Patient characteristics of olfactory neuroblastoma: experience from a tertiary cancer centre 2000-2016 covering Eastern Denmark.

The aim of this study was to report incidence and patient characteristics of olfactory neuroblastoma (ONB) at a tertiary cancer institution during a 16-year period. A retrospective review was conducted on patients with ONB treated at Rigshospitalet, Copenhagen from 2000 to 2016 covering Eastern Denmark. Patient demographics, symptoms, stage, pathology-reports, treatment, and outcome were extracted from the patient records and the Danish pathology register. The tumours were graded both histologically and clinically using Hyam's and Kadish classifications, respectively. We identified a total of 14 patients (ten males, four females, median age 57 years, range 17-81 years). Four patients were in Kadish stage A, one stage B, and seven stage C. According to Hyam's classification, two tumours were grade I, nine grade II, and three grade III. All patients were treated with surgery, eight in combination with radiotherapy, where one received proton therapy, and one a combination with chemotherapy. At a median follow-up time of 58 months, the 5-year overall survival was 90% (95% CI 61; 99). ONB is a rare disease; complete radical surgery alone or combined with radiotherapy offered good oncologic control and outcome. Long-term follow-up of ONB should be mandatory.

Accuracy and precision of manual segmentation of the maxillary sinus in MR images-a method study.

OBJECTIVE: To assess the accuracy and precision of segmentation of the maxillary sinus in MR images to evaluate the potential usefulness of this modality in longitudinal studies of sinus development. METHODS: A total of 15 healthy subjects who had been both craniofacial CT and MR scanned were included and the 30 maxillary sinus volumes were evaluated using segmentation. Two of the authors did segmentation of MRI and one of these authors did double segmentation. Agreement in results between CT and MRI as well as inter- and intraexaminer errors were evaluated by statistical and three-dimensional analysis. RESULTS: The intraclass correlation coefficient for volume measurements for both method error, inter- and intraexaminer agreement were > 0.9 [maximal 95% confidence interval of 0.989-0.997, p < 0.001] and the limit of agreement for all parameters were < 5.1%. Segmentation errors were quantified in terms of overlap [Dice Coefficient (DICE) > 0.9 = excellent agreement] and border distance [95% percentile Hausdorff Distance (HD) < 2 mm = acceptable agreement]. The results were replicable and not influenced by systematic errors. CONCLUSION: We found a high accuracy and precision of manual segmentation of the maxillary sinus in MR images. The largest mean errors were found close to the orbit and the teeth. Advances in knowledge: MRI can be used for 3D models of the paranasal sinuses with equally good results as CT and allows longitudinal follow-up of sinus development.

An Uncommon Case of Pediatric Esthesioneuroblastoma Presenting as SIADH: 18F-FDG PET/CT in Staging and Post-Therapeutic Assessment.

Esthesioneuroblastoma (ENB) is an uncommon neuroendocrine tumor originating from the olfactory neuroepithelium and accounts for 3-6% of all intranasal tumors [¹]. ENBs can be locally aggressive and cause invasion and destruction of surrounding structures. Histological grading and clinical stage at presentation are highly predictive of survival and especially presence of lymph node and distant metastases are determining prognostic factors [²,³,4,5]. Thus, reliable imaging is essential in these patients. Conventional imaging modalities for staging ENB are magnetic resonance imaging (MRI) and computed tomography (CT). However, fluorine-18 fluoro-2-deoxy-d-glucose positron emission tomography/CT (18F-FDG PET/CT) has been reported as a valuable adjunct and was found to upstage 36% of ENB patients compared to conventional imaging [6]. We present a case demonstrating the diagnostic work-up and follow-up with 18F-FDG PET/CT in a young patient with ENB with a highly atypical clinical presentation.

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

AIMS: 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. METHODS AND RESULTS: Forty-seven candidate cases were screened for presence of HPV. Six cases were identified and genotyped as HPV types 33, 35, and 56. All six cases had areas of dysplastic mucosal lining and showed remarkable heterogeneous morphologies. MYB, MYBL1, and NFIB genes were intact and, interestingly, staining for MYB protein was largely negative in contrast to what was found in ACC. One patient experienced a local recurrence 11 years after initial treatment and the remaining five patients were alive without evidence of disease. CONCLUSION: We report six new cases of HPV-related ACC-like carcinoma and found that, although in a small material, the prognosis for these patients seems more favourable than for ACC. For the distinction between ACC and HPV-related ACC-like carcinoma, p16, MYB immunohistochemistry or investigation of MYB, MYBL1 and NFIB gene status are valuable.

Sentinel Node in Oral Cancer: The Nuclear Medicine Aspects. A Survey from the Sentinel European Node Trial.

PURPOSE: Nuclear imaging plays a crucial role in lymphatic mapping of oral cancer. This evaluation represents a subanalysis of the original multicenter SENT trial data set, involving 434 patients with T1-T2, N0, and M0 oral squamous cell carcinoma. The impact of acquisition techniques, tracer injection timing relative to surgery, and causes of false-negative rate were assessed. METHODS: Three to 24 hours before surgery, all patients received a dose of Tc-nanocolloid (10-175 MBq), followed by lymphoscintigraphy. According to institutional protocols, all patients underwent preoperative dynamic/static scan and/or SPECT/CT. RESULTS: Lymphoscintigraphy identified 723 lymphatic basins. 1398 sentinel lymph nodes (SNs) were biopsied (3.2 SN per patient; range, 1-10). Dynamic scan allowed the differentiation of sentinel nodes from second tier lymph nodes. SPECT/CT allowed more accurate anatomical localization and estimated SN depth more efficiently. After pathological examination, 9.9% of the SN excised (138 of 1398 SNs) showed metastases. The first neck level (NL) containing SN+ was NL I in 28.6%, NL IIa in 44.8%, NL IIb in 2.8%, NL III in 17.1%, and NL IV in 6.7% of positive patients. Approximately 96% of positive SNs were localized in the first and second lymphatic basin visualized using lymphoscintigraphy. After neck dissection, the SN+ was the only lymph node containing metastasis in approximately 80% of patients. CONCLUSIONS: Best results were observed using a dynamic scan in combination with SPECT/CT. A shorter interval between tracer injection, imaging, and surgery resulted in a lower false-negative rate. At least 2 NLs have to be harvested, as this may increase the detection of lymphatic metastases.

[Nasal fractures in adults]. / Diagnostik og behandling af næsefraktur hos voksne

The risk of complications warrants treatment of most dislocated nasal fractures. Other injuries including other facial fractures and septal haematoma must be treated if present at the initial presentation. The usual treatment for a simple nasal fracture is closed reduction in local anaesthesia after five to seven days. Complicated cases require open reduction in general anaesthesia. Later revision of the deviated nose may become necessary in patients suffering from complications such as persistent nasal stenosis and/or deformity.

Rate of recurrence and malignant transformation in 88 cases with inverted papilloma between 1998-2008.

Conclusions The recurrence rate of IP in the current study is comparable to international and national studies. When the primary tumour was located in the frontal or the sphenoid sinus, the tumour seemed more likely to recur. Some recurrences were more than 2 years after primary surgery, suggesting continued need for long-term follow-up. The rate of malignant transformation in inverted papilloma cases has not changed in Denmark. Objectives Inverted papillomas are benign tumours located in the nasal cavity and paranasal sinuses. They are known for their tendency to recur after surgery and show invasive growth, causing bone remodulation and the association with malignant transformation. The introduction of endoscopic sinus surgery and computer aided sinus surgery over the last decades has made this tumour more approachable with less cosmetic and functional damage. The objective of this study is to establish whether the recurrence rate and the rate of malignant transformation of IP have changed with the application of these new techniques. Method A retrospective study between 1998-2008 including 88 cases with inverted papilloma. Results In total, 25.3% had recurrence. Combined surgical approach with endoscope/open approach had the lowest rate of recurrence. A malignant transformation in the postoperative histological examination was found in 8.9%.

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.

Three-year follow-up of sentinel node-negative patients with early oral cavity squamous cell carcinoma.

BACKGROUND: Resection of the primary tumor followed by sentinel node biopsy (SNB) for the clinically N0 patient has been implemented in our Head and Neck University Center. The purpose of this study was to report on the outcome for patients with negative SNB. METHODS: From April 2007 to October 2009, 53 consecutive SNB-negative patients with oral cavity squamous cell carcinoma (SCC) T1 to T2 were accrued. Follow-up was done continuously with the most recent examination in October 2011. The location of the sentinel lymph nodes was determined using dynamic and planar lymphoscintigraphy and single photon emission CT (SPECT)-CT. Intraoperatively, a hand-held gamma probe was applied. The harvested sentinel lymph nodes underwent histopathologic examination using step-serial sectioning at 150-µm intervals and immunohistochemistry. In the follow-up period, we observed and examined the SNB-negative patients for recurrence, morbidity, and mortality. RESULTS: Fifty-three SNB-negative patients were identified. Eight patients received adjuvant radiotherapy (RT) because of incomplete excision on the T site after the primary operation. An additional 2 patients received RT because of recurrences on the T site and N site. One patient died of recurrence on the T site and N site without having received additional treatment. Six patients died of nonrelated causes. During follow-up, 3 patients with both T-site and N-site recurrence were found. No case of isolated recurrence on the N site only was found. Thirty-six SNB-negative patients treated only surgically with a median follow-up of 37 months (range, 25-52 months) and no recurrence remain under active review. CONCLUSION: Only 3 of the SNB-negative patients subsequently developed recurrence in the T site and N site. The remaining 36 patients had no N-site recurrence at median follow-up of 37 months.

Evaluation of sentinel lymph node size and shape as a predictor of occult metastasis in patients with squamous cell carcinoma of the oral cavity.

The aim of the study was to evaluate sentinel lymph node size as a predictor of metastasis in N0 patients with oral squamous cell carcinoma treated by individual sentinel node biopsy (SNB) guided neck dissection. In addition, to evaluate lymph node shape as an indicator of malignancy. A retrospective study based on data from 50 patients with clinically N0 neck and oral squamous cell carcinoma stage T1-2N0M0, SNB and consecutive neck dissection was performed. Excised sentinel nodes were measured in three axes by the surgeons before undergoing histopathological examination. Measured sentinel node axis lengths were compared with the histopathological results. Data were analysed using Microsoft Excel 2008 for Mac, version 12.0. A total of 167 sentinel nodes was excised with a median of 3.3 per patient. Following SNB 18% of the patients was upstaged at the subsequent histopathological examination. This correlates to 7% of the total number of sentinel nodes. The diameters of all three axes were compared for both negative and positive nodes. The positive nodes were not significantly larger. The sensitivity and specificity of lymph node size as a criterion for staging were calculated at several thresholds. There was no tendency that lymph node shape changed towards spherical when positive for metastases. There is a tendency that the risk of metastases and upstaging increases with increasing maximum and partly minimum diameter. However, in this study it was not possible to establish a suitable threshold level with both high sensitivity and specificity based on size and shape. Other features of the lymph node must be considered if an accurate staging of N0 patients is to be performed.

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

BACKGROUND: 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. METHODS: In all, 109 patients (n = 109) from 15 European centers, with cT1/2,N0 tumors, and a positive sentinel lymph node were identified. Kaplan-Meier and univariate and multivariate logistic regression analysis were used to identify variables that predicted for additional positive nodes and their position within the neck. RESULTS: A total of 122 neck dissections were performed in 109 patients. Additional positive nodes were found in 34.4% of cases (42/122: 18 same, 21 adjacent, and 3 nonadjacent neck level). Additional nodes, especially if outside the sentinel node basin, had an impact on outcome. CONCLUSIONS: The results are preliminary but suggest that both the number and the position of positive sentinel nodes may identify different prognostic groups that may allow further tailoring of management plans.

The prevalence of occult metastases in nonsentinel lymph nodes after step-serial sectioning and immunohistochemistry in cN0 oral squamous cell carcinoma.

OBJECTIVES: To examine the prevalence of isolated tumor cells (ITC) and micrometastases (MM) in nonsentinel lymph nodes (NSN) using additional step-serial sectioning and immunohistochemistry (IHC) as for sentinel lymph nodes (SN). STUDY DESIGN: Prospective, consecutive, and clinically controlled trial. METHODS: Fifty-one patients with oral cavity squamous cell carcinoma (OSCC) T1-T2 and clinically N0 neck underwent surgical treatment including sentinel-node biopsy (SNB) assisted selective neck dissection (SND). The location of the SN was determined using dynamic and planar lymphoscintigraphy and SPECT-CT. The harvested NSN from the neck dissections underwent the same histopathologic examinations as the SN using step-serial sectioning (SSS) at 150-micron intervals. Two sections from each level were stained with hematoxylin-eosin (H&E) and cytokeratin antibodies (AE1/AE3) and examined for tumor deposits. Results were compared with the previous routine examination of the NSN. RESULTS: A total of 403 NSN were examined with a median of 8 per patient. A total of 1/51 patients (2%) had involvement of an additional NSN not found on routine examination. This was the only lymph node with involvement not detected previously. However, this patient had metastases in SN and in another NSN detected on routine examination. The overall incidence of occult metastasis (SN + NSN) was 21.6% (11/51) as previously reported. CONCLUSIONS: The incidence of occult metastases in NSN after additional SSS and IHC was 2%. The risk of NSN involvement would seem to be extremely low in patients with early OSCC and negative SN. This study further validates SNB as an accurate staging tool for cN0 early OSCC.

Observation of tardive laryngeal edema after blunt trauma to the neck is not necessary: a 10-year retrospective analysis.

Patients exposed to blunt laryngeal trauma not requiring immediate attention are usually observed for 24 h in the ward due to the risk of airway obstruction. In some cases without laryngeal edema on initial examination, edema may develop later. This condition is defined as tardive laryngeal edema (TLE) as opposed to progressive laryngeal edema, where the edema is present initially. Though specialists internationally report on TLE-even with severe airway obstruction-we could not find any publications describing it, and the specific definition seems to be used only in Denmark. In order to identify cases of TLE at our clinic a retrospective study over a period of 10 years was undertaken. Of 145 patients included, 6 developed insignificant TLE. None of the patients developed life-threatening TLE. The results of this study indicate that TLE is a rare condition and we suggest that severe life-threatening TLE does not exist. We propose that patients with no laryngeal edema on first examination and with no laryngeal fractures can safely be discharged after primary examination.

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.

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.

Heterotopic neuroglial tissue: two cases involving the tongue and the buccal region.

We report two rare cases of extranasal heterotopic neuroglial tissue and review the literature on the topic. The clinical, histological, and immunohistochemical features are presented. Both patients had lesions extranasally, even though the sinonasal region is the predominant site for these heterotopias. The first lesion was located in the buccal area in an 8-year-old boy and the second lesion in the tongue of a 2-year-old boy. They had relatively small lesions with few clinical symptoms. Complete excision was made and the follow-up was unremarkable. Heterotopic neuroglial tissue is considered to be a congenital condition. Complete excision of these lesions is recommended in spite of the lack of malignant potential, but because of the possibility of continuous growth.

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. STUDY DESIGN: Prospective cohort study. METHODS: Fifty-one patients with clinically N0 neck underwent SNB-assisted neck dissection. The localization of the sentinel node (SN) was determined using dynamic and planar lymphoscintigraphy and single photon emission computed tomography-computed tomography. Histopathologic examination of the harvested SN was performed using step-serial sectioning with hematoxylin-eosin (H&E) and immunohistochemistry on formalin-fixed, paraffin-embedded tissue. RESULTS: A total of 181 SNs were excised with a median of 3 (range 1-7) SNs per patient. Four percent (2 of 51) of patients with subclinical (occult) lymph node metastasis would have been identified using routine H&E staining, whereas the 18% (9 of 49) were upstaged as a result of additional histopathology when the H&E evaluation was negative. Overall, the incidence of subclinical metastases was 22% (11 of 51). CONCLUSION: In this study, SNB-assisted neck dissection proved to be technically feasible in identifying subclinical metastasis, thus accurately staging the neck with a high degree of sensitivity in patients with oral SCC T1 to 2N0M0 when additional histopathology was performed. The vast majority of patients in this study would have been spared selective neck dissection had reliance on SNB been used and selective neck dissection performed only in the case of a positive SN. Future studies should focus on determining whether SNB alone reduces patient morbidity and whether this is as equally effective in the treatment of cervical nodal metastases as compared with selective neck dissection in patients with oral SCC.

[Treatment of patients with oral squamous cell carcinomas (T1-T2N0M0). Initial experiences with national guidelines]. / Behandling af patienter med orale planocellulaere karcinomer. De første erfaringer med nationale retningslinjer.

INTRODUCTION: In 2003 the national guidelines for the treatment of patients with oral squamous cell carcinomas (OSCC) were established. Patients with clinically negative neck are now treated with surgery as opposed to radiotherapy previously. The aim of this study is to evaluate the surgical morbidity for these patients. MATERIALS AND METHODS: This study included patients with primary diagnosed OSCC classified as T1-T2N0M0 treated between June 2003 and June 2005 at the Department of Otolaryngology--Head & Neck Surgery, Copenhagen University Hospital. The patients had their charts reviewed and 30 went to a clinical examination and were interviewed about complaints following the surgical treatment. RESULTS: 60 patients were included. In order to be able to determine the complications of the surgical treatment, 30 of the 60 patients were excluded from the clinical examination. All patients attended and the median follow-up was 9 months. The transient complication most frequently registered was postoperative bleeding. The most frequent permanent complications were damage of the marginal branch (10%) and the sensory nerves, the major auricular nerve and the lingual nerve (13%). Patients undergoing bilateral neck dissection have an increased risk of complications. CONCLUSION: The majority of complications were transient, and the patients had few complaints after the operation. The most frequently encountered complication was nerve damage, but the general morbidity was estimated to be reasonable. It is important that the guidelines are followed consistently and that the surgical skills are evaluated.

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.