistic regression model. Multivariate Cox proportional hazards regression analysis showed that the TSR (P = 0.002) and perineural invasion (P = 0.011) were associated with OS. Occult neck metastasis (P = 0.032) was associated with DFS. These findings indicate that assessment of the TSR might be useful in prognostication for early-stage OSCC patients. Moreover, the TSR is effective in allowing an accurate evaluation of the risk of occult neck metastasis, and this may be easily applicable in the routine pathological diagnosis and clinical decision-making for elective neck dissection.     

Malignant tumours of the parotid gland: management of the neck (including the clinically negative neck) and a literature review

Major salivary gland malignancies are rare, constituting 1%-3% of head-neck tumours. The surgical management of the clinically negative neck (cN0) does not have a univocal consensus yet. We have carried out a retrospective study on 119 cases of malignant parotid tumours that were surgically treated between January 1999 and January 2014. Our aim was to analyse preoperative findings (cytotype, cTNM) and to correlate these with postoperative results (grading, histotype, occult neck metastasis) in patients with parotid tumours to obtain an appropriate indication for neck management. In cN0 patients with a T1, T2 low-grade cancer a wait-and-see approach is preferred. Instead, in cNO patients with high-grade or low-grade T3, T4 tumours an elective neck dissection (END) is always planned. Levels II, III and IV, at least, must be dissected. The decision to dissect level V or I depends on the location of the primary tumour. In the cN0 group 19 of 58 (32.7%) patients who underwent an END had occult metastases. In clinically positive neck (cN+) patients a Modified Radical Neck Dissection (MRND), at least, must be performed. The criteria to add adjuvant radiotherapy (PORT) include deep lobe parotid tumours, advanced lesions (T3-T4), microscopic (R2) or macroscopic (R1) residual disease after surgery, high grade tumours, perineural diffusion, lymph node metastasis, capsular rupture, and local recurrence after previous surgery. Kaplan-Meier analyses have shown a reduction in the overall survival (OS) from 100% to 91% and in disease-free survival (DFS) from 100% to 95.5% for the NO-PORT and PORT group, respectively. In our study, the cN0 pN+ patients had a higher degree of DFS compared to the cN+.     

DNA content in malignant salivary gland tumours

Objective:  Our aim was to evaluate the DNA content in malignant salivary gland tumours using image cytometry and its possible relationships with clinical and morphologic findings, disease course and prognosis.
Patients and methods:  The study sample comprised 31 patients diagnosed and treated for primary malignant salivary gland tumours. Formalin-fixed, paraffin-embedded surgical specimens of all patients were Feulgen-stained for DNA content analysis by image cytometry. Statistical analysis was used to investigate possible relationships between DNA content variables and clinical and histological findings, disease course and patient survival.
Results:  Seventeen (55%) cases of our sample were graded as DNA diploid, four (13%) as DNA aneuploid and 10 (32%) as DNA multiploid. In 15 (48%) cases, the 5c exceeding rate (5cER) was higher than 1.7%. DNA ploidy correlated with N stage and tumour size. DNA ploidy and 5cER had a statistically significant prognostic influence on overall and disease-free survival in univariate analysis. However, in multivariate analysis, stage classification was the only parameter with an independent prognosis value.
Conclusion:  Abnormal DNA content is a common finding in salivary gland cancers. Our results suggest an important role of DNA content analysis in the evaluation of these tumours.     

Heterogeneity of squamous cell carcinomas of the head and neck in relation to clinicopathological variables

We analysed 32 primary, 8 recurrent and 16 metastatic squamous cell carcinomas of the head and neck by flow cytometry to assess tumoural heterogeneity. Intratumoural heterogeneity was found in 9 of 30 primary tumours (30%). All heterogeneous tumours had diploid and aneuploid cell lines. DNA indices were different from those of the primary tumours in 3 of the 8 recurrent lesions (38%) and in 8 of the 12 metastatic lesions (67%). The results indicate that new cell lines evolve during the process of recurrence and metastasis. The incidence of recurrence, metastasis, and heterogeneity increased with the size of the tumour. Histologically, there were tumours in which the degree of differentiation and mode of invasion of primary lesions were not consistent with the results of flow cytometry in both homogeneous and heterogeneous tumours. In conclusion, multiple sampling for flow cytometric analysis is essential for better characterization of oral carcinomas.     

临床舌鳞癌N0患者的颈部处理

目的 :探讨舌鳞癌N0 的治疗方法。方法 :对四川大学华西口腔医院 1986～ 1998年间 14 5例舌鳞癌N0患者进行回顾性研究。对T1患者切除原发灶 ,颈部观察 ,对于T2 以上患者或无法随访者采取选择性颈清扫 ,术后随访 3年以上或至死亡。各组间的比较采用卡方检验。结果 :12 3例行选择性颈淋巴清扫术 (END) ,3 3例术后病理证实淋巴结转移 ,2 2例颈部观察组中 4例出现颈淋巴转移。淋巴结隐匿性转移率为 2 5 .5 2 % ,且随临床T分期的增高而增高。总体颈部失控死亡率 ,观察组 (18.18% )与END组 (5 .69% )相比 ,差异有显著性 (P <0 .0 5 )。T1期观察组和END组的颈部失控死亡率分别为 7.69%和 4.5 5 % ,两组间差异无显著性 (P >0 .0 5 ) ,而将T2 、T3 期作为中期病变合并 ,观察组 (3 3 .3 3 % )和END组 (0 % )差异显著 (P <0 .0 0 1)。结论 :舌鳞癌颈部隐匿性转移率较高 ,对T2 期以上N0 舌鳞癌患者应考虑行选择性颈清扫术 ,可提高其颈部控制率和生存率     

The role of elective supraomohyoidal neck dissection in the treatment of early, node-negative oral squamous cell carcinoma (OSCC): A retrospective analysis of 122 cases

The adequate treatment of the neck in early, clinically node-negative oral squamous cell carcinoma (OSCC) remains controversial. To assess whether elective supraomohyoid neck dissection is reasonable and efficient in early, locally circumscribed OSCC, the outcomes of treatment of 122 patients with an OSCC of clinical UICC stage I or II were retrospectively analysed in this study. Occult lymph node metastases were detected in 13.9% (17/122) of cases. They were more frequently found in T2 compared to T1 tumours (19.7% (14/71) vs. 5.9% (3/51), p = 0.03), age, gender and grading had no influence on the prevalence of occult lymph node metastases (all p-values > 0.05) in a multivariate logistic regression model. Subsequent multivariate survival analysis found that the presence of occult metastases was an independent predictor of reduced disease-free survival after 5 years (82.2% vs. 62.5%, p = 0.004, and 61.9% vs. 17.8%, p < 0.001, respectively). Elective supraomohyoid neck dissection detects occult metastases in early, node-negative OSCC, and patients with early OSCC exhibiting occult metastases should be considered as high risk patients, warranting additional therapeutic regimes.     

Eosinophils may predict occult lymph node metastasis in early oral cancer

Objective

The aim of this study was to investigate whether tumor-associated tissue eosinophilia (TATE) in early oral squamous cell carcinoma (OSCC) would aid in predicting occult lymph node metastasis.

Patients and methods

Seventy-one patients undergoing elective neck dissection for T1 and T2 OSCC were evaluated for clinical features, prognosis, and TATE. The degree of TATE in OSCC was statistically analyzed in relation to the clinicopathological features, tumor invasion, occult lymph node metastasis, and survival using χ ² test and Kaplan–Meier method.

Results

Statistical analysis revealed that intense TATE was a significant feature (p?=?0.004) to predict occult lymph node metastasis in patients with early OSCC. All regional recurrences of the OSCC occurred in patients showing intense TATE.

Conclusions

These results suggest that intense TATE can be clinically used as a predictive factor for occult lymph node metastasis.

Clinical relevance

The presence of intense TATE is an adjunctive histopathological marker to reinforce the indication of elective neck dissection of the patients with early OSCC.     

选择性颈淋巴清扫术及其适应证的评价

作者通过对３８２例行颈淋巴清扫术的口腔癌患者的回顾性研究，对选择性（即预防性）颈清扫术及其适应证进行评估。本研究重点分析了各种相关因素与颈淋巴结转移的关系。结果表明：各种口腔癌的颈淋巴结总转移率为４４％（１６７／３８２）。而在术前未扪及肿大淋巴结者即隐匿性转移率为２３％（１９／８４）。颈淋巴转移的发生频率与原发灶的大小、部位、肿瘤细胞的分化程度和肿瘤类型等密切相关。特别是颈淋巴结的状况是评估颈部转移的重要信息。本研究强调对原发灶及颈淋巴的仔细检查和综合分析，有助于更准确判断是否有颈淋巴转移及是否应行ＥＮＤ。     

DNA-Ploidie und proliferative Aktivität bei Speicheldrüsentumoren

DNA ploidy and S-Phase fraction (SPF) of 279 salivary gland tumours were analysed using high-resolution DNA flow cytometry. All 229 benign neoplasms were diploid while 12 of 50 malignant tumours showed cell populations with aneuploid DNA content. The SPF values of diploid malignancies were significantly higher if compared with pleomorphic adenomas but did not differ from that of the zystadenolymphoma (Warthin tumour) group. While aneuploidy represents a distinct indicator of malignancy SPF values are of minor relevance for dignity assessment in salivary gland tumours.     

Management of the clinically N0 neck in early-stage oral squamous cell carcinoma (OSCC). An EACMFS position paper

Metastasis of oral squamous cell carcinoma (OSCC) to the cervical lymph nodes has a significant impact on prognosis. Accurate staging of the neck is important in order to deliver appropriate treatment for locoregional control of the disease and for prognosis.The management of the neck in early, low volume disease (clinically T₁/T₂ oral cavity tumours) has long been debated. The risk of occult nodal involvement in cT₁/T₂ OSCC is estimated around 20–30%.We describe the natural evolutionary history of OSCC and its patterns of spread and metastasis to the local lymphatic basins. We discuss most published literature and studies on management of the clinically negative neck (cN₀). Particular focus is given to prospective randomized trials comparing the outcomes of upfront elective neck dissection against the observational stance, and we summarize the results of the sentinel node biopsy studies.The paper discusses the significance of the primary tumour histological characteristics and specifically the tumour's depth of invasion (DOI) and its impact on predicting nodal metastasis. The DOI has been incorporated in the TNM staging highlighting its significance in aiding the treatment decision making and this is reflected in world-wide oncological guidelines.The critical analysis of all available literature amalgamates the existing evidence in early OSCC and provides recommendations in the management of the clinically N₀ neck.     

111例cN0口腔鳞状细胞癌患者颈部淋巴结转移临床分析

目的 探讨颈部淋巴结阴性（clinically negative cervical lymph node,cN0）的口腔鳞癌（oral squamous cell carcinoma, OSCC）患者发生颈淋巴结隐匿性转移的规律和相关影响因素。方法 收集承德医学院附属医院2007年5月—2017年5月接受颈淋巴结清扫术的111例cN0口腔鳞癌患者的临床和病理资料,进行回顾性分析。采用SPSS 17.0软件包中χ²检验,分析隐匿性转移与年龄、性别、原发灶部位及病理分级的关系。结果 111例cN0口腔鳞癌患者中,总隐匿性转移率为27.03%（30/111）。cN0口腔鳞癌患者淋巴结转移率与性别、年龄及发病部位无显著相关（P>0.05）,与病理分期存在显著相关（P<0.05）。结论 肿瘤分化程度越低,颈淋巴结隐匿性转移率越高。临床上对此类患者,应积极行颈淋巴清扫术。     

Value of anatomic site,histology and clinicopathological parameters for prediction of lymph node metastasis and overall survival in head and neck melanomas

IntroductionHead and neck melanoma compromises a group of aggressive tumours with varying clinical courses. This analysis was performed to find anatomic and clinicopathological parameters predictive for lymph node metastasis and overall survival.Material and methodsData and outcome of 246 patients with a malignant melanoma in the head and neck region were retrospectively analyzed for predictive parameters.ResultsLentigo maligna melanoma (n = 115) was the most frequent histology, followed by superficial spreading (n = 63) and nodular melanoma (n = 52). More than half of the melanomas (n = 138) were in the face. Tumours of the face and anterior scalp metastasized to lymph nodes of the neck and parotid gland, whereas tumours of the posterior scalp and neck also metastasized to the nuchal region. Advanced Clark level, presence of tumour ulceration and younger age were the strongest predictors of lymph node metastasis in multivariate regression analysis (p < 0.05), but anatomic site, histological subtype and tumour thickness were also associated with lymph node metastasis. Lymph node metastases, distant metastases, ulceration, nodular subtype and non-facial site of origin were the strongest negative prognostic parameters for disease-specific overall survival (p < 0.05). In contrast, the width of resection margin (<1 cm vs. 1–2 cm vs. >2 cm) did not correlate with tumour recurrence and overall survival (p > 0.05).ConclusionHistological subtype diagnosis, anatomic site of origin as well as the established factors tumour thickness, ulceration and depth of invasion are prognostic indicators of cervical lymph node metastasis and overall survival. A resection margin of at least 1 cm seems sufficient in head and neck melanoma. The status of sentinel lymph node biopsy and neck dissection has to be proven within the next years.     

Sentinel lymph node biopsy for early oral cancer – accuracy and considerations in patient selection

Sentinel lymph node biopsy (SLNB) for staging oral squamous cell carcinoma (OSCC) patients presenting with early (T1 and T2 N0) disease in preference to elective neck dissection (END) remains controversial worldwide. A retrospective analysis of 145 patients who underwent sentinel lymph node biopsy for a previously untreated early oral cancer between 2010 and 2020 was performed. The primary outcome measures were predictors of occult metastases, accuracy of SLNB and disease specific plus overall survival. The negative predictive value, the false negative rate, and sensitivity for SLNB were 97%, 7.8%, and 92%, respectively. Depth of invasion (DOI) was a significant predictor of N status, overall survival, and disease specific survival. There was a significant difference in the incidence of the neck node metastasis in patients with DOI <5mm compared to those with DOI >5mm. For tumours >5mm there was a moderate to good correlation between radiological depth on contrast enhanced computed tomography (CECT) and histopathological DOI. Preoperative estimation of DOI may be a useful tool in the counselling of patients in the selection of either SLNB or END for N staging purposes in early OSCC.     

Intraosseous carcinoma of the anterior maxilla identified as the occult primary tumour of carcinoma of unknown primary

Carcinoma of unknown primary (CUP) is defined as lymph node metastasis without a detectable origin until after the initial treatment has been performed. The most common occult primary site in the head and neck, as revealed by a review of the published literature, is the oropharynx. An occult primary site in the oral region is extremely rare. We report a rare case of head and neck CUP (HNCUP) in a 69-year-old female patient, wherein the occult primary lesion was a primary intraosseous carcinoma (PIOC) invading the anterior maxilla. During the course of the initial diagnostic workup, no primary lesion could be identified; however, cervical lymph node metastasis to left levels IB and IIA were observed in the patient. A neck dissection followed by adjuvant radiotherapy was performed. However, the PIOC of the anterior maxilla was identified 6 months after neck treatment and was confirmed as the occult primary tumour of the HNCUP. This case is quite rare and required a comprehensive workup to guide optimal treatment. Careful follow-up or active biopsy should be considered if osteolytic changes are observed in the jaw.     

舌鳞癌无区域性淋巴结转移患者的颈部处理

目的 评价对于舌鳞癌无区域性淋巴结转移患者造反性颈淋巴清扫的必要性。方法对１３０例舌癌颈淋巴结临床阴性的患者用Ｃｏｘ回归模型（Ｃｏｘ ｒｅｇｒｅｓｓｉｏｎ ｍｏｄｅｒ,Ｃｏｘ模型）多因素分析方法,分析了影响颈部转移的因素,同时比较颈部淋马清扫与否两组的生存效果。结果 原发灶Ｔ分级、治疗方法及放疗与颈淋巴结复发有明显相关意义,是否颈淋巴清扫及其他几个因素则与复发无关,其生存率表明差异无显著性,生存率     

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.

     

An update on the latest evidence for managing the clinically negative neck (cN0) in oral squamous cell carcinoma

The single most important prognostic indicator for survival in oral squamous cell carcinoma (OSCC) is the presence of lymph node metastases in the neck. While the treatment of the clinically node positive (cN+) neck is well established, the management of the clinically negative neck (cN0) is controversial. Various strategies have been advocated including close observation including regular ultrasound imaging, elective neck dissection and sentinel lymph node biopsy. Neck dissection surgery is not without potential morbidity with shoulder dysfunction being the main complication. A number of factors are associated with increased risk of neck node metastasis including primary tumour thickness and peri‐neural invasion. A recent prospective randomised trial has found survival benefit following neck dissection even in patients with a cN0 neck at presentation. We discuss the latest evidence for managing the cN0 in OSCC and include our own experience on the role of neck dissection in certain cases.     

DNA ploidy analysis in salivary gland tumours by image cytometry

AIM: To determine whether DNA ploidy by image cytometry is a good diagnostic tool to distinguish benign and malignant salivary gland tumours. METHODS: A total of 62 salivary gland tumours were studied. Cases were histologically diagnosed [haematoxylin and eosin (H&E)]. According to the World Health Organization (WHO) classification, there were 14 mucoepidermoid carcinomas (MEC), 11 adenoid cystic carcinomas (ACC), 10 pleomorphic adenomas (PA), 10 carcinoma ex PA (CEPA), 9 acinic cell carcinomas (ACCa), 3 polymorphous low-grade adenocarcinomas (PLGA), 2 papillary cystadenocarcinomas (PC), 1 myoepithelial carcinoma (MC), 1 undifferentiated carcinoma (UC) and 1 mucinous adenocarcinoma (MA). Paraffin sections (40 microm) were micro-dissected to isolate tumour areas; cell nuclei were extracted and Feulgen-stained cytospin monolayers were analysed using a DNA image cytometry system. For each case, DNA index (DI) was calculated relative to internal controls (lymphocytes; DI=1.0). Cases were categorized as diploid or aneuploid and the proportion of cells over 5c was also calculated. RESULTS: Fifty-three of 62 salivary gland tumours were uniformly diploid. Only nine cases were aneuploid: five CEPA, one low-grade MEC, one PC, one UC and one MA. CONCLUSIONS: The vast majority of salivary gland tumours were diploid. High-grade malignancies may be aneuploid, and ploidy may be useful to identify malignant change in atypical PA. Further, larger studies are needed to confirm our results and to further evaluate the usefulness of the technique in high-grade lesions.