Anders Bilde

Joint Practice Guidelines for Radionuclide Lymphoscintigraphy for Sentinel Node Localization in Oral/Oropharyngeal Squamous Cell Carcinoma

Involvement of the cervical lymph nodes is the most important prognostic factor for patients with oral/oropharyngeal squamous cell carcinoma (OSCC), and the decision of whether to electively treat patients with clinically negative necks remains a controversial topic. Sentinel node biopsy (SNB) provides a minimally invasive method for determining the disease status of the cervical node basin, without the need for a formal neck dissection. This technique potentially improves the accuracy of histologic nodal staging and avoids overtreating three-quarters of this patient population, minimizing associated morbidity. The technique has been validated for patients with OSCC, and larger-scale studies are in progress to determine its exact role in the management of this patient population. This document is designed to outline the current best practice guidelines for the provision of SNB in patients with early-stage OSCC, and to provide a framework for the currently evolving recommendations for its use. Preparation of this guideline was carried out by a multidisciplinary surgical/nuclear medicine/pathology expert panel under the joint auspices of the European Association of Nuclear Medicine (EANM) Oncology Committee and the Sentinel European Node Trial (SENT) Committee.

The role of SPECT-CT in the lymphoscintigraphic identification of sentinel nodes in patients with oral cancer

Conclusion: SPECT-CT may improve the localization of sentinel nodes (SNs) in patients with oral squamous cell carcinoma (OSCC). Compared with planar lymphoscintigraphy SPECT-CT detected more SNs and provided additional anatomical and spatial information about their localization. New generation SPECT with higher resolution CT scanners are expected to provide more accurate information about the localization of SNs. Objective: To assess the role of combined SPECT-CT in SN identification in the clinically negative neck of patients with OSCC. Materials and methods: Lymphoscintigraphy comprising planar and SPECT-CT acquisition was performed in 34 consecutive patients with OSCC stage I and II (T1-2N0M0) prior to sentinel node biopsy (SNB) and selective neck dissection. The number of SNs and anatomical location was recorded according to lymphoscintigraphy and operative findings. Results: SNB was conducted in 33 patients. SNs were identified in 94% (32/34) of the patients using SPECT-CT. In 91% (29/32) of the patients SNs were harvested from all of the levels involved on SPECT-CT. SPECT-CT imaging demonstrated extra SNs compared with planar lymphoscintigraphic imaging in 47% (15/32) of patients. In seven cases the anatomical level of SN according to SPECT-CT was reclassified during surgery. The overall incidence of lymph node metastases was 19% (6/32). There were no false negative SNs.

Sentinel European Node Trial (SENT): 3-year results of sentinel node biopsy in oral cancer

PURPOSE Optimum management of the N0 neck is unresolved in oral cancer. Sentinel node biopsy (SNB) can reliably detect microscopic lymph node metastasis. The object of this study was to establish whether the technique was both reliable in staging the N0 neck and a safe oncological procedure in patients with early-stage oral squamous cell carcinoma. METHODS An European Organisation for Research and Treatment of Cancer-approved prospective, observational study commenced in 2005. Fourteen European centres recruited 415 patients with radiologically staged T1-T2N0 squamous cell carcinoma. SNB was undertaken with an average of 3.2 nodes removed per patient. Patients were excluded if the sentinel node (SN) could not be identified. A positive SN led to a neck dissection within 3 weeks. Analysis was performed at 3-year follow-up. RESULTS An SN was found in 99.5% of cases. Positive SNs were found in 23% (94 in 415). A false-negative result occurred in 14% (15 in 109) of patients, of whom eight were subsequently rescued by salvage therapy. Recurrence after a positive SNB and subsequent neck dissection occurred in 22 patients, of which 16 (73%) were in the neck and just six patients were rescued. Only minor complications (3%) were reported following SNB. Disease-specific survival was 94%. The sensitivity of SNB was 86% and the negative predictive value 95%. CONCLUSION These data show that SNB is a reliable and safe oncological technique for staging the clinically N0 neck in patients with T1 and T2 oral cancer. EORTC Protocol 24021: Sentinel Node Biopsy in the Management of Oral and Oropharyngeal Squamous Cell Carcinoma.

Need for Intensive Histopathologic Analysis to Determine Lymph Node Metastases When Using Sentinel Node Biopsy in Oral Cancer

Objective: To determine the predictive value of sentinel node biopsy (SNB)‐assisted neck dissection in patients with oral squamous cell carcinoma (SCC) stage T1 to 2N0M0 and to determine the incidence of subclinical metastases.

Sentinel node biopsy: the technique and the feasibility in head and neck cancer.

Management of the clinically N₀ neck in head and neck squamous cell carcinoma is still under debate. Tumour spread to the neck is the most important prognostic factor in head and neck cancer patients. The sentinel node technique comprises the identification of the sentinel node by means of dye or isotope or a combination, and surgical removal followed by histological examination. We have reviewed the preliminary reports indicating that sentinel node identification is technically feasible in head and neck cancer surgery, i.e. in solitary and unilaterally oral and pharyngeal cancer stages T1 and T2 with clinical N₀. However, the existing reports enrole observational studies, thus randomised trials should be considered to gain maximum valid data to prove that sentinel node biopsy has an effect on parameters such as loco-regional control and survival.

Molecular markers in the surgical margin of oral carcinomas

BACKGROUND Local or regional lymph node recurrence is the most common pattern of treatment failure in oral squamous cell carcinoma (SCC). The local recurrence rate is 30% even when the surgical resection margin is diagnosed as tumour free. Accumulation of genetic changes in histologically normal epithelium in the surgical resection margin may explain the local recurrence rate. The purpose of this study is to investigate the presence of senescence markers, which may represent early malignant changes in the margin that in routine pathological evaluations are classified as histologically normal. METHODS Formalin-fixed, paraffin-embedded surgical specimens from 16 consecutive patients with oral SCC and a clear surgical margin were obtained. The margin was analysed by immunohistochemistry for p53, p16, Chk2, Laminin-5 and glycosylated oncofetal fibronectin. RESULTS Two patterns of p53 expression were found in the histologically normal epithelium in the surgical resection margin. One was characterized by no protein expression in the majority of cells, except for small clusters of basal and parabasal cells with nuclear staining. The other was characterized by p53 expression in the nuclei of most basal cells. The expression of p16 was confined to small groups of cells in the basal cell layer whereas Chk2 was only seen in one case. Upregulation of the stromal proteins, Laminin-5 or glycosylated oncofetal fibronectin, was only seen at regions of invasion. CONCLUSION Small groups of cells expressing p53 and p16 were found in the surgical resection margin that appeared to be histologically normal and may represent early malignant changes.

Joint practice guidelines for radionuclide lymphoscintigraphy for sentinel node localization in oral/oropharyngeal squamous cell carcinoma

Involvement of the cervical lymph nodes is the most important prognostic factor for patients with oral/oropharyngeal squamous cell carcinoma (OSCC), and the decision whether to electively treat patients with clinically negative necks remains a controversial topic. Sentinel node biopsy (SNB) provides a minimally invasive method of determining the disease status of the cervical node basin, without the need for a formal neck dissection. This technique potentially improves the accuracy of histological nodal staging and avoids over-treating three-quarters of this patient population, minimizing associated morbidity. The technique has been validated for patients with OSCC, and larger-scale studies are in progress to determine its exact role in the management of this patient population. This article was designed to outline the current best practice guidelines for the provision of SNB in patients with early-stage OSCC, and to provide a framework for the currently evolving recommendations for its use. These guidelines were prepared by a multidisciplinary surgical/nuclear medicine/pathology expert panel under the joint auspices of the European Association of Nuclear Medicine (EANM) Oncology Committee and the Sentinel European Node Trial Committee.

The Danish national guidelines for treatment of oral squamous cell carcinoma

The treatment strategy for oral squamous cell carcinoma in Denmark has traditionally varied between the different head and neck oncology centres. A study group within the Danish Society for Head and Neck Oncology (DSHHO) was formed with the aim of optimising and standardising the treatment strategy. The approach was to use single modality treatment for stage I, stage II and some stage III and combined modality treatment for stage III and IV. Surgery was the preferred treatment when it was considered possible to perform a radical excision of the tumour and possible lymph node metastases with acceptable aesthetic and functional outcome. The implementation of a recognised national guideline facilitates prospective studies on a large well-characterised cohort. This increases the possibility of obtaining valid data on parameters such as morbidity, loco-regional control and survival. In addition the establishment of a reference program facilitates national monitoring of the treatment using defined indicators and standards.

Human papillomavirus-related carcinoma with adenoid cystic-like features of the sinonasal tract: clinical and morphological characterization of six new cases

Human papillomavirus (HPV) is known as causative for squamous cell carcinoma (SCC) of the oropharynx, but is also found not infrequently in carcinomas of the sinonasal tract. Recently, a subset of these carcinomas was recognized to harbour HPV33 and have a significant morphological overlap with adenoid cystic carcinoma (ACC), a rare and aggressive carcinoma originating in the minor salivary glands. Termed ‘HPV‐related carcinoma with ACC‐like features’, only nine cases have been reported. To clarify the occurrence of these tumours we screened a large material for the presence of HPV‐related ACC‐like carcinoma. The identified tumours were characterized immunohistochemically and with fluorescence in‐situ hybridization, and clinicopathological information for all cases is presented.

Implications of a positive sentinel node in oral squamous cell carcinoma.

The role of sentinel node biopsy in head and neck cancer is currently being explored. Patients with positive sentinel nodes were investigated to establish if additional metastases were present in the neck, their distribution, and their impact on outcome.