Expression Analysis of Circulating microRNAs in Saliva and Plasma for the Identification of Clinically Relevant Biomarkers for Oral Squamous Cell Carcinoma and Oral Potentially Malignant Disorders.

This study aims to evaluate the expression of salivary and plasmatic miRNAs as diagnostic biomarkers in patients with oral squamous cell carcinoma (OSCC) and oral potentially malignant disorders (OPMDs). A total of 25 patients were divided into three groups, according to their diagnosis: OSCC patients (n = 14); OPMDs patients (n = 6); and healthy controls (n = 5). At the time at diagnosis/enrolment, patients underwent salivary and plasmatic collection. The expression of miRNA -21, -31, -138, -145, -184, and -424 were evaluated by real-time PCR. An F-test and ANOVA test were performed to evaluate the miRNA levels (significance at p < 0.05). By comparing miRNA expression levels from saliva, a statistically significant difference emerged in the expression of miR-138 and miR-424 between the three groups (p < 0.05). In particular, these two miRNAs showed decreased expression levels in saliva samples from OSCC and OPMD patients compared to those from healthy controls. On the other hand, miRNA expression levels in plasma were low in all the groups, and no statistically significant differences were found. Overall, our results showed that liquid biopsy from saliva may be a useful tool for the identification of diagnostic molecular biomarkers in OSCC and OPMDs.

The Impact of Standing Electric Scooters on Maxillofacial Fractures: An Italian Multi-Centric Epidemiological Study.

Objectives: This study aimed to determine the impact of standing electric scooters on maxillofacial on the Italian territory. Methods: The authors analyzed the epidemiology of the injuries to define electric mobility's impact on maxillofacial surgery practice. For this retrospective cohort study, data were collected by unifying the standing e-scooter-related fractures database from 10 Italian maxillofacial surgery departments. The reference period considered was from January 2020 to December 2023. The main data considered included age, gender, type of access, time slot of admission, type of admission, alcohol level, helmet use, dynamics of the accident, and area of the fracture. Results: A total of 79 patients were enrolled. The average age of the participants was approximately 31 years. The blood alcohol level was found to be above the Italian norm in 15 cases (19%). Only one patient wore a helmet. The most affected facial third was the middle one with 36 cases (45.5%), followed by the lower one (31, 39.3%). The most recurrent patterns were fractures of the orbito-malar-zygomatic complex (15, 19%), followed by multifocal (bifocal, trifocal) fractures of the mandible (14, 17.5%). Conclusions: This study demonstrated how maxillofacial fractures related to the use of electric scooters are associated with complex patterns, associated with a high rate of post-surgical aftermaths.

Head and Neck Airbag Penetrating Injuries.

BACKGROUND: Airbags have significantly decreased fatalities in frontal vehicle accidents, but their deployment can lead to more severe injuries and rarely death. The authors present a case of a penetrating injury causing tissue loss in the left cheek, an "explosion" of the zygomatic arch, and facial nerve damage, discussing the management in the contest of literature examining similar injuries in the head and neck region. MATERIALS AND METHODS: Reviewing English literature from 1995 to 2023, 9 patients experienced severe airbag-related penetrating head and neck injuries, in 3 cases resulting in death. In addition, we describe the case of a young male reporting a deep cheek laceration with facial nerve damage, tissue loss, and comminuted maxilla-zygomatic fracture; 48 hours after trauma, he underwent surgical reconstruction using a bilobed flap, direct suture of the resected masseter muscle, closed reduction of the comminuted zygomatic arch fracture, and direct neurorrhaphy of the lacerated facial nerve. RESULTS: Five months after surgery, facial nerve function recovery was observed. Mouth opening was restored, but a mixed low-medium hearing loss persisted for high frequencies. In another case marginal nerve damage was reported, but management is not described. CONCLUSION: The use of seat belts and airbags has led to a significant reduction in the incidence of facial fractures and fatalities after motor vehicle accidents, but at the same time, in some cases, complex facial trauma and/or penetrating injury can be observed. In case of suspected or certain facial nerve damage, it is mandatory to perform exploration and eventual reconstruction within 72 hours.

Bone-flap-harvest-related donor site morbidity in reconstructive jaw microsurgery: Retrospective analysis based on 220 patients over a ten-year period.

Microsurgery is the gold standard for hard and soft tissue reconstruction in head and neck neoplasia and malformations. Fibular, iliac crest, and scapular free flaps are the main choices for reconstructive surgery of the jaws. Although widely described in the literature, no statistical comparison analysis of the donor site morbidity of these has been performed to our knowledge. Therefore, in this study, the medical records of patients who underwent microsurgical jaw reconstruction at the Maxillofacial Oncological Reconstructive Surgery Unit of Umberto I General Hospital in Rome between 2011 and 2021 were analysed retrospectively. Inclusion criteria were complete clinical and radiological records, microsurgical reconstruction harvesting one of the three flaps, and a minimum follow up of 12 months. Principal donor site complications were recorded and compared among the flaps. The data were analysed using IBM SPSS Statistics (28.0.1.1, IBM Corp). The study enrolled 220 patients: 103 with deep circumflex iliac artery (DCIA) flaps, 87 with fibular free flaps (FFF), and 30 with scapular bone flaps (SBF). The main DCIA donor site complications were dysaesthesia (13.6%), abdominal hernia (2.9%), dehiscence (1.9%), infection (1.9%), and anterior superior iliac spinal fracture (1.9%). Similarly, the main FFF complications were dehiscence (8%), skin graft necrosis (6.9%), infection (5.7%), and dysaesthesia (3.4%). Subcutaneous seroma occurred in 13.3% of SBF patients and dehiscence in 6.7%. Regional dysaesthesia occurred significantly (p < 0.05) more often in DCIA than FFF or SBF patients. Dehiscence was significantly (p < 0.05) more frequent in FFF than DCIA or SBF patients. All flaps were safe and associated with low donor site morbidity. The jaws should be reconstructed selecting the flap that best satisfies the reconstructive needs based on the patient's clinical features.

Limberg Flap for Lateral Midface Reconstruction.

Several local skin flaps and tissue rearrangement techniques have been described in the literature, including the rhomboid flap. The Limberg flap is one of the most versatile local flaps that can be used for reconstruction of a wide range of skin defects in different parts of the body. The purpose of this study is to demonstrate the safety and applicability of the Limberg flap for reconstruction of skin facial defects, particularly after cutaneous tumor resection. The following article presents a retrospective case series of 8 patients in whom the Limberg flap was used to reconstruct skin defects resulting from malignant tumor resections in the lateral part of the face. No restrictions were collected regarding etiology, location, size, age, sex, or any other patient factors. The recruited patients were treated in the Maxillofacial Surgery Unit of Floraspe Renzetti Hospital of Lanciano and the study was conducted in collaboration with Sapienza University of Rome, from April 2023 to April 2024. All the flaps settled with no complications and all the patients were FOD (free of disease) 6 months after surgery. So, in accordance with the literature, the Limberg flap turns out to be a rapid and reliable option that could be easily applied for small (size around 1-2 cm) and medium-sized (size around 2-4 cm) cutaneous defects of the face even for the oldest and/or emaciated patients.

Sports-related Mandibular Fractures in the Center of Italy: A Retrospective Study.

The main causes of injuries to the lower and middle third of the facial skeleton are traffic accidents, accidental falls, assaults, and sport. Regarding sports-related maxillofacial trauma, an 8-year retrospective study was conducted at the Department of Oral and Maxillofacial Surgery of the Policlinico Umberto I in Rome, Italy. In all, 329 patients were included, of which we analyzed 35 patients with sports-related mandibular fractures. Specifically, we assessed the type of mandibular fracture reported, age, gender, number of fracture lines, association with other maxillofacial fractures, and treatment options. The causes of sports-related injuries are often multifactorial. Therefore, the aim of our study was to understand the correlation between the type of sport practiced and the most frequently reported pattern of mandibular fracture, highlighting how, depending on the sport, the mechanism of action is different and may correlate with a specific type of mandibular fracture.

The role of CD73 in predicting the response to immunotherapy in head and neck cancer patients.

Immunotherapy has a crucial role in the treatment of recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). However, only a small percentage of patients achieve long-term benefit in terms of overall response and survival. It was shown that HNSCC has an immunosuppressive microenvironment due to high levels of regulatory T cells and immunosuppressive molecules, such as LAG3 and CD73. The aim of our study was to investigate if the expression of CD73 by neoplastic and immune cells could affect the efficacy of anti-PD-1 immunotherapy. We reviewed data from 50 patients with R/M HNSCC receiving first line immunotherapy with or without chemotherapy based on a combined positive score (CPS). CD73 expression by cancer and immune cells was evaluated on pre-treatment and the percentage of stained cells was recorded. We analysed the association between CD73 expression on neoplastic and immune cells and early progression (EP), defined as progression occurring within 3 months. In 88 % of patients the primary tumour site was in the oral cavity or larynx. All patients received pembrolizumab associated in 40 % of cases to chemotherapy. CD73 was positive in 82 % and 96 % of cases on neoplastic and immune cells, respectively. The median value of CD73 was 32 % for neoplastic cells and 10 % for the immune ones. We observed a significant association between the CD73 expression on neoplastic cells over the median value and EP disease. We didn't record a correlation between the expression of CD73 on immune cells and early progression. Our findings suggest that higher expression of CD73 on neoplastic cells could predict resistance to immunotherapy in patients with CPS positive R/M HNSCC. The addition of this biomarker to routine evaluation of CPS could help to select the patients primary resistant to anti-PD-1 immunotherapy.

MR-Neurography of the facial nerve in parotid tumors: intra-parotid nerve visualization and surgical correlation.

PURPOSE: One of the most severe complications in surgery of parotid tumors is facial palsy. Imaging of the intra-parotid facial nerve is challenging due to small dimensions. Our aim was to assess, in patients with parotid tumors, the ability of high-resolution 3D double-echo steady-state sequence with water excitation (DE3D-WE) (1) to visualize the extracranial facial nerve and its tracts, (2) to evaluate their relationship to the parotid lesion and (3) to compare MRI and surgical findings. METHODS: A retrospective study was conducted including all patients with parotid tumors, who underwent MRI from April 2022 to December 2023. Two radiologists independently reviewed DE3D-WE images, assessing quality of visualization of the facial nerve bilaterally and localizing the nerve's divisions in relation to the tumor. MRI data were compared with surgical findings. RESULTS: Forty consecutive patients were included (M:F = 22:18; mean age 56.3 ± 17.4 years). DE3D-WE could excellently visualize the nerve main trunk and the temporofacial division in all cases. The cervicofacial branch was visible in 99% of cases and visibility was good. Distal divisions were displayed in 34% of cases with a higher visibility on the tumor side (p < 0.05). Interrater agreement was high (weighted kappa 0.94 ± 0.01 [95% CI 0.92-0.97]). Compared to surgery accuracy of MRI in localizing the nerve was 100% for the main trunk, 96% for the temporofacial and 89% for the cervicofacial branches. CONCLUSIONS: Facial nerve MR-neurography represents a reliable tool. DE3D-WE can play an important role in surgical planning of patients with parotid tumors, reducing the risk of nerve injury.

Pembrolizumab-based first-line treatment for PD-L1-positive, recurrent or metastatic head and neck squamous cell carcinoma: a retrospective analysis.

BACKGROUND: The KEYNOTE-048 trial showed that pembrolizumab-based first-line treatment for R/M HNSCC led to improved OS in the PD-L1 CPS ≥ 1 population when compared to the EXTREME regimen. However, the R/M HNSCC real-world population is generally frailer, often presenting with multiple comorbidities, worse performance status and older age than the population included in phase III clinical trials. METHODS: This is a retrospective, single-centre analysis of patients with R/M HNSCC treated with pembrolizumab-based first-line treatment. RESULTS: From February 2021 to March 2023, 92 patients were treated with pembrolizumab-based first-line treatment. Patients treated with pembrolizumab-based chemoimmunotherapy had better ECOG PS and younger age than those treated with pembrolizumab monotherapy. Median PFS and OS were 4 months and 8 months, respectively. PFS was similar among patients treated with pembrolizumab-based chemoimmunotherapy and pembrolizumab monotherapy, while patients treated with pembrolizumab monotherapy had worse OS (log-rank p =.001, HR 2.7). PFS and OS were improved in patients with PD-L1 CPS > = 20 (PFS: log-rank p =.005, HR 0.50; OS: log-rank p =.04, HR 0.57). Patients with higher ECOG PS scores had worse PFS and OS (PFS, log-rank p =.004; OS, log-rank p = 6e-04). In multivariable analysis, ECOG PS2 was associated with worse PFS and OS. CONCLUSIONS: PFS in our real-world cohort was similar to the KEYNOTE-048 reference while OS was numerically inferior. A deeper understanding of clinical variables that might affect survival outcomes of patients with R/M HNSCC beyond ECOG PS and PD-L1 CPS is urgently needed.

Paediatric endoscopic endonasal middle skull base reconstruction: retrospective analysis of 78 patients treated in a single tertiary care paediatric center.

INTRODUCTION: Skull base pathologies in the paediatric population are rare and require treatment by multiple qualified specialists. The endoscopic endonasal approach has revolutionized surgical treatment because it is less invasive than existing treatments.The goal of this study was to retrospectively review our experience with the reconstruction of paediatric skull middle base defects and associated complications. MATERIALS AND METHODS: We analysed medical records from patients aged ≤ 18 years who were treated at our centre between 2013 and 2021. Patients treated with an endoscopic skull base approach and reconstruction, and who had complete clinical and radiological documentation and a minimum follow-up of 12 months, were included in the analysis. Personal data, reconstructive techniques, and complications were analysed. RESULTS: A total of 78 patients met the inclusion criteria and were enrolled in the study. Of these patients, 32 were male and 46 were female, and the mean age was 11.5 years. The main signs and symptoms were as follows: bitemporal hemianopsia in 53 cases, visual impairment in 23 cases, and headache in 30 cases. The most frequent aetiologies were craniopharyngioma (38 cases), pituitary adenoma (23 cases), and clivus chordoma (4 cases). All patients were treated via a pure endoscopic approach. For reconstruction, a multilayer technique was used in 18 cases, naso-septal flap in 43 cases, Gasket-Seal technique in 12 cases, and heterologous reconstruction in 5 cases. Only six patients presented a major complication: two had a postoperative cerebral spinal fluid leak, one developed a brain abscess, and three had diabetes insipidus.The mean follow-up period was 23.4 months.There were no statistically significant differences in postoperative CSF leak in relation to different reconstructive techniques. CONCLUSION: Endoscopic endonasal skull base surgery is a safe and effective treatment for paediatric middle skull base pathologies. Reconstruction techniques have a high success rate of 96.5-100%, and the rate of associated complications is < 3%.

Extranodal follicular dendritic cell sarcoma of the tonsil: An extremely rare clinical entity.

Follicular dentritic cell sarcomatous neoplasms originate from dendritic cells contained within the lymph nodes. In extranodal location, these neoplasms, are rare clinical entities, and even more so, their location in the head-neck region is extremely rare. Only 17 cases of primary dendritic cell sarcoma of the tonsil are reported in the literature at present. Being such a rare entity, histopathological diagnosis can be complex and requires great expertise and proper immunohistochemical analysis [1]. We present a case of a 48-year-old young man diagnosed with follicular dendritic cell sarcoma of the tonsil who underwent, probably for the first time in the literature, transoral robotic surgical resection.

Analysis of Surgical Complications in Mandibular Fractures in the Center of Italy: A Retrospective Study.

Mandibular fractures are the second most common maxillofacial fractures. The prevalent treatment for this kind of fractures is either a surgical procedure such as maxillomandibular fixation or open reduction and internal fixation or a combination of both. Sometimes the patients might develop locoregional postoperative complications. The most frequently reported complications are trigeminal V3 injury and surgical site infection. A 4-year retrospective study was performed at the Department of Oral and Maxillofacial Surgery, Policlinico Umberto I of Rome, Italy, and the postoperative complications after mandibular fracture surgical treatment were collected. The authors studied the characteristics of each complication and the correlation with the type of mandibular fracture and the surgical treatment chosen.

Long-Term Aesthetic Cicatrization Analysis of Lower Eyelid Incision for Orbital Floor Fracture Approach.

Orbital fractures are among the most frequent facial injuries. Of the 3 most widely described approaches in the literature, the lower eyelid approach is the authors' preference. This study retrospectively analyzed the patients treated at the Trauma Center of the Umberto I Hospital, Sapienza University of Rome from January 2010 to December 2020. Inclusion criteria were as follows: diagnosis of pure/impure orbital bone fracture, complete clinical and radiological documentation, and a minimum of 12 months follow-up. Sex, age, etiology, treatment, and associated complications were analyzed using IBM SPSS Statistics. Two internationally validated scales were used for the functional and esthetic long-term evaluation: the Patient and Observer Scar Assessment Scale (POSAS) and the Vancouver one. The scales were compiled by the patient himself and by 3 independent expert observers. Of the 543 patients who underwent surgery in the specified period, 208 fully met the inclusion criteria. One hundred forty-two (68.2%) were males and 66 (31.8%) were females, with a mean age of 40.68 years. The main cause was represented by assaults (33.1%). One hundred seventy-nine patients had a pure orbital fracture (83.8%) and 29 an impure one (16.2%). The most frequent symptoms at the time of diagnosis were diplopia (31.2%), followed by anesthesia of the second trigeminal branch (24.3%). Open reduction with internal fixation was the preferred treatment and proved to be effective in reducing the main signs and symptoms of the fracture in a statistically significant way ( P < 0.05). Long-term esthetic results of the lower eyelid, using the Vancouver and POSASs, were respectively as follows: Vancouver Scar Scale mean total score was 2.41 (range: 0-8), observer POSAS mean total score was 1.83 (range: 1.2-3.9), observer general opinion mean score was 1.66, patient POSAS mean total score was 2.23 (range: 1.33-3.7), and patient general opinion mean score was 2.87. The lower eyelid approach has proven to be reproducible, with a fast-learning curve and a low complication rate. The analysis conducted highlighted an excellent long-term esthetic-functional result. Further studies will be needed to statistically compare the results obtained with other orbital floor surgical approaches.

Assessment of deep plane facelift in facial feminization surgery: A prospective pilot study.

Facial feminization surgery (FFS) is often the first procedure requested by patients wishing to undergo gender-affirming surgery. This study aims to evaluate the applicability and effectiveness of deep plane facelifts in FFS. The authors conducted a prospective study that included patients who requested a deep plane facelift as a standalone procedure to achieve a more feminine facial appearance as the only procedure of FFS. These patients underwent deep plane facelifts to achieve a more feminine oval face shape and increased tissue projection of the zygomatic-malar region. To assess the effectiveness of the procedure and patient satisfaction, the Face-Q scales, Face and Neck lift Objective Photo-Numerical Assessment Scale, the Satisfaction With Life Scale, and the Subjective Happiness Scale were applied preoperatively and one year after surgery. Thirty-six patients were included in the study. A statistically significant difference (p < 0.005) was observed between pre and postoperative scores. The repositioning of the malar fat pads increased the malar volume, providing a more oval overall shape of the face, which is typically feminine. No major complications were observed. Despite our encouraging results, new studies with a larger sample of patients are needed to support the benefits of the deep plane facelift as part of FFS to elevate this technique from an ancillary to a routine procedure for patients undergoing gender affirmation surgery.

Risk of Oral Squamous Cell Carcinoma in One Hundred Patients with Oral Lichen Planus: A Follow-Up Study of Umberto I University Hospital of Rome.

This study aims to retrospectively assess the potential risk of malignant transformation in patients with diagnosed oral lichen planus (OLP) between 2015 and 2022, and to evaluate the influence of different risk factors. The department's database and medical records from 2015 to 2022 were searched for patients with a confirmed diagnosis of OLP based on both clinical and histological parameters. A total of 100 patients (59 females and 41 males) were found with a mean age of 64.03 years. In the considered period, the percentage of diagnosed OLP patients was 1.6%, while the percentage of diagnosed OLP patients with transformation to oral squamous cell carcinoma (OSCC) was 0.18%. A statistically significant difference was found with age (p = 0.038), tobacco status (p = 0.022), and radiotherapy (p = 0.041). The analysis revealed the presence of significant risk in ex-smokers (>20 pack-years), with an odds ratio (OR) of 10.0000 (95% confidence interval (95% CI) 1.5793-63.3186); in alcohol-drinker patients, with an OR of 4.0519 (95% CI 1.0182-16.1253); in ex-smoker and alcohol-drinker patients, with OR of 17.6250 (95% CI 2.2464-138.2808); and in patients who had undergone radiotherapy, with OR of 6.3000 (95% CI 1.2661-31.3484). The malignant transformation of oral lichen planus was slightly higher than thought, and the results revealed a possible association with age, tobacco and alcohol status, and history of radiotherapy. An elevated risk of malignant transformation was observed in heavy ex-smoker patients, alcohol-drinker patients, and alcohol-drinker patients with a history of smoking (ex-smokers). Persuading the patient to quit tobacco and alcohol consumption and periodic follow-ups are recommended in general, but particularly in the presence of these risk factors.

Dermal Regeneration Template: Reconstruction in Oral Cancer Defects.

Background: Post ablative oral mucosal defect resulting from the removal of tumors can be treated with various techniques. Purpose: In this paper, we are showing what, in our experience, are the advantages and disadvantages given using biosynthetic skin substitutes when dealing with this kind of lesions. Materials and methods: Patients included in the sample came to our attention with both neoplastic lesions (11 subjects) and important scar retraction after previous oncologic surgery (1 subject). All patients underwent trans-oral resection surgery following the same surgical protocol and post ablative oral mucosal defect were treated using the dermal regeneration template. The surgical defect location, size, and time of removal of the silicone layer varied from one subject to the other. Results: Most patients showed good healing with reduced scarring and adequate remucosalisation of the defect. The main complications were shown in a palatal lesion treated with concomitant osteal resection, which developed an oroantral fistula at follow up, and tongue lesions which showed some scarring. Conclusions: Given our experience, we would advise using dermal substitutes when reconstructing oral defects only after a cautious evaluation of the area of the lesion, the gap size, the possible adherence of the membrane to the gap, and the presence of tissue supporting the overlying membrane.

Correction: Brauner et al. Dental Management of Maxillofacial Ballistic Trauma. J. Pers. Med. 2022, 12, 934.

The authors wish to make the following correction to this paper [...].

The observational clinical registry (cohort design) of the European Reference Network on Rare Adult Solid Cancers: The protocol for the rare head and neck cancers.

INTRODUCTION: Care for head and neck cancers is complex in particular for the rare ones. Knowledge is limited and histological heterogeneity adds complexity to the rarity. There is a wide consensus that to support clinical research on rare cancer, clinical registries should be developed within networks specializing in rare cancers. In the EU, a unique opportunity is provided by the European Reference Networks (ERN). The ERN EURACAN is dedicated to rare adults solid cancers, here we present the protocol of the EURACAN registry on rare head and neck cancers (ClinicalTrials.gov Identifier: NCT05483374). STUDY DESIGN: Registry-based cohort study including only people with rare head and neck cancers. OBJECTIVES: to help describe the natural history of rare head and neck cancers;to evaluate factors that influence prognosis;to assess treatment effectiveness;to measure indicators of quality of care. METHODS: Settings and participants It is an hospital based registry established in hospitals with expertise in head and neck cancers. Only adult patients with epithelial tumours of nasopharynx; nasal cavity and paranasal sinuses; salivary gland cancer in large and small salivary glands; and middle ear will be included in the registry. This registry won't select a sample of patients. Each patient in the facility who meets the above mentioned inclusion criteria will be followed prospectively and longitudinally with follow-up at cancer progression and / or cancer relapse or patient death. It is a secondary use of data which will be collected from the clinical records. The data collected for the registry will not entail further examinations or admissions to the facility and/or additional appointments to those normally provided for the patient follow-up. Variables Data will be collected on patient characteristics (eg. patient demographics, lifestyle, medical history, health status); exposure data (eg. disease, procedures, treatments of interest) and outcomes (e.g. survival, progression, progression-free survival, etc.). In addition, data on potential confounders (e.g. comorbidity; functional status etc.) will be also collected. Statistical methods The data analyses will include descriptive statistics showing patterns of patients' and cancers' variables and indicators describing the quality of care. Multivariable Cox's proportional hazards model and Hazard ratios (HR) for all-cause or cause specific mortality will be used to determine independent predictors of overall survival, recurrence etc. Variables to include in the multivariable regression model will be selected based on the results of univariable analysis. The role of confounding or effect modifiers will be evaluated using stratified analysis or sensitivity analysis. To assess treatment effectiveness, multivariable models with propensity score adjustment and progression-free survival will be performed. Adequate statistical (eg. marginal structural model) methods will be used if time-varying treatments/confounders and confounding by indication (selective prescribing) will be present. RESULTS: The registry initiated recruiting in May 2022. The estimated completion date is December 2030 upon agreement on the achievement of all the registry objectives. As of October 2022, the registry is recruiting. There will be a risk of limited representativeness due to the hospital-based nature of the registry and to the fact that hospital contributing to the registry are expert centres for these rare cancers. Clinical Follow-up could also be an issue but active search of the life status of the patients will be guaranteed.