Materiały źródłowe

• #1 Olfactory neuroblastoma (esthesioneuroblastoma) – UpToDate

  https://www.uptodate.com/contents/5183

  Olfactory neuroblastoma, also referred to as esthesioneuroblastoma, is a rare malignant tumor of neuroectodermal origin with neuroendocrine differentiation. Olfactory neuroblastomas are thought to arise from the olfactory epithelium. […] Olfactory neuroblastoma makes up approximately two percent of all sinonasal tumors and has an incidence of 0.4 per million population.

• #2 Esthesioneuroblastoma (ENB) | PPT

  https://www.slideshare.net/slideshow/esthesioneuroblastoma-enb/66045121

  Esthesioneuroblastoma (ENB) is a rare malignant tumor that arises from the olfactory epithelium in the nasal cavity. […] The exact cell origin of esthesioneuroblastoma is controversial. Jacobson vomeronasal organ Sphenopalatine ganglion Ectodermal olfactory placode, Autonomic ganglia in the nasal mucosa, Olfactory epithelium. Presence of neuro filaments in esthesioneuroblastoma supports a neuronal crest origin. Recently ENB has found to express the human homologue (HASH) of the MASH (mammalian homologues of drosophila achaete-scute) gene. ENB should be regarded as originating from the basal cells of the olfactory neuroepithelium. […] No clear etiology in humans. […] Esthesioneuroblastoma occurs in a wide range of age groups (3-90 y). There exists a bimodal peak of occurrence in the third and sixth decades of life.

• #3 Genetic and molecular alterations in olfactory neuroblastoma: implications for pathogenesis, prognosis and treatment | Oncotarget

  https://www.oncotarget.com/article/9683/text/

  Olfactory neuroblastoma (ONB, Esthesioneuroblastoma) is an infrequent neoplasm of the head and neck area derived from olfactory neuroepithelium. […] We present briefly ONB molecular pathogenesis and propose potential therapeutic targets and prognostic factors. Possible therapeutic targets in ONB include: receptor tyrosine kinases (c-kit, PDGFR-b, TrkB; EGFR); somatostatin receptor; FGF-FGFR1 signaling; Sonic hedgehog pathway; apoptosis-related pathways (Bcl-2, TRAIL) and neoangiogenesis (VEGF; KDR). […] The first molecular genetic analysis of ONB was performed by Carney et al. in 1995. The authors performed modified reverse-transcription polymerase chain reaction (RT-PCR) and found the ONB expressing Drosophila achaete-scute gene (hASH1), but not Olfactory Marker Protein (OMP) mRNA. HASH1 is involved in immature olfactory neuronal development, whereas OMP is a marker of mature cells. This indicates ONB originates from immature neural crest cells of the olfactory epithelium.

• #4 Genetic and molecular alterations in olfactory neuroblastoma: implications for pathogenesis, prognosis and treatment

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5239575/

  Olfactory neuroblastoma (ONB, Esthesioneuroblastoma) is an infrequent neoplasm of the head and neck area derived from olfactory neuroepithelium. […] We present briefly ONB molecular pathogenesis and propose potential therapeutic targets and prognostic factors. Possible therapeutic targets in ONB include: receptor tyrosine kinases (c-kit, PDGFR-b, TrkB; EGFR); somatostatin receptor; FGF-FGFR1 signaling; Sonic hedgehog pathway; apoptosis-related pathways (Bcl-2, TRAIL) and neoangiogenesis (VEGF; KDR). […] In this review article we report about main genetic disturbances, their correlation with prognosis, we describe concepts of molecular pathogenesis and potential targetable pathways in ONB. […] The first molecular genetic analysis of ONB was performed by Carney et al. in 1995. […] This indicates ONB originates from immature neural crest cells of the olfactory epithelium.

• #5 Esthesioneuroblastoma: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/278047-overview

  Esthesioneuroblastomas (ENBs) are undifferentiated tumors of neuroectodermal origin derived from the olfactory epithelium. […] The tumor cells are mitotically active and are the precursor cells that develop into sustentacular and neuronal cells. […] Inconsistent histologic presentations initially led to controversy surrounding the exact histologic origin of ENBs, and this ambiguity can confound clinical and prognostic decisions. […] To date, no certain genetic factor has been identified that can accurately assist in the diagnosis or predict prognosis. […] Analysis of ENBs with array comparative genomic hybridization revealed complex gene copy number profiles, which varied by tumor stage. […] Of the many alterations were identified in this study, chromosomal gains in 7q11 and 20q and deletions in 2q, 5q, 6p, 6q, and 18q have been confirmed by at least 2 other studies. […] Interestingly, 20q is a region that has been implicated in other cancers, including breast, ovarian, and squamous cell carcinoma. […] Still, further experimentation will be required to determine the role of these genomic regions in ENB.

• #6 Esthesioneuroblastoma | Neupsy Key

  https://neupsykey.com/esthesioneuroblastoma-3/

  Esthesioneuroblastoma is of neural crest origin and arises from the basal stem cells of the olfactory neuroepithelium. […] The tumor is phenotypically intermediate between a pure neural (e.g., neuroblastoma) and a neuroendocrine epithelial neoplasm (e.g., carcinoid, small cell carcinoma), and there are case reports of the tumor secreting vasopressin. […] Esthesioneuroblastoma arises from the olfactory epithelium of the superior nasal cavity and is most commonly a rapidly growing, aggressive neoplasm. […] Over time the tumor involves the nasal cavity more extensively and most commonly spreads locally into the paranasal sinuses, orbit, and anterior cranial fossa via the cribriform plate. […] Local recurrence has been reported in up to 60% of patients treated with surgery and radiation, with the majority of recurrences being seen within the first 12 to 24 months.

• #7 Esthesioneuroblastoma – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK539694/

  Esthesioneuroblastoma is thought to arise from specialized sensory neuroepithelial olfactory cells. […] The detection of PTCH1, GL/1, and GL/2 in 70%, 70%, and 65%, respectively, of human esthesioneuroblastoma specimens, suggests that the SHH signaling pathway may be involved in the pathogenesis of this neoplasm. […] Esthesioneuroblastoma demonstrates numerous chromosomal aberrations, deletions, and gains, but with no consistent pattern.

• #8 Esthesioneuroblastoma overview – wikidoc

  https://www.wikidoc.org/index.php/Esthesioneuroblastoma_overview

  Genes involved in the pathogenesis of esthesioneuroblastoma include chromosomal gains in 7q11 and 20q and deletions in 2q, 5q, 6p, 6q, and 18q. […] On gross pathology, soft and hemorrhagic, polypoid appearance, and rich and fragile vascular supply of the tumor are characteristic findings of esthesioneuroblastoma. […] On microscopic histopathological analysis, arrangements of cells into rosettes or pseudorosettes are characteristic findings of esthesioneuroblastoma. […] Genes involved in the pathogenesis of esthesioneuroblastoma include chromosomal gains in 7q11 and 20q and deletions in 2q, 5q, 6p, 6q, and 18q.

• #9 Esthesioneuroblastoma causes – wikidoc

  https://www.wikidoc.org/index.php/Esthesioneuroblastoma_causes

  Genes involved in the pathogenesis of esthesioneuroblastoma include chromosomal gains in 7q11 and 20q and deletions in 2q, 5q, 6p, 6q, and 18q. […] A tool called array comparative genomic hybridization was applied to the analysis of esthesioneuroblastomas. Although many alterations were identified by this study, chromosomal gains in 7q11 and 20q and deletions in 2q, 5q, 6p, 6q, and 18q have been confirmed by at least two other studies. […] Although still investigational, the demonstration of human achaete-scute homologue HASH1 gene expression could become the diagnostic procedure of choice. The HASH1 gene is expressed in immature olfactory cells and is involved in olfactory neuronal differentiation; therefore, it could be useful in distinguishing esthesioneuroblastoma from other poorly differentiated small blue cell tumors.

• #10 Genetic and molecular alterations in olfactory neuroblastoma: implications for pathogenesis, prognosis and treatment | Oncotarget

  https://www.oncotarget.com/article/9683/text/

  Mutant TP53 is a driver of genetic alteration in various malignancies, like high-grade ovarian and colorectal carcinoma. […] Aberrations of p53 probably appear at later stages during tumor development or progression and are not involved in the initial tumorigenesis. […] In this review article we report about main genetic disturbances, their correlation with prognosis, we describe concepts of molecular pathogenesis and potential targetable pathways in ONB. […] A recent study of 10 cases by Valli et al. argues that ONB has none recurrent chromosomal imbalances except gain of chromosome 19, which is consistent with Riazimands findings. […] All these data indicate ONB as being characterized by high-level yet heterogeneous chromosomal instability (CIN). […] Frequent amplifications of DNA at 20q in ONB may lead to transcription factor ZNF217 overexpression.

• #11 Genomic analysis identifies frequent deletions of Dystrophin in olfactory neuroblastoma | Nature Communications

  https://www.nature.com/articles/s41467-018-07578-z

  Olfactory neuroblastoma (ONB) is a rare malignant neoplasm arising in the upper portion of the sinonasal cavity. […] To better understand the genetic bases for ONB, here we perform whole exome and whole genome sequencing as well as single nucleotide polymorphism array analyses in a series of ONB patient samples. […] This high prevalence implicates an unexpected functional role for genes causing hereditary muscular dystrophies in ONB. […] These studies demonstrate that ONB has frequent somatic deletions involving the DMD locus and implicates a central role for genes causing hereditary muscular dystrophies in ONB pathogenesis. […] In sum, 13 of our 14 ONBs had a somatic deletion in the genes that are involved in muscular dystrophies, perhaps providing new insights into the pathophysiology of these tumors. […] The high rate of DMD deletions found in ONBs coupled with the emerging tumor suppressor activity of dystrophin suggests a central role for DMD in the pathogenesis of this tumor type.

• #12 Esthesioneuroblastoma – Wikipedia

  https://en.wikipedia.org/wiki/Esthesioneuroblastoma

  Esthesioneuroblastoma is a rare cancer of the nasal cavity. Arising from the upper nasal tract, esthesioneuroblastoma is believed to originate from sensory neuroepithelial cells, also known as neuroectodermal olfactory cells. […] There is limited research on the genetic role in esthesioneuroblastoma development. Of the research to date, the sonic hedgehog pathway, MYC and KDR genes are implicated for esthesioneuroblastoma. […] Mutations in dystrophin and Laminin, alpha 2 (LAMA2) have also been implicated in this disease. […] Esthesioneuroblastoma is of neurocrest origin, arising from olfactory sensory cells in the olfactory epithelium. […] Esthesioneuroblastoma consists of lobular sheets with neurofibrullar fibers and rosettes. […] Hyam’s classifications are an important way of determining prognosis. […] In severe, Kadish class C tumors, Haym’s grades of pathology are important for prognosis.

• #13 Esthesioneuroblastoma | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/21373

  Esthesioneuroblastoma is thought to arise from specialized sensory neuroepithelial olfactory cells. […] Esthesioneuroblastoma demonstrates numerous chromosomal aberrations, deletions, and gains, but with no consistent pattern. […] In one study, a specific deletion on chromosome 11 and a gain on chromosome 1p correlated with metastasis and a worse prognosis. […] The detection of PTCH1, GL/1, and GL/2 in 70%, 70%, and 65%, respectively, of human esthesioneuroblastoma specimens, suggests that the SHH signaling pathway may be involved in the pathogenesis of this neoplasm.

• #14 Genetic and molecular alterations in olfactory neuroblastoma: implications for pathogenesis, prognosis and treatment | Oncotarget

  https://www.oncotarget.com/article/9683/

  Olfactory neuroblastoma (ONB, Esthesioneuroblastoma) is an infrequent neoplasm of the head and neck area derived from olfactory neuroepithelium. […] We present briefly ONB molecular pathogenesis and propose potential therapeutic targets and prognostic factors. […] Possible therapeutic targets in ONB include: receptor tyrosine kinases (c-kit, PDGFR-b, TrkB; EGFR); somatostatin receptor; FGF-FGFR1 signaling; Sonic hedgehog pathway; apoptosis-related pathways (Bcl-2, TRAIL) and neoangiogenesis (VEGF; KDR).

• #15 Genetic and molecular alterations in olfactory neuroblastoma: implications for pathogenesis, prognosis and treatment

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5239575/

  RNA interference studies revealed hASH1 inhibition to lead to cell cycle arrest, so its overexpression may act as a trigger for cancer formation from olfactory epithelial cells. […] The moment at which a tumor acquires the ability to form new vessels as an effect of imbalance between pro-angiogenic and anti-angiogenic factors is called angiogenic switch, and neoangiogenesis is widely believed to promote tumor spread. […] hASH1 activates BCL-2 transcription, so Bcl-2 inhibitors are promising candidates for treatment of high-grade ONB; also blocking of hASH1 can potentially block Bcl-2 activity. […] ONB cells express three main neurotrophin receptors: high affinity (TrkA, TrkB) and low affinity (p75NR) receptors. […] Overexpression of TrkB in pediatric NB is associated with an unfavorable prognosis and resistance to chemotherapy.

• #16 Genetic and molecular alterations in olfactory neuroblastoma: implications for pathogenesis, prognosis and treatment | Oncotarget

  https://www.oncotarget.com/article/9683/text/

  RNA interference studies revealed hASH1 inhibition to lead to cell cycle arrest, so its overexpression may act as a trigger for cancer formation from olfactory epithelial cells. […] The moment at which a tumor acquires the ability to form new vessels as an effect of imbalance between pro-angiogenic and anti-angiogenic factors is called angiogenic switch, and neoangiogenesis is widely believed to promote tumor spread. […] hASH1 activates BCL-2 transcription, so Bcl-2 inhibitors are promising candidates for treatment of high-grade ONB; also blocking of hASH1 can potentially block Bcl-2 activity. […] ONB cells express three main neurotrophin receptors: high affinity (TrkA, TrkB) and low affinity (p75NR) receptors. The first two are strongly expressed in almost all ONB cases, whereas p75NR is expressed in 60-100%.

• #17 Genetic and molecular alterations in olfactory neuroblastoma: implications for pathogenesis, prognosis and treatment

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5239575/

  Mutant TP53 is a driver of genetic alteration in various malignancies, like high-grade ovarian and colorectal carcinoma. […] Aberrations of p53 probably appear at later stages during tumor development or progression and are not involved in the initial tumorigenesis. […] These controversies raise a question for the best clinical application of histopathological grading in clinics. […] The status of the resection margin was reported to positively correlate with survival. […] At molecular level, high human telomerase reverse transcriptase (hTERT) immunoexpression is associated with metastasis occurrence and may be used as an ancillary prognostic marker. […] Prospective studies should be performed to assess a possible role of these alterations in ONB. […] This may indicate that TP53 mutation could be an unfavorable prognostic and predictive factor in ONB.

• #18 Esthesioneuroblastoma – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/esthesioneuroblastoma/symptoms-causes/syc-20351075

  Experts haven’t found the exact cause of esthesioneuroblastoma. In general, cancer happens when cells get changes in their DNA. A cell’s DNA holds the instructions that tell a cell what to do. The changes tell the cells to make many more cells quickly. The changes give the cells the ability to keep living when healthy cells would naturally die. This causes too many cells. […] The cells might form a mass called a tumor. The tumor can grow to invade and destroy healthy body tissue. In time, cells can break away and spread to other parts of the body. […] Complications of esthesioneuroblastoma may include: Cancer that grows into nearby organs and tissues. Esthesioneuroblastoma can grow and get into the sinuses, eyes and brain. […] Spread of the cancer, known as metastasis. Esthesioneuroblastoma can spread to other parts of the body, such as the lymph nodes, bone marrow, lungs, liver, skin and bones.

• #19 Esthesioneuroblastoma: Causes, Symptoms, Diagnosis, Treatment

  https://www.prepladder.com/neet-pg-study-material/radiology/esthesioneuroblastoma-causes-symptoms-diagnosis-treatment-and-complications

  Esthesioneuroblastoma is an uncommon type of cancer that originates in the nasal cavity or upper section of the nose. Olfactory neuroblastoma is an alternate term for esthesioneuroblastoma. […] The exact etiology of esthesioneuroblastoma remains unknown to specialists. Cancer is typically brought on by changes to a cell’s DNA. A cell’s DNA contains instructions that tell it what to do. The changes give the cells instructions to multiply quickly. The alterations enable the cells to survive when they would have ordinarily died. This results in an excess of cells. […] The cells could group to form a tumor-like bulk. The tumor can grow and consume healthy body tissue. Cells may split off and spread to different parts of the body over time.

• #20 Treatment outcomes and prognostic factors of esthesioneuroblastoma— a retrospective study from South India – ecancer

  https://ecancer.org/es/journal/article/1584-treatment-outcomes-and-prognostic-factors-of-esthesioneuroblastoma-a-retrospective-study-from-south-india

  Esthesioneuroblastoma (ENB) or olfactory neuroblastoma is a rare malignant neoplasm arising from the neural crest cells of the olfactory epithelium. […] The aetiology of this rare round cell tumour is unclear, but it is postulated that viral, genetic and environmental factors play a role in its development. […] The complex anatomical location and the difficulty in achieving a clear surgical margin due to the infiltrative nature of the lesion often pose challenges in treatment. […] The role of chemotherapy is not completely understood in the multimodal setting, relating to tumour stage and pathology. […] Advanced modified Kadish stage, lymph node involvement and orbital invasion are associated with poor outcomes. […] Multiple studies have identified different genetic and cytogenetic alterations in ENB. The most common chromosomal alterations include deletion on chromosome 11 and gain on chromosome 1p, which is associated with poor prognosis. […] Alterations in p53, EGFR, KIT, RET, APC, FGFR2, PDGFRA, SMAD4 and CTNNB1 genes are also associated with ENB.

• #21 Pathology Outlines – Olfactory neuroblastoma

  https://www.pathologyoutlines.com/topic/nasalolfactoryneuroblastoma.html

  Malignant neuroectodermal tumor commonly located at superior aspect of nasal cavity showing neuroblastic differentiation (El-Naggar: WHO Classification of Head and Neck Tumours, 4th Edition, 2017) […] Thought to arise from olfactory membrane or olfactory placode (plate-like thickening of embryonic ectoderm from which a nerve ganglion or sensory organ will develop) which extends from roof of nasal cavity in fetus to midnasal septum and superior turbinate […] Theorized to originate from specialized sensory neuroepithelium located in superior nasal cavity, including cribriform plate of ethmoid, nasal roof, superior nasal concha and superior nasal septum (Mod Pathol 2017;30:S1, Head Neck Pathol 2009;3:252) […] None identified […] Recent next generation sequencing studies have shown that olfactory neuroblastoma has high level but heterogenous chromosomal instability and copy number alterations (Oncotarget 2016;7:52584) […] Absence of characteristic fusions of other small blue round cell tumors that may occur in the sinonasal tract, e.g. Ewing sarcoma EWSR1 fusion and alveolar rhabdomyosarcoma PAX3 or PAX7 fusion.

• #22 Aggressiveness of esthesioneuroblastoma: a rare case report and review of literature | Paul | Oncology in Clinical Practice

  https://journals.viamedica.pl/oncology_in_clinical_practice/article/view/90051

  Within ENBs, tumors with different biological behavior ranging from localized forms with slow progression to aggressive and metastatic forms at onset are seen. […] The role of adjuvant and salvage chemotherapy in recurrent and residual cases has also been studied intensively to improve outcomes. […] The optimal treatment of ENB demonstrates the benefit of adjuvant therapy, particularly radiation therapy. […] Our case demonstrates that subtotal resection is an independent index of poor outcome, with trauma during resection leading to more chances of local progression.

• #23 Esthesioneuroblastoma | Neupsy Key

  https://neupsykey.com/esthesioneuroblastoma-3/

  Cervical nodal metastases are present in 5% to 10% of patients at presentation and confer a significantly worse prognosis. […] Distant metastases have been reported in up to 7% of patients at the time of initial presentation and occur in up to 25% of patients over the course of the disease. […] Complete surgical resection is the mainstay of esthesioneuroblastoma therapy.

• #24 Long-term analysis of multimodality treatment outcomes and prognosis of esthesioneuroblastomas: a single center results of 138 patients | Radiation Oncology | Full Text

  https://ro-journal.biomedcentral.com/articles/10.1186/s13014-020-01667-4

  The aim of this study is to evaluate the efficacy of different treatment strategies and the potential prognostic factors of esthesioneuroblastoma (ENB). […] Esthesioneuroblastoma (ENB) is an uncommon malignant neoplasm which accounts for only 3 to 6% of all cancers in the nasal cavity and paranasal sinuses. It has been generally believed that ENB arises from basal cells of the olfactory neuroepithelium within the superior nasal vault. […] Orbital invasion, intracranial invasion, lymph node metastasis and advanced Kadish disease at initial diagnosis were significantly associated with inferior prognosis. […] Regarding the treatment modality, the optimal strategy remained surgery with radiotherapy-based multimodality treatment. The concurrent chemoradiotherapy may play a more beneficial role.

• #25 Long-term analysis of multimodality treatment outcomes and prognosis of esthesioneuroblastomas: a single center results of 138 patients | Radiation Oncology | Full Text

  https://ro-journal.biomedcentral.com/articles/10.1186/s13014-020-01667-4

  In multivariate analysis, lymph node metastasis was an independent prognostic factor affecting DMFS, whereas treatment modality was a significant independent factor affecting OS and LRFFS. […] The prognostic value of the orbital and intracranial invasion has been reflected in the American Joint Committee on Cancer (AJCC) classification of nasal cavity and ethmoid sinus tumor, which defined the orbital invasion as T3 disease and intracranial invasion as T4b disease. […] The literature illustrated that the incidence of cervical lymph node metastasis at initial diagnosis ranges from 7% to more than 20%. It has been proven that cervical lymph node metastasis is an important adverse prognosis factor affecting survival.

• #26 Esthesioneuroblastoma – EyeWiki

  https://eyewiki.org/Esthesioneuroblastoma

  The Hyams system divides the spectrum of disease into four histopathologic grades, ranging from most differentiated (grade I), to least differentiated (grade IV), based on features such as tumor architecture, mitotic activity, nuclear polymorphism and presence of necrosis. […] The Kadash staging system grades tumors based on their extent of spread, and has been shown to correlate with disease-free survival time. […] Dulguerov also devised a TNM system for ENB, to include nodal status. […] The use of chemotherapy remains more controversial. […] A combination of cisplatin and etoposide appears to be the most common chemotherapeutic regimen for ENB, translated from early clinical trials on neuroectodermal tumors such as medulloblastoma. […] Although no clear consensus exists on when chemotherapy should be used, some published papers advocate for chemotherapy use in all cases to improve local control.

• #27 Esthesioneuroblastoma – EyeWiki

  https://eyewiki.org/Esthesioneuroblastoma

  Esthesioneuroblastoma is a tumor derived from neural crest cells that arises from the olfactory epithelium lining the sinonasal cavity. […] Because of its rare occurrence, there is debate amongst grading system, prognosis and clinical management. […] Histological diagnosis is important to rule out ENB versus other sinonasal malignancies, as ENB survival and control rates are much higher compared to non-ENB diagnoses. […] Typical histology shows a lobular architecture with fibrovascular septae, small round-to-oval blue cells, prominent nuclear membranes, and scant cytoplasm. […] Immunohistochemistry stains are necessary for diagnosis. […] These stains, however, can be weakly positive making a diagnosis of ENB from sinonasal undifferentiated carcinoma, sinonasal neuroendocrine carcinoma, lymphoma, and melanoma, among others, challenging.

• #28 Genomic characterization of an esthesioneuroblastoma with spinal metastases: illustrative case in: Journal of Neurosurgery: Case Lessons Volume 6 Issue 23 (2023) Journals

  https://thejns.org/caselessons/view/journals/j-neurosurg-case-lessons/6/23/article-CASE23164.xml

  Esthesioneuroblastoma (ENB) is a rare neoplasm of the sinonasal tract. Currently, the optimal treatment includes maximal resection combined with radiotherapy and/or chemotherapy. Although ENBs often recur and have an aggressive clinical course, spinal metastases are extremely rare and the underlying molecular mechanisms are poorly understood. […] The authors performed targeted exome sequencing on both the resected primary tumor and biopsied spinal metastases, which revealed 12 total variants of unknown clinical significance in genes associated with the PI3K/AKT/mTOR pathway, chromatin remodeling, DNA repair, and cell proliferation. […] This report discusses the potential impact of these variants on tumor progression and metastasis, as well as the implications for identifying potential new biomarkers and therapies.

• #29 Genomic characterization of an esthesioneuroblastoma with spinal metastases: illustrative case in: Journal of Neurosurgery: Case Lessons Volume 6 Issue 23 (2023) Journals

  https://thejns.org/caselessons/view/journals/j-neurosurg-case-lessons/6/23/article-CASE23164.xml

  A molecular understanding of the genomic influences on ENB progression may elucidate new targets and biomarkers. […] However, there are few data comparing metastatic versus primary lesions in individual patients, which carries value in understanding tumor evolution from the standpoint of therapeutic targets and the identification of biomarkers that may predict metastasis. […] Targeted exome sequencing revealed a total of 12 VUSs across the primary and metastatic tumors. […] Our patient did not have any mutations in the TP53 gene, but we did find multiple VUSs in genes associated with the PI3K/AKT/mTOR signaling pathway. […] Future functional studies are needed to test this hypothesis, as well as the potential for the IGF1R variant and other PI3K/AKT/mTOR-associated mutations to serve as biomarkers for ENB progression and metastasis.

• #30 Esthesioneuroblastoma Causes | Expert Surgeon | Aaron Cohen-Gadol, MD | Aaron Cohen-Gadol, MD

  https://www.aaroncohen-gadol.com/en/patients/esthesioneuroblastoma/causes

  The development of cancer is complex and a single cause is unlikely to be identified. […] It is possible that the tumor arises from a combination of genetic factors, environmental exposures, and random cellular changes. […] The exact causes of esthesioneuroblastoma remain unclear, but genetic mutations, environmental exposures, and possibly viral infections may contribute to its development. […] Long-term exposure to certain chemicals, dust, and industrial substances might increase the risk of developing esthesioneuroblastoma, though no definitive link has been proven. […] Due to the rarity of the tumor, more research is needed to identify clear causes and potential risk factors.

• #31 Genomic characterization of an esthesioneuroblastoma with spinal metastases: illustrative case in: Journal of Neurosurgery: Case Lessons Volume 6 Issue 23 (2023) Journals

  https://thejns.org/caselessons/view/journals/j-neurosurg-case-lessons/6/23/article-CASE23164.xml

  Identifying unique mutations may also offer opportunities for the development of metastatic-specific therapies. […] The presented case focuses on the genomic landscape of a paired primary and metastatic ENB in a single patient. However, it is essential to mention the role of other molecular mechanisms that contribute to ENB tumorigenesis.

• #32

  https://journals.lww.com/annals-of-medicine-and-surgery/fulltext/2025/02000/the_100_most_cited_papers_on.36.aspx

  Comprehending these intricate pathological characteristics—ranging from histological patterns to immunohistochemical markers and genetic alterations—holds paramount importance in deciphering the tumors behavior and tailoring individualized treatment strategies. […] Further elucidating the underlying molecular mechanisms and their implications in disease progression not only aids in refining prognostication but also offers promising avenues for targeted therapies, fostering advancements in the management of this intricate and rare nasal malignancy.

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