Psychophysical assessments of olfaction after endoscopic unilateral resection with post-operative radiotherapy in olfactory neuroblastomas.

Endoscopic resection with post-operative radiotherapy has been included in the standard therapeutic options for olfactory neuroblastomas (ONBs). Recent publications have indicated the feasibility of olfactory preservation after endoscopic unilateral resection of ONBs. This study validated residual olfaction using the psychophysical assessment, T & T olfactometer, in patients who underwent endoscopic unilateral resection with post-operative radiotherapy. A single-institutional retrospective review was performed to identify patients who underwent endoscopic unilateral resection of ONBs with olfaction monitoring using T & T olfactometer between 2009 and 2020. T & T olfactometry was performed before surgery, after surgery, before radiotherapy, and after completion of radiotherapy. Four patients (one female and three males) were identified. The mean observation period was 41.9 months, and all patients showed no evidence of disease. Three patients exhibited residual olfactory function with two patients having normal or pre-operative level olfaction, although T & T olfactometer results showed a temporary increase in recognition thresholds after surgery. As consequence, endoscopic unilateral resection can achieve satisfactory olfactory preservation in patients with early-stage ONBs.

Uncommonly sited rare tumour causing nasal obstruction.

​: ​The study aims to discuss a case of an uncommonly sited rare tumour causing nasal obstruction and a literature review of angioleiomyomas in the nose. A 64-year-old woman presented with blockage of the right nostril, associated with a visible swelling on the undersurface of the alar cartilage, in the lateral wall of the nasal cavity. Anterior rhinoscopy highlighted a 1 cm cystic lesion, with areas of firmness, present at the mucocutaneous junction with a broad base. It was not attached to the underlying cartilage. There was no ulceration or bleeding on palpation. Nasal endoscopy did not show any extension further and the rest of the nasal cavity was clear. Endonasal resection of the tumour using a two-handed technique. This paper highlights not only the importance of considering angioleiomyomas within a differential diagnosis of nasal obstructions but also the uncommon site. ​.

Chronic invasive fungal rhinosinusitis vs sinonasal squamous cell carcinoma: the differentiating value of MRI.

OBJECTIVES: To investigate MRI features in discriminating chronic invasive fungal rhinosinusitis (CIFRS) from sinonasal squamous cell carcinomas (SNSCC). METHODS: MRI findings of 33 patients with CIFRS and 47 patients with SNSCC were retrospectively reviewed and compared. Multivariate logistic regression analysis was performed to identify significant imaging features in distinguishing between CIFRS and SNSCC. The ROC curves and the AUC were used to evaluate diagnostic performance. RESULTS: There were significant differences in cavernous sinus involvement (p < 0.001), sphenoid sinus involvement (p < 0.001), meningeal involvement (p = 0.024), T2 signal intensity (p = 0.006), and enhancement pattern (p < 0.001) between CIFRS and SNSCC. Multivariate logistic regression analysis identified cavernous sinus involvement (odds ratio [OR] = 0.06, 95% confidence interval [95% CI] = 0.02-0.20) and sphenoid sinus involvement (OR = 0.14, 95% CI = 0.05-0.45) as significant indicators for CIFRS and T2 isointensity to gray matter (OR = 4.44, 95% CI = 1.22-16.22) was a significant indicator for SNSCC. ROC curve analysis showed the AUC from a combination of three imaging features was 0.95 in differentiating CIFRS and SNSCC. CONCLUSIONS: MRI showed significant differences between CIFRS and SNSCC features. In immunocompromised patients, a sinonasal hypointense mass on T2WI with septal enhancement or loss of contrast enhancement, and involvement of cavernous sinus, sphenoid sinus, and meninges strongly suggest CIFRS. KEY POINTS: • Chronic invasive fungal rhinosinusitis (CIFRS) is often difficult to distinguish from sinonasal squamous cell carcinomas (SNSCC) in clinical practice. • Cavernous sinus and sphenoid sinus involvement appear to be significant indicators for CIFRS. T2 isointensity to gray matter appears to be a significant indicator for SNSCC. • Loss of contrast enhancement and septal enhancement can be used to distinguish CIFRS from SNSCC with a high degree of specificity.

Low-Grade Papillary Schneiderian Carcinoma of the Sinonasal Cavity and Temporal Bone.

OBJECTIVES:: The aim of this study was to further characterize a newly described neoplasm, low-grade papillary Schneiderian carcinoma, occurring simultaneously in the sinonasal cavity and mastoid. Additionally, the authors review the only 2 similar cases within the literature and describe the common clinical features, radiographic findings, and pathologic characteristics of this exceptionally rare disease process. METHODS:: Chart review for single patient, review of literature. RESULTS:: The patient presented with bilateral nasal obstruction. Computed tomography revealed a left sinonasal mass with skull base hyperostosis, and follow-up magnetic resonance imaging showed a concomitant olfactory groove meningioma. Examination showed a bilateral, completely obstructing sinonasal mass with skip areas, and biopsy confirmed inverted papilloma (human papilloma virus strains 16 and 18 indeterminate). The patient underwent bilateral endoscopic sinus surgery, left medial maxillectomy, and left partial nasopharyngectomy. Given her multifocal disease, she was advised that she would require additional excision, but was lost to follow up. One year later she developed acute left facial paralysis. Magnetic resonance imaging demonstrated an enhancing mass in the left mastoid with enhancement along the Eustachian tube in addition to her known recurrent sinonasal disease. Simultaneous endoscopic sinus surgery and mastoidectomy were performed. Polypoid tissue was removed from the nasopharynx, mesotympanum, epitympanum, and retrofacial air cells. Immunohistochemistry showed that cells stained positive for p63 and dermCK and negative for synaptophysin. Morphologically, cells were bland, without classic stromal invasion, retaining their smooth, cystic, and papillary features, despite their increased depth within the tissue. Upon further review and consultation with an outside pathologist, a diagnosis of low-grade papillary Schneiderian carcinoma was made. The patient was referred for radiation therapy and is disease free at 3-month follow-up, with return of her facial function. CONCLUSIONS:: This case represents the first report of concurrent low-grade papillary Schneiderian carcinoma of both the nasal cavity and mastoid. It emphasizes the importance of recognizing this new entity through pathologic analysis and suspecting it when the clinical course does not follow an expected pattern.

Intralesional Bevacizumab for the Treatment of Recurrent Sinonasal Hemangioma.

INTRODUCTION:: Sinonasal hemangioma is a rare benign tumor of vascular endothelial cells. The pathogenesis is closely linked to abnormalities in the vascular endothelial growth factor signaling pathway. Multiple treatment modalities are available, though wide local excision remains the preferred treatment. Bevacizumab, an anti-vascular endothelial growth factor monoclonal antibody, has known efficacy against hemangiomas, though there are no cases of sinonasal hemangiomas managed with bevacizumab. METHODS:: Case report. RESULTS:: The authors review the case of a 67-year-old man with a left-sided nasal hemangioma originating from the nasal septum. He presented with progressive left nasal obstruction and recurrent epistaxis. At the time of his presentation, the lesion had recurred after 1 excision/polypectomy at an outside institution. He then underwent revision surgery via wide local excision and septoplasty. After tumor recurrence following the revision surgery, the hemangioma was noted to recur on 1 year postoperative surveillance nasal endoscopy. In-office intralesional injection of 50 mg bevacizumab was then performed under endoscopic visualization. No improvement in the tumor size was noted at 2 months after injection, with the tumor measuring 1.5 cm. At the 10-month surveillance clinical visit following injection, the tumor had dramatically involuted to 3 mm in greatest dimension. The patient reported complete resolution of his primary symptoms of epistaxis and nasal obstruction. CONCLUSIONS:: This report demonstrates the first reported successful treatment of a sinonasal hemangioma with intralesional bevacizumab. Intralesional bevacizumab confers an additional option for adjuvant treatment of sinonasal hemangiomas. Further evaluation of intralesional bevacizumab in the treatment of these tumors is warranted.

Hamartoma condromesenquimal nasoetmoidal con extensión intracraneal: a propósito de un caso / Nasoethmoidal condromesenchymal hamartoma with intracranial extension: a case report

El Hamartoma Condromesenquimal Nasal (HCMN) es una neoplasia descrita por McDermott et al en 1998 en pacientes pediátricos, con pocos casos reportados en adultos. Este tumor está constituido por tejido condroide o cartilaginoso así como por tejidos mesenquimales. Es una lesión expansiva, localmente destructiva y en algunos casos está descrita la extensión intracraneal. El comportamiento es habitualmente benigno y el tratamiento consiste en la resección quirurgica. Se presenta un caso de un paciente masculino de 8 meses de edad, quien presentaba aumento de volumen en región periorbitaria derecha, con pseudoptosis palpebral, paresia del nervio oculomotor derecho y rinorrea hialina. Mediante la Tomografia Computarizada (TC) craneal y la Resonancia Magnética (RM) cerebral se observó lesión ocupante de espacio naso fronto etmoidal. El estudio histopatológico e inmunohistoquimico determinó la presencia de tumor mesenquimal fibrocartilaginoso osificante: Hamartoma Condromesenquimal. Se revisan las características y el tratamiento de este tumor poco frecuente(AU)

The Chondromesenchymal Nasal Hamartoma (CMNH) is a rare neoplasm described in 1998 by McDermott et al in the pediatric age, with few cases reported in adults. This tumor is composed by chondroid or cartilaginous tissue as well as mesenchymal tissues. It is an expansive lesion, locally destructive and in some cases intracranial extension is described. Its behavior is usually benign and its treatment consists of surgical resection. The authors present an 8-month-old male patient with increase volume in the right periorbital region, palpebral ptosis, paresis of the right oculomotor nerve and hyaline rhinorrhea. Computed Tomography (CT) and Cerebral Magnetic Resonance Imaging (MRI) were perfomed and revealed a nasofrontoethmoidal space occupying lesion; a histopathological and inmunohistochemical study resulted in osseous fibrocartilaginous mesenchymal tumor: chondromesenchymal hamartoma. We review the characteristics and treatment of this rare tumor(AU)

Sinonasal quality of life after endoscopic resection of malignant sinonasal and skull base tumors.

OBJECTIVES: Improvement in sinonasal quality of life (QoL) following sinus surgery has been well-documented across the literature. To our knowledge, only one series has evaluated long-term QoL in patients undergoing tumor resection, and that study demonstrated no improvement in rhinologic QoL following malignant tumor resection at 2-year follow-up. The objective of the present study was to evaluate QoL in the 2 years following endoscopic malignant tumor resection. METHODS: A prospective cohort study was performed, including patients with both malignant and benign sinonasal tumors in a tertiary academic medical center. Patients undergoing endoscopic tumor resection who had completed Sinonasal Outcome Test 22 (SNOT-22) questionnaires were included in the cohort. SNOT-22 questionnaires were administered preoperatively and over a 2-year follow-up period at clinic visits. Longitudinal linear mixed-effects regression was used to compare preoperative QoL to QoL over the 2 years following surgery. RESULTS: Among 145 patients included in this study, 64 had malignant tumors. There was a statistically significant improvement in SNOT-22 score from baseline to 2 years for patients with both malignant tumors (37.0, 95% confidence Interval [CI] 32.0-42.1 at baseline; 26.5 95% CI 20.8-32.2 at 2 years; P < 0.001) and benign tumors (26.5, 95% CI 21.4-30.4 at baseline; 12.9 95% CI 7.6-18.2 at 2 years; P < 0.001). CONCLUSION: In contrast to previously reported series, in this cohort endoscopic resection of sinonasal tumors appears to be followed by an improvement in QoL, which is sustained over a 2-year period. LEVEL OF EVIDENCE: 2b. Laryngoscope, 128:789-793, 2018.

[Nasal glial heterotopia: Clinical and morphological characteristics]. / Kliniko-morfologicheskaia kharakteristika nazal'noi glial'noi geterotopii.

The paper describes a case of nasal glial heterotopia in a 10-month-old girl with a mixed (intranasal and subcutaneous) localization, which is accompanied by the divergence of the nasal bones. Histological examination supplemented by immunohistochemical reactions with antibodies to vimentin, S100 protein, neuron-specific enolase, as well as Ki-67 and smooth muscle actin confirmed the neural nature of the tumor. Fields of mature astrocytic glia including individual cells with neuronal differentiation were found among the fibrous and fibrovascular tissues. The paper provides a brief overview of the discussed pathology.

[The clinical observation of NK/T-cell lymphoma of the nasal type]. / Klinicheskoe nabliudenie NK/T-kletochnoi limfomy nazal'nogo tipa.

The objective of the present work was to present the results of the clinical analysis of the patient presenting with natural killer (NK)/T-cell lymphoma of the nasal type. We undertook the analysis of the medical documentation concerning the case of interest. It was shown that the development of progressive perforation of the nasal septum and the pronounced destructive changes in the intranasal and adjacent structures following the endonasal surgical interventions made necessary differential diagnostics between the condition under consideration and certain latent disorders (such as Wegener's granulomatosis, leprosy, syphilis, leishmaniasis, dirofilariasis tuberculosis, etc.). The study has demonstrated that the negative results of the analysis imply the necessity of special attention to the possibility of development of oncological diseases including hematological disorders (e.g. NK/T-cell lymphoma) and the repeat careful follow-up examination of the patients by the experienced experts.

Skin diseases of the nose.

OBJECTIVES: The goal of this study was to review the main lesion types of the nasal skin and appropriate treatment strategies rather than to present a comprehensive list of all diseases that affect the skin that can involve the nose. METHODS: We reviewed the main nasal skin lesion types and available treatment strategies. Nasal skin lesions were classified as benign, premalignant, or malignant. RESULTS: Benign lesions of the nose include nonmalignant tumoral lesions (i.e., freckles, comedo, adenoma sebaceum [Pringle disease], hydrocystoma, fibrous papules, sebaceous hyperplasia, and rhinophyma), autoimmune and inflammatory conditions (i.e., pemphigus, sarcoidosis, systemic lupus erythematosus, facial eosinophilic granuloma, rosacea, herpes zoster infection, leishmaniasis, and leprosy), and vascular lesions (i.e., telangiectasis, hemangioma, and spider nevus). Premalignant lesions are actinic keratosis and keratoacanthoma; and malignant tumors are melanoma, basal cell carcinoma, and squamous cell carcinoma. Regardless of whether or not they are malignant, all facial lesions can yield significant cosmetic discomfort that should be evaluated carefully before commencing any curative or corrective intervention. In general, benign lesions are treated with dermabrasive modalities, such as trichloroacetic acid, phenol, salicylate, and laser ablation. Electrocautery, cryosurgery, and surgical excision are also used, although these methods may result in scar formation, which can sometimes be more problematic than the original lesion itself. CONCLUSION: Any disease that affects the skin, especially those diseases that are triggered by ultraviolet exposure, can involve the face and nose. Cosmetic defects due both to the lesion itself and the intervention must be discussed with the patient, preferably in the presence of a first-degree relative, before commencement of treatment. As a result of heterogeneity of skin lesions of the nose, appropriate education of general practitioners as well as otorhinolaryngologists is mandatory.

Recurrent Olfactory Neuroblastoma Treated With Cetuximab and Sunitinib: A Case Report.

Olfactory neuroblastoma (ONB) is a rare cancer originating in the olfactory epithelium of the nasal vault. The recurrence rate of ONB is high, as the standard treatment of surgery followed by radiotherapy and/or chemotherapy is usually unsuccessful. The use of targeted therapy based on individual genomic variations after cancer relapse has not been reported. Here, we present the case of a 44-year-old man who was diagnosed with recurrent ONB and treated with a regimen developed using whole exome sequencing. Potential targets were first identified and then matched to appropriate drugs. Gene mutations in the genes encoding EGFR, FGFR2, KDR, and RET were discovered in the patient's tumor tissue by whole exome sequencing and the patient was treated with a combination of the targeted drugs cetuximab and sunitinib. Five days after treatment, enhancement magnetic resonance imaging showed a 65% reduction in tumor size, and the Visual analog scale headache scores went down to 2/10 from 10/10. Repeat imaging at 1 month showed a complete response.This study represents the first demonstration of an effective personalized treatment of ONB by targeted drugs, and sheds light on how precision medicine can be used to treat recurrent ONB that fails to respond to routine tumor resection, radiotherapy, and/or chemotherapy.

Apoptosis and Ki-67 as predictive factors for response to radiation therapy in feline nasal lymphomas.

Nasal lymphoma is the most common nasal tumor in cats and is generally a solitary and radiosensitive tumor. We retrospectively evaluated the response to radiation and survival time in relation to apoptosis and Ki-67 indices in feline nasal lymphomas treated with radiation therapy. The apoptotic and Ki-67 indices were evaluated with TUNEL and immunohistochemical staining in 30 biopsy tissues that were taken before any treatment. These two indices were compared, and differences between different treatment response groups were analyzed. The correlation between the median survival times (MST) and the indices was estimated using the Kaplan Meier method, and statistical differences between survival curves were analyzed using a log-rank method. With regard to apoptotic index, a statistical difference was observed between the samples taken from cats with complete response and stable disease (1.22% vs. 0.45%; P=0.045). The Ki-67 index in cats with both complete response and partial response was significantly higher than in cats with stable disease (44.4% and 39.6% vs. 16.3%; P<0.001 and P=0.008, respectively). The cats with a high level of apoptosis (>0.9%) nasal lymphoma were not significantly prolonged MSTs (P=0.202), however, high Ki-67-positive (>40%) cats experienced a statistically significant relationship with longer survival time (P=0.015). Our results indicate that spontaneous apoptotic and Ki-67 indices are strong predictors for response to radiation therapy in feline nasal lymphomas.

Esthesioneuroblastoma with large intracranial extension treated with Induction chemotherapy, de-bulking surgery and image guided intensity modulated radiotherapy.

INTRODUCTION: Esthesioneuroblastoma is a rare tumour of the sino-nasal tract. One-third cases present with intracranial extension. However, treatment options are limited for such cases. METHODOLOGY: We herein report a case with large intracranial extension treated with Induction chemotherapy, de-bulking surgery, and image guided intensity modulated radiotherapy. RESULTS: The patient was treated with IGIMRT technique to a dose of 64 Gy in 32 fractions. Cone bean CT verification was done twice a week to eliminate set up error. The patient achieved complete resolution of the disease and was disease free 6 months after completion of treatment. CONCLUSION: IGIMRT even after a de-bulking surgery may help to achieve long-term disease control for patients with large intracranial extension with minimal morbidity.

Role of Wnt signaling pathway in progression of sinonasal inverted papilloma to squamous cell carcinoma.

BACKGROUND: Sinonasal inverted papilloma (IP) is one of the most common benign tumors of the sinonasal area and malignant transformation has frequently been reported. However, the exact mechanism of the transition from benign lesion to malignancy is not known. The Wnt signaling pathway involves a network of multiple signaling glycoproteins that are known to play an important role in embryogenesis and carcinogenesis. OBJECTIVE: The purpose of this study was to evaluate the role of the Wnt pathway and signaling proteins in malignant transformation of IP to dysplasia and squamous cell carcinoma. METHODS: Expression of the Wnt signaling pathway proteins, including Wnt-1, beta-catenin, cyclin D1, and Dishevelled-1 (Dvl-1), were detected by immunohistochemistry by using 3-mm tissue core microarrays that consisted of 115 cores of IP tissue. Each of the IP cores was graded as I (prominent squamous metaplasia), II (inverted pattern), III (dysplasia), or IV (squamous cell carcinoma). The expression pattern of each protein and the correlation between the expression of each target protein and IP grade were evaluated. RESULTS: Membranous staining of beta-catenin showed a significant positive correlation with IP grade (ρ = 0.247, p < 0.001), as did staining of cyclin D1 (ρ = 0.365, p < 0.001), which showed a nuclear pattern and staining of Dvl-1 (ρ = 0.380, p < 0.001), which showed a membranous, cytoplasmic, and nuclear pattern. For Dvl-1, a nuclear expression pattern was more frequently observed in grade III and IV IP (p = 0.036). In the case of Wnt-1, cytoplasmic expression was observed; however, it did not show a significant correlation with IP grade (ρ = 0.141, p = 0.130). CONCLUSIONS: Wnt signaling proteins, including beta-catenin, cyclin D1, and Dvl-1, may play crucial roles in the malignant transformation of IP.

Reversing effect of sorcin in the drug resistance of human nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is one of the most common cancers originating in the nasopharynx, and chemoresistance is an essential aspect of NPC chemotherapy failure. Sorcin has been implicated in multidrug resistance (MDR) of many types of human tumor. However, the effect and mechanism of Sorcin in MDR of human NPC is not fully clear. In this report, we silenced Sorcin in human NPC CNE2/DDP cells, and explored the role of Sorcin in MDR reversal. The results showed an increased cytotoxicity of cisplatin and intracellular accumulation of Rhodamine-123 and glutathione depletion in Sorcin silencing CNE2/DDP cells. We also found a decreased messenger RNA and protein expression of multidrug resistance gene (MDR1), multidrug resistance-associated protein (MRP1), excision repair cross-complementing gene 1 (ERCC1), glutathione S-transferase-π (GST-n), RhoE, Bcl-2, and Survivin in Sorcin silencing CNE2/DDP cells. The increased expression of PTEN and decreased expression of p-Akt and NF-κB suggested that the key cellular signaling pathways were triggered by Sorcin silencing. We concluded that Sorcin silencing would contribute to establish a potent target point for MDR reversal.

14-3-3 gene expression exerts isoform-dependent functions in sinonasal pathophysiology.

The expression profiles of 14-3-3ß and θ isoforms, known to exert both oncogenic and antiapoptotic effects, were assessed in different entities of nasal pathophysiology. Flow cytometry and immunohistochemistry were used on paraffin-embedded sections of 51 inverted papillomas (IP), 26 nasal polyps (NP), 9 polyps with IP (NPIP) and 10 specimens of normal epithelium (NE). 14-3-3ß expression was significantly upregulated in IP as compared with both NP (p=0.015) and NE (p=0.002). 14-3-3ß was also increased in NPIP as compared with NE (p=0.008). 14-3-3ß cytoplasmic staining was more pronounced in basal cells of the respiratory epithelium although serous glands and the vascular system were often positive as well. High 14-3-3ß immunopositivity in IP patients concurred with increased proliferative activity shown by PCNA immunostaining (p=0.04). Expression of 14-3-3θ was also found increased in IP and NPIP patients, compared to NP (p=0.005, p=0.002 respectively) and NE (p=0.004 and p=0.001 respectively). 14-3-3θ cytoplasmic immunopositivity was detected in columnar epithelium, particularly in basal and subluminal cells, whereas no immunoreactivity was observed in NP and NE. Our results demonstrate differential expression of 14-3-3ß and θ isoforms in sinonasal pathophysiology, supporting their implication, respectively, in the proliferative and inflammatory process engaged in the formation of IP.

Bilateral adrenalectomy: lifesaving procedure in severe Cushing syndrome.

OBJECTIVE: To discuss the role of bilateral adrenalectomy in Cushing syndrome, as illustrated in a case of severe hypercortisolism that was unresponsive to combination agent medical therapy. METHODS: We report the clinical, laboratory, imaging, and pathologic findings in a patient with ectopic Cushing syndrome attributable to an adrenocorticotropic hormone (ACTH)-secreting neuroblastoma. In addition, we provide a literature review regarding olfactory neuroblastoma and discuss current and emerging therapeutic options for Cushing syndrome. RESULTS: A 59-year-old man presented with nasal congestion and neck swelling and was noted to have hypokalemia, hypertension, and hyperglycemia. A nasal biopsy demonstrated a poorly differentiated carcinoma with neuroendocrine features. He was subsequently diagnosed as having ACTH-dependent Cushing syndrome, but despite high-dose combination medical therapy, his condition rapidly deteriorated. Urgent bilateral adrenalectomy provided rapid control of the hypercortisolism, and the patient was later able to undergo an uncomplicated total macroscopic resection of his locally metastatic primary tumor. CONCLUSION: This report describes the challenges in the diagnosis and management of ACTH-dependent Cushing syndrome and highlights the important role that bilateral adrenalectomy can still have in patients with severe hypercortisolism causing life-threatening complications.