Augmentation of tumor expression of HLA-DR, CXCL9, and CXCL10 may improve olfactory neuroblastoma immunotherapeutic responses.

BACKGROUND: Olfactory neuroblastoma is a rare malignancy of the anterior skull base typically treated with surgery and adjuvant radiation. Although outcomes are fair for low-grade disease, patients with high-grade, recurrent, or metastatic disease oftentimes respond poorly to standard treatment methods. We hypothesized that an in-depth evaluation of the olfactory neuroblastoma tumor immune microenvironment would identify mechanisms of immune evasion in high-grade olfactory neuroblastoma as well as rational targetable mechanisms for future translational immunotherapeutic approaches. METHODS: Multispectral immunofluorescence and RNAScope evaluation of the tumor immune microenvironment was performed on forty-seven clinically annotated olfactory neuroblastoma samples. A retrospective chart review was performed and clinical correlations assessed. RESULTS: A significant T cell infiltration was noted in olfactory neuroblastoma samples with a stromal predilection, presence of myeloid-derived suppressor cells, and sparse natural killer cells. A striking decrease was observed in MHC-I expression in high-grade olfactory neuroblastoma compared to low-grade disease, representing a mechanism of immune evasion in high-grade disease. Mechanistically, the immune effector stromal predilection appears driven by low tumor cell MHC class II (HLA-DR), CXCL9, and CXCL10 expression as those tumors with increased tumor cell expression of each of these mediators correlated with significant increases in T cell infiltration. CONCLUSION: These data suggest that immunotherapeutic strategies that augment tumor cell expression of MHC class II, CXCL9, and CXCL10 may improve parenchymal trafficking of immune effector cells in olfactory neuroblastoma and augment immunotherapeutic responses.

Deep learning model for differentiating nasal cavity masses based on nasal endoscopy images.

BACKGROUND: Nasal polyps and inverted papillomas often look similar. Clinically, it is difficult to distinguish the masses by endoscopic examination. Therefore, in this study, we aimed to develop a deep learning algorithm for computer-aided diagnosis of nasal endoscopic images, which may provide a more accurate clinical diagnosis before pathologic confirmation of the nasal masses. METHODS: By performing deep learning of nasal endoscope images, we evaluated our computer-aided diagnosis system's assessment ability for nasal polyps and inverted papilloma and the feasibility of their clinical application. We used curriculum learning pre-trained with patches of nasal endoscopic images and full-sized images. The proposed model's performance for classifying nasal polyps, inverted papilloma, and normal tissue was analyzed using five-fold cross-validation. RESULTS: The normal scores for our best-performing network were 0.9520 for recall, 0.7900 for precision, 0.8648 for F1-score, 0.97 for the area under the curve, and 0.8273 for accuracy. For nasal polyps, the best performance was 0.8162, 0.8496, 0.8409, 0.89, and 0.8273, respectively, for recall, precision, F1-score, area under the curve, and accuracy. Finally, for inverted papilloma, the best performance was obtained for recall, precision, F1-score, area under the curve, and accuracy values of 0.5172, 0.8125, 0.6122, 0.83, and 0.8273, respectively. CONCLUSION: Although there were some misclassifications, the results of gradient-weighted class activation mapping were generally consistent with the areas under the curve determined by otolaryngologists. These results suggest that the convolutional neural network is highly reliable in resolving lesion locations in nasal endoscopic images.

The Two-Stage Folded Paramedian Forehead Flap Without Cartilage Grafts for Full Thickness Distal Nasal Defects: A Review of 35 Patients.

BACKGROUND: Full thickness defects of the ala, soft triangle, and nasal tip involving the nasal lining have traditionally been repaired with the three-stage folded paramedian forehead flap (FPFF), with a cartilage graft for support. For similar defects, the authors utilize the two-stage FPFF without cartilaginous support which provides reproducible functional and aesthetic results.  Objective: To describe the authors’ experience with the two-stage FPFF, including outcomes, complications, and design modifications to enhance functional and aesthetic success.  Methods: An IRB-approved retrospective database review of FPFF was performed at two sites. Using postoperative photographs, outcomes were assessed by blinded non-investigator dermatologist raters using a modified observer scar assessment scale. RESULTS: Thirty-five patients were reconstructed using the two-stage FPFF without cartilage grafts. Subjective assessment of scar vascularity, pigment, relief, and thickness by 3 independent reviewers yielded an overall cosmesis score of 8.4±1.9 (out of 40). CONCLUSION: The two-stage FPFF without cartilage grafts is a reliable, cosmetically elegant repair that can provide optimal functional and aesthetic results for complex unilateral distal nose defects.J Drugs Dermatol. 2024;23(4): doi:10.36849/JDD.7358.

Diagnostic accuracy of clinical visual assessment using endoscopic images for nasal cavity mass lesions.

Objectives: Discrimination of nasal cavity lesions using nasal endoscopy is challenging because of the differences in clinical manifestations and treatment strategies. We aimed to investigate the diagnostic accuracy of clinical visual assessment (CVA) of nasal cavity masses using endoscopic images and determine whether there is a difference according to pathologic class and the examiners' experience. Methods: We collected pathologically confirmed endoscopic images of normal findings, nasal polyp (NP), benign tumor, and malignant tumor (each class contained 100 images) randomly selected. Eighteen otolaryngologists, including six junior residents, six senior residents, and six board-certified rhinologists classified the test set images into four classes of lesions by CVA. Diagnostic performance according to the pathologic class and the examiner's experience level was evaluated based on overall accuracy, F1-score, confusion matrix, and area under the receiver operating characteristic curve (AUC). Results: Diagnostic performance was significantly different according to the pathological class of nasal cavity mass lesions with the overall accuracy reported high in the order of normal, NP, benign tumor, and malignant tumor (0.926 ± 0.100; 0.819 ± 0.135; 0.580 ± 0.112; 0.478 ± 0.187, respectively), F1 score (0.937 ± 0.076; 0.730 ± 0.093; 0.549 ± 0.080; 0.554 ± 0.146, respectively) and AUC value (0.96 ± 0.06; 0.84 ± 0.07; 0.70 ± 0.05; 0.71 ± 0.08, respectively). The expert rhinologist group achieved higher overall accuracy than the resident group (0.756 ± 0.157 vs. 0.680 ± 0.239, p < .05). Conclusion: CVA for nasal cavity mass was highly dependent on the pathologic class and examiner's experience. The overall accuracy was reliably high for normal findings, but low in classifying benign and malignant tumors. Differential diagnosis of lesions solely based on nasal endoscopic evaluation is challenging. Therefore, clinicians should consider further clinical evaluation for suspicious cases.

Advantages of the co2 laser use in the rare condition of nasal mucosa squamous cell carcinoma surgery in dogs-a clinical prospective study.

Nasal mucosa tumors are an uncommon process and very dificult to work on with surgery. Radiotherapy associated or not with chemotherapy is the standard method to treat the disease. However, its access it is in the majority of the case not possible, making the surgery the best choice to try to achieve the patient's control. The anatomy of the region makes the complete surgical resection very difficult to achieve using the common and conventional blade scalpel surgery. The study features the advantages of using a CO2 laser to perform nasal mucosa carcinoma surgery in 6 dogs (N = 6). For the work we used an Aesculigth CO2 surgical laser model -Vetscalpel®, with the settings of 12Watts in a Superpulse mode, and a 0.25-0.4 mm focus to dissect the nasal mucosa, and a 1.5 mm focus for vaporization of the area. All the masses were histopathologically characterized as squamous cells carcinoma. The CO2 surgical laser allow us to work in a bloodless region promoting a more accurate dissection of the nasal mucosa sparing therefore the underlying and adjacent tissues and being less invasive. Also, it was possible to do the vaporization of the entire surgical area interviened. None of the patients presented relapse of clinical signs. Only 2 individuals were alive at the end of the study, presenting a survival rate of 420 and 514 days, which is in the same line of literature results of the treatment with radiotherapy combined with chemotherapy wich shows a median of 474-580 days. The study demonstrates successful outcomes with CO2 laser surgery in treating nasal mucosa SCC in dogs, with patients experiencing improved survival rates compared to traditional treatment methods. This highlights the efficacy and potential of CO2 laser surgery as a valuable tool in managing aggressive nasal tumors in veterinary oncology.

The impact of multidisciplinary approaches on the outcomes of olfactory neuroblastoma treated with postoperative radiotherapy.

BACKGROUND: We investigated the outcomes of postoperative radiation therapy for olfactory neuroblastoma (ONB) and our cross-departmental collaboration to enhance the effectiveness of cancer treatment. METHODS: We retrospectively evaluated 22 patients with ONB who underwent postoperative radiotherapy after tumor resection. En bloc resection was performed; pathology specimens were prepared in coronal sections; and irradiation fields were determined after discussion with radiation oncologists, head and neck surgeons, and pathologists. RESULTS: The overall survival and local control rates were 95.5% and 100%, respectively, at a median 37-month follow-up. The 3- and 5-year disease-free survival (DFS) rates were 64.4% and 56.3%, respectively. Of the 22 patients, 9 (8 Kadish C and 1 Kadish B) had disease recurrence. Of the nine patients, five had positive margins and two had closed margins; cervical lymph node recurrence occurred in six, and distant metastasis with or without cervical lymph node recurrence occurred in three. DFS analysis of risk factors showed no statistically significant differences, but positive margins were a significant recurrence factor in multivariate analysis. CONCLUSIONS: The local control rate of ONB treated with postoperative radiation therapy was 100%. This may be attributed to cross-departmental cooperation between head and neck surgeons, pathologists, and radiation oncologists, which resulted in accurate matching of CT images for treatment planning with the location of the tumor and positive margins. Longer follow-up periods are required to evaluate the effectiveness of our strategy.

Treatment of unilateral olfactory neuroblastoma: Appropriate extent of surgical resection and potential for olfactory preservation.

Historically, comprehensive surgical resection for olfactory neuroblastoma has included the bilateral olfactory epithelium, cribriform plate, overlying dura, olfactory bulbs and tracts. This results in postoperative anosmia that may significantly impact a patient's quality of life without definitive added benefit in survival. The prevalence of occult intracranial disease is low, especially for Hyams grade I and II tumors. A unilateral approach sparing the contralateral cribriform plate and olfactory system can be considered for select cases of early stage, low-grade tumors when the disease does not cross midline to involve the contralateral olfactory cleft or septal mucosa and when midline dural margins can be cleared with frozen pathology. Approximately half of patients who undergo unilateral resection may have residual olfaction even with adjuvant unilateral radiation. Early data suggest favorable disease-free survival and overall survival for patients who underwent the unilateral approach; however, larger sample studies are needed to confirm comparability to bilateral resections regarding oncologic outcomes.

Squamous cell carcinoma of the nasal vestibule in the Netherlands: A clinical and epidemiological review of 763 cases (2008-2021).

BACKGROUND: Squamous cell carcinoma of the nasal vestibule (SCCNV) is a rare disease, distinctly different in presentation, treatment, and outcome from squamous cell carcinoma (SCC) of the nasal cavity and paranasal sinuses. However, these are often not analyzed separately. METHODS: The Netherlands Cancer Registry (NCR) and pathology reports from the Dutch Nationwide Pathology Databank (PALGA) were used to identify all newly diagnosed SCCNV cases in the Netherlands between 2008 and 2021. RESULTS: A total of 763 patients were included. The yearly incidence rate displayed a significant downward trend with an annual percentage change (APC) of -3.9%. The 5-year overall survival (OS) and disease-free survival were 69.0% and 77.2%, respectively. The 5-year relative survival was 77.9% and improved slightly over the inclusion period. OS for patients who were staged cT3 appeared to be worse than those staged cT4a, calling the applicability of the TNM-classification into question. CONCLUSION: SCC of the nasal vestibule is rare, with declining incidence rates. Introducing a specific topography code for SCCNV is recommended to enhance registration accuracy. The TNM classification seems poorly applicable to SCCNV, suggesting the need to explore alternative staging methods.

Extranodal nasal-type NK/T-cell lymphoma with CD20 positive: A case report and review of literature.

ABSTRACT: Extranodal nasal-type natural killer (NK)/T-cell lymphoma is a type of non-Hodgkin lymphoma. Neoplastic lymphocytes are positive for CD4, CD56, and CD20, a specific B-cell marker. CD20 positive NK/T-cell lymphoma is rare, with only nine reported cases. This paper reports a case of nasal-type NK/T-cell lymphoma with CD20 positivity in a 47-year-old woman. The patient presented with bilateral nasal congestion and bloody nasal cavity secretions for 2 months. Computed tomography revealed thickening of the nasal mucosa and posterior wall of the nasopharyngeal crest, and the left and right cervical lymph nodes were enlarged. On histopathology, the lesion was composed of medium-sized atypical lymphoid cells and vascular infringement. Immunohistochemical staining showed that the tumor cells were positive for CD20, CD3, CD56, and Epstein-Barr virus (EBV)-encoded RNA in situ hybridization. The patient was treated with radiotherapy for 2 months and is currently well.

Recurrent Wnt Pathway and ARID1A Alterations in Sinonasal Olfactory Carcinoma.

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.

Update on olfactory neuroblastoma.

Olfactory neuroblastomas are uncommon malignancies that arise from olfactory receptor cells located high in the nasal cavity. Accurate diagnosis plays a crucial role in determining clinical results and guiding treatment decisions. Diagnosis can be a major challenge for pathologists, especially when dealing with tumours with poor differentiation. The discovery of several molecular and immunohistochemical markers would help to overcome classification difficulties. Due to the paucity of large-scale studies, standardisation of diagnosis, treatment and prediction of outcome remains a challenge. Surgical resection by endoscopic techniques with the addition of postoperative irradiation is the treatment of choice. In addition, it is advisable to consider elective neck irradiation to minimise the risk of nodal recurrence. Molecular characterisation will help not only to make more accurate diagnoses but also to identify specific molecular targets that can be used to develop personalised treatment options tailored to each patient. The present review aims to summarise the current state of knowledge on histopathological diagnosis, the molecular biology and management of this disease.

Sinonasal teratocarcinosarcoma in an adolescent male: A case report of an unusual neoplasm.

ABSTRACT: Sinonasal teratocarcinosarcoma (SNTCS) is an extremely rare and aggressive malignant tumor arising in the sinonasal tract, having a combined clinicopathological feature of teratoma and carcinosarcoma. It shows a male predominance and affects adults with an age range of 18-79 years and a mean age of 60 years. Here, we report a case of SNTCS in a 14-year-old male patient who presented with swelling over the upper right alveolus and pain in the right jaw for 2 months. The tumor was completely removed by right total maxillectomy with orbital mess reconstruction, and postoperative radiotherapy with chemotherapy was given. The follow-up of the patient for 2 years has shown evidence of recurrence and is now on palliative care.

A case report on a nasal and oral cavity involving large solitary fibrous tumor and comprehensive review of case literature.

Solitary fibrous tumor (SFT) represents an uncommon spindle cell sarcoma predominantly situated within soft tissue, with a notably infrequent occurrence in the nasal cavity and paranasal sinuses. In this report, we present a case involving a middle-aged male with a sizable solitary fibrous tumor affecting both the nasal and oral cavities.

[Inverted papilloma of the nose and paranasal sinuses : Diagnosis, treatment, and malignant transformation]. / Invertiertes Papillom der Nase und Nasennebenhöhlen : Diagnostik, Therapie und maligne Transformation.

Inverted papilloma (IP) are benign tumors that show a locally aggressive behavior, a high rate of recurrence, and a potential for malignant transformation. Specific radiological signs such as hyperostosis at the origin of the IP and convoluted cerebriform patterns, as well as the typical endoscopic aspect, can lead to diagnosis and enable preoperative planning of surgical access and the extent of surgery. Endonasal endoscopic techniques are considered the gold standard and the introduction of extended surgical techniques such as the prelacrimal approach, frontal drillout, or orbital transposition facilitate complete subperiosteal resection with preservation of important physiological structures. There is a risk of synchronous and metachronous squamous cell carcinomas (IP-SCC). Research focuses on radiological criteria to differentiate benign IP from IP-SCC, genetic and epigenetic factors in the process of malignant transformation, and estimation of the risk of IP progressing to IP-SCC.

A Case of Nasal Glial Heterotopia That Can Be Misdiagnosed as Storiform Patterned Sclerotic Fibroma/Collagenoma.

OBJECTIVE: Nasal glioma, also known as nasal glial heterotopia, is a rare tumor-like lesion that often affects newborns or infants with no hereditary predisposition. CASE REPORT: A 4-year-old child with a growth on the nasal dorsum since birth was diagnosed with nasal glial heterotopia/nasal glioma. The lesion showed a sclerotic fibroma/collagenoma-like storiform pattern with entrapped glial tissue that was S100 and GFAP positive. CONCLUSION: When a biopsy of the nasal dorsum demonstrates sclerotic microscopic findings with a storiform pattern, nasal glioma should be considered before making a diagnosis in the collagen-rich tissue spectrum (collagenoma or Gardner's fibroma), and an immunohistochemical panel should be requested to demonstrate the presence of an unrecognized light microscopically visible glial component.

Nasal spindle cell tumor: A case report and literature review.

BACKGROUND: Spindle cell tumors are rare and can occur in any organ or tissue. Due to their rarity the clinicopathological features and diagnostic protocols have not been adequately studied. However, it has become necessary to develop differential diagnosis of spindle cell tumors. Here, we report a case of a nasal spindle cell tumor diagnosed at our hospital in attempt to contribute to this gap in literature. KEY POINTS FROM THE CASE: A male in his 30s was admitted to our hospital with nasal obstruction that had persisted for several years. Electronic fibrolaryngoscopy revealed a smooth neoplasm within the nasal cavity. MAIN LESSONS TO BE LEARNED FROM THIS CASE REPORT: The results of this case emphasize that spindle cell tumors have large morphological variations, and it is difficult to determine the origin of tumor cells using hematoxylin and eosin staining alone. Therefore, it is necessary to improve the immunohistochemistry and combine it with clinical symptoms to diagnose the disease.

Characterizing Immune Infiltration in Esthesioneuroblastoma Subtypes Through Gene Expression Deconvolution.

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/mm2 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.