Malignant tumors of the external auditory canal: diagnosis, treatment, genetic landscape, biomarkers, and clinical outcome.

Malignant tumors of the external auditory canal (EAC) are rare neoplasms that appear in the head and neck area. A common feature of these malignancies is their rarity, as well as their delayed diagnosis due to the appearance of non-specific symptoms that mimic various benign otologic conditions. The reported histological types of cancer of the external ear are: squamous cell carcinoma, basal cell carcinoma, malignant melanoma, Merkel cell carcinoma, angiosarcoma, adnexal carcinoma (including ceruminous adenocarcinoma and adenoid cystic carcinoma), and lymphoma (Lancet Oncol. 2005;6:411-20. doi: 10.1016/S1470-2045(05)70208-4). Several therapeutic interventions have been proposed, primarily orientated towards the cure of the patient, placing the surgical excision of the lesions at the tip of the spear. Subsequently and depending on the clinical stage and the pathological characteristics of the tumor, radiation, chemotherapy, a combination thereof, or some form of palliative treatment for particularly advanced cases, may be recommended. The aim of all the above-mentioned approaches is the complete resection of the mass with negative surgical margins along with lymph node dissection, the elimination of any residual disease or metastasis, and the improvement of survival. The anatomical complexity of the region will always remain a demanding challenge. Nevertheless, advances in the fields of ear microsurgery, imaging, radiation, molecular biology, and genomics have led to remarkable outcomes compared to the past, with a view to the patient's quality of life. Large, well-organized, and prospective studies with the participation of multiple centers in contrast to existing retrospective studies with a limited number of patients will help to establish universally accepted guidelines. The exploration of the molecular and genetic background of these cancers in conjunction with the search for new biomarkers and target molecules seems promising for providing upgraded and more personalized treatment modalities for the future.

Nasopharyngeal cyst in an adolescent boy: differential diagnosis - embryological and anatomical considerations.

In the current article, we present a case of an adolescent boy with a nasopharyngeal cyst that induced nasal and Eustachian tube obstruction. Nasopharyngeal cysts can be found incidentally during imaging examinations such as MRI; however, a symptomatic nasopharyngeal cyst is a rare finding in the paediatric population. The cyst was treated successfully by marsupialisation, and the histological diagnosis revealed an adenoidal retention cyst. The differential diagnosis of a nasopharyngeal cyst is always challenging since developmental cysts such as Rathke's pouch cysts, Torwaldt's and branchial cleft cysts may be encountered at the nasopharynx. The current article also intends to present the diagnostic and therapeutic approach to a nasopharyngeal cyst, emphasising anatomical and embryological considerations that address its differential diagnosis.

A Foreign Body Lodged in the Glottis of a Toddler for a Prolonged Time: Anatomical Considerations and Review of the Literature.

Our scope is to present the unusual case of an impacted foreign body in a child's larynx for a prolonged period due to recurrent misdiagnosis and review the literature emphasizing the laryngeal foreign body. A toddler girl from a rural region was initially referred to a primary pediatric care center due to a sudden choking episode. The mother made an unsuccessful attempt to pull out a possible foreign body by blind finger sweeping. After 22 days of recurrent misdiagnosis and unsuccessful conservative therapies, the child developed hoarseness of voice and dyspnea during physical exertion. The patient underwent a flexible nasopharyngolaryngeal endoscopy, which observed a foreign body in the glottis, and an emergency microlaryngoscopy. Persistence of laryngeal symptoms in a child with a sudden choking episode should always raise the suspicion of a respiratory tract foreign body impaction. The most appropriate therapeutical approach is rigid bronchoscopy under general anesthesia.

Embryological, anatomical and clinical considerations on pleuroperitoneal communication.

The pleural and peritoneal cavity share many related features due to their common celomic origin. Normally these two spaces are completely separated with the development of the diaphragm. Defects in diaphragm morphogenesis may result in congenital diaphragmatic hernias, which is the most known form of communication between the pleural and peritoneal cavity. However, in several cases, findings of pleuroperitoneal communication (PPC) have been described in adults through an apparently intact diaphragm. In this comprehensive review we systematically evaluate clinical scenarios of this form of "unexpected" PPC as reported in the literature and focus on the possible mechanisms involved.

Lateral semicircular canal dilatation in a patient with congenital hearing loss due to α-tectorin mutation: microanatomical considerations.

The tectorial membrane is crucial in the physiology of the auditory neuroepithelium. Mutations in one of its functional molecules, α-tectorin, lead to autosomal dominant and recessive congenital mid-frequency, non-syndromic hearing loss.Typically, α-tectorin mutations are not accompanied by any morphological abnormalities of the labyrinth. For the first time, we present a case of a toddler boy with congenital hearing loss due to TECTA gene mutation and concomitant bilateral dilation of the lateral semicircular canals.The expression of glycoproteins, like α-tectorin, varies between the distinct labyrinth acellular membranes. Various mutations in the TECTA gene may affect additional glycoproteins that share a high percentage of sequence similarity at the amino acid level with α-tectorin. The mutated glycoproteins differ in the hydration level of their side chains of glycosaminoglycans. Hydration level could affect the mass of the ampullary cupula of the lateral semicircular canal leading to its dilation during embryogenesis.

Hamartomatous polyp of the palatine tonsil: histological considerations and review of the literature.

The hamartomatous polyp is a rare benign hamartoma of the palatine tonsil, usually encountered during the second decade of life. It may be reported under various terms in the literature, like lymphangioma of the tonsil, angiofibrolipoma, lymphangiomatous tonsillar polyp and lymphangiectatic fibrous polyp. Macroscopically, it appears as a large, pale, pedunculated mass. Typically, a hamartomatous polyp is asymptomatic or manifests mild symptoms, like foreign body sensation. It is not related to a generalised lymphatic malformation process. Despite its typical appearance, an excisional biopsy is necessary to rule out a malignancy. Histological findings are consistent with a squamous epithelial covering, a core of loose fibrous and adipose tissue with sparse lymphoid aggregations and dilated lymphatic channels filled with lymph and lymphocytes. Several embryologically based theories suggested its pathogenesis; however, recurrent tonsillitis does not play an established role. A typical tonsillectomy is suggested as a sufficient therapeutical approach with no tendency for recurrence.

Pathogenesis of Nasal Polyposis: Current Trends.

Chronic Rhinosinusitis (CRS) is characterized by edema of the sub-epithelial layers, but, only specific types of CRS are developing polyps. Nasal polyposis may develop under different pathogenetic mechanisms rendering the typical macroscopic classification of CRS, with or without nasal polyps, rather deficient. Currently, we approach nasal polyposis, in terms of diagnosis and treatment, according to its endotype, which means that we focus on the specific cells and cytokines that are participating in its pathogenesis. It appears that the molecular procedures that contribute to polyp formation, initiating with a Th-2 response of the adaptive immune system, are local phenomena occurring in the sub-epithelial layers of the mucosa. Several hypotheses are trying to approach the etiology that drives the immune response towards Th-2 type. Extrinsic factors, like fungi, Staphylococcus superantigens, biofilms, and altered microbiome can contribute to a modified and intense local reaction of the immune system. Some hypotheses based on intrinsic factors like the elimination of Treg lymphocytes, low local vitamin-D levels, high levels of leukotrienes, epithelial to mesenchymal transition (EMT) induced by hypoxia, and altered levels of NO, add pieces to the puzzle of the pathogenesis of nasal polyposis. Currently, the most complete theory is that of epithelial immune barrier dysfunction. Intrinsic and extrinsic conditions can damage the epithelial barrier rendering sub-epithelial layers more vulnerable to invasion by pathogens that trigger a Th-2 response of the adaptive immune system. Th2 cytokines, subsequently, induce the accumulation of eosinophils and IgE together with the remodeling of the stroma in the sub-epithelial layers leading, eventually, to the formation of nasal polyps.

Novel Indices to Improve the Diagnostic Ability of Nocturnal Oximetry in Children with OSAS.

Nocturnal pulse oximetry (NOx) is an alternative diagnostic test for obstructive sleep apnea syndrome (OSAS) in childhood yet with variable diagnostic performance. Our aim was to apply advanced signal analysis to develop novel and more accurate NOx indices. We studied 45 children aged 3-10 years who underwent adenotonsillectomy for adenotonsillar hypertrophy and OSAS symptoms. Participants performed NOx before and three months after surgery, and the changes in McGill oximetry score (MOS), oxygen desaturation ≥3% index (ODI3), and the novel parameters-cumulative saturation area (CSA) and oxygen saturation sample entropy (SSE)-were assessed. There was a significant improvement (p < 0.001) in all NOx indices. When pre- and post-adenotonsillectomy NOx recordings were compared, the MOS had an area under the curve (AUC) of 0.811 with 63.2% sensitivity and 100% specificity at a cutoff >1. The AUC of ODI3 was 0.994, with 97.8% sensitivity and 91.1% specificity at a cutoff of >3.6 events per hour. The CSA and SSE had an AUC of 1.00, with 100% sensitivity and specificity at a cutoff of >293 and >0.99, respectively. We conclude that the herein-introduced indices-CSA and SSE-hold promise in improving the diagnostic ability of NOx in children suspected of OSAS.

Hearing screening test in neonates born to COVID-19-positive mothers.

SARS-CoV-2, the responsible virus for the COVID-19 pandemic, has demonstrated neurotropic properties indicated by cases presenting with auditory and vestibular system insults. The expression of ACE-2 receptors in the placenta and the detection of IgM antibodies against the virus in the fetuses of pregnant women suffering from COVID-19 render vertical transmission of the infection to the fetus possible. Thus, our study aims to examine whether, similar to other viruses like CMV, SARS-CoV-2 is responsible for congenital hearing loss. This is a retrospective study in a regional pediatric hospital. The medical records of newborns (n = 111) born by mothers positive for COVID-19 during pregnancy who underwent screening hearing tests with Transient Evoked Otoacoustic Emissions (TEOAE) and Automatic Auditory Brainstem Response (AABR) from February 2020 to June 2022 were reviewed. Neonates with additional aggravating factors for congenital hearing loss were excluded from the study. For the study period, nine mothers were found positive during the first trimester, twenty mothers in the second trimester, and eighty-three mothers in the third trimester. TEOAEs test and AABR test scored PASS bilaterally in all neonates tested. CONCLUSION: Infection with COVID-19 during pregnancy was not a risk factor for hearing loss, similar to other studies. WHAT IS KNOWN: • The pathogenetic mechanism of the viral-induced impairment of the organ of Corti includes direct damage to the hair cells and indirect damage due to the induction of the innate inflammatory response. • Early data suggested that the SARS-CoV-2 virus also has neurotropic properties with manifestations from the sensory epithelia. WHAT IS NEW: • Although the intrauterine infection remains controversial, the expression of the ACE-2 receptor on the placenta and the detection of IgM antibodies, as well as the covid-19 genome in fetuses, make the vertical transmission tenable. • In our study, the newborn hearing screening results indicate that COVID-19 infection during pregnancy is not a risk factor for hearing loss.

Multiple Wasp Stings on a Child's Supraglottis.

Hymenoptera stings are notorious for producing severe anaphylaxis; localized effects (edema, erythema) are far more common, especially in children. However, even an innocent focused lesion may be life-threatening when the sting is directed to the airway. We present the case of a child enduring consecutive wasp stings on the supraglottis.

Epithelial-to-Mesenchymal Transition in Metastasis: Focus on Laryngeal Carcinoma.

In epithelial neoplasms, such as laryngeal carcinoma, the survival indexes deteriorate abruptly when the tumor becomes metastatic. A molecular phenomenon that normally appears during embryogenesis, epithelial-to-mesenchymal transition (EMT), is reactivated at the initial stage of metastasis when tumor cells invade the adjacent stroma. The hallmarks of this phenomenon are the abolishment of the epithelial and acquisition of mesenchymal traits by tumor cells which enhance their migratory capacity. EMT signaling is mediated by complex molecular pathways that regulate the expression of crucial molecules contributing to the tumor's metastatic potential. Effectors of EMT include loss of adhesion, cytoskeleton remodeling, evasion of apoptosis and immune surveillance, upregulation of metalloproteinases, neovascularization, acquisition of stem-cell properties, and the activation of tumor stroma. However, the current approach to EMT involves a holistic model that incorporates the acquisition of potentials beyond mesenchymal transition. As EMT is inevitably associated with a reverse mesenchymal-to-epithelial transition (MET), a model of partial EMT is currently accepted, signifying the cell plasticity associated with invasion and metastasis. In this review, we identify the cumulative evidence which suggests that various aspects of EMT theory apply to laryngeal carcinoma, a tumor of significant morbidity and mortality, introducing novel molecular targets with prognostic and therapeutic potential.

The Eustachian Tube Dysfunction in Children: Anatomical Considerations and Current Trends in Invasive Therapeutic Approaches.

The eustachian tube (ET) has a crucial role in the physiology of the middle ear. Thus, any condition that renders the tube dysfunctional is directly implicated with middle ear pathophysiology, like in the case of acute otitis media and otitis media with effusion. Children are more vulnerable to pathologies of the middle ear, primarily due to the immature development of their eustachian tubes. Otitis media with effusion, apart from being a burden for hearing, with direct consequences for speech development, may also be implicated in cholesteatoma formation. Medical therapy is not practically effective for the treatment of effusion. Moreover, the established surgical approaches, like grommets and adenoidectomy, deal only indirectly with the problem since they are not addressing the dysfunctional ET itself. An emerging interventional approach that intends to restore the function of the tube is the transnasal balloon dilation of the cartilaginous part of the ET. Growing international experience indicates that this promising technique is safe and effective. In the current review, we aim to provide background information on the anatomy, physiology, and pathophysiology of the ET and to present the progress of the balloon dilation technique with emphasis on pediatric patients.

Surgery for adenotonsillar hypertrophy and otitis media in children is less demanded in quarantine times.

OBJECTIVES: In the COVID-19 era, extreme measures of social distancing have contained the spread of common viral respiratory infections, which are involved in the pathogenesis of Adenotonsillar Hypertrophy (ATH), and Chronic Otitis Media with Effusion (COME), the two commonest chronic ENT diseases of childhood. This study examines the lockdown effect on the number of procedures performed for these two conditions. METHODS: The consecutive charts of 650 and 195 children being operated respectively for ATH and COME during the quarantine (05/2020-02/2021) and unrestrained (05/2019-02/2020) periods were retrospectively reviewed. Surgical treatment of ankyloglossia, performed in 103 patients during the same periods was employed as a control procedure. RESULTS: Adenotonsillectomies and tympanostomies significantly decreased in the lockdown phase by 52% (P < 0.001) and 74% (P < 0.001), respectively, whereas control procedure counts increased by 25%. In terms of seasonal variation, ATH-related surgeries were significantly reduced during the winter season of the pandemic by 73% (P < 0.001), in comparison with the corresponding months of the unrestrained period. School-aged children received significantly fewer operations for ATH (-59%) than preschoolers (-42%), as a result of the lockdown (P = 0.044). CONCLUSION: When the child's exposure to respiratory pathogens is minimal, as in the case of lockdown, a noticeable decline occurs in the incidence of ATH and COME indicated for surgical treatment. Chronic low-grade inflammation, boosted by repetitive viral infections seems to underlie both conditions. Timely, effective isolation measures might reverse the disease process and keep the child away from the Operating Room.

Ultrasound-guided removal of impalpable, radiolucent vegetative foreign bodies embedded into facial soft tissues of a toddler.

Otolaryngologists frequently encounter children with foreign bodies retained inside the lumen of their upper aerodigestive tract. However, total capture in the soft tissues happens rarely, and could be clinically, as well as radiographically, silent. Ultrasonography is a safe and effective imaging modality, aiding both diagnosis and surgical treatment. We report on a 14-month girl with chronic, fluctuating cheek edema and erythema, induced by an impalpable, radiolucent bundle of organic fibers embedded intramuscularly. Foreign body identification and atraumatic removal were facilitated by real-time ultrasound scanning.

Androgen receptor in laryngeal carcinoma: could there be an androgen-refractory tumor?

Androgen receptors (ARs) which are implicated in the pathogenesis of several malignancies can also be a possible downstream effector in laryngeal cancer. In the present study, 97 invasive squamous laryngeal carcinomas were studied by immunohistochemistry for protein expression of AR. Androgen receptors were expressed in 52.6% of tumor specimens, suggesting their implication in the pathogenesis of this tumor. Our study's aim was to investigate the hypothetical scenario of an androgen refractory laryngeal carcinoma where androgen receptors can be activated by nodal molecules in the course of an Epithelial-to-mesenchymal transition (EMT) phenomenon. In line with this we correlated AR expression with the expression of ILK, p-Akt, E-cadherin, ß-catenin in our sample as well as with tumor grade and TNM stage. A reverse correlation between nuclear AR and cytoplasmic ILK expression was evidenced, indicating an interaction of those molecules in laryngeal carcinoma. Finally in our material, in those carcinomas that were expressing ARs, stronger nuclear expression of the receptor was characterized by poorer cell differentiation and correlated with the acquisition of EMT features like E-cadherin loss and ß-catenin translocation raising a question whether activated ARs can drive an EMT procedure.

Differential beta-catenin expression between glottic and supraglottic laryngeal carcinoma.

Glottic carcinomas present with a favorable prognosis comparing to supraglottic. This fact is mainly attributed to differences in anatomical, histological and embryological aspects. It is possible that differential molecular anatomy between the two distinct anatomical entities contributes to this clinical observation as well. The current study intended to evaluate, by immunohistochemistry in paraffin-embedded tissue samples from 97 invasive squamous laryngeal carcinomas, the possible differential expression of crucial molecules for malignant cell's function such as integrin-linked kinase, phosphorylated Akt, E-cadherin, beta-catenin, androgen receptor, estrogen receptor-beta and vimentin between glottic and supraglottic laryngeal carcinomas. We documented a correlation of supraglottic laryngeal carcinomas with high grade (p = 0.001) and enhanced tumor TNM stage (p < 0.001). The supraglottic location was correlated with the abolishment of beta-catenin from the membrane (p = 0.025). However, the diverse anatomical locations are not characterized by statistically significant differential expression of ILK, p-Akt, AR, ER-beta, E-cadherin and vimentin. Our results show that it is possible that molecular factors, such as beta-catenin, are differently expressed in glottic and supraglottic carcinomas, leading to the distinct clinical behavior of those tumors.

Estrogen receptor-beta expression in human laryngeal carcinoma: correlation with the expression of epithelial-mesenchymal transition specific biomarkers.

Laryngeal carcinoma is a malignancy of the respiratory tract with a significantly higher male to female ratio, suggesting involvement of gender-depended factors in the pathogenesis. Estrogen influences the pathological processes of hormone-dependent cancers, such as breast, prostate and ovarian cancers, through its receptors, estrogen receptor-alpha (ER-alpha) and -beta (ER-beta). While ER-alpha promotes cell proliferation, recent studies indicate that ER-beta is protective against carcinoma progression into an invasive state. However, it is unclear whether ER-beta plays a role in laryngeal cancer. In the present study we examined the expression of ER-beta in 80 invasive human squamous laryngeal carcinomas by immunohistochemistry and correlated ER-beta expression with markers of epithelial-mesenchymal transition (EMT). ER-beta was expressed in 83% of tumour specimens where it was localized in the nuclei of tumour cells. The expression of ER-beta correlated positively with the maintenance of E-cadherin and beta-catenin at cell junctions and negatively with the loss of E-cadherin, nuclear translocation of beta-catenin and increased TNM stage. We concluded that estrogen receptor-beta expression is documented in laryngeal cancer indicating a possible role in the pathogenesis of this malignancy. It is suggested that ER-beta could protect tumour cells from acquiring aggressive EMT features such as E-cadherin downregulation and nuclear beta-catenin activation.

Integrin-linked kinase cytoplasmic and nuclear expression in laryngeal carcinomas.

Integrin-linked kinase (ILK) has been implicated in the development and progression of several human malignancies. Previous in vitro studies also implicate ILK in the activation of Akt and beta-catenin as well as in the regulation of E-cadherin expression. However, the role of ILK in human laryngeal cancer and its possible in vivo downstream effectors in the disease are currently unknown. We examined by immunohistochemistry the protein expression of ILK, phosphorylated-Akt (p-Akt), E-cadherin, and beta-catenin in 97 invasive squamous laryngeal carcinomas. Increased cytoplasmic and nuclear expression of ILK and p-Akt decreased membranous expression of E-cadherin and nuclear accumulation of beta-catenin was found in 87.6%, 85.6%, 71.1%, and 43.3% of cases, respectively. Our results suggest that ILK expression may be implicated in human laryngeal carcinoma and its localization in the nucleus possibly proposes novel nuclear functions of this molecule. In addition, enhanced ILK expression correlates with activation of Akt but not with downregulation of E-cadherin and activation of beta-catenin. Finally, in our material while activated Akt seems to characterize well-differentiated tumors, loss of E-cadherin and activation of beta-catenin correlated with high grade carcinomas.