A large, locally aggressive giant cell tumour arising from the laryngeal cartilage: A Rare Case Report.

Giant cell tumour is a growth predominantly found in long bones of the body. Giant cell tumour has a rare occurrence in the head and neck. A case of a 31 year old male with no known comorbidities at the ENT Department, Shifa International Hospital, Islamabad presented with anterior neck swelling and hoarseness of voice. Patient was diagnosed as having Giant Cell Tumour of Larynx (GTCL) proven on FNA cytology and post-operative biopsy. GCTL is an uncommon entity with only 45 reported cases in the world.

Laryngeal cartilage calcifications on lateral cephalometric radiographs.

The aim of this study was to determine the influence of age and gender on the incidence of calcification in laryngeal cartilage diagnosed on lateral cephalometric radiographs routinely taken for orthodontic diagnosis. The lateral cephalometric radiographs of 957 patients who met the study criteria were analyzed from among the 1000 lateral radiographs originally collected. The images were evaluated independently by two investigators. Given the dichotomous dependent variable (calcification or no calcification), a mixed logistic regression model was used to test how age and gender affected calcification. The effect of age and gender reliably determined the likelihood of laryngeal cartilage calcification. The greatest differences in the degree of calcification by gender were found at ages 20-25 years. The degree of calcification increased with age, reaching 100% in women at age 30 and in men at age 50. In women, the degree of calcification was higher than in men from the age of 13 years and levelled off at the age of 50 years. The interrater agreement was strong k = 0.97, z = 30.0, p < .001. Calcification can be detected by orthodontists trained in lateral cephalogram analysis and can be used as a screening or diagnostic tool to detect calcified areas in the larynx.

Laryngeal Cartilage Regeneration of Nude Rats by Transplantation of Mesenchymal Stem Cells Derived from Human-Induced Pluripotent Stem Cells.

Previous studies transplanted human-induced pluripotent stem cells (hiPSCs)-derived mesenchymal stem cells (iMSCs) into thyroid cartilage defect of X-liked severe combined immunodeficiency (X-SCID) rats and confirmed transplanted cell survival and cartilage regeneration. Thus, this study aimed to investigate the contribution of iMSC transplantation to thyroid cartilage regeneration of nude rats. iMSCs were induced from hiPSCs via a neural crest cell lineage. Then, clumps formed from an iMSC/extracellular matrix complex were transplanted into thyroid cartilage defects in nude rats. The larynx was removed and histological and immunohistochemical analyses were performed 4 or 8 weeks after the transplantation. Human nuclear antigen (HNA)-positive cells were observed in 11 of 12 (91.7%) rats, which indicated that transplanted iMSCs survived in thyroid cartilage defects in nude rats. HNA-positive cells co-expressed SOX9, and type II collagen was identified around HNA-positive cells in 8 of 12 rats (66.7%), which indicated cartilage-like regeneration. Cartilage-like regeneration in nude rats in this study was comparable to the previous report on X-SCID rats (HNA-positive cells were observed in all 14 rats and cartilage-like regeneration was observed in 10 of 14 rats). This result suggests that nude rats could be an alternative to X-SCID rats in thyroid cartilage regeneration experiments using iMSCs, and this nude rat cartilage transplantation model may develop cartilage regeneration research concerning fewer problems such as infection due to immunosuppression.

Mieloma múltiple con afectación laríngea: causa atípica de disfonía / Multiple myeloma with laryngeal affectation: an uncommon cause of dysphonia

Las neoplasias de células plasmáticas suponen un conjunto de enfermedades caracterizadas por la proliferación tumoral de dichas células en forma de lesión única (plasmocitoma) o enfermedad sistémica (mieloma). La afectación cartilaginosa laríngea es inusual y su manifestación clínica es similar a la de un carcinoma laríngeo. Describimos el caso de un paciente varón de 70 años con disfonía tras un diagnóstico reciente de mieloma múltiple. Después de realizar los estudios radiológico e inmunohistoquímico se diagnosticó la afectación laríngea por este tumor. Actualmente el paciente está siendo tratado con lenalidomida, dexametasona y bortezomib.(AU)

Plasma cell proliferation leads to the formation of a single tumour (plasmacytoma) or to systemic disease (myeloma). Plasma cell myeloma involving laryngeal cartilage is unusual and clinical manifestations are similar to those of laryngeal carcinoma. We report the case of a 70-year-old man with disphonia after a recent diagnosis of multiple myeloma. Radiological and immunohistochemical studies showed laryngeal involvement. The patient is currently under treatment with lenalidomide, dexamethasone, and bortezomib.(AU)

Age related changes in thyroid and cricoid cartilages: An autopsy based radiological analysis.

Forensic age estimation is an invaluable aspect of human identification. Out of these many means of age estimation, few regions with untapped potential for assistance in forensic age estimation are the age-related changes in the laryngeal cartilages. As the age advances, the thyroid and cricoid cartilages undergo gradual calcification in an individual. These age-related changes can be visualized in both the living and the dead using conventional radiography and can be objectively assessed. The objective of the present study was to evaluate the age-related changes in the laryngeal cartilages and the results may be utilized for age estimation in forensic examinations. The laryngeal cartilages were carefully dissected using standard procedures from 75 cadavers of age ranging from 17 to 65 years, during the post-mortem examination. The laryngeal cartilages were radiographed and replaced in the body cavity before culminating the post-mortem examination. The calcification of both cartilages was studied by using the standard grading method. Calcification scores of individual regions of both the laryngeal cartilages show a statistically significant positive correlation with chronological age (P < 0.05). Regression models derived from the degree of calcification of thyroid and cricoid cartilages showed standard error of estimates that ranged between 9.90 and 11.07 years. Considering the standard error of estimates of the regression analysis, the present study concludes that these regression models can be used in adjunct with other methods of age estimation such as the skeletal and dental age or when such methods are not viable as in cases of charred or mutilated remains.

Clinicopathologic characteristics of laryngeal chondrosarcoma: An analysis of the National Cancer Database.

OBJECTIVES: Laryngeal Chondrosarcoma (LC) is a rare malignancy with limited studies documenting its clinicopathologic characteristics and treatment options. This study reports demographic and clinical determinants of outcomes for this rare tumor. METHODS: The National Cancer Database (NCDB) was queried for cases of LC reported from 2004-2016. 274 cases that met inclusion criteria were analyzed for demographic and clinicopathologic characteristics. Kaplan-Meier (KM) and Cox proportional hazard analyses were conducted to identify variables that impacted the overall survival of these patients. RESULTS: LC was found to be more common in males (74.8%). The mean age of patients was 61.8 years and 92.3% of the patients were white. 91.3% of patients were treated with only surgical resection, most commonly: partial laryngectomy (31.6%), total laryngectomy (25.7%), and local resection (22.4%). 98.8% of patients had no evidence of nodal disease and 99.6% of patients did not have distant metastasis at presentation. KM analysis revealed a 5-year overall survival (5YOS) of 89.0%. Age, insurance status, facility type, and surgery type were significant predictors of 5YOS (p<0.05). On Cox Proportional Hazard analysis, private insurance significantly improved survival (HR 0.21; p = 0.048) while increasing age was a poor prognostic indicator (HR 1.10; p = 0.004). CONCLUSION: The majority of LC patients present with no nodal involvement or distant metastasis at diagnosis, and overall this tumor has a favorable prognosis. Increasing age was found to be a poor prognostic factor while private insurance status was associated with improved survival.

Adult Age Estimation of CT Image Reconstruction of the Laryngeal Cartilages and Hyoid Bone Based on Data Mining.

ABSTRACT: Objective To explore the feasibility of the CT image reconstruction of laryngeal cartilage and hyoid bone in adult age estimation using data mining methods. Methods The neck thin slice CT scans of 413 individuals aged 18 to <80 years were collected and divided into test set and train set, randomly. According to grading methods such as TURK et al., all samples were graded comprehensively. The process of thyroid cartilage ossification was divided into 6 stages, the process of cricoid cartilage ossification was divided into 5 stages, and the synosteosis between the greater horn of hyoid and hyoid body was divided into 3 stages. Multiple linear regression model, support vector regression model, and Bayesian ridge regression model were developed for adult age estimation by scikit-learn 0.17 machine learning kit （Python language）. Leave-one-out cross-validation and the test set were used to further evaluate performance of the models. Results All indicators were moderately or poorly associated with age. The model with the highest accuracy in male age estimation was the support vector regression model, with a mean absolute error of 8.67 years, much higher than the other two models. The model with the highest accuracy in female adult age estimation was the support vector regression model, with a mean absolute error of 12.69 years, but its accuracy differences with the other two models had no statistical significance. Conclusion Data mining technology can improve the accuracy of adult age estimation, but the accuracy of adult age estimation based on laryngeal cartilage and hyoid bone is still not satisfactory, so it should be combined with other indicators in practice.

Early side effects of radiation treatment for head and neck cancer.

Purpose of this review of medical literature is to present the immediate side effects of radiation therapy for head and neck cancer and their treatment. The likelihood and severity of these immediate side effects depends on a number of factors, including the total dose of radiation delivered, over what time it was delivered and what parts of the head and neck received radiation. Early side effects include: inflammation of the oropharyngeal mucosa (mucositis), painful swallowing (odynophagia), difficulty swallowing (dysphagia), hoarseness, lack of saliva (xerostomia), orofacial pain, laryngeal radionecrosis, dermatitis, hair loss, nausea, vomiting, inadequate nutrition and hydration, and weight loss. These complications can interfere with, and delay treatment. Most of these side effects generally dissipate over time. In conclusion, radiation treatment for the head and neck cancer causes significant early side effects. Many of these side effects present difficult challenges to the patients. Their recognition and treatment can significantly improve the patients' health, long-term survival and quality of life. The review provides information that can assist head and cancer survivors deal with radiation side effects.

In vivo regeneration of rat laryngeal cartilage with mesenchymal stem cells derived from human induced pluripotent stem cells via neural crest cells.

The laryngotracheal cartilage is a cardinal framework for the maintenance of the airway for breathing, which occasionally requires reconstruction. Because hyaline cartilage has a poor intrinsic regenerative ability, various regenerative approaches have been attempted to regenerate laryngotracheal cartilage. The use of autologous mesenchymal stem cells (MSCs) for cartilage regeneration has been widely investigated. However, long-term culture may limit proliferative capacity. Human-induced pluripotent stem cell-derived MSCs (iMSCs) can circumvent this problem due to their unlimited proliferative capacity. This study aimed to investigate the efficacy of iMSCs in the regeneration of thyroid cartilage in immunodeficient rats. Herein, we induced iMSCs through neural crest cell intermediates. For the relevance to prospective future clinical application, induction was conducted under xeno-free/serum-free conditions. Then, clumps fabricated from an iMSC/extracellular matrix complex (C-iMSC) were transplanted into thyroid cartilage defects in immunodeficient rats. Histological examinations revealed cartilage-like regenerated tissue and human nuclear antigen (HNA)-positive surviving transplanted cells in the regenerated lesion. HNA-positive cells co-expressed SOX9, and type II collagen was identified around HNA-positive cells. These results indicated that the transplanted C-iMSCs promoted thyroid cartilage regeneration and some of the iMSCs differentiated into chondrogenic lineage cells. Induced MSCs may be a promising candidate cell therapy for human laryngotracheal reconstruction.

Anatomic and histologic analysis of paca larynx (Cuniculus paca, Linnaeus 1766) / [Análise anatômica e histológica da laringe da paca (Cuniculus paca, Linnaeus 1766)]

Paca (Cuniculus paca) has encouraged research as an experimental model both in the human medicine and veterinary, as well as the economic exploitation of its meat cuts, which favored its zootechnical use. There are no anatomical, microscopic descriptions and measurements of the larynx in this rodent. Eight pacas were dissected from the wild animal's sector of the Faculty of Agricultural and Veterinary Sciences of the University of the State of São Paulo. The larynx was observed located in the ventral region of the neck, ventral to the esophagus, connecting the pharynx to the trachea, with cylindrical and irregular shape. Laryngeal cartilages (epiglottic, thyroid, cricoid and arytenoid) are interconnected and have different shapes. Thyroid showed greater length and width, compared to the others. Laryngeal cartilages were submitted to histological processing and stained with hematoxylin-eosin and Masson's trichrome. The epiglottic cartilage was stained with toluidine blue. Laryngeal cartilages thyroid, cricoid and the lower portion of the arytenoids are of hyaline origin and, in contrast, the epiglottis and the upper portion of the arytenoids are elastic. This latter cartilage demonstrated taste buds. The results will be able to auxiliate in veterinary care and as well as the conservation programs for this rodent.(AU)

A paca (Cuniculus paca) tem encorajado inúmeras pesquisas, tornando-a modelo experimental tanto em humanos como na veterinária, além da exploração econômica de seus cortes cárneos, que favoreceu diretamente sua importância zootécnica. Não há descrições anatômicas, microscópicas e mensurações da laringe desse roedor. Foram dissecadas oito laringes de pacas, provenientes do setor de Animais Silvestres da Faculdade de Ciências Agrárias e Veterinárias - Universidade Estadual Paulista. Observou-se que a laringe localiza-se na região ventral do pescoço, ventral ao esôfago, conectando a faringe à traqueia, possuindo formato cilíndrico e irregular. As cartilagens laríngeas (epiglote, tireóide, cricóide e aritenóidea) são interligadas e possuem formatos variados. A cartilagem tireóide demonstrou-se maior em comprimento e largura, comparativamente às demais. As cartilagens laríngeas foram submetidas a processamento histológico e coradas em hematoxilina-eosina e tricrômio de Masson. A cartilagem epiglote foi corada em azul de toluidina. As cartilagens laríngeas tireóide, cricóide e a porção inferior das aritenóides são de origem hialina; em contrapartida, a epiglote e a porção superior das aritenóides, de origem elástica. Esta última cartilagem demonstrou corpúsculos gustativos. Os resultados poderão auxiliar tanto nos atendimentos veterinários quanto nos programas de conservação desse roedor.(AU)

Myeloma of Laryngeal Cartilage: Literature Review and Case Study.

BACKGROUND: Myeloma of laryngeal cartilage (MLC) is a rare plasma cell neoplasm which has not been well characterized. However, it is an important differential diagnosis of laryngeal cartilage mass as it can indicate the presence of underlying systemic hematological diseases, such as multiple myeloma (MM), that is associated with poor prognosis. This article is the first of its kind and aims to educate clinicians on future diagnosis and management of similar cases. METHODS: Search of MLC was performed on the medical literature databases of Medline, PUBMED, and EMBASE. Additionally, institutional database at Gold Coast University Hospital Radiology Department was queried for relevant cases. Based on 16 cases that met the inclusion criteria, the etiology, epidemiology, clinical evaluation, investigations, management, and prognosis of MLC was summarized. RESULTS: Of all, 94% of MLC occur in males and 81% in those older than 60 years. It is more commonly a manifestation of systemic MM, rather than localized extramedullary plasmacytoma (EMP), 81% and 19% respectively. Additionally, 67% of laryngeal EMPs progress to MM within 3 years from initial diagnosis. Although treatments involving both local and systemic therapy were effective at relieving local symptoms, 39% of MLC patients died during the follow-up period-all of which were due to septicemia caused by secondary infections. CONCLUSION: Myeloma of laryngeal cartilage is a relatively rare condition that requires accurate diagnosis in order to promptly manage the potentially underlying systemic hematological disease. Currently, more case reports and analytical studies are required to provide evidence-based guidance on etiology, diagnosis, and management of this condition.

The Healing Effect of Amniotic Membrane in Laryngeal Defects in Rabbit Model.

OBJECTIVE: Fibrosis and scar formation following laryngeal repairing is a major concern. This study evaluated the efficacy of applying amniotic membrane (AM) as a biologic dressing to reduce fibrosis and inflammation and promote cartilage repair. STUDY DESIGN: Experimental animal study. METHODS: Nine male white Dutch rabbits were selected. A standard defect (5 mm) was created in right and left thyroid lamina. In the right side, two layers of AM were applied while the left side was kept intact for future comparison. Histologic examination with criteria of inflammation, fibrosis, and cartilage regeneration was performed 2, 4, and 6 weeks following AM application. All procedures were done according to animal ethics rules. RESULTS: Histologic and gross examination showed that AM application was able to reduce inflammation and fibrosis and improve cartilage regeneration significantly. CONCLUSION: As a useful intervention, AM application can reduce inflammation and fibrosis and enhance cartilage regeneration, following laryngeal defect repair. LEVEL OF EVIDENCE: NA Laryngoscope, 131:E527-E533, 2021.

Occult Metastasis in Laryngeal Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis.

OBJECTIVE: The incidence of occult metastasis (OM) in laryngeal squamous cell carcinoma (SCC) is still widely debated. In this systematic review, we aim to determine the rate of OM in laryngeal SCC, its impact on recurrence, and the role of elective neck dissection (END) in the management of the clinically negative neck. METHODS: A systematic review of the English-language literature in Web of Science, PubMed, MEDLINE, and Cochrane Library databases on occult metastasis in laryngeal SCC from 1977 to 2018 was conducted. Studies evaluating occult metastasis (OM) in patients with laryngeal SCC with clinically negative necks undergoing surgery were included. Studies evaluating other head and neck subsites, clinically node positive, and salvage patients were excluded. RESULTS: Twenty-one articles with a total of 5630 patients were included. The overall rate of OM was 20.5% and was 23% and 12.2% in supraglottic and glottic tumors, respectively. The OM rate in T1-T2 tumors was 13% and 25% in T3-T4 tumors. T3-T4 tumors had significantly greater odds of developing OM compared to T1-T2 tumors (Odds Ratio [OR] = 2.61, 95% Confidence Interval [CI] = 1.92-3.55, P < .00001). Patients with OM were more likely to develop distant metastasis (OR = 5.65, 95% CI = 3.36-9.51, P < .00001). CONCLUSIONS: Patients with advanced T-stage laryngeal SCC should undergo elective neck treatment. More aggressive treatment for patients with history of OM should be considered due to the risk of subsequent regional and distant metastasis. LEVEL OF EVIDENCE: II.

Laryngeal Reconstruction Using Tissue-Engineered Implants in Pigs: A Pilot Study.

OBJECTIVE/HYPOTHESIS: There are currently no treatments available that restore dynamic laryngeal function after hemilaryngectomy. We have shown that dynamic function can be restored post hemilaryngectomy in a rat model. Here, we report in a first of its kind, proof of concept study that this previously published technique is scalable to a porcine model. STUDY DESIGN: Animal study. METHODS: Muscle and fat biopsies were taken from three Yucatan minipigs. Muscle progenitor cells (MPCs) and adipose stem cells (ASCs) were isolated and cultured for 3 weeks. The minipigs underwent a left laterovertical partial laryngectomy sparing the left arytenoid cartilage and transecting the recurrent laryngeal nerve. Each layer was replaced with a tissue-engineered implant: 1) an acellular mucosal layer composed of densified Type I oligomeric collagen, 2) a skeletal muscle layer composed of autologous MPCs and aligned oligomeric collagen differentiated and induced to express motor endplates (MEE), and 3) a cartilage layer composed of autologous ASCs and densified oligomeric collagen differentiated to cartilage. Healing was monitored at 2 and 4 weeks post-op, and at the 8 week study endpoint. RESULTS: Animals demonstrated appropriate weight gain, no aspiration events, and audible phonation. Video laryngoscopy showed progressive healing with vascularization and re-epithelialization present at 4 weeks. On histology, there was no immune reaction to the implants and there was complete integration into host tissue with nerve and vascular ingrowth. CONCLUSIONS: This pilot study represents a first in which a transmural vertical partial laryngectomy was performed and successfully repaired with a customized, autologous stem cell-derived multi-layered tissue-engineered implant. LEVEL OF EVIDENCE: NA Laryngoscope, 131:2277-2284, 2021.

Adult Age Estimation of CT Image Reconstruction of the Laryngeal Cartilages and Hyoid Bone Based on Data Mining / 法医学杂志

Objective To explore the feasibility of the CT image reconstruction of laryngeal cartilage and hyoid bone in adult age estimation using data mining methods. Methods The neck thin slice CT scans of 413 individuals aged 18 to <80 years were collected and divided into test set and train set, randomly. According to grading methods such as TURK et al., all samples were graded comprehensively. The process of thyroid cartilage ossification was divided into 6 stages, the process of cricoid cartilage ossification was divided into 5 stages, and the synosteosis between the greater horn of hyoid and hyoid body was divided into 3 stages. Multiple linear regression model, support vector regression model, and Bayesian ridge regression model were developed for adult age estimation by scikit-learn 0.17 machine learning kit （Python language）. Leave-one-out cross-validation and the test set were used to further evaluate performance of the models. Results All indicators were moderately or poorly associated with age. The model with the highest accuracy in male age estimation was the support vector regression model, with a mean absolute error of 8.67 years, much higher than the other two models. The model with the highest accuracy in female adult age estimation was the support vector regression model, with a mean absolute error of 12.69 years, but its accuracy differences with the other two models had no statistical significance. Conclusion Data mining technology can improve the accuracy of adult age estimation, but the accuracy of adult age estimation based on laryngeal cartilage and hyoid bone is still not satisfactory, so it should be combined with other indicators in practice.

Asphyxia Homicides in Finland, 1983-2012.

Finland has one of the highest homicide rates in Western Europe, and almost every tenth homicide is caused by asphyxiation. Reliable statistics, a strict legislation, and an exceptionally high medico-legal autopsy rate formed a base for a nationwide analysis of asphyxia homicides (n = 383) during 30 years. The cases were identified through multiple records, and all the forensic pathology case files were studied in detail. In more than one out of five cases, there were indications of staging, and the homicide was revealed first at autopsy in close to one in ten cases. The vast majority of the homicides took place in private locations and involved persons known to each other. Every third victim was an intimate partner, and every tenth a child. Almost half of the victims died from manual strangulation, one in three from ligature strangulation. Smothering, choking, neck compression with a firm object, and thoracic compression were more rare methods. Drownings were excluded from this study material. Of all the victims, 7% had no observable external injuries. Petechiae were recorded in approximately in 61%, laryngohyoid fractures in 47%, and vocal cord hemorrhages in 16% of the cases. Every tenth female victim had genital injuries. Toxicological analyses were performed in close to all of the cases, and almost three out of four victims tested positive for blood alcohol. The various aspects of the demographics and autopsy findings covered in this study contribute reliable and accurate data to further strengthen the spectrum of observable medico-legal characteristics of asphyxia homicides.