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Cancer Cell Jun 2024The olfactory epithelium undergoes neuronal regeneration from basal stem cells and is susceptible to olfactory neuroblastoma (ONB), a rare tumor of unclear origins....
The olfactory epithelium undergoes neuronal regeneration from basal stem cells and is susceptible to olfactory neuroblastoma (ONB), a rare tumor of unclear origins. Employing alterations in Rb1/Trp53/Myc (RPM), we establish a genetically engineered mouse model of high-grade metastatic ONB exhibiting a NEUROD1 immature neuronal phenotype. We demonstrate that globose basal cells (GBCs) are a permissive cell of origin for ONB and that ONBs exhibit cell fate heterogeneity that mimics normal GBC developmental trajectories. ASCL1 loss in RPM ONB leads to emergence of non-neuronal histopathologies, including a POU2F3 microvillar-like state. Similar to small-cell lung cancer (SCLC), mouse and human ONBs exhibit mutually exclusive NEUROD1 and POU2F3-like states, an immune-cold tumor microenvironment, intratumoral cell fate heterogeneity comprising neuronal and non-neuronal lineages, and cell fate plasticity-evidenced by barcode-based lineage tracing and single-cell transcriptomics. Collectively, our findings highlight conserved similarities between ONB and neuroendocrine tumors with significant implications for ONB classification and treatment.
Topics: Animals; Mice; Small Cell Lung Carcinoma; Humans; Esthesioneuroblastoma, Olfactory; Cell Lineage; Lung Neoplasms; Basic Helix-Loop-Helix Transcription Factors; Tumor Microenvironment; Nose Neoplasms; Olfactory Mucosa; Disease Models, Animal; Tumor Suppressor Protein p53
PubMed: 38788720
DOI: 10.1016/j.ccell.2024.05.003 -
Acta Neurochirurgica May 2024Extracorporeal irradiation of tumorous calvaria (EITC) can be performed to restore function and form of the skull after resection of bone-invasive meningioma. We sought...
BACKGROUND
Extracorporeal irradiation of tumorous calvaria (EITC) can be performed to restore function and form of the skull after resection of bone-invasive meningioma. We sought to examine the rate of tumour recurrence and other selected outcomes in patients undergoing meningioma resection and EITC.
METHODS
Retrospective single-centre study of adult patients undergoing meningioma resection and EITC between January 2015 and November 2022 at a tertiary neurosurgical centre. Patient demographics, surgery data, tumour data, use of adjuvant therapy, surgical complications, and tumour recurrences were collected.
RESULTS
Eighteen patients with 11 (61%) CNS WHO grade 1, 6 (33%) grade 2, and 1 (6%) grade 3 meningiomas were included. Median follow-up was 42 months (range 3-88). Five (28%) patients had a recurrence, but none were associated with the bone flap. Two (11%) wound infections requiring explant surgery occurred. Six (33%) patients required a further operation. Two operations were for recurrences, one was for infection, one was a washout and wound exploration but no evidence of infection was found, one patient requested the removal of a small titanium implant, and one patient required a ventriculoperitoneal shunt for a persistent CSF collection. There were no cases of bone flap resorption and cosmetic outcome was not routinely recorded.
CONCLUSION
EITC is feasible and fast to perform with good outcomes and cost-effectiveness compared to other reconstructive methods. We observed similar recurrence rates and lower infection rates requiring explant compared to the largest series of cranioplasty in meningioma. Cosmetic outcome is universally under-reported and should be reported in future studies.
Topics: Humans; Meningioma; Female; Male; Middle Aged; Meningeal Neoplasms; Aged; Craniotomy; Retrospective Studies; Adult; Surgical Flaps; Neoplasm Recurrence, Local; Treatment Outcome
PubMed: 38787452
DOI: 10.1007/s00701-024-06126-7 -
Frontiers in Immunology 2024Glioma is a malignant tumor of the central nervous system (CNS). Currently, effective treatment options for gliomas are still lacking. Neutrophils, as an important... (Review)
Review
Glioma is a malignant tumor of the central nervous system (CNS). Currently, effective treatment options for gliomas are still lacking. Neutrophils, as an important member of the tumor microenvironment (TME), are widely distributed in circulation. Recently, the discovery of cranial-meningeal channels and intracranial lymphatic vessels has provided new insights into the origins of neutrophils in the CNS. Neutrophils in the brain may originate more from the skull and adjacent vertebral bone marrow. They cross the blood-brain barrier (BBB) under the action of chemokines and enter the brain parenchyma, subsequently migrating to the glioma TME and undergoing phenotypic changes upon contact with tumor cells. Under glycolytic metabolism model, neutrophils show complex and dual functions in different stages of cancer progression, including participation in the malignant progression, immune suppression, and anti-tumor effects of gliomas. Additionally, neutrophils in the TME interact with other immune cells, playing a crucial role in cancer immunotherapy. Targeting neutrophils may be a novel generation of immunotherapy and improve the efficacy of cancer treatments. This article reviews the molecular mechanisms of neutrophils infiltrating the central nervous system from the external environment, detailing the origin, functions, classifications, and targeted therapies of neutrophils in the context of glioma.
Topics: Humans; Tumor Microenvironment; Glioma; Neutrophils; Immunotherapy; Brain Neoplasms; Animals; Blood-Brain Barrier; Neutrophil Infiltration
PubMed: 38779679
DOI: 10.3389/fimmu.2024.1393173 -
Journal of Medical Case Reports May 2024Mucosal melanoma, an aggressive type of malignancy different from the cutaneous melanomas commonly seen in the head and neck region, represents < 1% of all malignant...
BACKGROUND
Mucosal melanoma, an aggressive type of malignancy different from the cutaneous melanomas commonly seen in the head and neck region, represents < 1% of all malignant melanomas. The pathogenesis of mucosal melanoma is unknown. Targetable mutations commonly seen in cutaneous melanoma, such as in the BRAF and NRAS genes, have a lower incidence in mucosal melanoma. Mucosal melanoma carries a distinct mutational pattern from cutaneous melanoma. Surgery with negative margins is the first-line treatment for mucosal melanoma, and systemic therapy is not well defined. Talimogene laherparepvec, an oncolytic viral immunotherapy, is United States Food and Drug Administration approved for the treatment of advanced malignant cutaneous melanoma, with local therapeutic benefits. Mucosal melanoma was initially excluded from talimogene laherparepvec's initial phase III clinical trial.
CASE PRESENTATION
We present the case of a white female patient in her 40s with past medical history of systemic lupus erythematous, scleroderma, and estrogen-receptor-positive invasive ductal breast carcinoma. Following a bilateral mastectomy, the patient was found to have BRAF-negative mucosal melanoma of her hard palate with a soft palate skip lesion. Owing to the presence of a skip mucosal lesion as well as the anticipated defect and need for free-flap reconstructive surgery, nonsurgical management was considered. The patient was referred to medical oncology, where-based on the patient's complicated medical history and the risk of immunotherapy possibly worsening her prior autoimmune diseases-local talimogene laherparepvec injections were chosen as the primary therapy for her mucosal lesions. Though talimogene laherparepvec is approved for the treatment of cutaneous melanoma, there are limited data available on the use of talimogene laherparepvec in mucosal melanomas.
CONCLUSION
The patient had a complete local tumor response at both the primary lesion as well as the skip lesion with the local injections. She had no side effects and maintained a high quality of life during treatment.
Topics: Humans; Melanoma; Female; Biological Products; Adult; Herpesvirus 1, Human; Mouth Mucosa; Injections, Intralesional; Treatment Outcome; Antineoplastic Agents, Immunological; Oncolytic Virotherapy; Palatal Neoplasms
PubMed: 38778387
DOI: 10.1186/s13256-024-04554-8 -
Journal of Medical Case Reports May 2024A central giant cell granuloma (CGCG) is a benign, proliferative, intraosseous, and non-odontogenic lesion occurring primarily in children and young adults. On the...
BACKGROUND
A central giant cell granuloma (CGCG) is a benign, proliferative, intraosseous, and non-odontogenic lesion occurring primarily in children and young adults. On the histological level, it is characterized by numerous multinucleated giant cells scattered randomly throughout a sea of spindle-shaped mesenchymal stromal cells which are dispersed throughout the fibrovascular connective tissue stroma containing areas of haemorrhage. When it comes to radiographic features, CGCG can have an array of variations, ranging from well-defined expansile lesions to ill-defined and destructive lesions, with or without expansion.
CASE PRESENTATION
This case report reviews an 11-year-old Caucasian patient with a chief complaint of slow-growing swelling involving the right posterior mandibular region. The cone beam computed tomography (CBCT) revealed an ill-defined mixed lesion mimicking both fibro-osseous lesion and hemangioma. However, microscopic examination revealed multinucleated giant cells in a fibrous stroma suggestive of central giant cell granuloma.
CONCLUSION
Our intent in reporting this case is to highlight the importance of thorough clinical, radiographical and histopathological examination for accurate diagnosis and therapeutic interventions as well as to emphasize the importance of taking different possibilities into consideration when examining bony swellings in the head and neck region.
Topics: Child; Humans; Male; Cone-Beam Computed Tomography; Diagnosis, Differential; Granuloma, Giant Cell; Hemangioma; Mandible; Mandibular Diseases; Mandibular Neoplasms
PubMed: 38769587
DOI: 10.1186/s13256-024-04571-7 -
Prague Medical Report 2024Salivary gland neoplasms account for 3% of all head and neck tumours. Pleomorphic adenoma (PA) is the most common salivary gland tumour that mainly occurs in the parotid...
Salivary gland neoplasms account for 3% of all head and neck tumours. Pleomorphic adenoma (PA) is the most common salivary gland tumour that mainly occurs in the parotid gland, followed by minor salivary glands of the oral cavity, however, the occurrence of PA inside the jaw bones is exceedingly rare and very few cases have been reported in the literature. Inside jaw bones these lesions tend to imitate large osteolytic lesions encompass a diagnostic challenge. An exhaustive review of the literature revealed only 10 cases of central pleomorphic adenoma. We present a rare case of primary PA that occurred inside the mandible and was provisionally diagnosed as ameloblastoma.
Topics: Humans; Male; Adenoma, Pleomorphic; Ameloblastoma; Diagnosis, Differential; Mandibular Neoplasms; Adult
PubMed: 38761048
DOI: 10.14712/23362936.2024.14 -
Acta Neuropathologica May 2024Pituitary neuroendocrine tumors (PitNETs) exhibiting aggressive, treatment-refractory behavior are the rare subset that progress after surgery, conventional medical...
Pituitary neuroendocrine tumors (PitNETs) exhibiting aggressive, treatment-refractory behavior are the rare subset that progress after surgery, conventional medical therapies, and an initial course of radiation and are characterized by unrelenting growth and/or metastatic dissemination. Two groups of patients with PitNETs were sequenced: a prospective group of patients (n = 66) who consented to sequencing prior to surgery and a retrospective group (n = 26) comprised of aggressive/higher risk PitNETs. A higher mutational burden and fraction of loss of heterozygosity (LOH) was found in the aggressive, treatment-refractory PitNETs compared to the benign tumors (p = 1.3 × 10 and p = 8.5 × 10, respectively). Within the corticotroph lineage, a characteristic pattern of recurrent chromosomal LOH in 12 specific chromosomes was associated with treatment-refractoriness (occurring in 11 of 14 treatment-refractory versus 1 of 14 benign corticotroph PitNETs, p = 1.7 × 10). Across the cohort, a higher fraction of LOH was identified in tumors with TP53 mutations (p = 3.3 × 10). A machine learning approach identified loss of heterozygosity as the most predictive variable for aggressive, treatment-refractory behavior, outperforming the most common gene-level alteration, TP53, with an accuracy of 0.88 (95% CI: 0.70-0.96). Aggressive, treatment-refractory PitNETs are characterized by significant aneuploidy due to widespread chromosomal LOH, most prominently in the corticotroph tumors. This LOH predicts treatment-refractoriness with high accuracy and represents a novel biomarker for this poorly defined PitNET category.
Topics: Humans; Loss of Heterozygosity; Pituitary Neoplasms; Neuroendocrine Tumors; Male; Female; Middle Aged; Adult; Aged; Retrospective Studies; Mutation; Prospective Studies
PubMed: 38758238
DOI: 10.1007/s00401-024-02736-8 -
Zhongguo Xiu Fu Chong Jian Wai Ke Za... May 2024To explore the feasibility and effectiveness of mixed reality technology for localizing perforator vessels in the repair of mandibular defects using free fibular flap.
OBJECTIVE
To explore the feasibility and effectiveness of mixed reality technology for localizing perforator vessels in the repair of mandibular defects using free fibular flap.
METHODS
Between June 2020 and June 2023, 12 patients with mandibular defects were repaired with free fibular flap. There were 8 males and 4 females, with an average age of 61 years (range, 35-78 years). There were 9 cases of ameloblastomas and 3 cases of squamous cell carcinomas involving the mandible. The disease duration ranged from 15 days to 2 years (median, 14.2 months). The length of mandibular defects ranged from 5 to 14 cm (mean, 8.5 cm). The area of soft tissue defects ranged from 5 cm×4 cm to 8 cm×6 cm. Preoperative enhanced CT scans of the maxillofacial region and CT angiography of the lower limbs were performed, and the data was used to create three-dimensional models of the mandible and lower limb perforator vessels. During operation, the mixed reality technology was used to overlay the three-dimensional model of perforator vessels onto the body surface for harvesting the free fibular flap. The length of the fibula harvested ranged from 6 to 15 cm, with a mean of 9.5 cm; the size of the flap ranged from 6 cm×5 cm to 10 cm×8 cm. The donor sites were sutured directly in 7 cases and repaired with free skin grafting in 5 cases.
RESULTS
Thirty perforator vessels were located by mixed reality technology before operation, with an average of 2.5 vessels per case; the distance between the exit point of the perforator vessels located before operation and the actual exit point ranged from 1 to 4 mm, with a mean of 2.8 mm. All fibular flaps survived; 1 case had necrosis at the distal end of flap, which healed after dressing changes. One donor site had infection, which healed after anti-inflammatory dressing changes; the remaining incisions healed by first intention, and the grafts survived smoothly. All patients were followed up 8-36 months (median, 21 months). The repaired facial appearance was satisfactory, with no flap swelling. Among the patients underwent postoperative radiotherapy, 2 patients had normal bone healing and 1 had delayed healing at 6 months.
CONCLUSION
In free fibular flap reconstruction of mandibular defects, the use of mixed reality technology for perforator vessel localization can achieve three-dimensional visualization, simplify surgical procedures, and reduce errors.
Topics: Humans; Male; Middle Aged; Female; Adult; Free Tissue Flaps; Aged; Fibula; Mandible; Plastic Surgery Procedures; Carcinoma, Squamous Cell; Mandibular Neoplasms; Mandibular Reconstruction; Perforator Flap; Ameloblastoma
PubMed: 38752246
DOI: 10.7507/1002-1892.202402027 -
Brain Tumor Research and Treatment Apr 2024Eosinophilic granuloma (EG), a subtype of Langerhans cell histiocytosis (LCH), the monostotic form, is a rare condition characterized by a solitary bone lesion. It is...
Eosinophilic granuloma (EG), a subtype of Langerhans cell histiocytosis (LCH), the monostotic form, is a rare condition characterized by a solitary bone lesion. It is even more unusual for this condition to be accompanied by an epidural hematoma (EDH). This case is unique in that it is the first to involve delayed EDH following a seizure. We describe a remarkable example of EG accompanied by an EDH and consider the rarity of this comorbidity. A 32-month-old boy developed a rapidly growing skull mass following a minor head injury. During surgical preparation for a biopsy, the patient experienced a single convulsion. Imaging following the seizure revealed an EDH in the vicinity of the mass. The mass was excised and confirmed to be an EG, but with positive margins. The patient underwent chemotherapy after systemic skeletal evaluation, in accordance with the LCH III protocol established by the Histiocytosis Society. EG is a rare neoplasm that typically presents as a painless growth on the skull that gradually enlarges over time. The correlation between EG and EDH is exceedingly uncommon, with only a few documented cases. This case study underscores the significance of considering EG in the differential diagnosis of an expanding cranium mass, even when associated with EDH. Prompt diagnosis and treatment can prevent serious complications and improve patient outcomes.
PubMed: 38742265
DOI: 10.14791/btrt.2024.0018 -
Indian Journal of Dental Research :... Oct 2023Ossifying fibromas are rare, non-aggressive benign tumours of the bone, commonly involving the posterior mandible in middle-aged individuals with a female predilection.
INTRODUCTION
Ossifying fibromas are rare, non-aggressive benign tumours of the bone, commonly involving the posterior mandible in middle-aged individuals with a female predilection.
FINDINGS
Clinical manifestations include asymptomatic expansion of the mandible with infrequent maxillary lesions, pain, malocclusion, and compromised quality of life including aesthetic perception. Owing to multiplicity of features, tendency of recurrence, and possibility of malignant transformation, the diagnosis, treatment, and post-operative management of ossifying fibroma are always a challenge.
TAKEAWAY LESSONS
Study aims to report a clinical case of extensive swelling involving the coronoid process and condyle on the right side to crossing the mid-line of the mandible with compromised functions and aesthetics. The article describes the clinical, histopathological, and radiological features of the case. The possible treatment and challenges encountered are discussed.
Topics: Humans; Fibroma, Ossifying; Mandibular Neoplasms; Female; Radiography, Panoramic; Adult
PubMed: 38739833
DOI: 10.4103/ijdr.ijdr_134_21