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1.
Sci Rep ; 10(1): 9065, 2020 06 03.
Article in English | MEDLINE | ID: mdl-32493984

ABSTRACT

Modulation of tumor microenvironment is an emerging frontier for new therapeutics. However in meningiomas, the most frequent adult brain tumor, the correlation of microenvironment with tumor phenotype is scarcely studied. We applied a variety of systems biology approaches to bulk tumor transcriptomics to explore the immune environments of both skull base and convexity (hemispheric) meningiomas. We hypothesized that the more benign biology of skull base meningiomas parallels the relative composition and activity of immune cells that oppose tumor growth and/or survival. We firstly applied gene co-expression networks to tumor bulk transcriptomics from 107 meningiomas (derived from 3 independent studies) and found immune processes to be the sole biological mechanism correlated with anatomical location while correcting for tumour grade. We then derived tumor immune cell fractions from bulk transcriptomics data and examined the immune cell-cytokine interactions using a network-based approach. We demonstrate that oncolytic Gamma-Delta T cells dominate skull base meningiomas while mast cells and neutrophils, known to play a role in oncogenesis, show greater activity in convexity tumors. Our results are the first to suggest the importance of tumor microenvironment in meningioma biology in the context of anatomic location and immune landscape. These findings may help better inform surgical decision making and yield location-specific therapies through modulation of immune microenvironment.


Subject(s)
Gene Expression/immunology , Meningeal Neoplasms/immunology , Meningioma/immunology , Skull Base Neoplasms/immunology , Brain/immunology , Brain/pathology , Brain Neoplasms/immunology , Brain Neoplasms/pathology , Female , Humans , Male , Meningeal Neoplasms/pathology , Meningioma/pathology , Neoplasm Grading , Neutrophils/immunology , Skull Base/immunology , Skull Base/pathology , Skull Base Neoplasms/pathology , T-Lymphocytes/immunology , Transcriptome/immunology , Tumor Microenvironment/immunology
2.
Laryngoscope ; 130(11): 2574-2580, 2020 11.
Article in English | MEDLINE | ID: mdl-31841234

ABSTRACT

OBJECTIVE: IgG4-related disease (IgG4-RD) is a recently recognized disease characterized by fibroinflammatory infiltrates rich in IgG4+ plasma cells that can present as isolated tumor-like lesions of the head and neck. The objective of the current study was to describe the cranial base manifestations of IgG4-RD. METHODS: Review of all cases at three tertiary-referral centers since disease description in 2003. RESULTS: Eleven patients were identified at a median age at presentation of 58 years (IQR, 38-65; 55% male). Ten (91%) patients had isolated skull base masses without systemic disease. Cranial neuropathies were commonly observed in the abducens (45%), trigeminal (18%), and facial nerves (18%). Lesions frequently involved the cavernous sinus (55%; 6/11) with extension to the petroclival junction in 50% (3/6). Infiltration of the internal auditory canal was present in 27% (3/11) with one case demonstrating erosion of the bony labyrinth. Preliminary clinical diagnoses commonly included nasopharyngeal cancer, pituitary macroadenoma, cholesteatoma, and meningioma / multiple meningioma syndrome. Local biopsy demonstrated >30 IgG4-positive plasma cells per high-powered field or an IgG4:IgG ratio greater than 40% in all cases. Rapid and durable clinical improvement was seen in 91% following corticosteroid and rituximab therapy. CONCLUSIONS: IgG4-RD nonspecifically presents as a rare cause of the skull base mass. Often presenting without concomitant systemic disease, local diagnostic biopsies are required. Obtaining adequate tissue specimen is complicated by densely fibrotic cranial base lesions that are frequently in close proximity to critical neurovascular structures. Primary medical therapy with corticosteroids and rituximab is effective in most patients. LEVEL OF EVIDENCE: 4 Laryngoscope, 130:2574-2580, 2020.


Subject(s)
Head and Neck Neoplasms/immunology , Immunoglobulin G4-Related Disease/complications , Skull Base Neoplasms/immunology , Adult , Aged , Female , Humans , Immunoglobulin G/blood , Immunoglobulin G4-Related Disease/immunology , Male , Middle Aged , Plasma Cells/immunology , Skull Base/immunology
3.
Acta Neurol Belg ; 119(3): 431-437, 2019 Sep.
Article in English | MEDLINE | ID: mdl-30840222

ABSTRACT

Skull base osteomyelitis is a serious disease with a high risk of complications including neuroinfection. Typically, the inflammation of the skull base results from infection from neighboring tissues. In case of malignant otitis externa, inflammation disseminates from the external auditory canal. In this study, we present our experience with seven patients diagnosed with skull base osteomyelitis that began with otitis externa and have been treated in our department for the last 10 years. Department Patient Database was searched for the diagnosis skull base osteomyelitis. The search covered the last 10 years. The search revealed seven patients who met the above-described criteria. Medical records of those patients were carefully analyzed including age, gender, symptoms and signs, diagnostics details, treatment, performed procedures, number of hospitalization days, comorbid diseases, and complications including any cranial nerve palsy. Detailed analysis of medical records of patients included in this study showed that skull base osteomyelitis presents a challenge for diagnosis and treatment. Treatment strategy requires prolonged aggressive intravenous antibiotic therapy, and in some cases combined with surgical intervention. Cranial nerve paresis indicates progression of the disease and is associated with longer hospital stay. Similar relationship is observed in patients with skull base osteomyelitis that required surgery. Diabetes in patient's medical history may complicate the healing process. Diabetes, neural involvement, and surgery may overlap each other resulting in longer hospital stay. Cranial nerve paresis may not resolve completely and some neural deficits become persistent.


Subject(s)
Length of Stay , Osteomyelitis/diagnosis , Osteomyelitis/therapy , Outcome Assessment, Health Care , Skull Base , Adult , Aged , Aged, 80 and over , Cranial Nerve Diseases/etiology , Cranial Nerve Diseases/therapy , Female , Humans , Male , Middle Aged , Osteomyelitis/etiology , Otitis Externa/complications , Paresis/etiology , Paresis/therapy , Prognosis , Retrospective Studies , Skull Base/immunology , Skull Base/pathology
4.
Otolaryngol Head Neck Surg ; 151(3): 496-502, 2014 Sep.
Article in English | MEDLINE | ID: mdl-24812077

ABSTRACT

OBJECTIVE: IgG4-related disease (IgG4RD) causing sinonasal and skull base pathology is uncommonly described. We present a series of suspected IgG4RD patients, with a pertinent review of the literature to highlight diagnostic challenges. STUDY DESIGN: Case series. SETTING: Academic tertiary care center. SUBJECTS AND METHODS: Case series of patients with IgG4RD or suspected IgG4RD involving the sinonasal cavity and skull base. RESULTS: We present 4 patients with atypical sinonasal and/or skull base disease who were noted to have IgG4-positive plasma cell infiltration on immunohistochemistry of biopsy specimens. IgG4RD, a recently described entity affecting multiple organs, is characterized by lymphoplasmacytic infiltration and often elevated serum IgG4. IgG4RD can masquerade as malignancy or infection but responds to glucocorticosteroid and immunosuppressant therapy. IgG4RD has been infrequently reported presenting as sinonasal or skull base lesions, and definitive diagnostic criteria for these regions are not established. In our series, IgG4RD was suspected in all 4 patients, but only 1 met all current criteria for definitive diagnosis. All 4 patients, however, responded to corticosteroid therapy, and 1 was placed on long-term azathioprine. CONCLUSION: IgG4RD is rarely described in the sinonasal cavity and skull base, and specific diagnostic criteria for such disease have not been defined. We present a series of patients with IgG4-positive plasma cell inflammatory pathology who were suspected to have IgG4RD. Our series highlights diagnostic challenges associated with these patients. Tumefactive and destructive sinonasal-skull base lesions with a plasma cell-rich infiltrate should incite suspicion of IgG4RD, and immunohistochemistry for IgG4-positive plasma cells should be performed.


Subject(s)
Adrenal Cortex Hormones/administration & dosage , Autoimmune Diseases/diagnosis , Immunoglobulin G/immunology , Paranasal Sinus Diseases/immunology , Plasma Cells/immunology , Skull Base/immunology , Aged , Autoimmune Diseases/drug therapy , Biopsy, Needle , Female , Humans , Immunoglobulin G/blood , Immunohistochemistry , Inflammation/immunology , Inflammation/pathology , Magnetic Resonance Imaging/methods , Male , Middle Aged , Paranasal Sinus Diseases/diagnosis , Paranasal Sinus Diseases/drug therapy , Plasma Cells/pathology , Risk Assessment , Sampling Studies , Skull Base/physiopathology , Tomography, X-Ray Computed/methods , Treatment Outcome
5.
Neurosurgery ; 72(2 Suppl Operative): ons194-207; discussion ons207, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23190637

ABSTRACT

BACKGROUND: The facial nerve has a short intracranial course but crosses critical and frequently accessed surgical structures during cranial base surgery. When performing approaches to complex intracranial regions, it is essential to understand the nerve's conventional and topographic anatomy from different surgical perspectives as well as its relationship with surrounding structures. OBJECTIVE: To describe the entire intracranial course of the facial nerve as observed via different neurosurgical approaches and to provide an analytical evaluation of the degree of nerve exposure achieved with each approach. METHODS: Anterior petrosectomies (middle fossa, extended middle fossa), posterior petrosectomies (translabyrinthine, retrolabyrinthine, transcochlear), a retrosigmoid, a far lateral, and anterior transfacial (extended maxillectomy, mandibular swing) approaches were performed on 10 adult cadaveric heads (20 sides). The degree of facial nerve exposure achieved per segment for each approach was assessed and graded independently by 3 surgeons. RESULTS: The anterior petrosal approaches offered good visualization of the nerve in the cerebellopontine angle and intracanalicular portion superiorly, whereas the posterior petrosectomies provided more direct visualization without the need for cerebellar retraction. The far lateral approach exposed part of the posterior and the entire inferior quadrants, whereas the retrosigmoid approach exposed parts of the superior and inferior quadrants and the entire posterior quadrant. Anterior and anteroinferior exposure of the facial nerve was achieved via the transfacial approaches. CONCLUSION: The surgical route used must rely on the size, nature, and general location of the lesion, as well as on the capability of the particular approach to better expose the appropriate segment of the facial nerve.


Subject(s)
Facial Nerve/anatomy & histology , Skull Base/immunology , Skull Base/surgery , Cadaver , Humans
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