Single-cell transcriptomic landscape and the microenvironment of normal adjacent tissues in hypopharyngeal carcinoma.

BACKGROUND: The cellular origin of hypopharyngeal diseases is crucial for further diagnosis and treatment, and the microenvironment in tissues may also be associated with specific cell types at the same time. Normal adjacent tissues (NATs) of hypopharyngeal carcinoma differ from non-tumor-bearing tissues, and can influenced by the tumor. However, the heterogeneity in kinds of disease samples remains little known, and the transcriptomic profile about biological information associated with disease occurrence and clinical outcome contained in it has yet to be fully evaluated. For these reasons, we should quickly investigate the taxonomic and transcriptomic information of NATs in human hypopharynx. RESULTS: Single-cell suspensions of normal adjacent tissues (NATs) of hypopharyngeal carcinoma were obtained and single-cell RNA sequencing (scRNA-seq) was performed. We present scRNA-seq data from 39,315 high-quality cells in the hypopharyngeal from five human donors, nine clusters of normal adjacent human hypopharyngeal cells were presented, including epithelial cells, endothelial cells (ECs), mononuclear phagocyte system cells (MPs), fibroblasts, T cells, plasma cells, B cells, mural cells and mast cells. Nonimmune components in the microenvironment, including epithelial cells, endothelial cells, fibroblasts and the subpopulations of them were performed. CONCLUSIONS: Our data provide a solid basis for the study of single-cell landscape in human normal adjacent hypopharyngeal tissues biology and related diseases.

Predictive value of local control by 4'-[methyl-11C]-thiotymidine PET volume parameters in p16-negative oropharyngeal, hypopharyngeal, and supraglottic squamous cell carcinoma.

PURPOSE: We investigated the potential of baseline 4'-[methyl- 11 C]-thiothymidine ([ 11 C]4DST) PET for predicting loco-regional control of head and neck squamous cell carcinoma (HNSCC). METHODS: A retrospective analysis was performed using volumetric parameters, such as SUVmax, proliferative tumor volume (PTV), and total lesion proliferation (TLP), of pretreatment [ 11 C]4DST PET for 91 patients with HNSCC with primary lesions in the oral cavity, hypopharynx, supraglottis, and oropharynx, which included p16-negative patients. PTV and TLP were calculated for primary lesions and metastatic lymph nodes combined. We examined the association among the parameters and relapse-free survival and whether case selection focused on biological characteristics improved the accuracy of prognosis prediction. RESULTS: The area under the curves (AUCs) using PTV and TLP were high for the oropharyngeal/hypopharyngeal/supraglottis groups (0.91 and 0.87, respectively), whereas that of SUVmax was 0.66 ( P  < 0.01). On the other hand, the oral group had lower AUCs for PTV and TLP (0.72 and 0.77, respectively). When all cases were examined, the AUCs using PTV and TLP were 0.84 and 0.83, respectively. CONCLUSION: Baseline [ 11 C]4DST PET/CT volume-based parameters can provide important prognostic information with p16-negative oropharyngeal, hypopharyngeal, and supraglottic cancer patients.

Pedicled flaps reconstruction of hypopharynx and laryngeal defects: Successful preservation of laryngeal function in patients with advanced hypopharyngeal cancer.

BACKGROUND: Preserving laryngeal function and reconstructing the hypopharynx in advanced hypopharyngeal cancer pose significant challenges for head and neck surgeons. METHODS: A 48-year-old male patient was diagnosed with advanced hypopharyngeal cancer originating from the left pyriform sinus. The tumor extended into the hypopharynx, left vocal cord, ventricular fold, partial aryepiglottic fold, and a segment of the cervical esophagus. A curative tumor resection was performed, and a well-thought-out strategy was employed for hypopharyngeal repair and laryngeal reconstruction. RESULTS: Following the surgery, the patient demonstrated exceptional flap survival, and the tracheostomy tube was removed at the 6-month mark. No surgery-related complications were observed, and both swallowing and vocal functions exhibited a robust recovery. CONCLUSION: Our reconstruction strategy proves effective in preserving laryngeal function among patients with advanced hypopharyngeal cancer.

Transoral robotic vertical partial laryngectomy (hemilaryngectomy) extended to the hypopharynx.

Locally advanced laryngeal cancers treatment often involves total laryngectomy, which some patients are unwilling to undergo, even if this choice reduces their survival probability. Therefore, the objective of laryngeal oncologic surgery is not only to remove the tumor, but also to preserve the organ and its functions. To overcome these concerns, several partial laryngectomy techniques have been developed. This article describes the surgical technique and a case study of a 64-year-old male patient with locally advanced laryngeal squamous cell carcinoma who underwent vertical partial laryngectomy extending to the subglottis and hypopharynx using transoral robotic surgery (TORS) with a da Vinci Single Port surgical robot. The video and article provide a detailed description of the surgical technique, which resulted in successful tumor removal with excellent oncological and functional outcomes.

Successful endoscopic resection for well-differentiated neuroendocrine tumor, Grade 1, in the hypopharynx.

Well-differentiated neuroendocrine tumor, Grade 1 (NET, G1), in the hypopharynx is extremely rare. A 62-year-old woman was referred to our clinic with a tumor in the postcricoid area. The tumor was diagnosed NET on biopsy and there were no metastatic findings on CT, therefore we performed endoscopic resection. Histologic examination revealed well-differentiated neuroendocrine tumor, Grade 1. This case was an extremely rare and valuable case in which endoscopic images can be observed in detail. Endoscopic resection was performed and successful endoscopic and histological resection was achieved.

Salvage total laryngectomy for squamous cell carcinoma of the larynx and hypopharynx: Validated prognostic nomograms predicting oncological outcomes.

BACKGROUND: Salvage total laryngectomy (STL) is a preferred treatment for patients with residual, recurrent, and second primary squamous cell carcinoma of the larynx/hypopharynx after (chemo)radiation. To individually estimate postoperative oncological outcomes, we designed and validated prognostic nomograms. METHODS: We used a dataset of 290 patients who underwent STL. Nomograms predicting 2- and 5-year OS, DFS, and DSS were developed, using variables which are identified pre- or postoperatively. The nomograms were externally validated on a dataset of 109 patients. RESULTS: The nomograms based on postoperative variables performed better than those based on preoperative variables (OS: C = 0.68 vs. 0.64; DFS: C = 0.70 vs. 0.64; DSS: C = 0.74 vs. 0.64). The nomogram predicting DSS based on postoperative variables performed best. CONCLUSIONS: The presented prognostic nomograms for predicting oncological outcomes in patients who undergo STL are tools which allow for a reliable prognostic assessment.

Hypopharyngeal Diffuse Large B-Cell Lymphoma in a 74-Year-Old Man Presenting with Dysphagia: A Case Report.

BACKGROUND Malignant lymphomas can occur at various sites. Hypopharyngeal tumors are at risk for airway obstruction and require rapid diagnosis and treatment. Most hypopharyngeal malignancies are squamous cell carcinomas; other tumors are rare. To date, only a few cases of malignant hypopharyngeal lymphoma have been reported, and its specific characteristics are unknown. Herein, we report a case of right hypopharyngeal diffuse large B-cell lymphoma (DLBCL) in a 74-year-old man with dysphagia. CASE REPORT A 74-year-old man presented to our hospital with dysphagia. He had no relevant medical history. Endoscopic examination revealed a right hypopharyngeal tumor. The surface of the tumor was smooth, with no evidence of hemorrhage. Computed tomography revealed a 40-mm mass located in the hypopharynx. We performed a tracheotomy and biopsy of the tumor. Histopathological examination revealed a diffuse proliferation of large atypical B cells with negative staining for Epstein-Barr virus by in situ hybridization. Immunohistochemical staining was positive for CD20 but negative for CD3 and CD10. The patient was administered chemotherapy. The tumor reduced in size, and the patient recovered completely. During the two-year follow up, no recurrence of cancer was observed. CONCLUSIONS Although most hypopharyngeal tumors are squamous cell carcinomas (SCCs), the possibility of other types of tumors should also be considered. Malignant lymphoma of the hypopharynx is rare, and more cases need to be studied and reported in the future.

Encephalitis in a patient with hypopharynx cancer treated with immune checkpoint inhibitors and radiotherapy: a case report and review of the literature.

Hypopharyngeal cancer (HPC) has one of the most unfavorable prognoses among head and neck squamous cell carcinomas. Immunotherapy in combination with chemotherapy, the same as conventional induction chemotherapy, has emerged as a vital part of the induction therapy protocol for HPC. Meanwhile, the incidence of immune-related adverse events is increasing. In this light, we present the first reported case of immune-associated encephalitis in a patient with hypopharyngeal cancer treated with Camrelizumab (a PD-1 inhibitor). After receiving immunotherapy combined with chemotherapy as induction therapy, along with concurrent chemoradiotherapy, the patient presented with symptoms of fatigue, tremors, drowsiness, and an abnormal signal in the right temporal lobe as shown on a brain magnetic resonance imaging (MRI). Despite the minor elevation in protein and IgG index observed in the lumbar puncture, there is no evidence of abnormal autoantibodies or evidence of pathogenic infection. Following a thorough multidisciplinary consultation, the patient is suspected to be afflicted with immune-related autoimmune encephalitis. Intravenous methylprednisolone was prescribed as an empirical treatment at an initial dosage of 120 mg/day for 3 days, followed by steroid tapering. Finally, the patient experienced complete neurologic and radiographic (brain MRI) recovery. This case serves as a critical reminder that encephalitis is a potential diagnosis that should never be overlooked in patients undergoing immunotherapy who present with abnormal signs of the brain. The timely diagnosis and initiation of immunosuppressive therapy are key components of treating ICI-associated encephalitis.

Successful surgery with preservation of laryngeal function in a patient with collision primary squamous cell carcinoma and adenoid cystic carcinoma in the hypopharynx and synchronous esophageal carcinoma: A case report.

BACKGROUND: The definition of "collision tumor" is the coexistence of two histologically and morphologically distinct tumors within the same anatomical area without histological admixture. Collision tumors featuring primary squamous cell and adenoid cystic carcinomas of the hypopharynx, combined with synchronous esophageal carcinoma, are very rare. METHODS: We describe a patient with a collision tumor of the hypopharynx and synchronous esophageal carcinoma who underwent partial laryngectomy, with preservation of laryngeal function, and radical esophageal resection featuring esophageal reconstruction using a gastric tube. Surgery was successful. RESULTS: Postoperative radiotherapy was recommended after surgery; the patient exhibited no recurrence or distant metastasis to the 17-month follow-up. CONCLUSION: To the best of our knowledge, this is the first report of collision of primary squamous cell carcinoma and adenoid cystic carcinoma in the hypopharynx and synchronous esophageal carcinoma. We performed appropriate surgery and prescribed postoperative radiotherapy. This preserved laryngeal function.

HPV Infection in Squamous Cell Carcinoma of the Hypopharynx, Larynx, and Oropharynx With Multisite Involvement.

The prevalence and prognostic significance of high-risk human papillomavirus (HR-HPV) have been well-established in oropharyngeal squamous cell carcinoma (OPSCC), but not in hypopharyngeal squamous cell carcinoma (HPSCC) or laryngeal squamous cell carcinoma (LSCC). Moreover, HR-HPV infection in squamous cell carcinoma with multisite involvement has not been examined. To clarify these issues, we retrospectively collected 480 invasive tumors from 467 patients with HPSCC, LSCC, or OPSCC, and comprehensively analyzed the detailed tumor localization, transcriptionally active HR-HPV infection by messenger RNA in situ hybridization, and immunohistochemical staining for p16 and Rb. HR-HPV infection was observed in 115/480 tumors (24%). Human papillomavirus (HPV)-positive cases were closely related with p16 positivity and the partial loss pattern of Rb. HR-HPV was detected in 104 of 161 tumors (64.6%) in the pure OPSCC group and only 1 of 253 tumors (0.4%) in the pure HP/LSCC group; the positive case occurred in the vocal cords. In the multisite-involving combined-type squamous cell carcinoma group, HPV infection was observed in 10/40 (25%) cases, and the 10 HPV-positive cases had OPSCC extending to the larynx or hypopharynx. Among high T-stage (T3/T4) cases of pure OPSCC, HPV-positive cases showed a better prognosis ( P =0.0144), whereas the HPV-positive combined OPSCC group did not show a better prognosis ( P =0.9428), as compared with HPV-negative counterpart. The results suggest that HR-HPV infection in pure HPSCC and LSCC may be extremely rare. HR-HPV infection seems to be present in a substantial proportion of patients with combined OPSCC and HPSCC/LSCC, but it may not improve prognosis at such advanced disease stages. Confirmation of these points awaits future studies with larger cohorts.

Thunderbeat®: a new step forward in transoral surgery-systematic review of literature and our experience.

INTRODUCTION: Minimally invasive surgery is today the main challenge of ENT surgeons who aim to achieve oncological radicality with less aesthetic and functional impact. This is the basis for the widespread transoral surgical techniques, as the Thunderbeat®. OBJECTIVE: To date, the use of Thunderbeat® in transoral surgery is still little known and widespread. So, this study analyzes, with a systematic review, current literature about the transoral use of Thunderbeat® and shows our case studies. METHODS: The research was carried out on Pubmed, Scopus, Web of Science and Cochrane databases using specific keywords. Then, a retrospective study was carried out on 10 patients who underwent transoral surgery by Thunderbeat® in our ENT Clinic. Both in our cases and in the systematic review the following parameters have been evaluated: treated anatomical site and subsite, histological diagnosis, type of surgery, duration of nasogastric tube and hospitalization, post-operative complications, tracheostomy, resection margin status. RESULTS: The review included 3 articles that described transoral use of Thunderbeat® for a total of 31 patients suffering from oropharyngeal, hypopharyngeal and/or laryngeal carcinoma. Nasogastric tube was removed after 21.5 days on average, temporary tracheostomy was performed in 6 patients. The main complications were: bleeding (12.90%) and pharyngocutaneous fistula (29.03%). Thunderbeat® shaft was 35 cm long and 5 mm large. Our case studies included 5 males and 5 females, mean age 64.4 ± 10.28, with oropharyngeal or supraglottic carcinoma, parapharyngeal pleomorphic adenoma and cavernous hemangioma of the tongue base. Temporary tracheostomy was performed in 8 patients. Free resection margins were achieved in all cases (100%). No peri-operative complications occurred. Nasogastric tube was removed after 5.3 ± 2 days on average. All patients were discharged without tracheal tube and NGT after 18.2 ± 4.72 days on average. CONCLUSION: This study demonstrated that Thunderbeat® has several advantages over other transoral surgical approaches, such as CO2 laser and robotic surgery, in terms of best combination of oncological and functional success, less post-operative complications and costs. So, it could represent a step forward in transoral surgery.

Outcomes for Organ Preservation with Chemoradiation Therapy for T4 Larynx and Hypopharynx Cancer.

OBJECTIVE: Limited data is available to guide non-surgical management of Stage T4 larynx and hypopharynx cancer patients who have inoperable disease or refuse surgery. We aim to review the nonoperative management of T4 laryngeal and hypopharyngeal cancer and report the long-term therapeutic and functional outcomes. METHODS: We reviewed the nonoperative management of T4 laryngeal (n = 44) and hypopharyngeal (n = 53) cancer from 1997 to 2015 and performed a univariate analysis (UVA). RESULTS: The 2-/5-year OS rates were 73%/38% for larynx patients and 52%/29% for hypopharynx patients. Locoregional failure (LRF) occurred in 25% and 19% of larynx and hypopharynx patients, respectively. On UVA of the larynx subset, N3 nodal status and non-intensity-modulated radiation therapy were negatively associated with OS; treatment with radiation therapy alone impacted disease-free survival; and age >70 was associated with LRF. On UVA of the hypopharynx subset, only T4b status significantly impacted OS. In the larynx and hypopharynx groups, 68% and 85% received a percutaneous endoscopic gastrostomy (PEG) tube and 32% and 40% received a tracheostomy tube, respectively. At the last follow-up visit, 66% of our larynx cohort had neither tracheostomy or PEG placed and 40% of our hypopharynx cohort had neither. CONCLUSION: We report better than previously noted outcomes among T4 larynx and hypopharynx patients who have unresectable disease or refuse surgery. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:1138-1145, 2023.

Giant Fibrovascular Polyp as an Unusual Cause of Globus Pharyngeus.

Differential diagnosis of globus sensation in an otherwise asymptomatic patient should include hypopharyngeal fibrovascular polyp to avoid potentially fatal complications like airway compromise following regurgitation. We present a case of a 74-year-old man with a 13-cm long hypopharyngeal fibrovascular polyp with 9 months history of globus sensation. A narrow stalk of the giant polyp allowed endoscopic removal and complete resection with the CO2 laser. Histopathological examination was conclusive for the fibrovascular polyp.

Metastatic Papillary Thyroid Cancer Mimicking Hypopharyngeal Carcinoma.

ABSTRACT: Papillary thyroid cancer (PTC) metastasizing to the hypopharynx is extremely rare. Here, we describe FDG PET/CT findings of lesions in the posterior hypopharyngeal wall and left parapharyngeal space in a 58-year-old man who complained of blood in the sputum. The patient had a history of postoperative PTC. Therefore, hypopharyngeal carcinoma with lymph node metastasis was suspected. However, metastasis of PTC was pathologically confirmed after surgery. Hypopharyngeal metastasis of PTC is rare, which should be differentiated from hypopharyngeal carcinoma with metastasis.

Factors Influencing Postoperative Prognosis in Patients with Hypopharyngeal and Laryngeal Carcinoma.

OBJECTIVES: Despite the increasingly modern surgical techniques in the oncology field, the factors that influence postoperative prognosis in patients with hypopharyngeal and laryngeal carcinoma (HLC) remain unclear. The study aimed to evaluate the factors influencing the prognosis of HLC patients with pathological diagnosis of squamous cell carcinoma, and the findings are intended to direct follow-up management strategies. METHODS: A retrospective cohort study was performed. The study population included 407 postoperative patients with HLC from 2011 to 2015. Univariate and multivariate analyses were used to examine the prognostic factors identified. RESULTS: Based on univariate analysis results, smoking and alcohol history, tumor differentiation, preoperative radiotherapy, primary tumor sites, flap reconstruction, lymph node invasion (LNI), and preoperative albumin levels (PAL) significantly affects the prognosis of HLC patients (P < .05). Meanwhile, multivariate analysis revealed that smoking pack-year (OR = 1.002, 95% CI = 1.001 ∼ 1.003), primary tumor sites (OR = 6.241, 95% CI = 1.715 ∼ 18.433), LNI (OR = 2.869, 95% CI = 1.095 ∼ 8.743), and PAL (OR = .020, 95% CI = .004 ∼ 0.104) were associated with complications. Tumor differentiation (OR = 0.650, 95% CI = .383 ∼ 0.855), primary tumor sites (OR = 12.392, 95% CI = 3.290 ∼ 26.679), LNI (OR = 16.323, 95% CI = 2.726 ∼ 47.729), preoperative radiotherapy (OR = 9.300, 95% CI = 3.182 ∼ 27.181), and PAL (OR = .321, 95% CI = .141 ∼ .732) were associated with overall survival rates. CONCLUSION: Smoking and alcohol history, tumor differentiation, LNI, primary tumor sites, flap reconstruction, PAL, and preoperative radiotherapy are crucial factors that influence the postoperative prognosis of patients with HLC. In addition, a monogram of five factors was established to predict the survival rates of HLC patients.

Diagnostic test accuracy of sentinel lymph node biopsy in squamous cell carcinoma of the oropharynx, larynx, and hypopharynx: A systematic review and meta-analysis.

The aim of this meta-analysis was to determine the diagnostic test accuracy of sentinel lymph node biopsy (SLNB) in patients with oropharyngeal, laryngeal, and hypopharyngeal squamous cell carcinoma (SCC). For this purpose, MEDLINE, EMBASE, and Web of Science were searched from inception to March 8, 2022. Included were studies evaluating diagnostic test accuracy of SLNB to identify cervical lymph node metastases with elective neck dissection or follow-up as reference. A bivariate generalized linear mixed model approach was used for the meta-analysis. Nineteen studies were eligible, evaluating 377 cases in total. The pooled estimates of sensitivity and negative predictive value were 0.93 (95% CI: 0.86-0.96) and 0.97 (95% CI: 0.94-0.98), respectively. The excellent accuracy of SLNB justifies a place in the diagnostic workup of patients with larynx and pharynx SCC. Randomized trials are required to demonstrate oncologic safety and benefits on treatment related morbidity and quality of life when omitting elective neck treatment based on SLNB.

Efficacy of free anterolateral thigh flap and free jejunum in reconstruction for hypopharyngeal and cervical esophagus. / æ¸¸ç¦»è‚¡å‰å¤–ä¾§çš®ç“£å’Œæ¸¸ç¦»ç©ºè‚ é‡å»ºä¸‹å’½é¢ˆæ®µé£Ÿç®¡çš„ç–—æ•ˆ.

OBJECTIVES: Because of its peculiar anatomical location, most patients with hypopharyngeal and cervical esophageal cancer are at advanced stage when they visit the hospital. At present, the treatment for hypopharyngeal and cervical esophageal cancer is primarily surgical resection and radiotherapy. However, due to the wide range of surgical resection, it can often lead to a large range of annular defects. Therefore, the upper digestive tract reconstruction after tumor resection is very important. We use the free anterolateral thigh flap (ALT) and free jejunum (FJ) transfer to reconstruct the hypopharyngeal and cervical esophagus, and to investigate the effect of both reconstruction methods on upper gastrointestinal tract defects. METHODS: A retrospective analysis was conducted to investigate the clinical data of 42 patients with hypopharyngeal and cervical esophageal cancer (Clinical Stage IV) from Jan. 2004 to Jan. 2016 in the Second Xiangya Hospital of Central South University. All patients underwent total laryngopharyngectomy and cervical esophageal resection. The hypopharyngeal circumferential and cervical esophageal defects were reconstructed with free ALT (n=22) or FJ (n=20). Four patients who underwent radiotherapy and chemotherapy before surgery did not receive radiotherapy or chemotherapy after surgery. The remaining 38 patients underwent postoperative radiotherapy and chemotherapy. All patients were followed up by telephone or outpatient review, with a follow-up deadline in Jan. 2021. We compared the differences between the 2 groups in postoperative complications, radiotherapy complications, and survival rate. The differences in individual characteristics between 2 groups were analyzed using Fisher test. The differences in postoperative and radiotherapy complications between two groups were analyzed using χ² test. The 3- and 5-year overall survival rates were calculated using Kaplan-Meier survival curve method. RESULTS: In the ALT group, the postoperative complications mainly included anastomotic fistula, chylous fistula and subcutaneous hematoma of the donor site. The radiotherapy complication was anastomotic stenosis. However, in the FJ group, the postoperative complications mainly included chylous fistula, intestinal obstruction, and intestinal fistula. The radiotherapy complications mainly contained anastomotic fistula and tissue flap necrosis. The cases of postoperative complications in the ALT group and the FJ group were 7 and 5, respectively (P=0.625), and the cases of radiotherapy complications were 3 and 4, respectively (P=0.563). The 3-year overall survival rates in the ALT group and the FJ group were 52.9% and 46.7%, respectively, and the 5-year total survival rates were 35.1% and 31.9%, respectively (P=0.53). The cases of anastomotic stenosis after radiotherapy in the ALT group were more than those in the FJ group (P=0.097). However, the cases of jejunal necrosis and anastomotic fistula after radiotherapy in the FJ group were more than those in the ALT group (P=0.066). CONCLUSIONS: There are no significant differences in postoperative and radiotherapy complications and 3-and 5-year survival rates between the ALT group and the FJ group. The reconstruction with ALT is prone to develop anastomotic stricture. The reconstruction with FJ cannot withstand high-dose radiotherapy. The ALT and FJ are effective methods in the reconstruction of hypopharynx and cervical esophagus. The treatment protocol should be carefully chosen based on its advantages and disadvantages of these 2 methods.

Multicentre study on resection margins in carcinoma of the oral cavity, oro-hypopharynx and larynx.

Objective: The prognostic significance of the resection margins is still subject of conflicting opinions. The purpose of this paper is to report the results of a study on the margins in carcinoma of the oral cavity, oro-hypopharynx and larynx. Methods: A multicentre prospective study was carried out between 2015 and 2018 with the participation of 10 Italian reference hospitals. The primary objective was to evaluate local control in patients with well-defined clinical characteristics and comprehensive histopathological information. Results: During the study period, 455 patients were enrolled; the minimum follow-up was 2 years. Previous treatment, grading and fresh specimen examination were identified as risk factors for local control in multivariate analysis. On the basis of these results, it seems possible to delineate "risk profiles" for different oncological outcomes. Discussion: The prognostic significance of the margins is reduced, and other risk factors emerge, which require diversified treatment and follow-up. Conclusions: Multidisciplinary treatment with adjuvant therapy, if indicated, reduces the prognostic importance of margins. Collaboration with a pathologist is an additional favourable prognostic factor and quality indicator.An appendix with literature review is present in the online version.