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.     

The metastatic potential of head and neck cutaneous malignant melanoma: is sentinel node biopsy useful?

Results from a large multicentre trial suggest that sentinel lymph node biopsy examination may benefit disease-free survival in patients with cutaneous malignant melanoma of intermediate thickness, but this is controversial. We recorded the outcomes of patients with these lesions in the head and neck with specific reference to regional lymph node metastases, to find out whether routine sentinel lymph node biopsy examination would have been beneficial. We reviewed pathology databases, multidisciplinary outcomes, and notes for all patients managed by a regional melanoma service between 2004 and 2009, and recorded key characteristics of the tumours. Details on patients with malignant melanoma of intermediate thickness (1.2–3.5 mm) were further analysed for the development of nodal metastases in the neck over a 3-year postoperative period. We compared our data with the rate of predicted nodal metastases generated from the trial. Of 132 patients with malignant melanoma of the head and neck, 33 (25%) had lesions of intermediate thickness, and nodal metastases developed in only one. The remaining 32 remained free of neck disease during the study period. Although trial data predicted that 16% (n = 5 in this sample) would show signs of metastasis and require neck dissection, on the basis of our data, practice in our unit will not change. Sentinel node biopsy examination for melanoma remains controversial because the natural history of metastatic spread of disease is not fully understood.     

Recent advances in the management of cutaneous malignant melanoma: our case cohort

Decades of research into the management of cutaneous malignant melanoma have proven it to be a ‘tough nut to crack’, and its incidence has continued to increase over the last 30 years. Surgery remains a gold standard for early-stage melanoma with five-year survival of 98% for stage I disease, and 90% for stage II. Nonetheless, patients with stage III disease are at a higher risk, resulting in local recurrence as well as distant metastasis. Research regarding the control of metastatic malignant melanoma of the head and neck has evolved. Currently the search is on to understand metastatic malignant melanoma as a heterogeneous disease both at the molecular and clinical level. This paper focuses on the latest systemic therapy for metastatic disease of the head and neck, including cytotoxic chemotherapy, immunotherapy, and target therapy. The new eighth edition of tumour staging, and the sequelae for malignant melanoma, sentinel lymph node biopsy (SLNB), surgical intervention, and its benefits and shortfalls, are discussed. Also, the outcome of our cohort series of patients with metastatic cutaneous malignant melanoma who were treated with systemic combination therapy in Dorset is presented.     

Primary head and neck mucosal melanoma: Predictors of survival and a case series on sentinel node biopsy

IntroductionHead and neck mucosal melanoma (HNMM) is a rare tumor with a poor outcome. The objective of this study was to assess outcome and prognostic factors for a cohort of patients treated in a head and neck cancer center. In addition, a case series on sentinel lymph node biopsy (SLNB) was included to evaluate it as a method for staging the node-negative neck.MethodsA retrospective study design was chosen, and 50 patients who were treated from 1973 to 2015 in our institution for primary HNMM were included. The Kaplan–Meier method was used to estimate survival rates. Uni- and multivariate analyses were used to study the influence of possible risk factors on the patients' outcome. These risk factors included patient demographics, tumor characteristics, and treatment modalities.ResultsAll patients were treated surgically and 50% received adjuvant treatment. The median disease specific survival (DSS) was 38 months, with a 5-year survival rate of 44%. Positive surgical margin (p = 0.004) and distant failure (p = 0.005) were associated with a worse DSS. The median disease-free survival (DFS) was 27 months, with a 5-year disease-free rate of 12%. Only tumor depth >5 mm (p = 0.002) was associated with a worse DFS. Five clinically node-negative patients received SLNB and only the two SLN-positive individuals suffered from distant failure. Radiotherapy, chemotherapy, and AJCC/UICC stage had no influence on any outcome measure.ConclusionsPositive surgical margin and distant failure are the only independent prognostic factors for DSS. Tumor depth can predict distant failure. SLNB may be a valuable staging tool for the node-negative neck.     

头颈部黏膜恶性黑色素瘤的临床分期

恶性黑色素瘤属于易复发和高转移率的恶性肿瘤。与头颈部鳞状细胞癌具有统一独立的肿瘤淋巴结转移(TNM)分期不同,头颈部黏膜恶性黑色素瘤的临床分期一直沿用皮肤恶性黑色素瘤的TNM分期。但头颈部黏膜在组织学结构上与皮肤有着显著的差异,所以头颈黏膜恶性黑色素瘤应该具有一套独立的分期体系,以利于临床上进行诊治和判断预后。下面就口腔、鼻腔和副鼻窦黏膜恶性黑色素瘤分期的研究进展作一综述。     

Sentinel lymph node biopsy for head and neck mucosal cancers – an update on the current evidence

Regional metastases are a prominent feature of mucosal‐associated head and neck squamous cell carcinomas and are an important prognostic factor. Sentinel lymph node biopsy (SLNB) is one modality that has potential to add to the accuracy of neck staging, although it is currently not used as widely in the head and neck as it is in other areas such as breast cancer. We review the efficacy of SLNB in head and neck mucosal squamous cell carcinomas and provide an overview of current practice and include details of technical advances.     

Melanoma: etiology, treatment, and dental implications

Melanoma is one of the most serious skin cancers. It arises from neural crest-derived melanocytes located in the epidermis or dermis of the skin. Melanoma also can arise from melanocytes located in other regions of the body such as the eye, meninges, digestive tract, mucosal surfaces, or lymph nodes. There are no proven causes of melanoma but the most commonly associated factor is episodic exposure to the sun. Melanoma is a common cancer that has been increasing in incidence for the last 35 years. The median age at the time of diagnosis is 53 years. It is much more common in whites than in people of color. Five-year survival rates for melanoma of the skin have been increasing since 1976. There are four types of melanoma: superficial spreading melanoma, nodular melanoma, lentigo maligna melanoma, and acral lintiginous melanoma. Clinical signs indicating possible melanoma are asymmetry, border irregularity, color variation, increase in diameter, elevation, ulceration, and bleeding of pigmented lesions. Histopathologic findings (tumor thickness, tumor invasion), surface ulceration, spread to lymph nodes, and distant metastases are used to project patient prognosis. Treatment consists of surgical excision, lymph node dissection, limb perfusion, regional chemotherapy infusion, radiation, intralesional immunotherapy, systemic chemotherapy, and/or interferon-alpha, depending on the staging of the melanoma. Oral melanomas are rare; however, approximately 20% of all melanomas are found in the head and neck region. The role of the dentist is to be alert for changes in pigmented lesions of the oral mucosa and skin of the head and neck. Lesions suspected of melanoma must be biopsied, which usually involves referral of the patient.     

Sentinel lymph node biopsy in malignant melanoma of the head and neck

Background

The aim of this retrospective study was to investigate sentinel lymph node biopsy in patients with head and neck melanoma.

Malignant melanoma of lingual gingiva with ipsilateral submandibular lymph node metastasis: a case report

Malignant melanoma is a neoplasm of epidermal melanocytes. It is one of the most biologically unpredictable and deadly of all human neoplasms. However, malignant melanoma in the oral cavity is a rare malignancy, accounting for 0.2% to 8% of all melanomas. It has a grave prognosis, with a 5 year survival of 10–20%. We present a case of malignant melanoma of lingual gingiva of left mandibular molars with ipsilateral submandibular lymph node metastasis. We performed peripheral osteotomy of primary lesion followed by modified radical neck dissection by sparing internal jugular vein and patient had received postoperative radiotherapy.     

An update on the current management of head and neck mucosal melanoma

Primary mucosal melanomas of the head and neck are rare and aggressive tumours that arise in the nasal cavity, paranasal sinuses and more rarely in the oral cavity. The current treatment options include radical surgical resection with adjuvant external beam radiotherapy being offered in high‐risk patients. Although the latter can improve regional control, it does not reduce overall survival. Elective neck dissection is recommended for nodular oral mucosal melanoma, but its role in the clinically node negative neck is controversial. Systemic therapies including the use of tyrosine kinase inhibitors for tumours with c‐KIT mutations are suitable for patients with advanced loco‐regional and/or metastatic disease, but current results are variable. Patients with head and neck mucosal melanoma have a poor prognosis due to the high incidence of metastatic disease. This review assesses the latest evidence in the diagnosis and management of primary oral and head and neck mucosal melanoma including details of systemic therapies.     

The relative cost of sentinel lymph node biopsy in early oral cancer

IntroductionThe European Sentinel Node (SENT) trial addressed the question of the clinically lymph node negative (cN0) neck in early oral squamous cell carcinoma (OSCC). Apart from reducing neck dissection numbers, sentinel lymph node biopsy (SLNB) may reduce treatment cost. Using a treatment model derived from SENT trial information, estimates were produced of relative treatment costs between patients managed through a traditional surgical or SLNB pathway.MethodsThe model created two management approaches, the traditional surgical pathway and SLNB pathway. Using SENT trial data regarding the proportion of patients with positive, negative and false negative SLNB's a relative cost ratio (RCR) for 100 hypothetical patients passing down each pathway was generated.ResultsFrom a cohort of 481 patients, 25% had a positive SLNB, 75% a negative result and 2.5% a false negative result. Treatment of 100 hypothetical patients using the SLNB pathway is 0.35–0.60 the cost of treating the same cohort using traditional surgery techniques. Even if 100% of SLNB's are positive the SLNB approach is 0.91 of the cost of the traditional surgical approach.ConclusionThe SLNB approach appears to be cheaper relative to the traditional surgical approach, especially when extrapolated to 100 hypothetical patients.     

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.     

Can we reduce excision margins for head and neck melanoma? A 12-year retrospective study

Although wide local excision is the standard treatment for primary melanoma, the surgical margin remains controversial. Melanomas of the head and neck exhibit higher recurrence rates and worse prognosis than lesions in other body locations, and their close proximity to critical anatomical and functional structures means that wide excision margins are often not feasible. Surgeons must therefore achieve a balance of oncological safety and functional and aesthetic needs. The aim of this study was to retrospectively analyse melanoma data over a 12-year period at a large skin surgery unit to identify potential differences in outcomes in patients who had reduced wide local excision margins for primary head and neck melanoma. The study would provide further evidence for the need for large randomised prospective trials to reduce excision margins for head and neck melanoma. Local cancer network data were retrospectively analysed over a period of 12 years (2008-2019). Data included site, initial stage, multidisciplinary team (MDT) meeting recommendations for excision margins and the actual wide local excision margin taken, recurrence rate, and disease-specific and absolute survival. A total of 222/305 patients (73%) had the recommended excision margin, while in 27% margins were reduced due to anatomical or functional considerations. Recurrence rates were similar (recommended 11.7% vs narrow 13.3% excision margins) (p = 0.64). The mean follow-up time for all patients was 48.5 months. In aesthetically and functionally sensitive areas of the head and neck, wide local excision margins need to be carefully considered after MDT discussion and discussion with the patient. This study suggests the need for further multicentre trials to address the uniqueness of head and neck melanoma.     

前哨淋巴结活检在口腔鳞状细胞癌治疗中的临床意义

目的 探讨前哨淋巴结活检（sentinel lymph node biopsy，SLNB）在口腔鳞状细胞癌临床应用中的可行性、准确性。方法 对31例口腔鳞状细胞癌患者术前使用核素扫描法行前哨淋巴结（sentinellymphnode，SLN）示踪，体表定位；术中γ-探测仪进一步识别SLN行前哨淋巴结活检，同时行颈淋巴清扫；术后对SLN和颈淋巴清扫的病理检查结果进行分析。结果 SLNB对全组病例颈部淋巴结转移状况评价的准确率为96．8％。灵敏度为92，3％，假阴性率为7．7％。结论 SLNB是口腔鳞状细胞癌治疗中的一项新技术，能高灵敏度的反映颈淋巴结状态，具有临床可实用性。     

Survival in node-positive early oral squamous cell carcinoma: sentinel node biopsy versus elective neck dissection

Patients undergoing sentinel node biopsy (SLNB) for early oral squamous cell carcinoma (OSCC) who harbour occult metastases (pN+ve) may be at greater risk of mortality due to prolonged overall treatment times than those identified as pN+ve on elective neck dissection (ELND). A retrospective comparative survival analysis was therefore undertaken to test this hypothesis. Patients were identified from the South Glasgow multidisciplinary team (MDT) database. Group 1 comprised 38 patients identified as pN+ve, or who were false negative, on sentinel lymph node biopsy (SLNB). Group 2 comprised 146 patients staged pN+ve on ELND. The groups were compared with the Kaplan Meier method and Cox proportional hazards model. In addition, a matched-pair analysis was performed. A unique and specifically designed algorithm was deployed to optimise the pairings. No difference in disease-specific or overall survival was found between the groups. Patients undergoing SLNB as the initial neck staging modality in early OSCC and are identified as pN+ve do not appear to be at a survival disadvantage compared with those staged with ELND.     

Staging of the neck in patients with oral cavity squamous cell carcinomas: a prospective comparison of PET, ultrasound, CT and MRI

BACKGROUND: The choice of treatment in patients with oral malignancies depends on accurate pretreatment staging and particularly the detection of lymph node involvement. Therefore staging of the neck should be as accurate as possible. PATIENTS: One hundred and six patients with histologically proven squamous cell carcinoma of the oral cavity. STUDY DESIGN: In a prospective study, PET using fluoro-desoxy-glucose (18F-FDG), ultrasound, CT and MRI of head and neck were compared with the postoperative histologic tissue evaluation. Two thousand one hundred and ninety-six neck lymph nodes of 106 patients were investigated. In all patients the tumour was resected and a lymph node dissection was performed. Results: The diagnostic procedures showed the following results when compared with the histological findings: PET: sensitivity 70%, specificity 82%, accuracy 75%; Ultrasound: 84%, 68%, 76%; CT: 66%, 74%, 70%; MRI: 64%, 69% 66%. Thus PET showed the highest specificity while ultrasound had the highest sensitivity compared with the other staging procedures. A nonsignificant correlation was found between the size of a lymph node metastasis and the ability to detect it. In 10 patients, second primary tumours or distant metastases were detected by PET only. CONCLUSION: Due to the high number of small lymph node metastases from oral cavity carcinoma, the non-invasive neck staging methods are limited to a maximum accuracy of 76%. Elective neck treatment should be mandatory for all patients with squamous cell carcinoma of the oral cavity.     

Is the addition of extranodal extension and lymph node yield of pN0 to the lymph node ratio useful as a prognostic parameter for patients with oral squamous cell carcinoma?

We investigated the value of the weighted lymph node ratio (WLNR), a new marker in pN0 patients that incorporates the number of metastatic lymph nodes with extranodal extension and the lymph node yield, for the prognosis and postsurgical management of oral squamous cell carcinoma (OSCC). We designed a retrospective study and enrolled patients with OSCC who were treated by neck dissection (ND). The predictor variable was WLNR, and the outcome variable was overall survival (OS). The Cox proportional-hazards model was used to identify independent prognostic factors. In 133 patients with OSCC, the WLNR cut-off value for predicting OS was 0.0363 (area under the curve 0.723, p<0.001). When stratified according to WLNR, there was a significant difference in OS (88.4% for low WLNR and 63.0% for high WLNR, p<0.001). Univariate analyses showed close associations between OS and age, dissection area, postoperative management, extranodal extension, number of positive lymph nodes, pN stage, WLNR, and nodal disease area. Cox multivariate analysis identified the WLNR as an independent predictive factor for OS (HR 3.273, 95% CI 1.227 to 8.731, p=0.018). As a predictive factor, a high WLNR (≥0.0363) in patients with pN0 disease, which included the addition of extranodal extension and lymph node yield to the LNR, was associated with diminished survival.     

Diagnostic yield of sentinel lymph node biopsy in oral squamous cell carcinoma T1/T2-N0: systematic review and meta-analysis

The objective of this study was to conduct a systematic review and meta-analysis on the efficacy of sentinel lymph node biopsy (SLNB) in T1/T2-N0 oral squamous cell carcinoma (OSCC). A systematic review of the literature on SLNB until March 2019 was conducted. The review was organized according to the PRISMA protocol, considering the following PICO (population, intervention, comparison, outcome) question: What is the sensitivity of sentinel lymph node biopsy in OSCC? ‘P’ was patients with head and neck squamous cell carcinoma T1/2-N0; ‘I’ was SLNB; ‘C’ was neck treated with elective neck dissection and haematoxylin–eosin histopathology; ‘O’ was sensitivity and specificity. A meta-analysis and meta-regression were performed on the selected studies. The sensitivity of SLNB was up to 88% (95% confidence interval (CI) 72–96%) and specificity was up to 99% (95% CI 96–100%). The area under the summary receiver operating characteristic curve was 0.99 (95% CI 0.98–1.00). In the four studies where immunohistochemistry was performed, both the sensitivity and specificity were higher than in the studies without immunohistochemistry: 93% (95% CI 88–97%) and 98% (95% CI 96–100%), respectively. In conclusion, SLNB is an effective technique for treating patients with some types of stage T1/2-N0 OSCC. Some parameters such as immunohistochemistry could determine the level of diagnostic accuracy.     

Retrospective study on the cutaneous head and neck melanoma in Dorset (UK)

Trends in the incidence and the sites of primary malignant melanoma on the skin of head and neck in Dorset as well as the outcome of treated cases were overviewed for the first time. Increase in incidence rate of cutaneous head and neck melanoma from 1.3 per 100,000 in 2004 to 3.1 per 100,000 in 2007 was recorded. The most prevalent histogenetic type of cutaneous malignant melanoma on head and neck in our study was melanoma of superficial spreading type 35.1% (n = 20) of all registered cases. Superficial spreading melanoma apart from being the most common type of malignant melanoma of the head and neck in Dorset also showed increase in the number of diagnosed cases of the reviewed years. It increased from 2 (22.2%) of all head and neck melanoma cases in 2004 to 7 (30.4%) in 2007. The average age at the time of diagnosis the cutaneous malignant melanoma of head and neck for both men and women was 73.5 years. Breslow thickness, Clark's level of invasion, tumour ulceration and anatomical site remained the most important prognostic factors. Correlation between Breslow thickness and Clark's level of invasion found to be stronger in men.     

Sentinel lymph node biopsies in early stage oral and oropharyngeal carcinoma: a retrospective single-centre experience

The aim of this retrospective study was to analyse a consecutive series of patients with oral and oropharyngeal carcinoma who had had sentinel lymph node biopsy (SLNB) at our hospital during 2008-2017. A total of 70 patients with clinically and radiologically confirmed primary oral (n = 67) or oropharyngeal (n = 3) carcinoma, with no signs of metastatic lymph nodes preoperatively (clinically N0) were included. Patients’ clinical and personal data, characteristics of the tumours, sentinel lymph node (SLN) status and outcomes were recorded. Eight patients had invaded SLN. Two patients with clear sentinel lymph node biopsies had recurrences in the cervical lymph nodes with no new primary tumour as origin. The negative predictive value (NPV) and sensitivity for SLNB were 97% and 80%, respectively. The depth of invasion was an individual predictor for cervical lymph node metastasis (p = 0.043). Single photo emission computed tomography (SPECT) detected fewer SLN in patients with invaded lymph nodes than in patients with clear lymph nodes (p = 0.018).Our data support the use of SLNB as a minimally invasive method for staging the cervical lymph nodes among patients with cN0 oral and oropharyngeal carcinoma. Our results further confirm that greater depth of invasion is associated with cervical lymph node metastases.