Hoxworth, Joseph M.

Background PFAPA (periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis) syndrome is diagnosed clinically. Adult-onset PFAPA syndrome is rare and often has a more diverse clinical presentation that its childhood counterpart. This is the first reported case of adult-onset PFAPA syndrome with complete response to lingual tonsillectomy. Case Summary A 41-year-old man was evaluated for periodic fevers associated with uvulitis, cervical lymphadenitis, pharyngitis, and lower extremity rash. He had a variable response to steroids and was intolerant of colchicine. Laboratory workup revealed intermittent elevation of erythrocyte sedimentation rate and C-reactive protein level. Computed tomography neck and laryngoscopy confirmed adenoidal and lingual tonsillar hypertrophy. He underwent adenoidectomy and lingual tonsillectomy with resolution of symptoms. Conclusions Hypertrophy of the remaining lymphoid structures within Waldeyer's ring may be associated with remote recurrence of PFAPA syndrome after tonsillectomy. Lingual tonsillectomy may be an alternative treatment strategy in select patients with PFAPA, prominent lingual hypertrophy, and incomplete response to steroids.

Abstract There have been increasing efforts to standardize MRI scanning protocols for both routine and clinical trial imaging of glioma. The recent BTIP guidelines propose acquisition of T2-weighted images after gadiolinium (Gd) based contrast injection and before post-contrast 3D T1-weighted (T1W) images to control timing of images after contrast administration. While Gd-contrast shortens T1W signal and appears hyperintense on magnetic resonance imaging (MRI), Gd-contrast also shortens T2W signal, which could result in unintended alternations in T2W signal intensities. This has potential implications for model-based approaches for GBM diagnosis and the differential diagnosis of other tumor types (e.g., lymphoma) that rely on T2W signal characteristics. To our knowledge, no neuroimaging studies have formally evaluated the impact of Gd contrast on T2W imaging. We acquired multi-echo T2 sequences (TE=14, 28, 41, 55, 69 ms) both prior to and after the administration of Gd for 5 patients suspected of having a brain tumor. Quantitative T2 maps were created by fitting the signal decay to a signal exponential with the Levenburg-Marqurdt algorithm. Percent difference maps were calculated to compare the quantitative T2 changes between the pre- and post-Gd T2 maps. Additionally, we performed a Wilcoxon Rank-Sum test comparing T2 values within regions of interest (ROIs) representing the tumor and normal appearing white matter (NAWM). Significant differences between the T2 values in the tumor and NAWM ROIs were seen for 4 and 3 of the patients, respectively (all p-values < 0.01). Our initial data suggests that the administration of Gd contrast may affect T2 values in both the tumor and NAWM, which could impact quantitative image-based models and diagnoses in glioma. We are currently replicating these preliminary results in an expanded cohort.

Abstract INTRODUCTION The quantification of intratumoral heterogeneity – through radiomics-based approaches - can help resolve the regionally distinct genetic drug targets that may co-exist within a single Glioblastoma (GBM) tumor. While this offers potential diagnostic value under the paradigm of individualized oncology, clinical decision-making must also consider the degree of uncertainty associated with each model. In this study, we evaluate the performance of a novel machine-learning (ML) algorithm, called Gaussian Process (GP) modeling, that can quantify the impact of multiple sources of uncertainty in ML model development and prediction accuracy, including variabilities in the copy number measurement, radiomics features, training sample characteristics, and training sample size. METHOD We collected 95 image-localized biopsies from 25 primary GBM patients. We coregistered stereotactic locations with preoperative multi-parametric MRI features (conventional MRI, DSC perfusion, Diffusion Tensor Imaging) to generate spatially matched pairs of MRI and copy number variants (CNV) for for each biopsy. We developed a Gaussian Process (GP) model to predict CNV for Epidermal Growth Factor Receptor (EGFR) based on MRI radiomic features in each patient. We used leave-one-patient-out cross validation to quantify prediction accuracy and model uncertainty. Spatial prediction and uncertainty (p-value) maps were overlaid to help visualize regional genetic variation of EGFR and uncertainty of the radiomic predictions. RESULT: The initial GP radiomics model for EGFR amplification (CNV > 3.5) produced a sensitivity of 0.8 and specificity of 0.8. Samples/regions associated with high uncertainty (p-value >0.05) correlated with either 1) extrapolation of radiomic features from the training set-defined feature space or 2) insufficient training samples in the feature space. CONCLUSION We present a ML-based model that quantifies spatial genetic heterogeneity in GBM, while also estimating model uncertainties that result from multi-source data variabilities. This approach lays the groundwork for prospective clinical integration of modeling-based diagnostic approaches in the paradigm of individualized medicine.

ObjectivesBiphenotypic sinonasal sarcoma (BSS) is a new, rare tumor characterized by concomitant neural and myogenic differentiation. The aim of this study is to describe the imaging characteristics and clinical outcomes of this neoplasm.MethodsA retrospective review of BSS patients surgically treated within a tertiary academic health care system was performed. Imaging characteristics and clinical outcomes were reviewed.ResultsFive patients underwent surgical resection of BSS tumors. Negative surgical margins were achieved in four (80%) patients. There were no deaths but two (40%) patients developed local recurrences during the postoperative follow‐up period (median follow‐up 31.4 months). Review of imaging characteristics revealed a median tumor size of 3.8 cm in greatest dimension. All tumors were unilateral and centered within the nasoethmoidal region. In all cases, the tumors extended to the nasal septum, lamina papyracea, and anterior skull base with variable degrees of erosion through these structures. On CT, involved bony structures demonstrated mixed lytic and sclerotic pattern, with definitive hyperostotic bone identified in four (80%) cases. On MRI, tumors were isointense‐to‐mixed iso/hypointense on both T1‐ and T2‐weighted sequences with one tumor demonstrating mixed T2 hyperintensity. All cases demonstrated gadolinium contrast enhancement.ConclusionsBSS is a locally aggressive tumor with a low risk of regional or distant metastases but has a significant rate of recurrence even with adequate resection. Despite its rarity, BSS should be considered in the differential diagnosis when imaging demonstrates a unilateral nasoethmoidal mass that is predominantly isointense to cerebral gray matter on T2‐weighted MRI and is hyperostotic on CT.Level of Evidence4

ObjectiveThe purpose of this article was to provide a combined pathologic and radiologic review of previous pathologically diagnosed facial nerve “hemangiomas” to confirm that these lesions are most characteristic of venous malformations rather than neoplasms.Study DesignRetrospective radiologic, clinical, and histopathologic review of all patients with a previous pathologically diagnosed facial nerve hemangioma of the temporal bone who underwent computed tomography or magnetic resonance imaging (MRI) were included. A consensus radiologic review for characteristic features and pathologic analysis was performed.Materials and MethodsA panel of 4 neuroradiologists retrospectively analyzed CT and MRI exams for 11 facial nerve hemangiomas and provided a consensus agreement on the characteristic imaging features. Concurrently, two neuropathologists reevaluated archived tissue specimens from these lesions and applied additional immunohistochemical and histochemical stains including D240, CD31, smooth muscle actin (SMA), Verhoeff Van Gieson (VVG) and glucose transporter 1 (GLUT1).ResultsLesions were composed of dilated vascular spaces with a simple, CD31‐positive endothelial lining and a smooth muscle component. All lesions were negative for markers found in arterial and lymphatic malformations and infantile hemangiomas. They had characteristic radiologic features previously ascribed to facial nerve hemangiomas. Namely, these lesions are typically T1 isointense or hypointense and T2 hyperintense relative to cerebral cortex and heterogeneously enhance on MRI. Bony canal expansion and erosion, intralesional calcification, and intracranial extension are common.ConclusionsOn the basis of this radiologic and pathologic review, these lesions are best characterized as venous malformations.Level of Evidence4

Objective The aim of this study was to perform an updated review of the imaging features of dysplastic cerebellar gangliocytoma (DCG). Methods Imaging findings were retrospectively reviewed in 14 patients with DCG. The analysis included size, location, cyst formation, calcification, intralesional hemorrhage, enhancement pattern, and apparent diffusion coefficient (ADC). Results In addition to revisiting many well-established imaging features of DCG, enhancement was much more common (64.3%) than previously reported, and small enhancing veins were also frequently encountered within or along the periphery of the lesions (50%). Dysplastic cerebellar gangliocytomas had an elevated ADC compared with normal cerebellum (967.8 ± 115.7 vs 770.4 ± 47.3 × 10−6 mm2/s; P < 0.0001). Conclusions Enhancement on magnetic resonance imaging within DCG should be an accepted imaging finding rather than being viewed as uncommon or atypical. Dysplastic cerebellar gangliocytomas typically have an elevated ADC compared with normal cerebellum, which may assist in differentiation from other posterior fossa neoplasms.

Objective: Evaluate prevalence and pattern of occipital pneumatization (OP). Patients: Individuals with imaging evidence of OP on computed tomography (CT). Intervention(s): High resolution CT scans of the temporal bone. Main Outcome Measure: The prevalence and pattern of OP on 1000 CT scans performed at a large academic healthcare system. Results: OP had a prevalence of 11.8% (n = 118) while occipital condyle pneumatization occurred in only 0.3%. Occipital air cells were right-sided in 27.1% (n = 32), left-sided in 51.7% (n = 61), and bilateral in 21.2% (n = 25), and OP was contiguous with the occipitomastoid suture. In cases of unilateral OP, the contralateral jugular foramen demonstrated relative enlargement ( p = 0.006), but a direct association could not be established. Conclusions: The occipital bone is an accessory site of skull base pneumatization in 11.8% of the population undergoing temporal bone CT, while air cell extension into the occipital condyle occurs more rarely. These occipital air cells have a left-sided predilection and are always in direct proximity to the occipitomastoid suture, suggesting developmental egress from the mastoid. OP is a normal variant and lacks features of craniocervical pneumatization, which is a rare disorder.