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Indian Journal of Otolaryngology and... Oct 2022Olfactory neuroblastoma (ONB) is a rare malignant neuroectodermal tumor of the nasal cavity. Olfactory neuroblastoma centered in the posterior right orbit with prominent...
Olfactory neuroblastoma (ONB) is a rare malignant neuroectodermal tumor of the nasal cavity. Olfactory neuroblastoma centered in the posterior right orbit with prominent orbital protrusion is even rare. Grading ONB is extremely important as individualized treatment plans must be formulated according to tumor grade. We report the case of a 67-year-old female who presented with the chief complaints of persistent nasal congestion with intermittent epistaxis and unilateral proptosis over the past five years. Radiological imaging was suggestive of a large heterogeneous mass in the right superior nasal cavity with extensions into the right medial orbit, nasopharynx, the right maxillary sinus, the anterior cranial fossa, right ethmoidal, frontal and bilateral sphenoidal sinuses, as well as into the right frontal lobe. Assessment of the radiologic features revealed the diagnostic possibility of olfactory neuroblastoma. A nasopharyngeal biopsy confirmed an olfactory neuroblastoma. Frontal osteoplastic craniotomy and excision of the intracranial part of the tumor from above and transnasal endoscopic removal of the mass in the nasal cavities, paranasal sinuses and right medial orbit from below was done. Evaluation of histopathological characteristics and immunohistochemical findings revealed a diagnosis of WHO grade IV olfactory neuroblastoma. Because of poor economic condition, the patient did not take adjuvant radiotherapy and chemoradiation and post-operative examination. We report a huge ONB centered in the posterior right orbit with prominent orbital protrusion. Magnetic resonance image and computed tomography are helpful for evaluating the appearance and the extent of ONB, as well as grading this tumor, which may aid therapeutic decisions and improve survival.
PubMed: 36452830
DOI: 10.1007/s12070-020-02359-x -
Advances in Anatomic Pathology Mar 2023Genetic profiling has caused an explosion in the subclassification of sinonasal malignancies. Distinguishing several of these tumor types by histomorphology alone has... (Review)
Review
INTRODUCTION
Genetic profiling has caused an explosion in the subclassification of sinonasal malignancies. Distinguishing several of these tumor types by histomorphology alone has been quite challenging, and although pathologic classification aims to be as specific as possible, it remains to be seen if this recent move toward tumor speciation bears clinical relevance, most particularly focused on subtyping for the sake of prognostication and treatment. One such recently described cohort, predominantly lumped under the moniker of sinonasal undifferentiated carcinoma (SNUC) is IDH2 -mutated sinonasal carcinoma, a high-grade carcinoma associated with mutations in the isocitrate dehydrogenase-2 ( IDH2 ) gene. A hotspot mutation in the R172 codon has been described in 50% to 80% of the tumors classified as SNUC, large cell neuroendocrine carcinomas, and rarely in cases classified as olfactory neuroblastoma. The use of immunohistochemical and molecular approaches is required to correctly identify this subset of sinonasal tumors, with further study necessary to elucidate their unique pathophysiology, ultimately determining whether a revision is required toward the current therapeutic approach.
AIMS
Here, we provide an overview of the IDH2- mutated sinonasal tumors, discuss histopathologic and clinical features, and focus on molecular diagnostics and novel immunohistochemical markers.
RESULTS
A review of the literature reveals 82 reported cases with IDH2 -mutated sinonasal tumors (IST), confirmed either by molecular studies or diagnostic immunohistochemical markers. The mean patient age is 60 years (female/male: 1/1.4), the median tumor size is 5 cm (range: 2.5 to 7.0 cm), and the most common location is the nasal cavity (81%). IST displays tumor necrosis and increased mitotes. Histopathologically, IST shows SNUC-like, large cell neuroendocrine carcinomas-like, or poorly differentiated carcinoma-like features (77%, 12%, and 9%, respectively). The molecular hotspot alterations in mitochondrial IDH2 are: R172S (61%), R172T (19%), R172G (7%), and R172M (3%). Sixty-five percent of tumors are surgically resectable, and all patients received chemotherapy, radiation therapy, or both. Rates of locoregional recurrence and distant metastasis are 60% and 40%, respectively. One-, 3- and 5-year survival rates are 83%, 50%, and 43%, respectively. In all but 1 study, IST is associated with better outcomes than IDH2 wild-type tumors and SMARCB1 -deficient sinonasal tumors.
Topics: Humans; Male; Female; Middle Aged; Maxillary Sinus Neoplasms; Carcinoma, Neuroendocrine; Neoplasms, Glandular and Epithelial; Mutation; Biomarkers, Tumor
PubMed: 36537260
DOI: 10.1097/PAP.0000000000000391 -
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 -
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 -
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 -
Lin Chuang Er Bi Yan Hou Tou Jing Wai... Mar 2021To explore the therapeutic effect and prognostic risk factors of olfactory neuroblastoma. Retrospective analysis of clinical data of 31 patients with olfactory...
To explore the therapeutic effect and prognostic risk factors of olfactory neuroblastoma. Retrospective analysis of clinical data of 31 patients with olfactory neuroblastoma. The Kaplan-Meier method was used for survival analysis to calculate the overall survival rate and progress-free survival rate. All 31 patients underwent surgical treatment and 7 patients died, of which 4 patients died of simple intracranial invasion and 3 patients died of concurrent distant metastasis (lung and spinal cord). The average death time was 40.7 (20-57) months. Statistical analysis showed that craniocerebral invasion (=0.035), age ≥60 years (=0.042), and Ki-67≥20%(=0.018) were closely related to the poor prognosis. It is speculated that the increase of T staging and modified Kadish staging are also predictors of poor prognosis. The 1-year and 5-year overall survival rates were 100.0% and 72.5%, and the 1-year and 5-year progress-free survival rates were 87.8% and 33.6% after first surgery. Conclusion:Surgery combined with radiotherapy and chemotherapy are the main treatments for olfactory neuroblastoma, but postoperative recurrence and metastasis are common. About 22.6% of the patients died during the follow-up. Advanced age, intracranial invasion and Ki-67≥20% are closely related to poor prognosis. The tumor was completely removed by the initial surgery and restricted in nasal cavity and sinuses are the key factors for a good prognosis.
Topics: Esthesioneuroblastoma, Olfactory; Humans; Middle Aged; Nasal Cavity; Neoplasm Recurrence, Local; Neoplasm Staging; Nose Neoplasms; Prognosis; Retrospective Studies; Survival Rate
PubMed: 33794606
DOI: 10.13201/j.issn.2096-7993.2021.03.007 -
Frontiers in Surgery 2021Our purpose was to estimate the safety and effectiveness of the endoscopic endonasal approach (EEA) in olfactory neuroblastoma (ONB) and determine whether preservation...
OBJECTIVE
Our purpose was to estimate the safety and effectiveness of the endoscopic endonasal approach (EEA) in olfactory neuroblastoma (ONB) and determine whether preservation of the dura and olfactory bulb could be considered in selected patients.
METHODS
We retrospectively reviewed patients diagnosed with ONBs between July 2010 and June 2021 at our institution, and collected data on demographic, disease stage, surgical approach, overall survival (OS), disease-free survival (DFS), and postoperative complications.
RESULTS
The study sample included 42 patients (8 treated for recurrence and 34 initial cases), 28 of which were men and 14 were women with a median age of 47.19 years. The mean duration from the beginning of treatment and follow-up time was 8.91 and 51 months, respectively. Among the 42 patients, 32 had unilateral lesions, and the rest had bilateral lesions. Patient symptoms were predominantly nasal, and four patients presented without any symptoms. The modified Kadish staging was A in three patients, B in 14 patients, C in 17 patients, and D in 8 patients. According to the preoperative examinations, five patients had cervical lymph node metastasis, and no patients had distant metastases. EEA was used in 38 patients, cranioendoscopic approach in 3, and open craniofacial approach in 1. The 5-year OS and DFS rates were 89.1 and 79.2%, respectively. The 2-year OS and DFS rates were both 89.1%. The overall surgical complication incidence was 9.52% (one cerebrospinal fluid rhinorrhea, one cervical hematoma, and two epileptic seizures).
CONCLUSION
The present results support the importance of earlier treatment for advanced ONB and the fact that it is safe and efficacious to treat ONBs EEA. The preservation of the dura can be considered for select patients-specifically those without skull base involvement and who underwent postoperative comprehensive therapy.
PubMed: 35178425
DOI: 10.3389/fsurg.2021.799405 -
Head and Neck Pathology Dec 2021Somatostatin receptor 2 (SSTR2) expression has previously been documented in olfactory neuroblastoma (ONB). Here, we fully characterize SSTR2 expression in ONB and...
Somatostatin receptor 2 (SSTR2) expression has previously been documented in olfactory neuroblastoma (ONB). Here, we fully characterize SSTR2 expression in ONB and correlate staining results with clinicopathologic parameters including Hyams grade. We also assess SSTR2 immunohistochemistry expression in various histologic mimics of ONB to assess its diagnostic functionality. 78 ONBs (51 primary biopsies/excisions and 27 recurrences/metastases) from 58 patients were stained for SSTR2. H-scores based on intensity (0-3 +) and percentage of tumor cells staining were assigned to all cases. 51 histologic mimics were stained and scored in an identical fashion. 77/78 (99%) ONB cases demonstrated SSTR2 staining (mean H-score: 189, range: 0-290). There were no significant differences in staining between primary tumors and recurrences/metastases (mean H-score: 185 vs 198). Primary low-grade ONB had somewhat stronger staining than high-grade tumors (mean H-score: 200 vs 174). SSTR2 expression had no prognostic value when considering disease-free or disease-specific survival. SSTR2 staining is significantly higher in ONB than its histologic mimics (mean H-score: 189 vs 12.9, p < 0.001) suggesting a potential use of the marker in diagnosis of ONB. In conclusion, SSTR2 is consistently expressed in ONB suggesting a role for somatostatin-analog based imaging and therapy in this disease. More generally, SSTR2 may be another marker of neuroendocrine differentiation in ONB.
Topics: Biomarkers, Tumor; Esthesioneuroblastoma, Olfactory; Humans; Immunohistochemistry; Nose Neoplasms; Receptors, Somatostatin
PubMed: 33929681
DOI: 10.1007/s12105-021-01329-1 -
Journal of Neurological Surgery Reports Jul 2023Esthesioneuroblastoma is a rare sinonasal malignancy that arises from the olfactory epithelium. The overall incidence of lymph node metastases is 25%. However, neck...
Esthesioneuroblastoma is a rare sinonasal malignancy that arises from the olfactory epithelium. The overall incidence of lymph node metastases is 25%. However, neck disease can present in a delayed fashion. As such, management of the clinically negative neck is controversial, with some advocating for elective neck treatment and others recommending observation with salvage treatment if necessary. At this time, no prospective head-to-head comparisons of elective versus salvage treatment have been performed.
PubMed: 37564630
DOI: 10.1055/s-0043-1770965 -
Diagnostics (Basel, Switzerland) Mar 2022The purpose of the current study was to assess the prevalence of cyst formation at the brain-tumor interface in olfactory neuroblastoma. We used the UCLA patient-based...
The purpose of the current study was to assess the prevalence of cyst formation at the brain-tumor interface in olfactory neuroblastoma. We used the UCLA patient-based Pathology and Radiology Head and Neck Database (UPP&R HAND) to identify the largest patient cohort reported to date with imaging and pathology data. Eighteen of thirty-one patients (58.1%) had evidence of intracranial extension on MRI, while four (22.0%) demonstrated cyst formation at the brain-tumor interface. The extent of intracranial extension was by far the strongest predictor for intracranial cyst formation, regardless of Hyams tumor grade, using a binary logistics regression model ( = 0.002) and ROC curve analysis (AUC 94.6%). Cyst formation at the brain-tumor interface was an uncommon imaging finding, and tends to occur with a larger component of intracranial tumor extension.
PubMed: 35328167
DOI: 10.3390/diagnostics12030614