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Modern Pathology : An Official Journal... May 2024Sinonasal tumors with neuroepithelial differentiation, defined by neuroectodermal elements reminiscent of olfactory neuroblastoma (ONB) and epithelial features such as...
Sinonasal tumors with neuroepithelial differentiation, defined by neuroectodermal elements reminiscent of olfactory neuroblastoma (ONB) and epithelial features such as keratin expression or gland formation, are a diagnostically challenging group that has never been formally included in sinonasal tumor classifications. Recently, we documented that most of these neuroepithelial neoplasms have distinctive histologic and immunohistochemical findings and proposed the term "olfactory carcinoma" to describe these tumors. However, the molecular characteristics of olfactory carcinoma have not yet been evaluated. In this study, we performed targeted molecular profiling of 23 sinonasal olfactory carcinomas to further clarify their pathogenesis and classification. All tumors included in this study were composed of high-grade neuroectodermal cells that were positive for pankeratin and at least 1 specific neuroendocrine marker. A significant subset of cases also displayed rosettes and neurofibrillary matrix, intermixed glands with variable cilia, peripheral p63/p40 expression, and S100 protein-positive sustentacular cells. Recurrent oncogenic molecular alterations were identified in 20 tumors, including Wnt pathway alterations affecting CTNNB1 (n = 8) and PPP2R1A (n = 2), ARID1A inactivation (n = 5), RUNX1 mutations (n = 3), and IDH2 hotspot mutations (n = 2). Overall, these findings do demonstrate the presence of recurrent molecular alterations in olfactory carcinoma, although this group of tumors does not appear to be defined by any single mutation. Minimal overlap with alterations previously reported in ONB also adds to histologic and immunohistochemical separation between ONB and olfactory carcinoma. Conversely, these molecular findings enhance the overlap between olfactory carcinoma and sinonasal neuroendocrine carcinomas. A small subset of neuroepithelial tumors might better fit into the superseding molecular category of IDH2-mutant sinonasal carcinoma. At this point, sinonasal neuroendocrine and neuroepithelial tumors may best be regarded as a histologic and molecular spectrum that includes core groups of ONB, olfactory carcinoma, neuroendocrine carcinoma, and IDH2-mutant sinonasal carcinoma.
Topics: Humans; Aged; Middle Aged; Male; Transcription Factors; Female; Wnt Signaling Pathway; DNA-Binding Proteins; Esthesioneuroblastoma, Olfactory; Biomarkers, Tumor; Paranasal Sinus Neoplasms; Adult; Nuclear Proteins; Mutation; Aged, 80 and over; Nose Neoplasms; Immunohistochemistry
PubMed: 38369189
DOI: 10.1016/j.modpat.2024.100448 -
World Neurosurgery Mar 2024Esthesioneuroblastoma (ENB) is a rare cancer deriving from the olfactory mucosa. Among the basal or neural genomic subtypes, the basal subtype is associated with poorer...
BACKGROUND
Esthesioneuroblastoma (ENB) is a rare cancer deriving from the olfactory mucosa. Among the basal or neural genomic subtypes, the basal subtype is associated with poorer survival, poor differentiation, and higher levels of tumor-infiltrating immune cells (TIICs). The immune microenvironment of these ENB subtypes remains unclear. We used an established machine learning algorithm on ENB transcriptomic profiles.
METHODS
The authors characterized 22 immune cell populations using the CIBERSORTx deconvolutional machine learning pipeline on RNA sequencing data from 18 ENB cases. The characterization aimed to elucidate differences in relative proportions and populations of TIICs between basal and neural ENB.
RESULTS
No differences in age, Hyams, Dulguerov, IDH2 mutation, or PD-L1 expression were seen between basal and neural subtypes of ENB (P > 0.05). Also, no difference in median overall survival was appreciated (52.0 ± 13.1 months vs. 50.0 ± 43.2 months, P = 0.5). As a cohort, M2 macrophages were the most abundant subpopulation (14%) followed by naïve B cells (13%) and CD4 memory resting T cells (12%). No gross differences in CD20, CD4, or CD8 cells/mm were apparent on gross histology (P > 0.05). However, further analysis showed that activated CD4 memory T cells were significantly increased in the basal ENBs, whereas resting dendritic cells were increased in the neural ENB subtype. The TIIC profiles alone could not differentiate between basal and neural ENB, but did suggest immunoprofile differences.
CONCLUSIONS
Basal and neural subtypes display distinct TIIC involvement, which may impact their difference in outcome. These findings provide the framework for further investigation in novel immunomodulation strategies for ENB.
Topics: Humans; Esthesioneuroblastoma, Olfactory; Mutation; Nose Neoplasms; Nasal Cavity; Gene Expression; Prognosis; Tumor Microenvironment
PubMed: 38246527
DOI: 10.1016/j.wneu.2024.01.063 -
Pathology, Research and Practice Jan 2024Recent studies have suggested that insulinoma-associated protein 1 (INSM1) is a useful marker for pathological diagnosis of neuroendocrine tumors. In the present study,...
OBJECTIVE
Recent studies have suggested that insulinoma-associated protein 1 (INSM1) is a useful marker for pathological diagnosis of neuroendocrine tumors. In the present study, we investigated the association between INSM1 expression and prognosis in patients with olfactory neuroblastoma (ONB) and assessed the usefulness of INSM1 as a prognostic biomarker in these patients.
METHOD
Immunohistochemistry was performed on 109 ONB patients who underwent endoscopic surgery at Beijing Tong Ren Hospital (Beijing, China) between June 2006 and November 2021 Patient age at the time of surgery ranged from 10 months to 72 years (mean age, 43.55 ± 13.47 years). In total, 63 (57.8%) and 46 (42.2%) tumors occurred in male and female patients, respectively. The percentages of grade I-IV cases were 13.8% (15/109), 36.7% (40/109), 29.4% (32/109) and 20.2% (22/109), respectively.
RESULTS
The expression rate (moderately/strongly positive) of INSM1 was significantly higher in high-grade (Ⅲ/Ⅳ; 83%; 45/54) than low-grade (Ⅰ/Ⅱ; 27%; 15/55) ONB cases. High expression levels of INSM1 were significantly positively associated with high pathological stage (p < 0.001), local recurrence, and death. Kaplan‑Meier analysis revealed that patients with high INSM1 expression had significantly shorter disease‑free survival (DFS) and mean survival (75.01 ± 10.71 vs. 158.56 ± 10.32) times, and shorter overall survival (OS). Multivariate Cox regression analysis revealed that INSM1 was an independent prognostic factor for DFS (HR: 4.963, 95%CI [2.11-10.84] p < 0.001) and OS (HR: 4.791, 95%CI [2.117-10.485], p < 0.001) after adjusting for sex, age, and tumor grade. In addition, INSM1 was an independent prognostic factor for DFS in patients treated with surgery (HR: 3.714, 95%CI [1.267-10.889], p = 0.017) and chemotherapy (HR: 5.574, 95%CI [1.584-19.612], p = 0.007).
CONCLUSION
INSM1 expression had a positive association with the prognosis of patients with ONB and could serve as a prognostic biomarker in these patients.
Topics: Humans; Male; Female; Adult; Middle Aged; Infant; Esthesioneuroblastoma, Olfactory; Biomarkers, Tumor; Insulinoma; Repressor Proteins; Prognosis; Pancreatic Neoplasms; Nose Neoplasms; Nasal Cavity
PubMed: 38171083
DOI: 10.1016/j.prp.2023.155040 -
European Archives of... Mar 2024To investigate the clinical characteristics of the syndrome of inappropriate antidiuretic hormone (SIADH) associated with nasal and paranasal malignant tumors.
PURPOSE
To investigate the clinical characteristics of the syndrome of inappropriate antidiuretic hormone (SIADH) associated with nasal and paranasal malignant tumors.
METHODS
Patients with locally advanced or recurrence/metastatic malignant tumors of the nasal and paranasal sinuses were included. The SIADH was diagnosed according to the diagnostic criteria. The clinical characteristics of SIADH patients were retrospectively analyzed.
RESULTS
Six patients (6/188, 3.2%) met the diagnostic criteria of SIADH, including four olfactory neuroblastoma (4/26, 15.4%), one neuroendocrine carcinoma (1/9, 11.1%), and one squamous cell carcinoma (1/63, 1.6%). Five patients (83.3%) had severe hyponatremia; however, the hyponatremia could be improved by fluid restriction or tolvaptan. Three patients' SIADH were recovered during the chemotherapy and the other three were recovered after the surgery.
CONCLUSION
The incidence of SIADH associated with nasal and paranasal malignant tumors is relatively more common in olfactory neuroblastoma and neuroendocrine carcinoma. The hyponatremia caused by SIADH may be corrected by fluid restriction or tolvaptan, and the SIADH may be recovered through anti-tumor therapy.
Topics: Humans; Inappropriate ADH Syndrome; Hyponatremia; Tolvaptan; Esthesioneuroblastoma, Olfactory; Retrospective Studies; Carcinoma, Neuroendocrine; Nose Neoplasms; Nasal Cavity
PubMed: 38163817
DOI: 10.1007/s00405-023-08347-5 -
Archive of Clinical Cases 2023Esthesioneuroblastoma is a tumor arising from olfactory neuroepithelium with an incidence of four per million. This case presents a rare nasal cavity neoplasm with...
Esthesioneuroblastoma is a tumor arising from olfactory neuroepithelium with an incidence of four per million. This case presents a rare nasal cavity neoplasm with hemorrhagic properties that may lead to significant sequelae. We present a 69-year-old male patient who presented with worsening altered mental status over the past 6-7 months. His Glasgow coma scale was a nine, showing a large mass centered at the cribriform plate with extension intracranially, sinonasal cavity, and bilateral orbits on diagnostics. Bifrontal craniotomy was performed one day after admission with resection of the tumor in the cranial fossa and intranasally, and decompression of the brainstem, frontal lobes, and third ventricle. After surgery, the patient was managed in the intensive care unit but continued to deteriorate. He was confirmed to have no meaningful brain activity and eventually deceased seven days after admission. Depending on the tumor stage, esthesioneuroblastoma can have a favorable prognosis with proper therapies. Different surgical techniques for ENB lead to the question of which therapeutic modality is the best because of the tumor's gross hemorrhagic properties. With adjunctive radiation therapy and/or chemotherapy, more research can bring light to proper surgical techniques.
PubMed: 38098697
DOI: 10.22551/2023.41.1004.10269 -
International Journal of Molecular... Nov 2023Nowadays, there is considerable attention toward the use of food waste from food processing as possible sources of compounds with health properties, such as anticancer...
Nowadays, there is considerable attention toward the use of food waste from food processing as possible sources of compounds with health properties, such as anticancer activity. An example is tomato processing, which is responsible for generating a remarkable amount of waste (leaves, peel, seeds). Therefore, our goal was to evaluate the potential anticancer property of tomato extracts, in particular "" tomato (DT) and "" tomato (PT), and to study their phytochemical composition. Liquid chromatography with tandem mass spectrometry (LC/MS-MS) results showed that these extracts are rich in alkaloids, flavonoids, fatty acids, lipids, and terpenes. Furthermore, their potential anticancer activity was evaluated in vitro by MTT assay. In particular, the percentage of cell viability was assessed in olfactory ensheathing cells (OECs), a particular glial cell type of the olfactory system, and in SH-SY5Y, a neuroblastoma cell line. All extracts (aqueous and ethanolic) did not lead to any significant change in the percentage of cell viability on OECs when compared with the control. Instead, in SH-SY5Y we observed a significant decrease in the percentage of cell viability, confirming their potential anticancer activity; this was more evident for the ethanolic extracts. In conclusion, tomato leaves extracts could be regarded as a valuable source of bioactive compounds, suitable for various applications in the food, nutraceutical, and pharmaceutical fields.
Topics: Humans; Solanum lycopersicum; Food Loss and Waste; Cell Survival; Neuroblastoma; Refuse Disposal; Alkaloids; Plant Extracts; Steroids; Seeds
PubMed: 38069237
DOI: 10.3390/ijms242316915 -
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 -
Journal of Neurosurgery. Case Lessons Dec 2023Exoscopy in neurosurgery offers various advantages, including increased freedom of the viewing axis while the surgeon maintains a comfortable upright position. However,...
BACKGROUND
Exoscopy in neurosurgery offers various advantages, including increased freedom of the viewing axis while the surgeon maintains a comfortable upright position. However, the optimal monitor positioning to avoid interference with surgical manipulation remains unresolved. Herein, the authors describe two cases in which a three-dimensional head-mounted display (3D-HMD) was introduced into a transcranial neurosurgical procedure using an exoscope.
OBSERVATIONS
Case 1 was a 50-year-old man who presented with recurrent epistaxis and was diagnosed with an olfactory neuroblastoma that extended from the nasal cavity to the anterior cranial base and infiltrated the right anterior cranial fossa. Case 2 was a 65-year-old man who presented with epistaxis and was diagnosed with a left-sided olfactory neuroblastoma. In both cases, en bloc tumor resection was successfully performed via a simultaneous exoscopic transcranial approach using a 3D-HMD and an endoscopic endonasal approach, eliminating the need to watch a large monitor beside the patient.
LESSONS
This is the first report of using a 3D-HMD in transcranial surgery. The 3D-HMD effectively addressed issues with the field of vision and concentration while preserving the effectiveness of traditional microscopic and exoscopic procedures when observed on a 3D monitor. Combining the 3D-HMD with an exoscope holds the potential to become a next-generation surgical approach.
PubMed: 38048570
DOI: 10.3171/CASE23594 -
Head & Neck Feb 2024A critical procedure in the transcribriform approach is the resection of the crista galli. However, the standard technique for crista galli resection has several...
A critical procedure in the transcribriform approach is the resection of the crista galli. However, the standard technique for crista galli resection has several disadvantages. We reviewed the cases of patients with olfactory neuroblastomas who underwent an endoscopic endonasal transcribriform approach using a newly developed technique for crista galli resection. We performed a cadaveric study to measure the superior accessibility limits using the proposed method. We included 38 patients with olfactory neuroblastomas in this study. The tumor invaded the posterior crista galli in four patients. The anterior end of the crista galli was not invaded by the tumor. Our cadaveric study showed that the dura was approachable to the point that was 7.4 ± 1.3 mm superior and 23.2 ± 7.2 mm lateral to the foramen cecum following crista galli removal. By resecting the crista galli in advance, manipulation of the superior dura became feasible.
Topics: Humans; Cadaver; Esthesioneuroblastoma, Olfactory; Ethmoid Bone; Nasal Cavity; Nose Neoplasms
PubMed: 38041523
DOI: 10.1002/hed.27590 -
Diagnostic Pathology Nov 2023Neuroblastoma is rare in the adult population, especially in thoracic or mediastinal locations, with only 25 previously reported cases. We report an additional example... (Review)
Review
Neuroblastoma is rare in the adult population, especially in thoracic or mediastinal locations, with only 25 previously reported cases. We report an additional example of primary thymic neuroblastoma in a previously asymptomatic 71-year-old man with an anterior mediastinal mass who underwent robotic excision with pericardium and adjacent lung. The tumor was a 5.2 cm partially encapsulated, white-tan and rubbery mass with grossly identifiable areas of necrosis (25%) and hemorrhage. Histologically, the specimen showed a rim of adipose tissue and residual thymic tissue with areas of cystic thymic epithelium and prominent lymphoid tissue containing Hassall's corpuscles. The tumor was composed of uniform, round cells with scant cytoplasm and small nuclei with inconspicuous nucleoli set within a background of conspicuous neuropil. Mitotic figures were easily found. By immunohistochemistry, the tumor cells expressed synaptophysin, chromogranin, NKX2.2 (diffuse, nuclear), GFAP (patchy), SMI31 (neurofilament) (focal, cytoplasmic), and TdT (diffuse, nuclear), while lacking expression of CD99, TTF-1, CK 20, MCPyV, PHOX2B, Olig2, OCT3/4, CD45, CD3 and PAX5. S100 protein was negative in the neuroblastic cells, with scattered positive cells in a vague sustentacular-like pattern. Fluorescence in situ hybridization for isochromosome 12p and EWSR1 gene rearrangement were negative. As thymic neuroblastoma is extremely rare in adults, a neuroblastic tumor of germ cell origin (either primary or metastatic) or spread from a sinonasal tract tumor should be excluded because of differing treatments and prognoses. The properties of these rare neoplasms appear similar to olfactory neuroblastoma rather than pediatric-type neuroblastoma.
Topics: Adult; Aged; Humans; Male; Biomarkers, Tumor; Immunohistochemistry; In Situ Hybridization, Fluorescence; Mediastinal Neoplasms; Mediastinum; Neuroblastoma
PubMed: 38031161
DOI: 10.1186/s13000-023-01417-6