Sentinel Lymph Node Biopsy (SLNB) for Early-Stage Head and Neck Squamous-Cell Carcinoma of the Tongue: Twenty Years of Experience at I.N.T. "G.Pascale".

Oral tongue squamous-cell carcinoma (OTSCC) is the most prevalent malignancy in the head and neck region. Lymphatic spread, particularly to cervical lymph nodes, significantly impacts 5-year survival rates, emphasizing the criticality of precise staging. Metastatic cervical lymph nodes can decrease survival rates by 50%. Yet, elective neck dissection (END) in T1-2 cN0 patients proves to be an overtreatment in around 80% of cases. To address this, sentinel lymph node biopsy (SLNB) was introduced, aiming to minimize postoperative morbidity. This study, conducted at the ENT and Maxillofacial Surgery department of the Istituto Nazionale Tumori in Naples, explores SLNB's efficacy in early-stage oral tongue squamous-cell carcinoma (OTSCC). From January 2020 to January 2022, 122 T1/T2 cN0 HNSCC patients were enrolled. Radioactive tracers and lymphoscintigraphy identified sentinel lymph nodes, aided by a gamma probe during surgery. Results revealed 24.6% SLN biopsy positivity, with 169 SLNs resected and a 21.9% positivity ratio. The study suggests SLNB's reliability for T1-2 cN0 OTSCC patient staging and early micrometastasis detection.

Pre-Treatment Neutrophil-to-Lymphocyte and Platelet-to-Lymphocyte Ratios as Predictors of Occult Cervical Metastasis in Clinically Negative Neck Supraglottic and Glottic Cancer.

Background. Among patients with diagnosis of Laryngeal Squamous Cell Carcinoma (LSCC), up to 37.5% of cases may have occult metastasis (OM), and this feature is linked to poor prognosis and high rate of local recurrence. The role of elective neck dissection (END) in clinically negative neck (cN0) LSCC remains controversial. It is of great value to search for low-cost and easily detectable indicators to predict the risk of OM in laryngeal cancer. Recent reports have shown that high values of the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) represent a negative prognostic factor in head and neck cancers. The aim of our study has been to investigate the value of pre-treatment NLR and PLR with regard to predicting occult cervical metastasis in cN0 supraglottic and glottic LSCC. Materials and methods. Data of patients affected by LSCC, who had been surgically treated by means of laryngectomy (total, horizontal partial and supracricoid) and END between January 2006 and January 2021, were retrospectively reviewed, using information retrieved from a database dedicated to such procedures in a single tertiary care referral institute. Results. A total of 387 patients were treated for LSCC at our Institute from 2006 to 2021, but only 108 of them met the inclusion criteria. The median age at the time of diagnosis was 64 years (range, 39-89 years). All the tumors were treated with a laryngectomy and an END. A total of 27.7% of patients were found positive for neck node metastasis (the pN+ group), while 78/108 (72.3%) patients were found to be negative for the presence of neck metastasis (the pN0 group). High values of NLR, but not PLR, significantly correlated with the probability of OM, and according to the iterative algorithm of Newton-Raphson, an NLR value of 2.26 corresponds to a probability of OM of 20%. Conclusion. Our analysis revealed a statistical correlation between high NLR pre-treatment values and positive neck OM in patients with LSCC.

Patients affected by squamous cell carcinoma of the head and neck: A population particularly prone to developing severe forms of COVID-19.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the recent Coronavirus Disease 2019 (COVID-19) pandemic, which has spread all over the world over the past year. Comorbidities appear to affect the prognosis of patients with such diseases, but the impact of cancer on the course of SARS-CoV2 has remained largely elusive. The aim of the present study is to analyze the outcome of patients affected by squamous cell carcinoma of the head and neck (SCCHN) and a number of their comorbidities, if infected with SARS-CoV2. The clinical data of 100 patients affected by SCCHN, who were undergoing treatment or who had finished their oncologic treatment in the past 6 months, were retrospectively collected and analysed. For each patient, the Charlson Comorbidity Index (CCI) was calculated to provide a score assessing the real weight of comorbidities on the patient's outcome at the time of diagnosis. It was discovered that these patients, besides the SCCHN, frequently presented at diagnosis with several other comorbidities, including hypertension, type 2 diabetes, cardiac arrhytmia, chronic obstructive pulmonary disease and various forms of vasculopathy (and thus a poor CCI). This feature suggest that, given the high frequency of various comorbidities in patients with SCCHN, additional SARS-CoV2 infection could have particularly devastating consequences.

Electrochemotherapy as a First Line Treatment in Recurrent Squamous Cell Carcinoma of the Oral Cavity and Oropharynx PDL-1 Negative and/or with Evident Contraindication to Immunotherapy: A Randomized Multicenter Controlled Trial.

BACKGROUND: A significant proportion of patients with head and neck squamous cell carcinoma (HNSCC) have advanced-stage disease (stages III to IVB) that do not respond to therapy despite aggressive, site-specific multimodality therapy. A great number of them will develop disease recurrence, with up to 60% risk of local failure and up to 30% risk of distant failure. Therapy can be very demanding for the patient especially when important anatomical structures are involved. For these reasons, therapies that preserve organ functionality in combination with effective local tumor control, like electrochemotherapy (ECT), are of great interest. Until few months ago, systemic cetuximab + platinum-based therapy + 5-fluorouracil represented the standard treatment for HNSCC relapses with a median overall survival of 10.1 months and an objective response rate of 36%. Recently the results of KEYNOTE-048 study were published and a new combination of monoclonal antibody named pembrolizumab and chemotherapy emerged as standard first line therapy of recurrent or metastatic tumor that overexpress tissue PDL-1 (Programmed Death 1 ligand). Nevertheless, a variable percentage from 10 to 15% of patients with recurrent/metastatic disease have a tumor that does not overexpress tissue PDL-1, and therefore, according to the results of the KEYNOTE-048 study, does not benefit from replacement of cetuximab with pembrolizumab. These patients will be treated with the "gold standard": cetuximab, cisplatin/carboplatin and 5-fluorouracil. AIM: To verify whether electrochemotherapy performed with bleomycin of HNSCC relapses of the oral cavity and oropharynx (single relapse on T) is able to lead to an increase in the objective response rate in comparison with the systemic treatment with cetuximab + platinum-based therapy + 5-fluorouracil in patients with PDL-1 negative tumors. METHODS: The phase IIb study involves the enrolment of 96 patients who meet the inclusion criteria (48 in the control arm and 48 in the treatment arm). The control arm involves the treatment of HNSCC with systemic treatment (cetuximab + platinum-based therapy + 5-fluorouracil). The treatment arm involves the ECT with bleomycin. The primary objective is to verify the objective response rate of patients in the control arm compared to the treatment arm.

Boosting the Immune Response with the Combination of Electrochemotherapy and Immunotherapy: A New Weapon for Squamous Cell Carcinoma of the Head and Neck?

Head and neck squamous cell carcinomas (SCCHN) are not rare malignancies and account for 7% of all solid tumors. Prognosis of SCCHN patients strongly depends on tumor extension, site of onset, and genetics. Advanced disease (recurrent/metastatic) is associated with poor prognosis, with a median overall survival of 13 months. In these patients, immunotherapy may represent an interesting option of treatment, given the good results reached by check-point inhibitors in clinical practice. Nevertheless, only a minor number of patients with advanced disease respond to immunotherapy, and, disease progressions/hyper-progressions are common. The latter could be a very difficult issue, especially in patients having a wide and highly symptomatic head/neck mass. Given the potentiality to boost the immune response of some local modalities, such as electrochemotherapy, a possible future approach may take into account the combination of electrochemotherapy and immunotherapy to treat patients affected by SCCHN, suffering from symptomatic lesions that need rapid debulking.

Transoral robotic surgery in head and neck district: a retrospective study on 67 patients treated in a single center.

BACKGROUND: The anatomical complexity of the oropharynx and the difficulty in reaching its distal portion have always conditioned the surgical accessibility.Robotic surgery represents an excellent alternative in the treatment of cervico-facial oncological diseases. METHODS: This series comprises all patients managed for head and neck cancer by Trans Oral Robotic Surgery TORS.The staging assessment, including neck ultrasound and total body PET/CT scan, was performed in each patient according to the TNM classification.All charts were recorded with the following data: name and surname, age, gender, date of surgery intra or post-operative hemorragia, tumor site, histology, TNM stage, robot set-up time, tumor resection time, whether or not tracheotomy was performed, whether or not neck dissection was performed, insertion of a nasogastric tube or gastrostomy, time to resumption of oral feeding, surgical margins, mean length of hospital stay, adjuvant treatment and follow-up. RESULTS: From February 2013 to February 2018, TORS was performed in 67 consecutive patients affected by head and neck tumours.We divided, our sample, in 3 subsites: supraglottic larynx, parapharyngeal space and oropharynx.Pathology reports confimed malignancy in 44 cases: 8 cases lymphomas, 36 cases of Squamous cell carcinoma (SCC), 5 cases of benign salivary glands tumors and 18 miscellaneous cases. Neck dissection was performed in 12 cases.Tracheotomy was perfomed in 3/67 cases for respiratory failures. A nasogastric tube was inserted at the end of the surgical procedure in 21 patients. The mean length of hospital stay was 10 days .Major complications included post-operative bleeding in 3 patients, 1 exitus for massive bleeding 20 days post-surgery and 1 respiratory failure treated with tracheotomy and monitoring in the Intensive Care Unit (ICU) for 3 days. CONCLUSIONS: Robotic surgery has been considered a valid alternative to traditional open treatment in many specializations with the advantages of an endoscopic procedure, with the same oncological and functional results and with fewer complications. The advantages of this type of surgical technique have been discussed, it is mandatory to focus on the indications and contraindications.

Oral lichen planus and other confounding factors in narrow band imaging (NBI) during routine inspection of oral cavity for early detection of oral squamous cell carcinoma: a retrospective pilot study.

BACKGROUND: Narrow Band Imaging is a noninvasive optical diagnostic tool. It allows the visualization of sub-mucosal vasculature; four patterns of shapes of submucosal capillaries can be recognized, increasingly associated with neoplastic transformation. With such characteristics, it has showed high effectiveness for detection of Oral Squamous Cell Carcinoma. Still, scientific literature highlights several bias/confounding factors, such as Oral Lichen Planus. We performed a retrospective observational study on patients routinely examined with Narrow Band Imaging, investigating for bias, confounding factors and conditions that may limit its applicability. METHODS: Age, sex, smoking, use of dentures, history of head & neck radiotherapy, history of Oral Squamous Cell Carcinoma, site of the lesion and thickness of the epithelium of origin were statistically evaluated as possible bias/confounding factors. Pearson's Chi-squared test, multivariate logistic regression, Positive Predictive Value, Negative Predictive Value, Sensitivity, Specificity, Positive Likelihood Ratio, Negative Likelihood Ratio and accuracy were calculated, normalizing the cohort with/without patients affected by Oral Lichen Planus, to acknowledge its role as bias/confounding factor. RESULTS: Five hundred fifty-six inspections were performed on 106 oral cavity lesions from 98 patients. Age, sex, smoking, use of dentures and anamnesis of Oral Squamous Cell Carcinoma were not found to influence Narrow Band Imaging. History of head & neck radiotherapy was not assessed due to insufficient sample. Epithelium thickness does not seem to interfere with feasibility. Presence of Oral Lichen Planus patients in the cohort led to false positives but not to false negatives. Among capillary patterns, number IV was the most significantly associated to Oral Squamous Cell Carcinoma (p < 0.001), not impaired by the presence of Oral Lichen Planus patients in the cohort (accuracy: 94.3, 95% confidence interval: 88.1-97.9%; odds ratio: 261.7, 95% confidence interval: 37.7-1815.5). CONCLUSION: Narrow Band Imaging showed high reliability in detection of Oral Squamous Cell Carcinoma in a cohort of patients with oral cavity lesions not normalized for bias/confounding factors. Still, Oral Lichen Planus may lead to false positives. Narrow Band Imaging could help in the follow-up of patients with multiple lesions through detection of capillary pattern IV, which seems to be the most significantly associated to neoplastic epithelium.

Electrochemotherapy as palliative treatment in patients with advanced head and neck tumours: Outcome analysis in 93 patients treated in a single institution.

PURPOSE: To describe outcomes of Electrochemotherapy as palliative treatment in patients with advanced head and neck (H&N) tumours. METHODS: Ninety-three patients (120 treatment sessions) with H&N recurrent and/or metastatic neoplasm were treated. Treatment response was assessed 4 weeks after ECT with clinical examination and two months after the first evaluation with a CT scan of the H&N for deep lesions evaluation. The grade of bleeding and pain before, at the end of treatment and one week after ECT were evaluated. RESULTS: Five percent of complete responses, 40% of partial responses were registered. Disease progression was seen in 20% of patients after the first ECT procedure, the remaining 34% of patients experienced stable disease. A good control of pain and bleeding was obtained, especially in patients with moderate symptoms before the treatment. No toxicities related to ECT were seen. CONCLUSIONS: ECT is an interesting antitumoral therapy in advanced chemo and radio-refractory H&N neoplasms. ECT is able to reduce frequent symptoms, such as pain and bleeding, improving quality of life without damage to healthy tissue and with limited side effects. Moreover, ECT reduces hospitalization time and may contribute to an overall reduction in healthcare costs associated with advanced H&N cancers care.

Phase II clinical study of valproic acid plus cisplatin and cetuximab in recurrent and/or metastatic squamous cell carcinoma of Head and Neck-V-CHANCE trial.

BACKGROUND: Recurrent/metastatic squamous cell carcinoma of the head and neck (SCCHN) has a poor prognosis and the combination of cisplatin and cetuximab, with or without 5-fluorouracil, is the gold standard treatment in this stage. Thus, the concomitant use of novel compounds represents a critical strategy to improve treatment results. Histone deacetylase inhibitors (HDACi) enhance the activity of several anticancer drugs including cisplatin and anti-Epidermal Growth Factor Receptor (anti-EGFR) compounds. Preclinical studies in models have shown that vorinostat is able to down regulate Epidermal Growth Factor Receptor (EGFR) expression and to revert epithelial to mesenchimal transition (EMT). Due to its histone deacetylase (HDAC) inhibiting activity and its safe use as a chronic therapy for epileptic disorders, valproic acid (VPA) has been considered a good candidate for anticancer therapy. A reasonable option may be to employ the combination of cisplatin, cetuximab and VPA in recurrent/metastatic SCCHN taking advantage of the possible positive interaction between histone deacetylase inhibitors, cisplatin and/or anti-EGFR. METHOD/DESIGN: V-CHANCE is a phase 2 clinical trial evaluating, in patients with recurrent/metastatic squamous cell carcinoma of the head and neck never treated with first-line chemotherapy, the concomitant standard administration of cisplatin (on day 1, every 3 weeks) and cetuximab (on day 1, weekly), in combination with oral VPA given daily from day -14 with a titration strategy in each patient (target serum level of 50-100 µg/ml). Primary end point is the objective response rate measured according to Response Evaluation Criteria in Solid Tumors (RECIST). Sample size, calculated according to Simon 2 stage minimax design will include 21 patients in the first stage with upper limit for rejection being 8 responses, and 39 patients in the second stage, with upper limit for rejection being 18 responses. Secondary endpoints are time to progression, duration of response, overall survival, safety. Objectives of the translational study are the evaluation on tumor samples of markers of treatment efficacy/resistance (i.e. γH2AX, p21/WAF, RAD51, XRCC1, EGFR, p-EGFR, Ki-67) and specific markers of VPA HDAC inhibitory activity (histones and proteins acetylation, Histone deacetylase isoforms) as well as valproate test, histones and proteins acetylation of peripheral blood mononuclear cell, tested on blood samples at baseline and at different time points during treatment. DISCUSSION: Overall, this study could provide a less toxic and more effective first-line chemotherapy regimen in patients with recurrent/metastatic squamous cell carcinoma of the head and neck by demonstrating the feasibility and efficacy of cisplatin/cetuximab plus valproic acid. Moreover, correlative studies could help to identify responder patients, and will add insights in the mechanism of the synergistic interaction between these agents. EUDRACT NUMBER: 2014-001523-69 TRIAL REGISTRATION: ClinicalTrials.gov number, NCT02624128.

Innovative Surgical Management of the Synovial Chondromatosis of Temporo-Mandibular Joints: Highly Conservative Surgical Technique.

Synovial chondromatosis (SC) is an uncommon disease characterized by a benign nodular cartilaginous proliferation arising from the joint synovium, bursae, or tendon sheaths. Although the temporomandibular joint is rarely affected by neoplastic lesions, SC is the most common neoplastic lesion of this joint. The treatment of this disease consists in the extraoral surgery with a wide removal of the lesion; in this study, the authors described a more conservative intraoral surgical approach. Patient with SC of temporomandibular joint typically refer a limitation in the mouth opening, together with a persistent not physiological mandibular protrusion and an appearance of a neoformation located at the right preauricular region: the authors reported 1 scholar patient. After biopsy of the neoformation, confirming the synovial chondromatosis, the patient underwent thus to the surgical excision of the tumor, via authors' conservative transoral approach, to facilitate the enucleation of the neoformation. The mass fully involved the pterygo-maxillary fossa with involvement of the parotid lodge and of the right TMJ: this multifocal extension suggested for a trans-oral surgical procedure, in the light of the suspicion of a possible malignant nature of the neoplasm. Our intraoral conservative approach to surgery is aimed to reduce the presence of unaesthetic scars in preauricular and facial regions, with surgical results undoubtedly comparable to the traditional surgical techniques much more aggressive. Our technique could be a valid, alternative, and safe approach to treat this rare and complex kind of oncological disease.

Optimal management of a patient with recurrent nasopharyngeal carcinoma.

Nasopharyngeal carcinoma is rare in western countries, accounting for less than 1% of all malignancies. Despite prognosis is satisfactory for newly diagnosed, non-metastatic disease, management of recurrent disease is challenging, with a survival expectancy of approximately 6 mo with the use of chemotherapy as the sole salvage treatment. We report a case of recurrent nasopharyngeal carcinoma treated with a combination of chemotherapy, radiotherapy and surgery in the context of a multidisciplinary approach. A durable complete response was achieved.

Hyalinizing clear cell carcinoma of the parotid gland: report of a recurrent case with aggressive cytomorphology and behavior diagnosed on fine-needle cytology sample.

A case of recurrent hyalinizing clear cell carcinoma (HCCC) of the parotid gland in a 46-year-old female is here introduced. The patient had undergone a left superficial parotidectomy 6 months ago in another institution for an alleged benign, circumscribed mass 2.4 cm in diameter of the left parotid gland. Histopathological examination revealed a poorly differentiated HCCC bearing a EWSR-1 translocation on FISH examination. Fine Needle Cytology (FNC) was performed on three separate soft tissue masses in the pre-masseterine area and a cytological diagnosis of recurrent, poorly differentiated, possibly aggressive variant of HCCC, was rendered. FISH performed on a destained Diff Quik stained smear demonstrated an ESWR-1 translocation, which supported the cytopathological diagnosis. The cytomorphologic features and the differential diagnosis of this aggressive variant of HCCC are briefly discussed.

Expression analysis of SPARC/osteonectin in oral squamous cell carcinoma patients: from saliva to surgical specimen.

Oral squamous cell carcinoma (OSCC) remains a significant cause of morbidity and mortality, with approximately 540,000 new cases annually worldwide. The molecular mechanisms related to the pathogenesis of this disease are still poorly understood. The discovery of a molecular marker that allows the early detection of this cancer, which can be easily identified in biological samples, such as saliva, without intervening in advanced stages, is a challenge. Numerous studies have identified a panel of molecular markers differently expressed in OSCC and normal oral mucosa. In particular, it was found an aberrant expression of matricellular glycoprotein SPARC. SPARC is involved in normal tissue remodeling, regulating the deposition of extracellular matrix, but also in neoplastic transformation. In fact, aberrant SPARC expression was detected both in stromal cells associated with cancer and in tumor cells. The aim of our study was the evaluation of SPARC on a retrospective series of 119 OSCC cases and the validation of the obtained data on a prospective series of 27 patients with OSCC, of whom we have previously collected saliva, and smeared material. The obtained results were correlated with each other and with clinical pathological parameters at our disposal. The study demonstrated a prognostic value of SPARC, especially with regard to its expression in the stroma surrounding OSCC (P < 0.05).

Integrated therapeutic approaches in head and neck cancer: the importance of multidisciplinary team management.

Multidisciplinary team (MDT) is of paramount importance in the approach to patients with head and neck cancer. Its aim is to provide the best diagnostic work-up, tumor staging, and treatment. Furthermore, the prognosis of patients who are managed by MDT is usually better. MDT has a great value in all presentation settings. The role of the pathologist in the team is of utmost importance, in particular with regards to information provided on Human Papilloma Virus (HPV) status, which has a well acknowledged independent prognostic value mainly in oropharyngeal carcinoma. In early stage disease, namely in T1-2 N0 M0 patients, the meetings within the MDT mainly involve surgeons and radiation therapists. Surgery represents the mainstay of treatment, while radiation therapy is a suitable alternative, in particular in patients with advanced age, poor performance status and comorbidities. In locally advanced disease, surgeons, medical oncologists and radiotherapists are the key people, since different approaches have been carried out. In operable patients, adjuvant chemoradiation is indicated when resection margins are involved or close, or in presence of extracapsular nodal spread. Concurrent chemoradiotherapy, preceded or not by induction chemotherapy, is the favourite approach in this setting when surgery is strictly not indicated. In recurrent/metastatic disease chemotherapy and best supportive care are the main options, although local treatments, such as reirradiation and salvage surgery, are also worth considering. The standard chemotherapy treatment has finally evolved after about 30 years, and strong efforts are being pursued to further improve the outcome, mainly with the addition of new drugs.

Sclerosing polycystic adenosis of the parotid gland: report of one case diagnosed by fine-needle cytology with in situ malignant transformation.

Sclerosing polycystic adenosis (SPA) is a rare pathological condition affecting the salivary glands, first described by Smith etal. in 1996. Even though this lesion is being increasingly diagnosed, less than 50 cases have been published in the world literature to date. In line with numerous other pathological analogies between breast and salivary gland lesions, SPA shares with fibrocystic disease of the breast many histopathological features, i.e., fibrosis, oncocytic (apocrine) changes, hyperplasia of ductal and acinar epithelium, cystic dilation of ducts, and, often, atypical epithelial changes. Most of the described cases have followed a benign clinical course, despite the frequent possibility of atypical hyperplasia in more than 50% of the cases and of the more than occasional in situ malignant transformation. In this article, we introduce a new case occurring in the parotid gland of a 57-year-old male showing atypical epithelial hyperplasia and low-grade in situ mucoepidermoid carcinoma. Fine-needle cytology (FNC) was performed on the lesion and, when a diagnosis of SPA was prospected, the variegated cytological features of the obtained sample posed several differential diagnostic problems. The spectrum of pathological lesions entering differential diagnosis comprised sebaceous adenoma, Warthin's tumors with presence of sebaceous remnants, and low-grade mucoepidermoid carcinoma. Histopathological examination disclosed SCA with intraductal neoplastic transformation resembling noninvasive low-grade mucoepidermoid carcinoma. The cytological diagnosis of SPA should be entertained whenever a polymorphous picture is found on FNC samples comprising oncocytic/apocrine changes, sebaceous cells, cystic background, and epithelial hyperplasia with low-grade cytological atypias.