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Cancers May 2021Olfactory neuroblastoma (ONB) is a rare sinonasal neoplasm with a peculiar behavior, for which limited prognostic factors are available. Herein, we investigate the...
Olfactory neuroblastoma (ONB) is a rare sinonasal neoplasm with a peculiar behavior, for which limited prognostic factors are available. Herein, we investigate the transcriptional pathways altered in ONB and correlate them with pathological features and clinical outcomes. We analyze 32 ONB patients treated with curative intent at two independent institutions from 2001 to 2019 for whom there is available pathologic and clinical data. We perform gene expression profiling on primary ONB samples and carry out functional enrichment analysis to investigate the key pathways associated with disease-free survival (DFS). The median age is 53.5 years; all patients undergo surgery and a pure endoscopic approach is adopted in the majority of cases (81.2%). Most patients have advanced disease (stages III-IV, 81.2%) and 84.4% undergo adjuvant (chemo)radiotherapy. The median follow-up is 35 months; 11 (26.8%) patients relapse. Clinical characteristics (gender, stage and Hyams' grade) are not associated with the outcomes. In contrast, TGF-beta binding, EMT, IFN-alpha response, angiogenesis, IL2-STAT5 and IL6-JAK-STAT3 signaling pathways are enriched in patients experiencing recurrence, and significantly associated with shorter DFS. Clustering of transcriptional profiles according to pathological features indicates two distinct molecular groups, defined by either cytokeratin-positive or -negative immunostaining. Definition of the characterizing ONB transcriptomic pathways may pave the way towards tailored treatment approaches.
PubMed: 34064009
DOI: 10.3390/cancers13112527 -
International Journal of Particle... 2021Treatment of sinonasal malignant tumors is challenging, and evidence to establish a standard treatment is limited. Our objective was to evaluate the efficacy and safety...
PURPOSE
Treatment of sinonasal malignant tumors is challenging, and evidence to establish a standard treatment is limited. Our objective was to evaluate the efficacy and safety of spot scanning proton therapy (SSPT) for sinonasal malignant tumors.
PATIENTS AND METHODS
We retrospectively analyzed patients with sinonasal malignant tumors (T1-4bN0-2M0) who underwent SSPT between May 2014 and September 2019. The prescription dose was typically either 60 GyRBE in 15 fractions or 60.8 GyRBE in 16 fractions for mucosal melanoma and 70.2 GyRBE in 26 fractions for other histologic subtypes. Endpoints included local control (LC), progression-free survival, overall survival (OS), and incidence of toxicity. Prognostic factors were analyzed using the Kaplan-Meier method and log-rank test.
RESULTS
Of 62 enrolled patients, the common histologic subtypes were mucosal melanoma (35%), squamous cell carcinoma (27%), adenoid cystic carcinoma (16%), and olfactory neuroblastoma (10%). Locally advanced stages were common (T3 in 42% and T4 in 53%). Treatment-naïve tumors and postsurgical recurrent tumors accounted for 73% and 27%, respectively. No patient had previous radiotherapy. The median follow-up was 17 months (range, 6-66) for all patients and 21.5 months (range, 6-66) for survivors. The 2-year LC, progression-free survival, and OS rates of all patients were 92%, 50%, and 76%, respectively. Univariate analysis revealed histology as a prognostic factor for OS, being higher in adenoid cystic carcinoma and olfactory neuroblastoma than in other tumors. Sixteen grade ≥3 late toxicities were observed in 12 patients (19%), including 11 events resulting in visual impairment; the most common was cataract. There was 1 grade 4 toxicity, and there were no grade 5 toxicities.
CONCLUSION
SSPT was well tolerated and yielded good LC for sinonasal malignant tumors. Although we consider SSPT to be a leading treatment modality, further studies are required to establish its status as a standard treatment.
PubMed: 34285946
DOI: 10.14338/IJPT-D-20-00043.1 -
Journal of Neurological Surgery. Part... Jun 2020Olfactory neuroblastoma (ONB) is a rare head and neck cancer believed to be originated from neural crest cells of the olfactory membrane located in the roof of the...
Olfactory neuroblastoma (ONB) is a rare head and neck cancer believed to be originated from neural crest cells of the olfactory membrane located in the roof of the nasal fossa. This study evaluates clinical outcomes and failure patterns in ONB patients of those patients treated with surgical resection at a high-volume tertiary cancer center. Thirty-nine ONB patients who underwent surgical resection at our institution from 1996 to 2017 were retrospectively identified. Univariate, multivariate, and survival analysis were calculated using Cox regression analysis and Kaplan-Meier log-rank. Median follow-up time was 59 months (range: 5.2-236 months). The median overall survival (OS) and disease-free survival (DFS) for the entire cohort were 15 and 7.6 years, respectively. The 5-year cumulative OS and DFS were 83 and 72%, respectively. The 5-year OS for low Hyams grade (LHG) versus high Hyams grade (HHG) was 95 versus 61% ( = 0.041). LHG was found in 66% of the early Kadish stage patients compared with 28% in the advanced Kadish stage patients ( = 0.057). On multivariate analysis, HHG and positive node status predicted for worse OS and only HHG predicted for worse DFS. Of note, five patients (all Kadish stage A) who received surgical resection alone had no observed deaths or recurrences with a median follow-up of 44 months (range: 5-235 months). In this retrospective cohort, patients with positive nodes or HHG have significantly worse clinical outcomes. Future studies should explore treatment intensification for HHG or positive nodes.
PubMed: 32500004
DOI: 10.1055/s-0039-1692479 -
Head and Neck Pathology Jun 2023Although the definitions of sinonasal neuroendocrine and neuroectodermal neoplasms did not change substantially in the 5th edition WHO Classification of Head and Neck... (Review)
Review
Proceedings of the 2023 North American Society of Head and Neck Pathology Companion Meeting, New Orleans, LA, March 12, 2023: Navigating New Developments in High Grade Sinonasal Neuroendocrine and Neuroectodermal Neoplasms.
Although the definitions of sinonasal neuroendocrine and neuroectodermal neoplasms did not change substantially in the 5th edition WHO Classification of Head and Neck Tumours, the diagnosis of olfactory neuroblastoma (ONB), small cell neuroendocrine carcinoma, and large cell neuroendocrine carcinoma remains quite challenging in practice. Ambiguities surrounding the amount of keratin expression allowable in ONB and the amount of neuroendocrine differentiation seen in sinonasal undifferentiated carcinoma (SNUC) lead to significant diagnostic discrepancies at the high grade end of this tumor spectrum. Furthermore, a group of problematic neuroepithelial tumors that show overlapping features of ONB and neuroendocrine carcinoma have never been recognized in formal classification schemes. Since publication of the 5th edition WHO, two new tumor entities have been proposed that help resolve these problems. Olfactory carcinoma is defined by high grade keratin-positive neuroectodermal cells with frequent intermixed glands and shows recurrent Wnt pathway, ARID1A, and RUNX1 alterations. IDH2-mutant sinonasal carcinoma is a molecularly-defined category that encompasses tumors with undifferentiated (SNUC), large cell neuroendocrine, and neuroepithelial phenotypes. This review will provide a practical overview of these emerging entities and their application to diagnostic challenges in the post-WHO sinonasal neuroendocrine and neuroectodermal tumor classification.
Topics: Humans; New Orleans; Carcinoma, Neuroendocrine; Paranasal Sinus Neoplasms; Maxillary Sinus Neoplasms; Esthesioneuroblastoma, Olfactory; Keratins; Nose Neoplasms; Nasal Cavity
PubMed: 37184733
DOI: 10.1007/s12105-023-01548-8 -
Head and Neck Pathology Mar 2023Nested is defined as "cellular clusters arranged in small groupings with intervening vascular or stromal networks, lacking lumens or glandular formation." Using this... (Review)
Review
BACKGROUND
Nested is defined as "cellular clusters arranged in small groupings with intervening vascular or stromal networks, lacking lumens or glandular formation." Using this definition, multiple neoplastic and non-neoplastic lesions of the head and neck come into the differential. We have broadly organized the differential diagnosis of "nested" tumors into entities with neuroendocrine differentiation, squamous differentiation, thyroid follicular cell differentiation, and other lesions.
METHODS
Review.
RESULTS
Many different entities have a nested appearance and the morphologic, immunohistochemical, clinical, and radiographic features contribute to the differential diagnosis. The different tumors covered in this review include neuroendocrine neoplasms, paraganglioma, middle ear neuroendocrine tumor (formerly known as middle ear adenoma), medullary thyroid carcinoma, poorly differentiated thyroid carcinoma, olfactory neuroblastoma, ectopic pituitary neuroendocrine tumor, hyalinizing trabecular tumor, solid subtype of papillary thyroid carcinoma, solid cell nests/C-cell hyperplasia, necrotizing sialometaplasia, and meningioma.
CONCLUSION
In this review, we discuss the morphologic and immunohistochemical features of the covered entities as a guide to differential diagnosis when nested-patterned head and neck lesions are encountered.
Topics: Humans; Thyroid Neoplasms; Carcinoma, Neuroendocrine; Neuroendocrine Tumors; Neck; Pituitary Neoplasms; Ear Neoplasms; Diagnosis, Differential
PubMed: 36928740
DOI: 10.1007/s12105-023-01534-0 -
Journal of Neurological Surgery Reports Jul 2022Esthesioneuroblastoma is a rare malignancy originating from the olfactory epithelium. Treatment consists of surgical resection with strong consideration for adjuvant...
Esthesioneuroblastoma is a rare malignancy originating from the olfactory epithelium. Treatment consists of surgical resection with strong consideration for adjuvant treatment in advanced Kadish stage and high Hyams grade. In the modern era, overall outcomes for esthesioneuroblastoma are favorable compared with many other sinonasal malignancies with 5-year overall survival estimated to be 80%. When selecting the optimal surgical approach, the surgeon must consider the approach that will allow for a negative margin resection and adequate reconstruction. In appropriately selected patients, endoscopic outcomes appear at least equivalent to open approaches and unilateral endoscopic approach may be used in select olfactory preservation cases.
PubMed: 35832684
DOI: 10.1055/s-0042-1753519 -
Current Oncology Reports Jul 2020Sinonasal cancers are a heterogenous group of rare cancers for which histopathological diagnosis can be very challenging and treatment options are limited for advanced... (Review)
Review
PURPOSE OF REVIEW
Sinonasal cancers are a heterogenous group of rare cancers for which histopathological diagnosis can be very challenging and treatment options are limited for advanced disease in particular. Here, we review the candidacy of novel diagnostic and prognostic biomarkers, and therapeutic targets for sinonasal cancers.
RECENT FINDINGS
Molecular multidimensional analyses of sinonasal cancers have been lagging behind other major cancers, but there are numerous publications describing the discovery of novel candidate biomarkers, e.g. the methylation classifier, originally developed for brain cancers, and gene expression panels for the prediction of response to induction chemotherapy in sinonasal undifferentiated carcinoma. The most promising biomarkers are summarized and discussed further with regard to their clinical applicability and future potential. Many of the described novel biomarkers for sinonasal cancers will eventually overcome the pitfalls associated with the frequently non-specific immunohistological tests. With comprehensive, multidimensional molecular testing of these tumours in collaborative consortia projects, our better understanding of the molecular mechanisms of sinonasal cancers and their carcinogenesis will determine the most useful diagnostic and prognostic biomarkers, allow stringent multi-institutional validation and guide trials on targeted therapies.
Topics: Biomarkers, Tumor; Humans; Nose Neoplasms; Paranasal Sinus Neoplasms
PubMed: 32725435
DOI: 10.1007/s11912-020-00947-2 -
Heliyon Nov 2023Olfactory dysfunction is associated with conditions such as respiratory tract infections, trauma, sinonasal diseases, and neurodegenerative diseases. During the...
BACKGROUND
Olfactory dysfunction is associated with conditions such as respiratory tract infections, trauma, sinonasal diseases, and neurodegenerative diseases. During the coronavirus disease 2019 pandemic, there was an increase in patients complaining of olfactory dysfunctions. Many studies have reported that olfactory dysfunction is associated with coronavirus disease 2019 and that the prognosis is usually favorable.
CASE PRESENTATION
Recently, we experienced a patient with olfactory dysfunction, which was aggravated after a coronavirus disease 2019 diagnosis. The patient had no other medical history, and their nasal endoscopic examination demonstrated no abnormal lesions. Through a psychophysical olfactory function test, the patient was diagnosed with anosmia. A paranasal sinus computed tomography demonstrated sclerotic bony changes in the cribriform plate area. A paranasal sinus magnetic resonance image study found an approximately 3.5 cm-sized olfactory neuroblastoma in the anterior cranial fossa.
CONCLUSIONS
We suggest clinicians remember the possibility of underlying intracranial lesions in patients with olfactory dysfunction even during the coronavirus disease 2019 pandemic and understand the guidelines of magnetic resonance imaging when evaluating olfactory dysfunction patients. Furthermore, we recommend that clinicians pay attention to the history of olfactory dysfunction before the symptoms progress and making a coronavirus disease 2019 diagnosis.
PubMed: 38053881
DOI: 10.1016/j.heliyon.2023.e22311 -
Modern Pathology : An Official Journal... May 2023Olfactory neuroblastoma (ONB, esthesioneuroblastoma) is a sinonasal cancer with an underdeveloped diagnostic toolkit, and is the subject of many incidents of tumor...
Olfactory neuroblastoma (ONB, esthesioneuroblastoma) is a sinonasal cancer with an underdeveloped diagnostic toolkit, and is the subject of many incidents of tumor misclassification throughout the literature. Despite its name, connections between the cancer and normal cells of the olfactory epithelium have not been systematically explored and markers of olfactory epithelial cell types are not deployed in clinical practice. Here, we utilize an integrated human-mouse single-cell atlas of the nasal mucosa, including the olfactory epithelium, to identify transcriptomic programs that link ONB to a specific population of stem/progenitor cells known as olfactory epithelial globose basal cells (GBCs). Expression of a GBC transcription factor NEUROD1 distinguishes both low- and high-grade ONB from sinonasal undifferentiated carcinoma, a potential histologic mimic with a distinctly unfavorable prognosis. Furthermore, we identify a reproducible subpopulation of highly proliferative ONB cells expressing the GBC stemness marker EZH2, suggesting that EZH2 inhibition may play a role in the targeted treatment of ONB. Finally, we study the cellular states comprising ONB parenchyma using single-cell transcriptomics and identify evidence of a conserved GBC transcriptional regulatory circuit that governs divergent neuronal-versus-sustentacular differentiation. These results link ONB to a specific cell type for the first time and identify conserved developmental pathways within ONB that inform diagnostic, prognostic, and mechanistic investigation.
Topics: Humans; Mice; Animals; Esthesioneuroblastoma, Olfactory; Paranasal Sinus Neoplasms; Neurons; Nose Neoplasms; Nasal Cavity
PubMed: 36841178
DOI: 10.1016/j.modpat.2023.100122 -
World Journal of Otorhinolaryngology -... Mar 2022Historically sinonasal malignancies were always addressed via open craniofacial surgery for an oncologic resection. Increasingly esthesioneuroblastomas are excised using... (Review)
Review
BACKGROUND
Historically sinonasal malignancies were always addressed via open craniofacial surgery for an oncologic resection. Increasingly esthesioneuroblastomas are excised using an exclusively endoscopic approach, however, the rarity of this disease limits the availability of long-term and large scale outcomes data.
OBJECTIVE
The primary objective is to evaluate the treatment modalities used and the overall survival of patients with esthesioneuroblastoma managed with exclusively endoscopic surgery.
METHODS
In accordance with PRISMA guidelines, PubMed was queried to identify studies describing outcomes associated with endoscopic management of esthesioneuroblastomas.
RESULTS
Forty-four out of 2462 articles met inclusion criteria, totaling 399 patients with esthesioneuroblastoma treated with an exclusively endoscopic approach. Seventy-two patients (18.0%) received adjuvant chemotherapy and 331 patients (83.0%) received postoperative radiation therapy. The average age was 50.6 years old (range 6-83). Of the 399 patients, 57 (16.6%) were Kadish stage A, 121 (35.2%) were Kadish stage B, 145 (42.2%) were Kadish stage C, and 21 (6.1%) were Kadish stage D. Pooled analysis demonstrated that 66.0% of patients had Hyams histologic Grade Ⅰ or Ⅱ, while 34.0% of patients had Grade Ⅲ or Ⅳ disease. Negative surgical margins were achieved in 86.9% of patients, and recurrence was identified in 10.3% of patients. Of those with 5-year follow-up, reported overall survival was 91.1%.
CONCLUSION
Exclusively endoscopic surgery for esthesioneuroblastoma is performed for a wide range of disease stages and grades, and the majority of these patients are also treated with adjuvant chemotherapy or radiation therapy. Reported overall recurrence rate is 10.3% and 5-year survival is 91.1%.
PubMed: 35619935
DOI: 10.1002/wjo2.10