-
Frontiers in Oncology 2023Olfactory neuroblastoma (ONB) is a rare neoplasm originating from the olfactory neuroepithelium representing 3-6% of tumors of the sinonasal tract. ONB require... (Review)
Review
Olfactory neuroblastoma (ONB) is a rare neoplasm originating from the olfactory neuroepithelium representing 3-6% of tumors of the sinonasal tract. ONB require multi-disciplinary care. Historically, the gold standard surgical procedure for ONB has been open craniofacial resection. In the last years, endoscopic endonasal approaches have been largely introduced with lower complication rates, shorter hospital stay, and similar clinical outcome. Radiotherapy plays an important role in the management of ONB, however there are not generally accepted recommendations for its application. Although there is agreement that multimodal therapy is needed, the optimal use of chemotherapy is still unknown. The rarity of the disease, makes difficult to draw definitive conclusions about the role of systemic treatment in induction and concomitant setting.
PubMed: 37909011
DOI: 10.3389/fonc.2023.1242453 -
European Journal of Cancer (Oxford,... Feb 2022Olfactory neuroblastoma (ONB) is a rare cancer of the sinonasal region. We provide a comprehensive analysis of this malignancy with molecular and clinical trial data on...
INTRODUCTION
Olfactory neuroblastoma (ONB) is a rare cancer of the sinonasal region. We provide a comprehensive analysis of this malignancy with molecular and clinical trial data on a subset of our cohort to report on the potential efficacy of somatostatin receptor 2 (SSTR2)-targeting imaging and therapy.
METHODS
We conducted a retrospective analysis of 404 primary, locally recurrent, and metastatic olfactory neuroblastoma (ONB) patients from 12 institutions in the United States of America, United Kingdom and Europe. Clinicopathological characteristics and treatment approach were evaluated. SSTR2 expression, SSTR2-targeted imaging and the efficacy of peptide receptor radionuclide therapy [PRRT](Lu-DOTATATE) were reported in a subset of our cohort (LUTHREE trial; NCT03454763).
RESULTS
Dural infiltration at presentation was a significant predictor of overall survival (OS) and disease-free survival (DFS) in primary cases (n = 278). Kadish-Morita staging and Dulguerov T-stage both had limitations regarding their prognostic value. Multivariable survival analysis demonstrated improved outcomes with lower stage and receipt of adjuvant radiotherapy. Prophylactic neck irradiation significantly reduces the rate of nodal recurrence. 82.4% of the cohort were positive for SSTR2; treatment of three metastatic cases with SSTR2-targeted peptide-radionuclide receptor therapy (PRRT) in the LUTHREE trial was well-tolerated and resulted in stable disease (SD).
CONCLUSIONS
This study presents pertinent clinical data from the largest dataset, to date, on ONB. We identify key prognostic markers and integrate these into an updated staging system, highlight the importance of adjuvant radiotherapy across all disease stages, the utility of prophylactic neck irradiation and the potential efficacy of targeting SSTR2 to manage disease.
Topics: Esthesioneuroblastoma, Olfactory; Humans; Nasal Cavity; Neuroblastoma; Nose Neoplasms; Positron-Emission Tomography; Radioisotopes; Radionuclide Imaging; Receptors, Somatostatin; Retrospective Studies
PubMed: 34980502
DOI: 10.1016/j.ejca.2021.09.046 -
Laryngoscope Investigative... Aug 2021Olfactory neuroblastoma (ONB) or esthesioneuroblastoma (ENB) is a rare malignancy of the nasal cavity believed to arise from the olfactory epithelium. The goal of this... (Review)
Review
BACKGROUND
Olfactory neuroblastoma (ONB) or esthesioneuroblastoma (ENB) is a rare malignancy of the nasal cavity believed to arise from the olfactory epithelium. The goal of this study was to systematically review the genomics, epigenetics, and cytogenetics of ONB and to understand the potential clinical implications of these studies.
METHODS
A systematic literature review was performed for articles published before May 2020 using Cochrane, Embase, Pubmed, and Scopus databases. Inclusion criteria included genomics, cytogenetics, and epigenetics studies on ONB. Exclusion criteria included studies not in English or systematic reviews. Articles and abstracts were reviewed by two independent reviewers to reduce bias during article selection and synthesis of results. Of the 36 studies included in this review, 24 were research articles and 12 were abstracts.
RESULTS
Although recurrent mutations among ONB tumors are uncommon, alterations in , , , , , , , , , , , , , , , and genes have been reported in several recent studies. In addition, cytogenetic studies revealed that the landscape of chromosomal aberrations varies widely amongst ONB tumors.
CONCLUSIONS
The rare character of ONB has limited the sample size available for cytogenetic, genomic, and epigenetic studies and contributes to the limitations of this systematic review. Comprehensive genomic and epigenomic studies with larger cohorts are warranted to validate the initial reports summarized in this review and to identify potential therapeutic targets for ONB.
PubMed: 34401496
DOI: 10.1002/lio2.597 -
Head and Neck Pathology Sep 2009Few neoplasms are unique to the sinonasal tract, but sinonasal undifferentiated carcinoma and olfactory neuroblastoma are malignant tumors which require unique... (Review)
Review
Few neoplasms are unique to the sinonasal tract, but sinonasal undifferentiated carcinoma and olfactory neuroblastoma are malignant tumors which require unique management. Due to the rarity of these tumors, practicing pathologists are not always aware of their distinctive clinical, radiographic, histologic, immunohistochemical, and molecular features. These cases are frequently submitted for consultation, further suggesting the diagnostic difficulties inherent to these tumors. Specifically, olfactory neuroblastoma is a neoplasm that can histologically mimic many tumors within the sinonasal tract, making recognition of this tumor important, as the management frequently requires a bicranial-facial surgical approach, a trephination procedure which can be quite technically difficult and challenging to achieve a good result. The management is therefore quite unique in comparison to other sinonasal tract malignancies, setting it apart diagnostically and managerially from other lesions.
Topics: Diagnosis, Differential; Esthesioneuroblastoma, Olfactory; Humans; Nasal Cavity; Nose Neoplasms
PubMed: 20596981
DOI: 10.1007/s12105-009-0125-2 -
Cancer Cell Jun 2024The olfactory epithelium undergoes neuronal regeneration from basal stem cells and is susceptible to olfactory neuroblastoma (ONB), a rare tumor of unclear origins....
The olfactory epithelium undergoes neuronal regeneration from basal stem cells and is susceptible to olfactory neuroblastoma (ONB), a rare tumor of unclear origins. Employing alterations in Rb1/Trp53/Myc (RPM), we establish a genetically engineered mouse model of high-grade metastatic ONB exhibiting a NEUROD1 immature neuronal phenotype. We demonstrate that globose basal cells (GBCs) are a permissive cell of origin for ONB and that ONBs exhibit cell fate heterogeneity that mimics normal GBC developmental trajectories. ASCL1 loss in RPM ONB leads to emergence of non-neuronal histopathologies, including a POU2F3 microvillar-like state. Similar to small-cell lung cancer (SCLC), mouse and human ONBs exhibit mutually exclusive NEUROD1 and POU2F3-like states, an immune-cold tumor microenvironment, intratumoral cell fate heterogeneity comprising neuronal and non-neuronal lineages, and cell fate plasticity-evidenced by barcode-based lineage tracing and single-cell transcriptomics. Collectively, our findings highlight conserved similarities between ONB and neuroendocrine tumors with significant implications for ONB classification and treatment.
Topics: Animals; Mice; Small Cell Lung Carcinoma; Humans; Esthesioneuroblastoma, Olfactory; Cell Lineage; Lung Neoplasms; Basic Helix-Loop-Helix Transcription Factors; Tumor Microenvironment; Nose Neoplasms; Olfactory Mucosa; Disease Models, Animal; Tumor Suppressor Protein p53
PubMed: 38788720
DOI: 10.1016/j.ccell.2024.05.003 -
South Asian Journal of Cancer Oct 2022Olfactory neuroblastoma is a rare epithelial malignancy arising from the odorant receptors in the nasal mucosa or along the cribriform plate of the ethmoid bone....
Olfactory neuroblastoma is a rare epithelial malignancy arising from the odorant receptors in the nasal mucosa or along the cribriform plate of the ethmoid bone. Clinical presentation includes nasal stuffiness, local pain, epistaxis, anosmia, visual impairment, proptosis, headache, and seizures. Radiologic imaging with CT or MRI, an ophthalmic evaluation, and histopathologic confirmation with immunohistochemistry are parts of the initial diagnostic workup. Although surgery, chemotherapy, and radiation have an equally important role in the management, earlier stages may preferably be treated with surgery or radiotherapy and the later stages with a multimodality approach. We conducted a retrospective review of 13 patients diagnosed with olfactory neuroblastoma, registered at Mehdi Nawaz Jung Regional Cancer Center over a decade (2010-2019). We analyzed the age and sex distribution, performance status at presentation, clinical symptomatology, and the Kadish stage. In addition, the therapeutic aspects of patients were studied. The most common presentation noted was nasal stuffiness, followed by epistaxis and proptosis. The majority of patients had good performance status at presentation. Ten patients presented with a Kadish stage C, while the remaining patients presented with Kadish stage B. Cervical nodal metastasis was seen in three patients, four patients received multimodality treatment with neoadjuvant chemoradiotherapy followed by surgery, two patients received neoadjuvant chemotherapy followed by radiation, two patients received only surgery, and one patient received surgery followed by adjuvant radiation. Conformal radiation techniques were used to deliver doses as high as 50 to 66 Gy in 2 Gy per fraction. Two patients presented with distant metastasis during follow-up, one with bone metastasis, and the other with retroperitoneal nodal metastasis; they received palliative chemotherapy and conformal radiation to the primary site. This study concludes that neoadjuvant chemotherapy followed by radiation gives the best outcomes. It has been observed that in multi-modality treatment, radiotherapy played a significant role in improving overall survival and better outcomes. Multidisciplinary discussions provide a better sequencing of management.
PubMed: 36756100
DOI: 10.1055/s-0041-1739181 -
Indian Journal of Otolaryngology and... Oct 2022Esthesioneuroblastoma (ENB) is a rare, aggressive and malignant sinonasal tumour. This tumour makes for a very interesting study because ever since its mention in...
Esthesioneuroblastoma (ENB) is a rare, aggressive and malignant sinonasal tumour. This tumour makes for a very interesting study because ever since its mention in medical literature, although quite a lot of research has been put into it, a lot is yet to be known about it. To summarize the available literature & document an article on the contemporary practises in the management of ENB. A comprehensive literature review was done using Google Scholar and PubMed database with the key words: "esthesioneuroblastoma", "olfactory neuroblastoma", "Kadish" and "Hyams". Articles published in English were used. Articles published till April 2021 were reviewed. ENB has a diverse histological appearance. This tumour has a bimodal age distribution without any gender predilection. Prompt identification and treatment is required for a favourable outcome and requires close collaboration of radiology, pathology, and rhinology. Staging, management and prognosis are determined by regional involvement in non-metastatic cases due to its proximity to neurological structures and locally destructive nature. Immunohistochemistry is a must for accurate diagnosis. Uni-modality of treatment has high chances of local recurrence. Multi-modality provides good results even in advanced stage. A combination of surgery and radiotherapy seems to be the optimum approach to treatment. The exact role of chemotherapy in treatment protocols is still unclear. Cervical lymph node metastases are commonly studied, however its management in patients who present without apparent nodal involvement is not yet clear. An extended follow-up period is recommended in all patients of ENB patients.
PubMed: 36452592
DOI: 10.1007/s12070-021-02726-2 -
Frontiers in Oncology 2023Olfactory neuroblastoma (ONB) is a rare malignant neoplasm of the olfactory mucosa. The paucity of genomic data has prevented the development of individualized ONB...
BACKGROUND
Olfactory neuroblastoma (ONB) is a rare malignant neoplasm of the olfactory mucosa. The paucity of genomic data has prevented the development of individualized ONB treatments. Here, we investigated the genomic and immune landscape of ONB in Chinese patients.
METHODS
Whole exome sequencing (WES) and multiplex immunofluorescence (MIF) analysis were performed on tissue samples from 19 Chinese ONB patients. Patients were divided into low- and high-grade groups.
RESULTS
Overall, 929 nonsynonymous alterations were identified in 18 (94.74%) ONB cases. The most prevalent altered cancer-related genes were (16%) and (16%). The most mutated oncogenic pathways were the WNT and RAS pathways. The median tumor mutation burden (TMB) was 0.45, ranging from 0 to 3.25. Only one case expressed PD-L1 (> 1%) in the tumor region. The percentage of CD8+ tumor-infiltrating lymphocytes (TILs) in the tumor region ranged from 0.03% to 84.9%, with a median of 1.08%. No significant differences were observed between the low- and high-grade groups for clinicopathological features, mutant genes, mutant pathways, TMB, tumor neoantigen burden (TNB), mutant-allele tumor heterogeneity (MATH), PD-L1 expression levels, or CD8+ TIL percentage. However, the low-grade group showed significantly more CD68+ macrophages in both the tumor and total region than the high-grade group. Notably, CD68+CD163- macrophages accounted for an average of 80.5% of CD68+ macrophages.
CONCLUSION
This study presents data on the genomic and immune landscape of ONB cases in China. and were the most prevalent altered cancer-related genes. The results of TMB, PD-L1, and CD8+ Tils suggest that ONB may be insensitive to immunotherapy. M1 macrophages may be positively associated with the prognosis of ONB.
IMPLICATIONS FOR PRACTICE
In this study, the most prevalent altered cancer-related genes were (16%) and (16%). The most mutated oncogenic pathways were the WNT and RAS pathways. The median tumor mutation burden (TMB) was 0.45, ranging from 0 to 3.25. Only one (1/15) case expressed PD-L1 (> 1%) in the tumor region. However, the low-grade group showed significantly more CD68+ macrophages in both the tumor and total region than the high-grade group. The higher level of CD68-related macrophages indicates that M1 macrophages potentially play an important role in ONB development that is possibly associated with prognosis.
PubMed: 38023213
DOI: 10.3389/fonc.2023.1226494