Erdheim-Chester Disease With Eyelid and Orbital Involvement: A Review of Treatment Modalities at One Institution From 2014 to 2022.

PURPOSE: To review all cases of Erdheim-Chester disease (ECD) with orbital involvement treated at Bascom Palmer Eye Institute in Miami, Florida from 2014 to 2022 and compare presentations, treatment modalities, and outcomes. METHODS: A retrospective chart review of all patients diagnosed with ECD who presented to Bascom Palmer Eye Institute from 2014 to 2022 was performed. Data collected included demographics, pretreatment history and ophthalmic examination, pathology report, treatment, subsequent examination, and relevant laboratory results. Histopathology, treatments, and outcomes were reviewed and compared between patients. RESULTS: Four cases were included. Primary treatments included vemurafenib (n = 2), cobimetinib (n = 1), and prednisone (n = 1). All patients demonstrated improvement of ophthalmic symptoms. Vemurafenib was the only medical treatment that was tolerated well and resulted in significant improvement in proptosis despite some reported dry eye; all other medications were discontinued due to intolerable side effects. CONCLUSIONS: BRAF inhibitors such as vemurafenib have been used as novel therapy in the treatment of ECD. Vemurafenib demonstrated its utility in reducing proptosis in ECD patients at one ophthalmic institution. Vemurafenib may be a favorable treatment option for BRAF-positive ECD patients presenting with orbital disease.

Cytokine Profiling of Cyst Fluid and Tumor-Associated Macrophages in Cystic Vestibular Schwannoma.

BACKGROUND: The vestibular schwannoma (VS) secretome can initiate monocyte recruitment and macrophage polarization to M1 (proinflammatory) and/or M2 (protumorigenic) phenotypes, which in turn secrete additional cytokines that contribute to the tumor microenvironment. Profiling cyst fluid and cerebrospinal fluid (CSF) in cystic VS provides a unique opportunity to understand mechanisms that may contribute to tumor progression and cyst formation. HYPOTHESIS: Cystic VSs secrete high levels of cytokines into cyst fluid and express abundant M1 and M2 macrophages. METHODS: Tumor, CSF, and cyst fluid were prospectively collected from 10 cystic VS patients. Eighty cytokines were measured in fluid samples using cytokine arrays and compared with normal CSF from normal donors. Immunofluorescence was performed for CD80 + M1 and CD163 + M2 macrophage markers. Demographic, audiometric, and radiographic information was obtained through retrospective chart review. RESULTS: Cyst fluid expressed more osteopontin and monocyte chemotactic protein-1 (MCP-1; p < 0.0001), when compared with normal CSF. Cyst fluid also expressed more protein ( p = 0.0020), particularly MCP-1 ( p < 0.0001), than paired CSF from the same subjects. MCP-1 expression in cyst fluid correlated with CD80 + staining in VS tissue ( r = 0.8852; p = 0.0015) but not CD163 + staining. CONCLUSION: Cyst fluid from cystic VS harbored high levels of osteopontin and MCP-1, which are cytokines important in monocyte recruitment and macrophage polarization. MCP-1 may have a significant role in molding the tumor microenvironment, by polarizing monocytes to CD80 + M1 macrophages in cystic VS. Further investigations into the role of cytokines and macrophages in VS may lead to new avenues for therapeutic intervention.

Thrombosed orbital varix of the inferior ophthalmic vein: A rare cause of acute unilateral proptosis.

Background: Orbital varices are rare, accounting for only 0-1.3% of orbital masses. They can be found incidentally or cause mild to serious sequelae, including hemorrhage and optic nerve compression. Case Description: We report a case of a 74-year-old male with progressively painful unilateral proptosis. Imaging revealed the presence of an orbital mass compatible with a thrombosed orbital varix of the inferior ophthalmic vein in the left inferior intraconal space. The patient was medically managed. On a follow-up outpatient clinic visit, he demonstrated remarkable clinical recovery and denied experiencing any symptoms. Follow-up computed tomography scan showed a stable mass with decreased proptosis in the left orbit consistent with the previously diagnosed orbital varix. One-year follow-up orbital magnetic resonance imaging without contrast showed slight increase in the intraconal mass. Conclusion: An orbital varix may present with mild to severe symptoms and management, depending on case severity, ranges from medical treatment to escalated surgical innervation. Our case is one of few progressive unilateral proptosis caused by a thrombosed varix of the inferior ophthalmic vein described in the literature. We encourage further investigation into the causes and epidemiology of orbital varices.

Malignant and Nonmalignant Sinonasal Tumors.

Sinonasal tumors are rare, diverse, complex lesions with overlapping demographic and clinical features. Malignant tumors are more common, with a grave prognosis, and require biopsy for accurate diagnosis. This article briefly reviews the classification of sinonasal tumors and provides imaging examples and imaging characteristics of each clinically important nasal and paranasal mass lesions. Although there are no true pathognomonic imaging features, it is important for the radiologist to have a broad knowledge of the various CT and MR imaging findings that can help narrow the differential diagnosis and aid in early diagnosis and mapping of tumor for treatment planning.

Microsurgical Management of Vestibular Schwannoma (Acoustic Neuroma): Facial Nerve Outcomes, Radiographic Analysis, Complications, and Long-Term Follow-Up in a Series of 420 Surgeries.

OBJECTIVE: The purpose of this study is to retrospectively evaluate the clinical and surgical outcomes of a large surgical series of vestibular schwannoma from North America over 20 years. METHODS: After institutional review board approval a retrospective review of the senior author's personal case logs to identify patients who had operations for vestibular schwannoma was performed. The clinical notes, operative record, preoperative and postoperative imagings, and long-term clinical follow-up notes were evaluated. RESULTS: A total of 415 patients who underwent 420 surgeries were identified from the years 1998-2021. The average length of follow-up was 3 years and 9 months. Overall, at last follow-up the rate of "good" facial nerve outcomes (House-Brackmann [HB] score I and II) was 86% and "poor" facial nerve outcomes (HB III-VI) was 14%. The amount of cerebellopontine angle extension (P = 0.023), tumor volume (P = 0.015), facial nerve consistency (P < 0.001), preoperative HB score (P < 0.001), and FN stimulation threshold at the end of the procedure (P < 0.001) were correlated to facial nerve function at the last follow-up. CONCLUSIONS: This study represents one of the largest recently reported surgical series of vestibular schwannoma in North American literature with available long term follow-up. Facial nerve outcomes correlated with cerebellopontine angle extension, tumor volume, facial nerve stimulation threshold, facial nerve consistency, preoperative facial nerve function, and history of a prior resection. Tumor recurrence remains significantly higher after subtotal resection. We believe the data supports a continuation of a strategy of general intent of gross total resection, greatly modifiable by intraoperative findings and judgment.

Rare presentation of angiomatosis in the paranasal sinuses mimicking juvenile nasopharyngeal angiofibroma in a 16 year old male.

Rare presentation of pediatric angiomatosis of the paranasal sinus and skull base presenting mimicking juvenile nasopharyngeal angiofibroma (JNA). This is a 16-year-old male who presented to the emergency room with acutely worsening headaches, decreased visual acuity, subjective diplopia on lateral gaze, and a skull base mass centered in the sphenoid cavity. Endoscopic biopsy at an outside facility was aborted due to profuse bleeding. Upon transfer to a tertiary care center, contrast MR demonstrated a heterogeneously and avidly enhancing vascular mass centered around the sphenoid and skull base originating from the internal maxillary artery with significant bilateral extension into the adjacent paranasal sinuses, sella, and cavernous sinus. History of presentation and imaging was suggestive of JNA. Patient underwent preoperative embolization followed by endoscopic endonasal transphenoidal resection with a skull base trained otolaryngologist and neurosurgeon. Final pathology confirmed angiomatosis. This is only the second reported case of paranasal sinus angiomatosis in the literature. Angiomatosis has a high rate of recurrence and failure of timely diagnosis can lead to requirement of repeated surgical intervention. Re-operations are associated with increased costs, patient dissatisfaction, and poorer surgical/clinical outcomes. Because angiomatosis can mimic JNA, hemangiomas, or other vascular tumors, it is essential to maintain a broad differential diagnosis that includes angiomatosis when evaluating sinonasal tumors.

Effect of AR42 in Primary Vestibular Schwannoma Cells and a Xenograft Model of Vestibular Schwannoma.

HYPOTHESIS: AR42, a histone deacetylase (HDAC) inhibitor, reduces viability of primary vestibular schwannoma (VS) cells and delays tumor progression and hearing loss (HL) in a xenograft model of VS. BACKGROUND: The impact of HDAC expression on AR42 response in primary VS cells is unknown, as well as the effects of AR42 on VS-associated HL and imbalance. METHODS: Primary human VS cells (n = 7) were treated with AR42 (0-3.0 µM), and viability assays were conducted. Immunohistochemistry and western blotting for phosphorylated-HDAC2 (pHDAC2) were performed on tumor chunks. Pharmacokinetic studies were conducted in Fischer rats using mass spectrometry. Merlin-deficient Schwann cells were grafted onto cochleovestibular nerves of immunodeficient rats and treated with vehicle (n=7) or AR42 (25 mg/kg/day for 4weeks; n=12). Tumor bioluminescence imaging, auditory brainstem response (ABR), and rotarod tests were conducted to 6weeks. Final tumor weight and toxicities were measured. RESULTS: AR42 caused dose-dependent reductions in viability of VS cells. Tumors with higher pHDAC2:HDAC2 ratios had greater reductions in viability with AR42. On pharmacokinetic studies, AR42 reached peak levels in nerve ~24 hours after oral administration. Although AR42-treated rats demonstrated mean ABR threshold shifts ~10 to 20 dB lower than controls, this did not persist nor reach significance. When compared to controls, AR42 did not affect tumor bioluminescence, tumor weight, and rotarod measurements. CONCLUSIONS: Response of primary VS cells to AR42 may be influenced by pHDAC2 expression in tumor. Although AR42 may delay HL in our xenograft model, it did not halt tumor growth or vestibular dysfunction. Further investigations are warranted to evaluate the AR42 effectiveness in NF2-associated VS.

Redefining Perineural Invasion in Head and Neck Cutaneous Squamous Cell Carcinoma.

OBJECTIVE: Perineural invasion (PNI) negatively affects disease-specific survival in patients with head and neck cutaneous squamous cell carcinoma (HNcSCC). We aim to analyze the prognostic implications of PNI-related features. STUDY DESIGN: Retrospective cohort study. SETTING: Academic tertiary care hospital. METHODS: Retrospective chart review was performed on 104 patients diagnosed with HNcSCC between January 2011 and October 2019 who underwent resection, parotidectomy, and neck dissection with more than 1 year of follow-up. PNI was classified as incidental (identified on histopathology alone) or clinical (present on radiography and/or physical exam). Primary outcome measures were overall survival and disease-free survival (DFS). Kaplan-Meier analysis, logistic regression, and Cox regression were performed. RESULTS: The overall 5-year DFS was 57.9%. Sixty-one patients had PNI. On histopathology, 28 lesions showed complete nerve encirclement, 10 involved >5 nerves, and 12 involved named nerves. Patients with facial weakness (P = .026) and positive margins (P = .0029) had a higher likelihood of histopathologic PNI, and positive margins retained significance on multivariable analysis (P = .0079). Worse DFS was seen in patients with PNI (P = .004), advanced tumor stage (P = .049), positive margins (P = .014), and >5 nerves involved (P = .0061). Furthermore, histopathologic PNI was a predictor of DFS (hazard ratio [HR], 3.07; 95% CI, 0.33-1.38; P = .0061) overall and in the clinical PNI cohort (HR, 3.43; 95% CI, 1.65-7.10; P = .00091). CONCLUSION: DFS was significantly worse in patients with PNI, facial nerve weakness, advanced T stage, positive margins, and multiple nerve involvement. Further characterization of PNI features may help improve prognostic predictions and identify patients who may benefit from more aggressive treatment.

Ga-68 DOTATATE PET/CT in the Evaluation of Paragangliomas and Other Indeterminate Lesions in the Head and Neck.

Background and Purpose: Paragangliomas (PGLs) are rare neuroendocrine tumors with imaging features that can overlap with other entities. This study hypothesizes that given overexpression of somatostatin receptor (SSTR) 2, PGLs can be differentiated on Ga-68 DOTATATE positron emission tomography/computed tomography (PET/CT) from other benign or malignant lesions. Materials and Methods: Ninety-six patients with known tumors of the head and neck who underwent Ga-68 DOTATATE PET/CT from May 2017 to December 2021 were retrospectively reviewed from a single institution. Of these, 43 patients had histopathological confirmation and 66 positive lesions were discovered on PET/CT. For each lesion, the SUV max, the SUV lesion to liver ratio, and the SUV lesion to spleen ratio were analyzed. Results: PGLs (n = 37) showed the most intense uptake, and the mean of SUVmax was 69.3 (range 3.7-225.9). Metastatic PGL and metastasis from other neuroendocrine tumors (n = 13) demonstrated intermediate uptake, the mean of SUVmax was 15.16 (range 2.3-40.3). Meningiomas (n = 3) had intermediate uptake, and the mean of SUVmax was 12.37 (range 2.5-19.4). One patient with esthesioneuroblastoma had 5 lesions in the head and neck, and the mean of SUVmax was 18.9 (range 6.9-49.4). Schwannomas (n = 4) had very low uptake, and the mean of SUVmax was 1.75 (range 1.1-2.2). Other rare cases with low uptake included 1 each of osteosarcoma, acinic cell carcinoma, ectopic thyroid tissue, and plasmacytoma, and the mean of SUVmax was 4.75 (range 2.3-6.1). Conclusions: Ga-68 DOTATATE PET/CT can be a useful adjunct in differentiating tumors in the head and neck. PGLs demonstrate the highest uptake. Meningioma, esthesioneuroblastoma, and neuroendocrine tumor metastasis have intermediate uptake. Schwannomas and other rare tumors exhibit low uptake.

Molecular and Cellular Mechanisms of Perineural Invasion in Oral Squamous Cell Carcinoma: Potential Targets for Therapeutic Intervention.

The most common oral cavity cancer is squamous cell carcinoma (SCC), of which perineural invasion (PNI) is a significant prognostic factor associated with decreased survival and an increased rate of locoregional recurrence. In the classical theory of PNI, cancer was believed to invade nerves directly through the path of least resistance in the perineural space; however, more recent evidence suggests that PNI requires reciprocal signaling interactions between tumor cells and nerve components, particularly Schwann cells. Specifically, head and neck SCC can express neurotrophins and neurotrophin receptors that may contribute to cancer migration towards nerves, PNI, and neuritogenesis towards cancer. Through reciprocal signaling, recent studies also suggest that Schwann cells may play an important role in promoting PNI by migrating toward cancer cells, intercalating, and dispersing cancer, and facilitating cancer migration toward nerves. The interactions of neurotrophins with their high affinity receptors is a new area of interest in the development of pharmaceutical therapies for many types of cancer. In this comprehensive review, we discuss diagnosis and treatment of oral cavity SCC, how PNI affects locoregional recurrence and survival, and the impact of adjuvant therapies on tumors with PNI. We also describe the molecular and cellular mechanisms associated with PNI, including the expression of neurotrophins and their receptors, and highlight potential targets for therapeutic intervention for PNI in oral SCC.

Incidence of high grade gliomas presenting as radiographically non-enhancing lesions: experience in 111 surgically treated non-enhancing gliomas with tissue diagnosis.

PURPOSE: Although non-enhancing lesions suspicious for glioma are usually assumed to be low grade glioma (LGG), some high grade glioma (HGG) do not enhance, which may lead to a delay in biopsy and/or resection, diagnosis, and treatment initiation. Thus, there is a clear need for a large-sample study that quantifies the rate of malignant, non-enhancing gliomas. METHODS: We retrospectively reviewed our series of 561 consecutive surgically treated gliomas with tissue diagnosis, 111 of which were non-enhancing, to determine the prevalence of high-grade histology in radiographically presumed LGG. Relative expression of tumor markers were also reported for non-enhancing lesions to investigate genetic correlates. RESULTS: We identified 561 surgically treated gliomas with tissue diagnosis from August 2012 to July 2018 and found that 111 patients (19.8%) demonstrated non-enhancing lesions suspicious for glioma on preoperative MRI. Thirty-one (27.9%) of the non-enhancing lesions were classified as HGGs (WHO Grade III or IV). Non-enhancing lesions were four times more likely to be HGG in patients older than 60 years than patients younger than 35 years (41.2% vs. 11.4%, Pearson Chi2 p < 0.001). Binomial logistic regression showed a significant inverse effect of age on the presence of IDH mutation in non-enhancing HGGs (p = 0.007). CONCLUSION: A clinically significant proportion (27.9%) of non-enhancing lesions were found to be HGG on final pathologic diagnosis. Thus, in patients with good functional and health status, especially those older than 60 years, we recommend obtaining tissue diagnosis of all lesions suspected to be glioma, even those that are non-enhancing, to guide diagnosis as well as early initiation of chemotherapy and radiation therapy.

Imaging Characteristics of a Hypervascular Pituitary Spindle Cell Oncocytoma on Magnetic Resonance Imaging and Digital Subtraction Angiography.

BACKGROUND: Spindle cell oncocytomas (SCOs) are rare neuroendocrine tumors of the posterior pituitary that are often misdiagnosed as nonfunctional pituitary tumors. Fewer than 50 cases of SCOs have been described in the literature, and many of these reports have documented the tumors to be hypervascular on imaging or histology. CASE DESCRIPTION: We present the first cerebral angiography imaging findings of an SCO before primary resection. The discovery of a prominent tumor blush, enlarged meningohypophyseal feeders bilaterally, and prominent tumor draining veins aided in preoperative planning and subsequent successful endoscopic transsphenoidal surgical resection. CONCLUSIONS: Despite being a rare entity, SCOs should be included in the differential diagnosis when working up a hypervascular sellar tumor. Flow voids may be present on initial magnetic resonance imaging evaluation. Subsequent digital subtraction angiography can be used to further investigate abnormal vasculature and aid in surgical planning.

Enhancing Linkages Between Healthy Diets, Local Agriculture, and Sustainable Food Systems: The School Meals Planner Package in Ghana.

BACKGROUND: Interventions that enhance linkages between healthy diets and local agriculture can promote sustainable food systems. Home-grown school feeding programs present a promising entry point for such interventions, through the delivery of nutritious menus and meals. OBJECTIVE: To describe the adaptation of the School Meals Planner Package to the programmatic and environmental reality in Ghana during the 2014 to 2015 school year. METHODS: Guided by a conceptual framework highlighting key considerations and trade-offs in menu design, an open-source software was developed that could be easily understood by program implementers. Readily available containers from markets were calibrated into "handy measures" to support the provision of adequate quantities of food indicated by menus. Schools and communities were sensitized to the benefits of locally sourced, nutrient-rich diets. A behavior change communication campaign including posters and songs promoting healthy diets was designed and disseminated in schools and communities. RESULTS: The School Meals Planner Package was introduced in 42 districts in Ghana, reaching more than 320 000 children. Monitoring reports and feedback on its use were positive, demonstrating how the tool can be used by planners and implementers alike to deliver nutritious, locally-sourced meals to schoolchildren. The value of the tool has been recognized at the highest levels by Ghana's government who have adopted it as official policy. CONCLUSIONS: The School Meals Planner Package supported the design of nutritious, locally sourced menus for the school feeding program in Ghana. The tool can be similarly adapted for other countries to meet context-specific needs.

Wooden Foreign Body in the Skull Base: How Did We Miss It?

BACKGROUND: Timely detection of intraorbital and skull base wooden foreign bodies is crucial. Wooden foreign bodies are difficult to detect on imaging. The radiologist may fail to identify wooden foreign bodies on two thirds of initial scans and can miss them in almost one third of total cases. CASE DESCRIPTION: A 66-year-old woman sustained a penetrating injury through the left upper eyelid with a small tree branch. The branch was immediately removed in the field, and she was provided with prompt medical care at a local hospital. Initial computed tomography (CT) scan diagnosis was "posttraumatic sinusitis," and this was treated empirically with vancomycin and piperacillin/tazobactam. On the eighth day after injury, she developed progressive swelling and pain of her eyelid with left trigeminal/supraorbital numbness and complete left ophthalmoplegia. A new CT scan showed an open "track" from the region of the left upper orbit/superior rectus to the contralateral sphenoid sinus, which raised suspicion for a retained foreign body. Further imaging confirmed the suspicion. Endoscopic sinus surgery was performed with extraction of the wooden object and evacuation of the left orbital infection. CONCLUSIONS: This case indicates that intraorbital and skull base wooden foreign bodies are elusive, demanding a high index of suspicion from both clinicians and radiologists to identify retained material in the setting of ocular or sinus trauma. For better identification of wooden foreign bodies, bone windows on CT should have a width of -1000 Hounsfield units with a soft tissue window level of -500 Hounsfield units.

Atypical radiographic features of skull base cholesterol granuloma.

Cholesterol granulomas (CGs) are the most common benign lesions of the petrous apex (PA) and have distinct computed tomography (CT) and magnetic resonance imaging (MRI) characteristics. On CT, CGs of the PA (PACG) present as expansile lesions with erosion of bony trabeculae. MRI shows a hyperintense lesion on T1-and T2-weighted images and do not enhance with gadolinium. The objective is to describe the radiographic features of CGs of the skull base that do not arise from the PA. This study is a retrospective review. Three patients were operated on for suspected recurrent endolymphatic sac tumor, intracranial cholesteatoma, and recurrent sphenoid wing meningioma based on CT and MRI findings. Pathology results were consistent with CG in all three cases. All patients had bone erosion on CT. These skull base CGs did not demonstrate similar MRI features. These lesions were hyperintense, iso-to-hyperintense, and hypointense on T1-weighted MRI, respectively. These CGs were hyperintense in two cases and iso-to-hyperintense in one case on T2-weighted MRI. These lesions either demonstrated central or rim enhancement after gadolinium administration. Skull base CGs that do not arise from the PA demonstrate a broad spectrum of radiographic characteristics on MRI that are not typical of PACG.

Cricotracheal separation after gunshot to the neck: report of a survivor with recovery of bilateral vocal fold function.

BACKGROUND: Traumatic tracheal injury via blunt or penetrating mechanism comes with a grave prognosis. Cricotracheal separation is a rare entity among these injuries and even more infrequent by means of penetrating trauma. Resultant airway discontinuity subsequent to these insults causes immense global hypoxia and tends to be uniformly fatal. OBJECTIVE: Our aim was to discuss emergent and surgical management of traumatic airway injury. CASE REPORT: We report the case of a 28-year-old male who sustained a gunshot wound to the neck resulting in laryngeal fracture and cricotracheal separation. We review the initial stabilization of his airway and detail the successive surgical management of his injury in the context of the current available literature, with an emphasis on timely airway stabilization when high suspicion for cricotracheal separation exists based on traumatic mechanism. CONCLUSIONS: Emergent management and stabilization of the airway is critical to survival in the context of trauma involving the neck and airway structures.

Discriminating radiation necrosis from tumor progression in gliomas: a systematic review what is the best imaging modality?

Differentiating post radiation necrosis from progression of glioma and pseudoprogression poses a diagnostic conundrum for many clinicians. As radiation therapy and temozolomide chemotherapy have become the mainstay of treatment for higher-grade gliomas, radiation necrosis and post treatment changes such as pseudoprogression have become a more relevant clinical problem for neurosurgeons and neurooncologists. Due to their radiological similarity to tumor progression, accurate recognition of these findings remains paramount given their vastly different treatment regimens and prognoses. However, no consensus has been reached on the optimal technique to discriminate between these two lesions. In order to clarify the types of imaging modalities for recurrent enhancing lesions, we conducted a systematic review of case reports, case series, and prospective studies to increase our current understanding of the imaging options for these common lesions and their efficacy. In particular, we were interested in distinguishing radiation necrosis from true tumor progression. A PubMed search was performed to include all relevant studies where the imaging was used to differentiate between radiation necrosis and recurrent gliomas with post-radiation enhancing lesions. After screening for certain parameters in our study, seventeen articles with 435 patients were included in our analysis including 10 retrospective and 7 prospective studies. The average time from the end of radiation therapy to the onset of a recurrent enhancing lesion was 13.2 months. The most sensitive and specific imaging modality was SPECT with a sensitivity of 87.6 % and specificity of 97.8 %. Based on our review, we conclude that certain imaging modalities may be preferred over other less sensitive/specific techniques. Overall, tests such as SPECT may be preferable in differentiating TP (tumor progression) from RN (radiation necrosis) due to its high specificity, while nonspecific imaging such as conventional MRI is not ideal.