Neuroendocrine and undifferentiated sinonasal and skull base tumors: An up-to-date narrative review.

Tumors located in the nasal cavity, paranasal sinuses and the skull base comprise a wide range of histologic subtypes. Among them, neuroendocrine and undifferentiated tumors are rare but noteworthy, because of their distinctive features, aggressive nature, and diagnostic complexities. A literature search was conducted in the PubMed/MEDLINE and the Scopus databases from 2019 until inception. The keywords "neuroendocrine", "undifferentiated", "nose", "sinonasal", "paranasal", "skull base" were used. Thirty-eight articles referring to neuroendocrine and undifferentiated tumors of the nose, paranasal sinuses and the skull base were finally included and analyzed. Neuroendocrine and undifferentiated tumors of the nose, paranasal sinuses and the skull base are infrequent malignancies, most commonly affecting middle-aged men. They usually present with non-specific symptoms, even though ocular or neurologic manifestations may occur. Prognosis is generally poor; however, novel targeted and immunological therapies have shown promising results. Sinonasal Neuroendocrine Carcinomas (SNECs) carry distinct histological and immunohistochemical features. Management consists of surgical resection coupled with systematic therapy. Sinonasal Undifferentiated Carcinomas (SNUCs) lack specific squamous or glandular features. They typically stain positive for pancytokeratin and INI1 antibody. Treatment includes induction chemotherapy, followed by a combination of chemotherapy and radiotherapy. Olfactory neuroblastomas (ONBs) have neuroepithelial or neuroblastic features. They show diffuse positivity for various markers, including synaptophysin, chromogranin, and neuron-specific enolase (NSE). Surgical resection plus radiotherapy is considered the treatment of choice. In conclusion, neuroendocrine and undifferentiated tumors arising from the nose, paranasal sinuses and the skull base represent a unique group of malignancies. A thorough understanding of their clinical features, molecular changes, diagnostic approaches, treatment modalities, and prognostic factors is critical for providing optimal patient care. Still, continued research efforts and multidisciplinary collaboration are warranted, in order to improve outcomes for patients diagnosed with these rare and aggressive tumors.

The First Cases of Sudden Sensorineural Hearing Loss Post Coronavirus Disease in Children.

To investigate the incidence, characteristics, diagnosis, treatment, and prognosis of coronavirus disease (COVID-19)-related sudden sensorineural hearing loss (SSNHL) in children, three cases of SSNHL after COVID-19 infection in children were analyzed. ENT clinical examination of all cases was normal. Only the third child had a first degree left-beating optokinetic nystagmus, compatible with right peripheral vestibulopathy. The audiogram indicated unilateral severe SSNHL in all frequencies. Computed tomography and magnetic resonance imaging of the brain and temporal bones also showed absence of pathology of the related structures. Oral methylprednisolone was administered to the first two cases, whereas intravenous methylprednisolone in a tapering form was administered to the third case. Additionally, the children underwent intratympanic dexamethasone injections and hyperbaric oxygen therapy with hearing improvement in lower and middle frequencies. The prognosis of COVID-19-related SSNHL in children is closely related to the onset of treatment. The combination of glucocorticoids, intratympanic dexamethasone injections, and hyperbaric oxygen therapy could be effective for COVID- 19-related SSNHL in children. Further large-scale, multicenter studies should be conducted to investigate the pathophysiology, diagnosis, treatment, and prognosis of COVID- 19-related SSNHL.

Venous malformation phleboliths mimicking submandibular sialadenitis in children.

To report one paediatric patient who presented with a rare venous vascular malformation as a mass in the left submandibular region with a clinical picture compatible with sialadenitis. Phleboliths are a specific feature of venous malformations due to venous stasis and may mimic sialoliths on various imaging modalities. Thus venous malformations are often misdiagnosed as sialadenitis due to sialolithiasis. Sialoliths are extremely rare in paediatric patients. In an early adolescent presenting with a submandibular mass and suspected sialadenitis arising from sialoliths, a detailed history, clinical examination and careful review of the radiological findings will allow the diagnosis of venous vascular malformation and provide the complete surgical resection. Our patient was initially referred with a presumed diagnosis of submandibular sialadenitis, and instead a venous malformation with phlebolith was diagnosed.

Low expression of miR-20b-5p indicates favorable prognosis in laryngeal squamous cell carcinoma, especially in patients with non-infiltrated regional lymph nodes.

PURPOSE: Tumor recurrence and distant metastasis are very common in laryngeal squamous cell carcinoma (LSCC). In this study, we examined the potential prognostic value of microRNA-20b-5p (miR-20b-5p), a component of the tumor-related miR-106a/363 cluster. MATERIALS AND METHODS: Total RNA was purified from 105 tissue specimens resected from patients having undergone surgical treatment for primary LSCC. After in vitro polyadenylation and reverse transcription, a sensitive real-time quantitative polymerase chain reaction (qPCR) methodology was applied for the relative quantification of miR-20b-5p levels. Then, we proceeded with biostatistical analysis, seeking to assess the prognostic value of miR-20b-5p expression in LSCC. RESULTS: miR-20b-5p positivity constitutes a predictor of inferior DFS and OS in LSCC (P < 0.001 and P = 0.002, respectively). The significant prognostic value of miR-20b-5p expression status seems to be independent of tumor size, histological grade, and TNM stage, as revealed by the multivariate bootstrap Cox regression analysis. Kaplan-Meier survival analysis showed also that miR-20b-5p expression status can stratify LSCC patients with non-infiltrated regional lymph nodes (N0) into two subgroups with distinct prognosis (P = 0.004 and P = 0.004, respectively). CONCLUSIONS: The miR-20b-5p expression status is a promising molecular tissue biomarker in LSCC, with an independent prognostic value, and thus merits further validation in larger cohorts of patients.

Expression of vimentin (VIM) and metastasis-associated 1 (MTA1) protein in laryngeal squamous cell carcinoma are associated with prognostic outcome of patients.

PURPOSE: Laryngeal squamous cell carcinoma (LSCC), a common type of head and neck cancer, is associated with high rates of metastasis and recurrence. In this study, we investigated the potential combinatorial prognostic value of NOTCH1, Vimentin (VIM), and Metastasis-associated 1 (MTA1) protein in LSCC, using immunohistochemistry. MATERIALS AND METHODS: Tissue specimens from 69 patients with LSCC were immunohistochemically evaluated for the protein expression of NOTCH1, VIM, and MTA1. Then, biostatistical analysis was performed, in order to assess the prognostic value of the expression of each one of these proteins. RESULTS: NOTCH1 expression status was not a significant prognosticator in LSCC, as shown in Kaplan-Meier survival analysis. On the contrary, both VIM and MTA1 seem to have an important prognostic potential, independently of TNM staging and histological grade of the tumor. In fact, positive VIM expression was shown to predict patients' relapse and poor outcome regarding patients' overall survival, in contrast with MTA1, the positive expression of which predicts higher disease-free survival (DFS) and overall survival (OS) rates in LSCC. CONCLUSIONS: VIM and MTA1 constitute potential tumor biomarkers in LSCC and could be integrated into a multiparametric prognostic model. Undoubtedly, their prognostic value needs further validation in larger cohorts of LSCC patients.

Distinctive expression profiles of Caveolin-1 and Notch-1 protein in patients with nasal polyps or sinonasal inverted papillomas.

BACKGROUND: Nasal polyposis (NP) and sinonasal inverted papillomas (SIP) are considered benign lesions capable of recurrence or malignant transformation although not with the same prevalence. Since fluctuations of Caveolin-1 and Notch-1 proteins expression have been reported in many pathologies, the current study aimed to investigate their involvement in the epithelial transformation observed in SIPs compared to NP. METHODS: Immunohistochemical expression of Caveolin-1 and Notch-1 proteins was assessed in 104 patients with sinonasal lesions (45 NP, 45 SIP and 14 NP with SIP), semiquantively (percentage times intensity). Proteins expression profiles were evaluated statistically for their correlation with patients demographic and clinicopathological variables (grade of dysplasia, inflammation, recurrence) as well as with markers of proliferation (Ki67) and apoptosis (7-AAD) as determined by flow cytometry analysis. RESULTS: SIP lesions presented increased Caveolin-1 immunopositivity compared to NP (62.2%, vs 40.9%; p = 0.045). Cytoplasmic staining was observed only in epithelium's basal and suprabasal layers. Caveolin-1 positivity was not related to Ki67 expression, apoptosis, inflammation or dysplasia, eventhough 81.8% of highly immunopositive lesions were dysplastic (p = 0.03). Also, smokers presented significantly increased immunopositivy (p = 0.03). In contrast SIP lesions presented reduced Notch-1 expression compared to NP (68.9% vs 100%; p < 0.001). Dysplastic lesions presented low Notch-1 immunopositivity (p < 0.001). Enhancement of Notch-1 gene expression was also associated with inflammation. CONCLUSIONS: The herein presented data suggest that the expression profiles of Caveolin-1 and Notch-1 proteins in sinonasal pathologies are distinctive and that could be explored as potential targets for the development of alternative therapeutic approaches.