Francesco Mattioli

Background: : The aims of this study are: to assess the association of tumor budding (TB) and worst pattern of invasion (WPOI) with other clinical and histopathological prognostic factors of oral tongue and floor squamous cell carcinoma (OTFSSC), to evaluate their impact on survival outcomes and to assess whether they can be considered independent prognostic factors with respect to pathological depth of invasion (pDOI). Methods: : A retrospective multicenter study was conducted on patients who underwent compartmental surgery for locally advanced OTFSCC. Results: : A total of 134 patients were enrolled in the study. WPOI was found to be an independent negative prognostic factor for the risk of N+ at diagnosis. Patients with infiltrative WPOI presented a statistically significant increased risk of recurrence and loco‐regional recurrence. Conclusions: : TB and WPOI are promising prognostic markers in the therapeutic management of OTFSCC, potentially guiding possible treatment intensification.

Purpose: Idiopathic subglottic stenosis (iSGS) is a rare, progressive fibroinflammatory disease that predominantly affects middle-aged women. Although endoscopic treatments have improved, recurrence rates remain high and no standardized therapeutic approach has been defined. This exploratory retrospective pilot study aimed to assess feasibility, safety and explore the preliminary signal of benefit of intralesional injection of centrifuged autologous lipoaspirate as an adjunct to endoscopic balloon dilation in patients with iSGS. Methods: A retrospective pilot observational study was conducted at the Tracheal Team of the University Hospital of M. and the Otorhinolaryngology Unit of S.O. Hospital, B., I., from 2015 to 2024. Twenty-six adult women with histologically confirmed iSGS and at least 12 months of follow-up were included. Patients received either standard endoscopic balloon dilation with intralesional corticosteroid injection (n=19) or balloon dilation followed by injection of centrifuged autologous lipoaspirate (n=7). The primary outcome was recurrence within 24 months, defined as the need for reintervention due to symptomatic restenosis. Secondary outcomes included time-to-recurrence, Subglottic Stenosis–6 (SGS-6) scores, and perioperative complications. Results: Overall, recurrence occurred in 16 of 26 patients (61.6%). Recurrence was lower in the lipoaspirate group (2/7, 28.6%) compared with the standard group (14/19, 73.7%), with Pearson’s χ² of 4.4 (P = 0.036; Fisher’s exact P=0.06). Median time-to-recurrence was longer in the lipoaspirate group (482 days) than in the standard group (240 days) (Long-rank test p=0.047). Conclusions: In this retrospective pilot study, patients with idiopathic subglottic stenosis treated with intralesional injection of centrifuged autologous lipoaspirate following endoscopic balloon dilation showed a preliminary signal of lower recurrence rate and longer recurrence-free survival.

Objectives The primary objective of this study was to identify potential prognostic factors influencing disease control and survival outcomes in patients with neck metastases (NLM) and/or intraparotid metastases (PLM) arising from cutaneous squamous cell carcinoma (cSCC) of the head and neck. A secondary aim was to compare patients with isolated NLM, isolated PLM, and concurrent NLM/PLM. Study design and methods An observational, retrospective multicenter study included 68 patients with nodal metastatic cSCC treated at the Head and Neck Units of Bologna, Modena, and Pescara (2014–2024). Clinical, pathological, and treatment variables were analyzed for associations with survival using univariate and multivariate Cox regression models (IBM SPSS). Results The cohort included 30 patients with isolated NLM (44%), 14 with isolated PLM (21%), and 24 with both NLM and PLM (35%). At 5 years, DFS was 33.8%, DSS 70.6%, and OS 69.1%. DFS was reduced by extranodal extension (ENE) in PLM (HR 3.95, 95% CI 1.65–9.48, p = .002). DSS was negatively influenced by perineural invasion (HR 4.53, 95% CI 1.02–34.44, p= 0.016), NLM ENE (HR 5.60, 95% CI 1.72–18.19, p = 0.004), and PLM ENE (HR 8.90, 95% CI 2.51–18.90, p < 0.001). OS was independently worsened by PNI (HR 6.16, 95% CI 1.20–31.39, p = 0.029), NLM ENE (HR 5.18, 95% CI 1.67–16.03, p= 0.004), and PLM ENE (HR 7.03, 95% CI 2.24–22.07, p < 0.001). Female sex (36% in isolated PLM vs 3% in isolated NLM, p = .004) and immunosuppression (67% in patients with both NLM and PLM, p = 0.02) were significantly associated with nodal dissemination pattern, but not with survival. Conclusion This study highlights the prognostic relevance of PNI, ENE, advanced nodal stage, and lack of adjuvant RT in nodal metastatic cSCC. Immunosuppression and female sex appear more related to higher nodal dissemination patterns than to survival.

Eosinophilic granulomatosis with polyangiitis (EGPA), among various organs and systems, can affect the upper respiratory tract. The otolaryngologist must be able to suspect the pathology with the appearance of the first signs and recognize its late complications. Laryngeal involvement is rare and difficult to diagnose. A patient suffering from Churg‐Strauss syndrome developed posterior glottic stenosis 5 years after diagnosis. A biopsy of the lesion confirmed the localized recurrence of EGPA. Rituximab therapy prevented further relapse after 12 months of follow‐up. In the current literature, only two case reports, both pediatric, deal with laryngeal organic manifestation of the disease. Nonspecific findings, such as corditis or dysphonia, may be found in patients with EGPA in up to 25% of cases. Thus, even though primary laryngeal manifestation is rare, inflammation can be a common finding. The case herein reported appears to be the first organic Churg Strauss syndrome laryngeal manifestation in an adult patient. Laryngoscope , 135:1771–1773, 2025

Objective: Open partial horizontal laryngectomies (OPHLs) represent a comparable alternative to total laryngectomy and nonsurgical protocols in selected cases. While short‐term functional outcomes of OPHLs have been widely investigated, few have focused on the effect of aging on residual laryngeal structures.Study Design: Retrospective cohort study.Setting: Tertiary care academic center.Methods: Patients who underwent OPHLs after at least 1 year follow‐up and optimal functional rehabilitation were included in the study.Swallowing function was assessed according to PAS (Penetration aspiration scale) and Pooling scores. Spectrogram analysis of voice was conducted according to Yanagihara classification and acoustic parameters were also recorded. Subjective questionnaire data about phonation and swallowing were also recorded. Data obtained were compared among patients according to age at time of surgery, evaluation and duration of follow‐up.Results: Ninety‐seven patients were enrolled with a mean age at surgery and evaluation of 63 and 70 years old, respectively. Median follow‐up length was 5 years. OPHL type II was mostly performed. No significant correlation was observed between most of the analyzed variables and patient's age at the time of surgery and at the time of evaluation. Some acoustic parameters were negatively correlated with follow‐up length, while Jitter, NHR (Noise‐Harmonic Ratio), and Global grade and Roughness were significantly higher in patients >65 years old.Conclusion: Patients who complete rehabilitation reach equally good results as their younger peers with stability over time. Finally, the effects of aging on residual larynx are of minor entity compared to the nonoperated patients.Level of Evidence: Level IV‐retrospective cohort study.

Primary tracheal tumors are rare, constituting approximately 0.1–0.4% of malignant diseases. Squamous cell carcinoma (SCC) and adenoid cystic carcinoma (ACC) account for about two-thirds of these tumors. Despite most primary tracheal cancers being eligible for surgery and/or radiotherapy, unresectable, recurrent and metastatic tumors may require systemic treatments. Unfortunately, the poor response to available chemotherapy as well as the lack of other real therapeutic alternatives affects the quality of life and outcome of patients suffering from more advanced disease. In this condition, target therapy against driver mutations could constitute an alternative to chemotherapy, and may help in disease control. The past two decades have seen extraordinary progress in developing novel target treatment options, shifting the treatment paradigm for several cancers such as lung cancer. The improvement of knowledge regarding the genetic and biological alterations, of major primary tracheal tumors, has opened up new treatment perspectives, suggesting the possible role of biological targeted therapies for the treatment of these rare tumors. The purpose of this review is to outline the state of knowledge regarding the molecular biology, and the preliminary data on target treatments of the main primary tracheal tumors, focusing on salivary-gland-derived cancers and squamous cell carcinoma.

Objective: This study aims to prospectively compare endoscopic, radiological, and pathological features of a cohort of patients with glottic laryngeal squamous cell carcinoma (LSCC) undergoing open partial horizontal laryngectomy (OPHL) type II/III or total laryngectomy to better understand the reliability of preoperative endoscopy and computed tomography (CT) to predict the inferior paraglottic space (iPGS) involvement.Methods: We prospectively compared the endoscopic, radiological, and pathological findings in patients with glottic LSCC who underwent OPHL II/III, or total laryngectomy.Results: Endoscopy achieved a diagnostic accuracy of 87.2% for the anterior iPGS (iPGSa) and 86.1% for the posterior iPGS (iPGSp). There was no statistically significant difference in terms of histopathologic iPGSa involvement between reduced (85%—17/20 pts) and absent (92%—24/26 pts) vocal cord mobility (p = 0.39). CT alone did not improve the diagnostic performance of the endoscopy, reaching a diagnostic accuracy of 62.9% and 73.7% for the iPGSa and iPGSp, respectively. When endoscopy and CT were combined, the diagnostic performance improved for the iPGSp, achieving a sensitivity (Se), specificity (Spe), positive predictive value (PPV), and negative predictive value (NPV) of 100%, 89.8%, 68.7%, and 100%, respectively. On the contrary, the combination of CT and endoscopy improved only the Se and NPV for the iPGSa with respect to the sole endoscopic assessment.Conclusions: Whenever motility impairment is present, a histopathologic invasion of the iPGS should be suspected. Endoscopic assessment of laryngeal motility achieved a satisfactory value of Se, Spe, PPV, and NPV in predicting the involvement of the iPGS. CT scan is still the mainstay imaging technique in the clinical staging of patients with LSCC.Level of Evidence: 4 Laryngoscope, 133:1184–1190, 2023

Laryngotracheal stenosis (LTS) is a complex and heterogeneous disease whose pathogenesis remains unclear. LTS is considered to be the result of aberrant wound-healing process that leads to fibrotic scarring, originating from different aetiology. Although iatrogenic aetiology is the main cause of subglottic or tracheal stenosis, also autoimmune and infectious diseases may be involved in causing LTS. Furthermore, fibrotic obstruction in the anatomic region under the glottis can also be diagnosed without apparent aetiology after a comprehensive workup; in this case, the pathological process is called idiopathic subglottic stenosis (iSGS). So far, the laryngotracheal scar resulting from airway injury due to different diseases was considered as inert tissue requiring surgical removal to restore airway patency. However, this assumption has recently been revised by regarding the tracheal scarring process as a fibroinflammatory event due to immunological alteration, similar to other fibrotic diseases. Recent acquisitions suggest that different factors, such as growth factors, cytokines, altered fibroblast function and genetic susceptibility, can all interact in a complex way leading to aberrant and fibrotic wound healing after an insult that acts as a trigger. However, also physiological derangement due to LTS could play a role in promoting dysregulated response to laryngo-tracheal mucosal injury, through biomechanical stress and mechanotransduction activation. The aim of this narrative review is to present the state-of-the-art knowledge regarding molecular mechanisms, as well as mechanical and physio-pathological features behind LTS.