Extramedullary plasmacytoma of the larynx - Case report.

Extramedullary plasmacytoma of the larynx is an extremely rare entity accounting for 0.04-0.45% of malignant tumours of the larynx. The objective of this clinical case report is to highlight the diagnosis and management of a unique case such as this. A 77-year-old gentleman presented with complaints of hoarseness for 1 year. Computed tomography image revealed a soft tissue mass lesion involving the right true vocal cord. Direct laryngoscopic biopsy was performed and subjected to histopathological examination, which showed collection of plasma cells. Immunohistochemistry confirmed the presence of Kappa and Lambda cells. Multiple myeloma (MM) was ruled out. The patient received radical intent radiation therapy using 3DCRT technique with a dose of 50Gy in 25# over 5 weeks. He experienced improvement in hoarseness on subsequent follow-up visits. At 1-year follow up, positron emission tomography computed tomography showed near total resolution of disease with no progression to MM. Radiation therapy alone is known to achieve good local control, recurrence free survival, and organ preservation in such cases.

Oncocytic papillary cystadenoma of the larynx: a case report.

BACKGROUND: Cystadenoma of the salivary glands is a rare benign clinical condition affecting both major and minor salivary glands equally. It constitutes approximately 2% of total neoplasms and 4.2-4.7% of benign formations in minor salivary glands. Typically presenting as a slow-growing, painless neoplasm, it can be distinguished from Cystadenolymphoma (Whartin's Tumor) by the absence of lymphoid elements in histological examination. While mostly located in the oral cavity and oropharynx, it can also be found in sinonasal mucosa, and rare cases have been identified in the larynx. CASE PRESENTATION: A 75-year-old Caucasian woman presented to the ear, nose, and throat department with complaints of dysphonia and headaches persisting for several months. Dysphonia had developed months after an unspecified vocal cord surgery elsewhere. Flexible laryngoscopy identified a left-sided cystic swelling affecting the supraglottic space, leading to respiratory obstruction and dysphonia. Head and neck computed tomography confirmed a 1.9 × 1.7 cm bilobed cystic mass originating from the left Morgagni ventricle. Microlaryngoscopy with CO2 laser excision and biopsy revealed a histopathological diagnosis of oncocytic papillary cystadenoma. Post-surgery, the patient fully recovered from dysphonia, with no significant complications noted. Long-term clinical surveillance was advised to detect potential recurrences promptly. CONCLUSION: Ectopic minor salivary gland tumors, both benign and malignant, should be taken into consideration as potential differential diagnosis for any swelling arising within the upper digestive tract mucosa. Ears, nose, and throat clinical examination completed by videolaryngoscopy can easily point out the location of the mass. Imaging is mandatory for differential diagnosis and for surgical planning. Surgical excision can provide both diagnosis and definitive cure.

Case with translating to multiple myeloma at 8 years after radiation therapy for extramedullary plasmacytoma of the larynx.

We report a case of extramedullary plasmacytoma of the larynx that was eradicated by radiotherapy; however, 8 years later, the disease had progressed to multiple myeloma. A mid -60s Japanese woman presented with a right-sided arytenoid mass in the larynx who underwent biopsy at another hospital. Based on the biopsy results, the patient was diagnosed with extramedullary plasma cell tumour and was referred to the Department of Otorhinolaryngology at our hospital. She received radiotherapy (50.4 Gy) and the laryngeal tumour was eradicated. Positron emission tomography/CT (PET-CT) revealed no abnormal accumulation in the larynx or whole body. After radiotherapy, the department of otorhinolaryngology, in consultation with Ddepartment of haematology performed follow-ups using laryngoscope, blood examination and PET-CT. Five years after the end of radiotherapy, the patient had no local recurrence or transition to multiple myeloma. However, 8 years later, blood examination and PET-CT revealed multiple myeloma. Laryngoscopy did not reveal any recurrent laryngeal tumour. Therefore, chemotherapy for multiple myeloma was administered at the department of haematology. Three months after the initiation of chemotherapy, the accumulation had disappeared in PET-CT. Three years have passed since chemotherapy initiation. At present, no recurrence or metastasis was observed in the larynx or whole body.

An Unknown Foreign laryngeal Object: an exotic complication of skull base osteoradionecrosis.

BACKGROUND: Osteoradionecrosis (ORN) of the skull base is a rare complication after head and neck radiation with a broad variety of subsequent complications. METHODS: A 68-year-old woman with a complex oncological history (right-sided sphenoid meningioma; left-sided neck metastasis of a Cancer of Unknown Primary-CUP) was admitted with a right-sided epi-/ oropharyngeal mass and severe pain exacerbations for further evaluation. CT scan revealed an advanced ORN of the skull base with subsequent abruption of the ventral part of the clivus. This dislocated part of the clivus wedged in the oropharynx for 48 h and then moved towards the larynx, resulting in dyspnea and almost complete airway obstruction. RESULTS: Due to the dangerous airway situation, an urgent exploration and removal of the dislocated clivus was necessary. After a potential cervical spine instability was ruled out, the patient's airway was initially secured with an awake tracheotomy and the clivus was removed transorally. The tracheostomy tube was removed during the ongoing inpatient stay, and the patient was discharged with significant pain relief. CONCLUSIONS: The present case illustrates an orphan complication of skull base ORN resulting in a major airway emergency situation.

Discrimination of vocal folds lesions by multiclass classification using autofluorescence spectroscopy: An ex vivo study.

BACKGROUND: Autofluorescence spectroscopy is effective for noninvasive detection but underutilized in tissue with various pathology analyses. This study evaluates whether AFS can be used to discriminate between different types of laryngeal lesions in view of assisting in vocal fold surgery and preoperative investigations. METHODS: A total of 1308 spectra were recorded from 29 vocal fold samples obtained from 23 patients. Multiclass analysis was performed on the spectral data, categorizing lesions into normal, benign, dysplastic, or carcinoma. RESULTS: Through an appropriate selection of spectral components and a cascading classification approach based on artificial neural networks, a classification rate of 97% was achieved for each lesion class, compared to 52% using autofluorescence intensity. CONCLUSIONS: The ex vivo study demonstrates the effectiveness of AFS combined with multivariate analysis for accurate classification of vocal fold lesions. Comprehensive analysis of spectral data significantly improves classification accuracy, such as distinguishing malignant from precancerous or benign lesions.

Oncological features and outcomes of laryngeal cancer surgery: a multicentric study.

BACKGROUND: Laryngeal cancer (LC) is among of the most frequent head and neck cancers, associated to a high social impact and mortality. Unfortunately, the current treatment outcomes of LC are often scant, with different factors affecting patient's prognosis (i.e., advanced age, advanced disease stage, lymph node involvement, tumor pathological features, type of intervention). The aims of the present study were: 1) to evaluate the epidemiological and clinical features of patients affected by LC; and 2) to focus on tumor risk factors affecting patient's overall survival (OS) and recurrences. METHODS: A retrospective analysis of all patients affected by LC and surgically treated at two different hospital settings has been performed. RESULTS: Two hundred twenty-five patients were enrolled in the present study; of these 189 were males (84%) and 36 (16%) were females. The most frequently performed surgery was total laryngectomy. Thirty-two (14.2%) patients experienced local recurrence, while 15 patients (6.6%) had regional recurrence and 15 distant metastases. Multivariate analysis showed that locoregional recurrence was associated to the occurrence of distant metastases (P=0.002, HR=25,35). Analyzing OS, the only statistically significant factor that correlated with an increased risk of mortality (P<0.015, HR=2,45) was locoregional recurrence. CONCLUSIONS: The present study confirms the literature data about age and sex distribution of LC, about tumors localization, lymph nodes metastasis and distant metastasis incidence and OS rate, based on T and N stage. Interestingly, within this series, the presence of locoregional recurrence or distant metastasis is related to a worst prognosis and a lower overall survival rate.

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.

Renal cell carcinoma (RCC) spreading to the larynx: an unusual condition.

A man in his mid-70s, heavy smoker with chronic alcohol consumption and a chronic exposure to insecticides and burning of crop residues was referred to the surgical oncology department because of a 4-month onset of hoarseness, dyspnoea and laryngeal stridor. He had a history of left nephrectomy due to Fuhrman IV clear cell renal cancer 2 years ago. The patient underwent a bronchoscopy which identified a deforming tumour of the left vallecula, occlusion of 90% of the lumen and did not allow a safe biopsy. Following discussion between the oncological team, total laryngectomy and bilateral neck dissection of levels II, III, IV and V were performed, finding a transglottic tumour of approximately 4×3 cm with extension to the right anterolateral thyroid cartilage. The pathology report described metastatic RCC. The patient recovered well postoperatively and started systemic therapy with a vascular endothelial growth factor receptors inhibitor.

Negative prognostic behaviour of PD-L1 expression in tongue and larynx squamous cell carcinoma and its significant predictive power in combination with PD-1 expression on TILs.

BACKGROUND: Biomarkers that can predict outcome will improve the efficacy of treatment for HNSCC patients. In this regard, we retrospectively evaluated the prognostic effect of PD1, PD-L1, and CD45RO in tongue and larynx squamous cell carcinomas. METHODS: FFPE tissue blocks of 63 larynx and 40 tongue squamous cell carcinoma samples were selected, cut into 3 µm sections, and immunohistochemically stained for PD1, PD-L1, and CD45RO. The slides were evaluated by an expert pathologist, and results were analysed using Chi-square, univariate, and multivariable Cox regression methods. RESULTS: TC-PD-L1 expression (P = 0.001) and its expression intensity (P = 0.002) were significantly correlated with a higher percentage of PD-1 + tumor infiltrating lymphocytes. In univariate survival analysis, TC-PD-L1 and its expression intensity had a significant impact on both DFS (HR: 0.203; P = 0.003 and HR: 0.320; P = 0.005) and OS (HR: 0.147; P = 0.002 and HR: 0.322; P = 0.005). Based on the multivariate analysis, PD1 (DFS: HR: 3.202; P = 0.011, OS: HR: 2.671; P = 0.027) and TC-PD-L1 (DFS: HR: 0.174; P = 0.006, OS: HR: 0.189; P = 0.009) were found to be independent prognostic markers. In the second part, scoring systems were defined based on the expression status of PD1 and PD-L1. Patients with higher scores were expected to have longer DFS and OS. In multivariate analysis, the PD1/TC-PD-L1 (DFS: P = 0.001, OS: P = 0.003) scoring systems showed superior prognostic effects. Interestingly, at the highest levels of this score, none of the patients experienced recurrence or cancer-caused death. CONCLUSION: Collectively, this study suggests negative prognostic behaviour for TC-PD-L1 protein and introduces the PD-1/TC-PD-L1 scoring system as a strong prognostic marker in OS and DFS prediction of tongue and larynx HNSCC patients.

Functional or radical surgical treatment of laryngeal chondrosarcoma, analysis of survival and prognostic factors: A REFCOR and NetSarc-ResOs multicenter study of 74 cases.

INTRODUCTION: Laryngeal chondrosarcoma (LCS) is a rare tumor of slow evolution whose treatment is poorly codified. For a long time, a radical treatment by total laryngectomy (TL) was proposed. More recent studies tend to propose a conservative surgical approach of the larynx. The objective of this study was to compare the overall survival (OS) of total laryngectomized patients (TL+) versus non-laryngectomized patients (TL-). The secondary objectives were to analyse the reoperation free survival (RFS), the total laryngectomy free survival (TLFS) and to identify the preoperative factors leading surgeons to propose TL. MATERIALS AND METHODS: A retrospective analysis of prospectively collected incident cases from the REFCOR and NetSarc-ResOs multicenter databases between March 1997 and June 2021 was conducted. A propensity score matching analysis was performed to compare the OS of TL+ and TL-patients. RESULTS: 74 patients were included. After propensity score, the 5-year OS of TL+ and TL-patients was comparable (100 %, p = 1). The 5-year RFS rate was 69.2 % (95 % CI [57.5-83.4]) and the 5-year TLFS was 61.7 % (95 % CI [50.4-75.5]). Cricoid involvement greater than 50 % (HR 3.58; IC 95 % [1.61-7.92] p < 0.001), an ASA score of 3 or 4 (HR 5.07; IC 95 % [1.64-15.67] p = 0.009) and involvement of several cartilages (HR 5.26; IC 95 % [1.17-23.6] p = 0.04) are prognostic factors for TL. Dyspnea caused by the tumour is a prognostic factor for reoperation (HR 2.59; IC 95 % [1.04-6.45] p = 0.03). CONCLUSION: These results demonstrate that conservative treatment should be considered as first-line treatment for laryngeal chondrosarcoma.

Outcome Comparison of Functional Laryngectomy for the Dysfunctional Larynx to Salvage Laryngectomy.

OBJECTIVE: To compare functional outcomes of total laryngectomy (TL) with microvascular free tissue transfer (MVFTT) reconstruction in the treatment of dysfunctional larynx (DL) versus salvage therapy for locally recurrent disease in patients with a history of laryngeal squamous cell carcinoma (SCC). METHODS: Retrospective review from a tertiary medical center between August 2015 and August 2022. RESULTS: Sixty-nine patients underwent TL with MVFTT following primary laryngeal radiation or chemoradiation; 15 (22%) patients underwent functional laryngectomy (FL) and 54 (78%) underwent a salvage laryngectomy (SL). There were no total flap failures. Four (6%) patients developed a pharyngocutaneous fistula; one (7%) FL patient and 3 (6%) in the SL cohort. There was no significant difference in average hospital length of stay (LOS) between the cohorts (8.6 ± 3.0 days vs. 12.8 ± 10.1 days, p = 0.12). All patients (100%) in the FL cohort achieved a total oral diet compared to 41 (76%) in the SL cohort (p = 0.03). Two (13%) and 10 (19%) patients developed pharyngoesophageal stenosis in the FL and SL cohorts, respectively (p = 1.0). Nine (60%) and 23 (43%) patients in the FL and SL cohorts underwent tracheoesophageal puncture (TEP) placement, with 89% and 91% achieving fluency, respectively (p = 0.23). CONCLUSION: Although the role of TL for the definitive treatment of laryngeal SCC has decreased over the past 30 years, organ-preservation protocols can impact speech, swallowing, and airway protection with life-threatening consequences. The use of elective FL with MVFTT for the treatment of DL results in similar or better functional outcomes compared to SL for recurrent disease. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:222-227, 2024.

Correlation of narrow-band imaging findings using the Ni and European Laryngeal Society classification systems during in-office flexible laryngoscopy with histopathology.

OBJECTIVE: This study used the European Laryngeal Society (2016) and Ni (2011 and 2019) classifications for narrow-band imaging and correlated the findings with histopathology. METHODS: Retrospective analysis was conducted by retrieving data of patients who underwent micro-laryngoscopy for suspicious glottic lesions. The narrow-band imaging findings were classified using both classification systems. Retrieved histopathology report findings were correlated with narrow-band imaging data. RESULTS: Using the European Laryngeal Society and Ni classifications, 37 (69.8 per cent) and 35 (66 per cent) patients, respectively, were suspected to have malignant lesions. Upon histopathology, 37 (69.8 per cent) lesions were malignant. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy using the European Laryngeal Society classification were 91.9 per cent, 81.3 per cent, 91.9 per cent, 81.3 per cent and 88.7 per cent, and using the Ni classification were 91.9 per cent, 93.8 per cent, 97.1 per cent, 83.3 per cent and 92.5 per cent, respectively. CONCLUSION: The Ni classification had better specificity and accuracy. The European Laryngeal Society classification is simple to use and may serve as a useful screening tool. For optimum results, both European Laryngeal Society and Ni classifications may be used together, in that order.

Treatment strategy in laryngeal chondrosarcoma: a multicenter study of 43 cases.

PURPOSE: Laryngeal chondrosarcoma is a rare tumor that mostly affects the cricoid cartilage. The aim of this study was to compare outcomes between the various treatments of this pathology as there are no official guidelines for this pathology. METHODS: A retrospective analysis of the pathology database of nine French tertiary care centers was conducted. Outcomes of patients treated by total laryngectomy were compared with those treated by more conservative approaches (endoscopic debulking, median thyrotomy, partial laryngectomy). Two Kaplan-Meier survival analyses were performed: one to assess the overall survival rate and the other to assess laryngeal preservation over time. RESULTS: A total of 43 patients were enrolled: 12 with total laryngectomy as the initial treatment, and 31 who initially underwent laryngeal-preserving treatment. With conservative treatment, laryngeal function was preserved in 96% and 75% of patients at 1 and 5 years, respectively. Conservative treatment did not reduce the overall survival rate. CONCLUSION: These results suggest that laryngeal preservation should be considered as the initial treatment in cases of laryngeal chondrosarcoma.

Induction Toripalimab and Chemotherapy for Organ Preservation in Locally Advanced Laryngeal and Hypopharyngeal Cancer: A Single-Arm Phase II Clinical Trial.

PURPOSE: The aim of this study was to assess the efficacy, toxicities, and potential role of larynx preservation of induction chemotherapy combined with programmed cell death protein 1 (PD-1) inhibitor in locally advanced laryngeal and hypopharyngeal cancer. PATIENTS AND METHODS: This is a single-arm phase II study. Patients with histopathologically confirmed, resectable locally advanced laryngeal/hypopharyngeal squamous cell carcinoma and Eastern Cooperative Oncology Group Performance Status 0-1 were eligible. Three cycles of induction chemotherapy (paclitaxel 175 mg/m2 d1, cisplatin 25 mg/m2 d1-3) combined with PD-1 inhibitor (toripalimab 240 mg d0) were administered. Response assessment was performed after induction chemoimmunotherapy using RECIST 1.1 criteria. Patients with a complete/partial response of the primary tumor received concurrent chemoradiation, followed by maintenance therapy of toripalimab. Otherwise, patients were referred to surgery, followed by adjuvant (chemo) radiation and maintenance therapy of toripalimab. The primary endpoint is a larynx preservation rate at 3 months postradiation. RESULTS: Twenty-seven patients were enrolled. Most cases exhibited stage IV disease (81.5%), with T4 representing 37.0%. Five patients underwent pretreatment tracheostomy because of impaired larynx function. Overall response rate of induction chemoimmunotherapy was 85.2%. At 3 months postradiation, the larynx preservation rate was 88.9%. With a median follow-up of 18.7 months, the 1-year overall survival rate, progression-free survival rate, and larynx preservation rate were 84.7%, 77.6%, and 88.7%, respectively. When excluding those with pretreatment tracheostomy, the 1-year larynx preservation rate was 95.5%. Exploratory analysis revealed that relapse correlated with enrichment of RNA signature of hypoxia and M2 macrophage-associated genes. CONCLUSIONS: Induction toripalimab combined with chemotherapy provided encouraging activity, promising larynx preservation rate and acceptable toxicity in this cohort of extensively locally advanced laryngeal and hypopharyngeal cancer.

Method for Collecting Single Epithelial Cells from the Mouse Larynx.

OBJECTIVE: The larynx is lined by specialized epithelial cell populations. Studying molecular changes occurring in individual epithelial cell types requires a reliable method for removing these cells from the larynx. Our objective was to develop a method to harvest individual epithelial cells from the mouse larynx while minimizing contamination from non-laryngeal sites and non-epithelial laryngeal cells. METHODS: Mice were euthanized, and the larynx was carefully exposed and separated from non-laryngeal sites. A small dental brush was inserted into the laryngeal inlet and rotated to obtain epithelial cells. Cells were transferred to collection media, counted, and cytospin preparations stained for laryngeal epithelial (i.e., Pan-Keratin, EpCAM, NGFR, p63, K5, ß-tubulin, MUC5AC) and non-epithelial (i.e., vimentin) cell markers. Histopathology was completed on brushed laryngeal tissue sections to evaluate the depth of cell collection. Preliminary Single-cell RNA sequencing (scRNA-seq) was performed to confirm this method can capture diverse laryngeal cell types. RESULTS: We collected 6000-8000 cells from a single larynx and 35000-40000 cells from combining brushings from three tissues. Histopathology demonstrated brushing removed the epithelial layer of the larynx and some underlying tissue. Immunofluorescence staining demonstrated the phenotype of harvested cells was primarily epithelial. Preliminary scRNA-seq was successfully conducted and displayed nine unique cell clusters. CONCLUSION: We developed a reliable method of harvesting individual epithelial cells from the mouse larynx. This method will be useful for collection of laryngeal cells for a variety of downstream cellular and molecular assays, including scRNA-seq, protein analyses, and cell-culture-based experiments, following laryngeal injury. LEVEL OF EVIDENCE: NA Laryngoscope, 134:786-794, 2024.

Association between Estrogen Exposure and Idiopathic Subglottic Stenosis.

OBJECTIVE: Idiopathic subglottic stenosis (iSGS) is a rare, recurrent, fibroinflammatory disease affecting the larynx and proximal trachea. Given it occurs primarily in adult females, estrogen is speculated to play a central pathophysiological role. This study aimed to evaluate relationships between estrogen exposure, disease progression, and recurrence. METHODS: North American Airway Collaborative (NoAAC) data of adults with iSGS obstructive airway lesions, who underwent index endoscopic airway dilation, were used to identify associations between estrogen exposure, disease characteristics, and time to recurrence (TTR), and interventions were analyzed using Kruskal-Wallis test and Pearson coefficient. Cox proportional hazards regression models compared hazard ratios by estrogen exposure. Kaplan-Meier curves were plotted for TTR based on menopausal status. RESULTS: In all, 533 females had complete estrogen data (33% premenopausal, 17% perimenopausal, 50% postmenopausal). Median estrogen exposure was 28 years. Overall, there was no dose-response relationship between estrogen exposure and disease recurrence. Premenopausal patients had significantly shorter time from symptom manifestation to diagnosis (1.17 vs. 1.42 years perimenopausal vs. 2.08 years postmenopausal, p < 0.001), shorter time from diagnosis to index endoscopic airway dilation (1.90 vs. 2.50 vs. 3.76 years, p = 0.005), and higher number of procedures (1.73 vs. 1.20 vs. 1.08 procedures, p < 0.001). CONCLUSIONS: We demonstrate premenopausal patients may have a more aggressive disease variant than their peri- and postmenopausal counterparts. However, it is unclear as to whether this is related to reduced estrogen in the peri- and postmenopausal states or the age-related physiology of wound healing and inflammation, regardless of estrogen. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:825-830, 2024.

Murine Model of Airway Fibrosis has Anatomic, Physiologic, and Molecular Congruency to Human iSGS.

OBJECTIVE: To narrow knowledge gaps in the pathophysiology of idiopathic subglottic stenosis (iSGS) through comparison of a murine subglottic stenosis model with iSGS. STUDY DESIGN: In vivo animal study. SETTING: Academic institution. METHODS: Murine samples/measurements were obtained from mice that underwent chemomechanical injury with a wire brush and bleomycin. Human samples/measurements were obtained from iSGS patients. Anatomic, physiologic, and epithelial molecular data were collected using histology, human peak expiratory flow (PEF) and murine airway conductance, gene expression analysis with quantitative polymerase chain reaction, and protein analysis with quantitative immunohistochemistry. RESULTS: Anatomic patterns of scars at the subglottis and proximal trachea seen in the murine model are similar to iSGS patients. Subglottic stenosis (SGS) mice had a decrease (P = .0194) in airway conductance compared to healthy controls, similar to a decrease (P = .0001) in predilation PEF versus postdilation in iSGS patients. There was decreased epithelial gene expression of E-cadherin (ECAD) (P < 0.01), occludin (OCLN) (P < .01), and cytokeratin-5 (CK5) (P < .05) and protein expression of ECAD (H/M: P < .001), OCLN (H: P < 0.05, M: P < .001), and CK5 (H: P < .001, M: P < .01) in murine SGS and iSGS versus controls. CONCLUSION: The murine SGS model shows anatomic, physiologic, and molecular congruency with human iSGS, making it a reasonable model to investigate iSGS. The molecular similarities in epithelial barrier dysfunction suggest it may best be suited to explore epithelial mechanisms of iSGS and therapies directed at epithelial reconstitution. This model provides a foundation to collect data that will improve understanding of iSGS, and, ultimately, translate into more accurate animal models for future use.

Idiopathic Subglottic Stenosis Is Associated With More Frequent and Abnormal Squamous Metaplasia.

OBJECTIVES: Gain insights into the pathophysiology of idiopathic subglottic stenosis (iSGS) by investigating differences in transcriptome of subglottic mucosal tissue between patients with iSGS and controls, and between tracheal and subglottic tissue within patients. METHODS: RNA sequencing was conducted on biopsied mucosal samples collected from subglottic and tracheal (in-patient control) regions in iSGS patients, and from subglottis in controls. The gene expression differences were validated on a protein level by (1) staining the tissue samples obtained from a second cohort of patients and controls; and (2) in vitro functional assays using primary subglottic epithelial cells from both iSGS patients and healthy donors. RESULTS: We found 7 upregulated genes in the subglottic region of iSGS patients relative to both the tracheal mucosa and subglottic region of controls. A gene ontology enrichment analysis found that the epithelial cell differentiation and cornification pathways are significant, involving specifically 3 of the genes: involucrin (IVL), small proline rich protein 1B (SPRR1B), and keratin 16 (KRT16). Involvement of these pathways suggests squamous metaplasia of the epithelium. Histological analyses of epithelium in subglottic mucosal biopsies revealed squamous metaplasia in 41% of the samples from iSGS patients and in 25% from controls. Immunohistochemical evaluation of the samples presented with squamous epithelium revealed increased expression of the protein encoded by SPRR1B, hyperproliferative basal cells, shedding of apical layers, and accompanying lesions in iSGS compared to CTRL. Cultured primary subglottic epithelial cells from iSGS patients had higher proliferation rates compared to healthy donors and squamous metaplastic differentiation formed thinner epithelia with increased expression proteins encoded by INV, SPRR1B, and KRT16, suggesting intrinsic dysfunction of basal cells in iSGS. CONCLUSIONS: Abnormal squamous differentiation of epithelial cells may contribute to the pathogenesis of iSGS. Patients having metaplastic epithelial phenotype may be sensitive to drugs that reverse it to a normal phenotype.

Value and role of surgical margins in transoral laser microsurgery of the larynx, literature review and clinical considerations.

PURPOSE: There is no agreement on the most appropriate post-operative pathway for the management of positive margins after laser cordectomy for early stage glottic tumours (T1-2N0M0). This literature review and meta-analysis aim to evaluate the post-operative treatment with the best oncological results among follow-up, radiotherapy (RT) and surgical second look. The parameters utilized were incidence of recurrence, overall (OS), disease-specific (DSS) and disease-free (DFS) survival and larynx preservation (LP). METHODS: The articles were found through a string typed into PubMed from 2007 to 2022. The studies with detailed oncological results were selected according to inclusion criteria, and then the meta-analysis was carried out. RESULTS: Sixteen studies met the inclusion criteria for 2808 patients. The positive margin was found in 748 patients (26.6%), of which 416 were referred to follow-up, 89 to RT and 242 to a surgical second look. A false positive margin was found in 58/104 patients (56%). The recurrence rate in patients with positive margins was significantly higher (p = 0.003). In OS, DSS, DFS and LP, the odds ratio (OR) value was always greater than 1, assessing the role of the positive margin as a risk factor. CONCLUSIONS: Prospective studies will be necessary to establish the role of positive margin as a prognostic factor. A surgical second look in case of positive margin seems to be the best option for the patient in terms of lower risk of recurrence and better oncological results. Better collaboration between surgeon and pathologist would be desirable to limit the real and false positive margins.