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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 -
International Journal of Molecular... Jan 2023Sinonasal neoplasms are uncommon diseases, characterized by heterogeneous biological behavior, which frequently results in challenges in differential diagnosis and... (Review)
Review
Sinonasal neoplasms are uncommon diseases, characterized by heterogeneous biological behavior, which frequently results in challenges in differential diagnosis and treatment choice. The aim of this review was to examine the pathogenesis and molecular mechanisms underlying the regulation of tumor initiation and growth, in order to better define diagnostic and therapeutic strategies as well as the prognostic impact of these rare neoplasms. A systematic review according to Preferred Reporting Items for Systematic Review and Meta-Analysis criteria was conducted between September and November 2022. The authors considered the three main histological patterns of sinonasal tumors, namely Squamous Cell Carcinoma, Intestinal-Type Adenocarcinoma, and Olfactory Neuroblastoma. In total, 246 articles were eventually included in the analysis. The genetic and epigenetic changes underlying the oncogenic process were discussed, through a qualitative synthesis of the included studies. The identification of a comprehensive model of carcinogenesis for each sinonasal cancer subtype is needed, in order to pave the way toward tailored treatment approaches and improve survival for this rare and challenging group of cancers.
Topics: Humans; Adenocarcinoma; Carcinoma, Squamous Cell; Nose Neoplasms; Paranasal Sinus Neoplasms; Paranasal Sinuses
PubMed: 36768990
DOI: 10.3390/ijms24032670 -
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 -
Cureus Jan 2023Olfactory neuroblastoma is a rare disease with no randomized clinical trials to guide treatment decision making. Surgery, radiation, and chemotherapy are all used for...
Olfactory neuroblastoma is a rare disease with no randomized clinical trials to guide treatment decision making. Surgery, radiation, and chemotherapy are all used for treatment, and prognosis is mostly determined by the histologic grade and clinical stage. While a neuroendocrine type of neoplasm is similar to small cell carcinoma, metastatic disease in olfactory neuroblastoma is rare. We present a case at our institution of an uncommon clinical course of relapsed olfactory neuroblastoma complicated by severe thrombocytopenia.
PubMed: 36741647
DOI: 10.7759/cureus.33297 -
Frontiers in Oncology 2022Olfactory neuroblastoma is a rare neoplasm that usually presents in the upper nasal cavity. Although its prognosis is highly unfavorable, effective treatment options are...
Olfactory neuroblastoma is a rare neoplasm that usually presents in the upper nasal cavity. Although its prognosis is highly unfavorable, effective treatment options are still lacking. Moreover, there is no standard treatment for patients with olfactory neuroblastoma that progressed to leptomeningeal carcinomatosis. Here we report an uncommon case of a 59-year-old woman who was diagnosed with olfactory neuroblastoma and leptomeningeal carcinomatosis. For a direct delivery of the drugs to the tumor, and to avoid the impact of lumbar puncture on the patient's quality of life, the intravenous chemotherapy plus intrathecal administration of MTX an Ommaya reservoir was chosen. The results were striking, with the disappearance of tumor cells in the cerebrospinal fluid and the relief of the patient's symptoms with PR. Our result indicates that chemotherapy an Ommaya reservoir offers a new potential therapy for patients with meningeal metastases.
PubMed: 36713576
DOI: 10.3389/fonc.2022.1060575 -
Frontiers in Neurology 2022Paraneoplastic peripheral neuropathy (PPN) caused by olfactory neuroblastoma (ONB) has not yet been reported.
BACKGROUND
Paraneoplastic peripheral neuropathy (PPN) caused by olfactory neuroblastoma (ONB) has not yet been reported.
CASE REPORT
We present a rare case of an adult who hospitalized repeatedly over the past 9 months for persistent pain and numbness in the limbs. This patient was initially diagnosed with chronic inflammatory demyelinating polyneuropathy (CIDP) and treated accordingly, but neurological symptoms did not improve significantly. After this admission, FDG-PET/CT showed focal hypermetabolism of a soft-tissue mass in the nasal cavity, and further lesion biopsy suggested ONB. Combined with positive serum anti-Hu antibody, the diagnosis of PPN associated with ONB was eventually made. Furthermore, the patient's neurological symptoms were relieved after removal of the primary tumor, confirming the accuracy of the diagnosis.
CONCLUSION
Our case not only expanded the clinical characteristics of ONB but also highlighted the importance of early and comprehensive tumor screening for the diagnosis of PPN.
PubMed: 36698887
DOI: 10.3389/fneur.2022.1002076 -
Brain Sciences Dec 2022Posterior reversible encephalopathy syndrome (PRES) is a rare but severe neurological syndrome that may stem from the use of some medications. Although its mechanism is...
Posterior reversible encephalopathy syndrome (PRES) is a rare but severe neurological syndrome that may stem from the use of some medications. Although its mechanism is not well-known, hypertension and endothelial dysfunction have been mentioned in previous literature as being related. Lenvatinib serves as a neoplastic agent that inhibits the tyrosine kinase of vascular endothelial growth factor receptors (VEGFR). VEGFR inhibitors result in endothelial dysfunction and consequent hypertension by nitric oxide pathway suppression and endothelin (ET)-1 stimulation. We hypothesized that VEGFR inhibitors would cause PRES. Herein, we report the case of a 40-year-old man with olfactory neuroblastoma who developed PRES while undergoing treatment with lenvatinib, 7 months after initiation. The symptoms included loss of consciousness and seizures. Fortunately, the symptoms and presence of PRES in imaging resolved, 7 days and 1 month, respectively, after cessation of lenvatinib.
PubMed: 36672016
DOI: 10.3390/brainsci13010033 -
Ectopic Olfactory Neuroblastoma: Systematic Review of a Rare Clinical Entity among Sinonasal Tumors.Journal of Neurological Surgery. Part... Apr 2024Ectopic olfactory neuroblastoma is an uncommon manifestation of an already rare neoplasm. We aimed to systematically review the literature for cases of ectopic...
Ectopic olfactory neuroblastoma is an uncommon manifestation of an already rare neoplasm. We aimed to systematically review the literature for cases of ectopic olfactory neuroblastoma to better characterize this rare disease entity and to present two new case reports. A search of the PubMed and Embase databases was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to identify English-language articles reporting cases of ectopic olfactory neuroblastoma, published from 1955 through November 2021. Sixty-six cases of ectopic olfactory neuroblastoma were identified in 62 articles including the current review. Ectopic olfactory neuroblastoma arose in a wide age range (2-89 years) without significant sex predilection. It occurred most commonly in the ethmoid (25%), maxillary (25%), and sphenoid (16%) sinuses. Seventy-three percent of cases presented with low Hyams grade (I and II). The most common symptoms were nasal obstruction (32%) and epistaxis (32%). Paraneoplastic syndromes were observed in 27% of patients. The most common treatment was surgical resection followed by adjuvant radiotherapy. Overall, 76% of all patients were disease-free at the time of last follow-up. Locoregional recurrences and distant metastases were found in 19 and 5% of cases, respectively. This systematic review describes previously reported cases of ectopic olfactory neuroblastoma, a disease entity with poorly understood characteristics. Physicians should consider olfactory neuroblastoma in the differential diagnosis for sinonasal masses, as their ectopic presentation may present considerable diagnostic and therapeutic difficulties. Patients with olfactory neuroblastoma may benefit from long-term follow-up and routine endoscopic examinations for surveillance of ectopic recurrences.
PubMed: 38463937
DOI: 10.1055/a-1993-7790 -
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 -
Indian Journal of Otolaryngology and... Dec 2022Malignant tumors of sinonasal region are rare and affect less than 1 in 100,000 people per year. They are histologically diverse group and potentially pose significant...
Malignant tumors of sinonasal region are rare and affect less than 1 in 100,000 people per year. They are histologically diverse group and potentially pose significant management problems due to their proximity to the orbit and intracranial cavity. Although squamous cell carcinoma (SCC) is most common malignant tumor of paranasal cavity, tumors like adenocarcinoma, olfactory neuroblastoma, malignant melanoma, adenoid cystic carcinoma, sarcomas, haemoproliferative tumors, e.g. lymphoma may also occur. Retrospectively study was done in a tertiary care institute from January 2008 to December 2018 in India. Inclusion criteria-all biopsy proven PNS malignancy patients operated by endoscopic approach, irrespective of age and gender. Exclusion criteria- patients diagnosed with nasopharyngeal carcinoma, skin involvement, gross orbital involvement (muscle invasion), metastasis, operated by open approaches. 46 patients who underwent endoscopic tumor removal were reviewed. 36 (78.2%) were males and 10 (4.6%) females. Most common tumor in our study was adenoid cystic carcinoma. Recurrence was seen in 6 patients. Palliative therapy was given to all patients with recurrence. Management of malignant PNS tumor involving anterior skull base is multidisciplinary. R0 resection should be main goal in all malignant PNS malignancy. Tumors invading unresectable areas like cavernous sinus, brain parenchyma, carotids can be left in these places followed by palliation except in cases of squamous cell carcinoma. If R0 cannot be achieved surgically in SCC than patient should be considered inoperable and send for palliation. T1-T3 PNS malignant tumors can be managed by endoscopic approach followed by adjuvant therapy after a period of 6 weeks. Endoscopic excision should be converted to endoscopic assisted open approach in case of T4 tumors. We have tried to give a management protocol for management of malignant PNS tumors. Level of evidence: II.
PubMed: 36514438
DOI: 10.1007/s12070-022-03141-x