Initial Management of BRAF V600E-Variant Anaplastic Thyroid Cancer: The FAST Multidisciplinary Group Consensus Statement.

Importance: BRAF/MEK inhibitors revolutionized the treatment of BRAF V600E-variant anaplastic thyroid carcinoma (BRAFv-ATC), offering improved outcomes for patients with this previously incurable disease. Observations: Anaplastic thyroid carcinoma (ATC) accounts for approximately half of thyroid cancer-related deaths. It presents as a rapidly growing tumor that often invades locoregional structures and spreads to distant sites early; therefore, prompt diagnosis, staging, and treatment initiation are of the essence in the treatment of ATC. Although most oncologists will encounter a patient with ATC in their practice, the rarity of this disease makes treatment challenging, particularly because those with BRAFv-ATC no longer have a dismal prognosis. BRAF/MEK kinase inhibitors have transformed the outlook and treatment of BRAFv-ATC. Therefore, molecular profiling to identify these patients is critical. More recently, the addition of immunotherapy to BRAF/MEK inhibitors as well as the use of the neoadjuvant approach were shown to further improve survival outcomes in BRAFv-ATC. Many of these recent advances have not yet been incorporated in the currently available guidelines, allowing for disparities in the treatment of patients with BRAFv-ATC across the US. With the increasing complexity in the management of BRAFv-ATC, this Consensus Statement aims to formulate guiding recommendations from a group of experts to facilitate therapeutic decision-making. Conclusions and Relevance: This Consensus Statement from the FAST (Facilitating Anaplastic Thyroid Cancer Specialized Treatment) group at MD Anderson Cancer Center emphasizes that rapid identification of a BRAF V600E pathogenic variant and timely initiation of sequential therapy are critical to avoid excess morbidity and mortality in patients with BRAFv-ATC. In the past decade, remarkable progress has been made in the treatment of patients with BRAFv-ATC, justifying these new evidence-based recommendations reached through a consensus of experts from a high-volume center.

Parathyroid carcinoma: Imaging features of initial presentation and recurrence. A single center experience.

BACKGROUND AND PURPOSE: Parathyroid carcinoma is the rarest endocrine neoplasm with very few published data discussing its imaging appearance with primary focus on ultrasound imaging features. We present our 23 years institutional experience to highlight multimodality imaging evaluation at presentation and at recurrence. MATERIAL AND METHODS: Retrospective chart review of clinical and pathological diagnosis of parathyroid carcinoma patients presented for initial or recurrent disease management at M.D. Anderson Cancer Center between the period of January 2000 and February 2023 was performed. Imaging findings on US, CT, PET/CT, and technetium-99m sestamibi were analyzed for initial and local recurrent parathyroid carcinoma. We further assess patterns of distant recurrence and its location. RESULTS: Twenty three patients with pathological and clinical diagnosis of initial (14 patients) or recurrent parathyroid carcinoma (14 patients) were included in this study. US findings of parathyroid carcinoma were larger lesions, increased/irregular vascularity, and non-circumscribed margins. Multiphasic CT findings of parathyroid carcinoma included an arterially enhancing lesion that is hypoenhancing relative to the thyroid and demonstrates no washout on delayed imaging. Highly suggestive findings for recurrent disease included a hypoechoic solid nodule (91.67%) with increased vascularity on ultrasound (81.8%) with corresponding enhancement on CT. CONCLUSION: Parathyroid carcinoma is a rare malignancy often diagnosed after surgical resection. We provided CT and US imaging features that are helpful in suggesting the diagnosis of parathyroid carcinoma and detection of early local recurrence.

Malignant and Nonmalignant Lesions of the Oral Cavity.

There is a broad spectrum of pathology that occurs in the oral cavity. Knowledge of the different anatomic subsites and contents of each is important for accurate diagnosis and treatment. Oral cavity tumors are predominantly malignant in nature, but there are many nonmalignant lesions of which the practicing clinician should be aware. This article will discuss the anatomy, imaging approaches, and imaging characteristics of nonmalignant and malignant pathology in the oral cavity.

Perineural Spread of Tumor in the Skull Base and Head and Neck.

Perineural tumor spread (PNS) is a well-recognized entity in head and neck cancers and represents a mode of metastasis along nerves. The trigeminal and facial nerves are most affected by PNS, and their connections are reviewed. MRI is the most sensitive modality for detecting PNS, and their anatomy and interconnections are reviewed. MRI is the most sensitive modality for detecting PNS, and imaging features of PNS and important imaging checkpoints are reviewed. Optimal imaging protocol and techniques are summarized as well as other entities that can mimic PNS.

Surgery After BRAF-Directed Therapy Is Associated with Improved Survival in BRAFV600E Mutant Anaplastic Thyroid Cancer: A Single-Center Retrospective Cohort Study.

Background: The aim of this study was to describe the oncologic outcomes of patients with BRAFV600E-mutated anaplastic thyroid cancer (ATC) who had neoadjuvant BRAF-directed therapy with subsequent surgery. For context, we also reviewed patients who received BRAF-directed therapy after surgery, and those who did not have surgery after BRAF-directed therapy. Methods: This was a single-center retrospective cohort study conducted at a tertiary care cancer center in Texas from 2017 to 2021. Fifty-seven consecutive patients with BRAFV600E-mutated ATC and at least 1 month of BRAF-directed therapy were included. Primary outcomes were overall survival (OS) and progression-free survival (PFS). Results: All patients had stage IVB (35%) or IVC (65%) ATC. Approximately 70% of patients treated with BRAF-directed therapy ultimately had surgical resection of residual disease. Patients who had neoadjuvant BRAF-directed therapy followed by surgery (n = 32) had 12-month OS of 93.6% [confidence interval (CI) 84.9-100] and PFS of 84.4% [CI 71.8-96.7]. Patients who had surgery before BRAF-directed therapy (n = 12) had 12-month OS of 74.1% [CI 48.7-99.5] and PFS of 50% [CI 21.7-78.3]. Finally, patients who did not receive surgery after BRAF-directed therapy (n = 13) had 12-month OS of 38.5% [CI 12.1-64.9] and PFS of 15.4% [CI 0-35.0]. Neoadjuvant BRAF-directed therapy reduced tumor size, extent of surgery, and surgical morbidity score. Subgroup analysis suggested that any residual ATC in the surgical specimen was associated with significantly worse 12-month OS and PFS (OS = 83.3% [CI 62.6-100], PFS = 61.5% [CI 35.1-88]) compared with patients with pathologic ATC complete response (OS = 100%, PFS = 100%). Conclusions: We observed that neoadjuvant BRAF-directed therapy reduced extent of surgery and surgical morbidity. While acknowledging potential selection bias, the 12-month OS rate appeared higher in patients who had BRAF-directed therapy followed by surgery as compared with BRAF-directed therapy without surgery; yet, it was not significantly different from surgery followed by BRAF-directed therapy. PFS appeared higher in patients treated with neoadjuvant BRAF-directed therapy relative to patients in the other groups. These promising results of neoadjuvant BRAF-directed therapy followed by surgery for BRAF-mutated ATC should be confirmed in prospective clinical trials.

Cerebral hemodynamic and metabolic dysregulation in the postradiation brain.

Technological advances in the delivery of radiation and other novel cancer therapies have significantly improved the 5-year survival rates over the last few decades. Although recent developments have helped to better manage the acute effects of radiation, the late effects such as impairment in cognition continue to remain of concern. Accruing data in the literature have implicated derangements in hemodynamic parameters and metabolic activity of the irradiated normal brain as predictive of cognitive impairment. Multiparametric imaging modalities have allowed us to precisely quantify functional and metabolic information, enhancing the anatomic and morphologic data provided by conventional MRI sequences, thereby contributing as noninvasive imaging-based biomarkers of radiation-induced brain injury. In this review, we have elaborated on the mechanisms of radiation-induced brain injury and discussed several novel imaging modalities, including MR spectroscopy, MR perfusion imaging, functional MR, SPECT, and PET that provide pathophysiological and functional insights into the postradiation brain, and its correlation with radiation dose as well as clinical neurocognitive outcomes. Additionally, we explored some innovative imaging modalities, such as quantitative blood oxygenation level-dependent imaging, susceptibility-based oxygenation measurement, and T2-based oxygenation measurement, that hold promise in delineating the potential mechanisms underlying deleterious neurocognitive changes seen in the postradiation setting. We aim that this comprehensive review of a range of imaging modalities will help elucidate the hemodynamic and metabolic injury mechanisms underlying cognitive impairment in the irradiated normal brain in order to optimize treatment regimens and improve the quality of life for these patients.

Imaging of the Thyroid: Practical Approach.

Imaging evaluation of the thyroid gland spans a plethora of modalities, including ultrasound imaging, cross-sectional studies, and nuclear medicine techniques. The overlapping of clinical and imaging findings of benign and malignant thyroid disease can make interpretation a complex undertaking. We aim to review and simplify the vast current literature and provide a practical approach to the imaging of thyroid disease for application in daily practice. Our approach highlights the keys to differentiating and diagnosing common benign and malignant disease affecting the thyroid gland.

Purulent chondritis of thyroid cartilage.

We report a case of a 77-year-old female with purulent chondritis of the thyroid cartilage who was initially referred for laryngeal neoplasm. Purulent chondritis of the laryngeal cartilage is a rare entity with three reports in the literature. The unique CT imaging features of expansile laryngeal cartilage with peripheral rim enhancement and central fluid-attenuation correlate to the abscess formation between the inner and outer perichondria. The correct imaging assessment prompts surgical management and avoid misdiagnosis.

Uncommon tumors of temporomandibular joint: An institutional experience and review.

BACKGROUND: The temporomandibular joint (TMJ) harbors a myriad of pathologic alterations including arthritides and benign and malignant neoplasms. METHODS: Herein, we describe our institutional experience of some uncommon and unusual synovial pathologies of the TMJ along with a review of literature. We searched through the archives of department of pathology and institutional electronic medical record for specimens of TMJ between 1999 and 2019. Hematoxylin and eosin slides were reviewed and data (final diagnosis, age, gender, clinical presentation, tumor size, treatment modality, recurrence, and vital status) were collected. RESULTS: A total of seven cases were identified including four cases of synovial chrondromatosis; and one case each of tenosynovial giant cell tumor, localized type, tenosynovial giant cell tumor, diffuse type, and synovial sarcoma. CONCLUSIONS: The article emphasizes on the clinical, radiologic, pathologic, and molecular features of these uncommon entities. The differential diagnosis of each entity is also discussed. Current updates in the management are also reviewed.

Hypoglossal nerve palsy due to carotid artery dissection: an uncommon presentation of a common problem.

Spontaneous internal carotid artery dissection occurs in patients of all ages, rarely presenting with hypoglossal nerve palsy. The characteristic imaging findings of internal carotid artery dissection and tongue denervation are reviewed in four patients. Recognition of internal carotid artery dissection is critical for appropriate treatment and to minimise the risk of thromboembolic-ischaemic complications. Radiologists must be aware of the radiological appearance of hypoglossal nerve palsy and maintain a high index of suspicion for internal carotid artery dissection when this finding is present.

Folate receptor overexpression can be visualized in real time during pituitary adenoma endoscopic transsphenoidal surgery with near-infrared imaging.

OBJECTIVE Pituitary adenomas account for approximately 10% of intracranial tumors and have an estimated prevalence of 15%-20% in the general US population. Resection is the primary treatment for pituitary adenomas, and the transsphenoidal approach remains the most common. The greatest challenge with pituitary adenomas is that 20% of patients develop tumor recurrence. Current approaches to reduce recurrence, such as intraoperative MRI, are costly, associated with high false-positive rates, and not recommended. Pituitary adenomas are known to overexpress folate receptor alpha (FRα), and it was hypothesized that OTL38, a folate analog conjugated to a near-infrared (NIR) fluorescent dye, could provide real-time intraoperative visual contrast of the tumor versus the surrounding nonneoplastic tissues. The preliminary results of this novel clinical trial are presented. METHODS Nineteen adult patients who presented with pituitary adenoma were enrolled. Patients were infused with OTL38 2-4 hours prior to surgery. A 4-mm endoscope with both visible and NIR light capabilities was used to visualize the pituitary adenoma and its margins in real time during surgery. The signal-to-background ratio (SBR) was recorded for each tumor and surrounding tissues at various endoscope-to-sella distances. Immunohistochemical analysis was performed to assess the FRα expression levels in all specimens and classify patients as having either high or low FRα expression. RESULTS Data from 15 patients (4 with null cell adenomas, 1 clinically silent gonadotroph, 1 totally silent somatotroph, 5 with a corticotroph, 3 with somatotrophs, and 1 somatocorticotroph) were analyzed in this preliminary analysis. Four patients were excluded for technical considerations. Intraoperative NIR imaging delineated the main tumors in all 15 patients with an average SBR of 1.9 ± 0.70. The FRα expression level of the adenomas and endoscope-to-sella distance had statistically significant impacts on the fluorescent SBRs. Additional considerations included adenoma functional status and time from OTL38 injection. SBRs were 3.0 ± 0.29 for tumors with high FRα expression (n = 3) and 1.6 ± 0.43 for tumors with low FRα expression (n = 12; p < 0.05). In 3 patients with immunohistochemistry-confirmed FRα overexpression (2 patients with null cell adenoma and 1 patient with clinically silent gonadotroph), intraoperative NIR imaging demonstrated perfect classification of the tumor margins with 100% sensitivity and 100% specificity. In addition, for these 3 patients, intraoperative residual fluorescence predicted postoperative MRI results with perfect concordance. CONCLUSIONS Pituitary adenomas and their margins can be intraoperatively visualized with the preoperative injection of OTL38, a folate analog conjugated to NIR dye. Tumor-to-background contrast is most pronounced in adenomas that overexpress FRα. Intraoperative SBR at the appropriate endoscope-to-sella distance can predict adenoma FRα expression status in real time. This work suggests that for adenomas with high FRα expression, it may be possible to identify margins and to predict postoperative MRI findings.

18FDG PET/CT in Routine Surveillance of Asymptomatic Patients following Treatment of Sinonasal Neoplasms.

Objective Sinonasal neoplasms have a high rate of recurrence following treatment, and current guidelines support the use of a variety of surveillance techniques. Recent work demonstrates that performance parameters of surveillance modalities may differ with sinonasal tumors in particular when compared with head and neck tumors overall. This study aims to characterize the value of 18fluorodeoxyglucose (18FDG) positron emission tomography/computed tomography (PET/CT) as a screening tool in asymptomatic patients. Study Design Retrospective cohort study. Setting Hospital of the University of Pennsylvania and Pennsylvania hospital. Methods Records of asymptomatic patients without suspicious endoscopy or suspicious imaging other than PET during the first 3 years following definitive treatment for sinonasal malignancy were screened and analyzed for inclusion in the cohort. Disease recurrence was determined by biopsy following suspicious PET evaluation. Results PET/CT scans (n = 111) were performed for 45 disease-free asymptomatic patients with no evidence of disease on endoscopy, and 6.3% were suspicious and prompted biopsy during this period, revealing 3 cases of disease recurrence. Overall specificity for PET/CT alone was 96.3% (95% CI, 90.7%-99.0%), with a negative predictive value of 99% (95% CI, 94.8%-100%). All recurrences were detected between 7 and 12 months, and all patients with true recurrence diagnosed by PET/CT had extrasinonasal involvement of tumor at the time of surgery. Conclusion We examined performance parameters of 18FDG PET/CT in asymptomatic patients with no evidence of disease on endoscopy during the posttreatment period for sinonasal malignancy. The ability of PET/CT to detect recurrences that may be missed by structural imaging or endoscopy makes it a valuable tool for clinicians.

Reversible dilatation of lumbar epidural venous plexus secondary to pelvic venous compression: mimicker of pathology.

Radiculopathy from dilated epidural varices is a rarely recognized phenomenon, and engorged varices may mimic a disc herniation, fistula or mass. We report a case of a distended bladder causing reversible pelvic venous congestion and resultant epidural venous plexus engorgement. We show marked engorgement of the epidural venous plexus and crowding of the cauda equina from a markedly distended bladder with resolution of these findings following bladder decompression. Familiarity with this clinical entity is crucial to avoid misdiagnosis and to prevent potential unnecessary surgical intervention.

Intraoperative Near-Infrared Optical Imaging Can Localize Gadolinium-Enhancing Gliomas During Surgery.

BACKGROUND: Although real-time localization of gliomas has improved with intraoperative image guidance systems, these tools are limited by brain shift, surgical cavity deformation, and expense. OBJECTIVE: To propose a novel method to perform near-infrared (NIR) imaging during glioma resections based on preclinical and clinical investigations, in order to localize tumors and to potentially identify residual disease. METHODS: Fifteen patients were identified and administered a Food and Drug Administration-approved, NIR contrast agent (Second Window indocyanine green [ICG], 5 mg/kg) before surgical resection. An NIR camera was utilized to localize the tumor before resection and to visualize surgical margins following resection. Neuropathology and magnetic resonance imaging data were used to assess the accuracy and precision of NIR fluorescence in identifying tumor tissue. RESULTS: NIR visualization of 15 gliomas (10 glioblastoma multiforme, 1 anaplastic astrocytoma, 2 low-grade astrocytoma, 1 juvenile pilocytic astrocytoma, and 1 ganglioglioma) was performed 22.7 hours (mean) after intravenous injection of ICG. During surgery, 12 of 15 tumors were visualized with the NIR camera. The mean signal-to-background ratio was 9.5 ± 0.8 and fluorescence was noted through the dura to a maximum parenchymal depth of 13 mm. The best predictor of positive fluorescence was enhancement on T1-weighted imaging; this correlated with signal-to-background ratio (P = .03). Nonenhancing tumors did not demonstrate NIR fluorescence. Using pathology as the gold standard, the technique demonstrated a sensitivity of 98% and specificity of 45% to identify tumor in gadolinium-enhancing specimens (n = 71). CONCLUSION: With the use of Second Window ICG, gadolinium-enhancing tumors can be localized through brain parenchyma intraoperatively. Its utility for margin detection is promising but limited by lower specificity. ABBREVIATIONS: 5-ALA, 5-aminolevulinic acidEPR, enhanced permeability and retentionFDA, Food and Drug AdministrationGBM, glioblastomaICG, indocyanine greenNIR, near-infraredNPV, negative predictive valuePPV, positive predictive valueROC, receiver operating characteristicROI, region of interestSBR, signal-to-background ratioWHO, World Health Organization.

Cranial Nerve Schwannomas: Diagnostic Imaging Approach.

Schwannomas are benign nerve sheath tumors that may arise along the complex course of the cranial nerves (CNs), anywhere in the head and neck. Sound knowledge of the CN anatomy and imaging features of schwannomas is paramount for making the correct diagnosis. In this article, we review approaches to diagnosing CN schwannomas by describing their imaging characteristics and the associated clinical presentations. Relevant anatomic considerations are highlighted by using illustrative examples and key differential diagnoses categorized according to regions, which include the anterior skull base, orbit, cavernous sinus, basal cisterns, and neck. The clinical presentations associated with CN schwannomas vary and range from no symptoms to symptoms caused by mass effect or CN deficits. Individuals with the inherited disorder neurofibromatosis type 2 are predisposed to multiple schwannomas. When a lesion follows the course of a CN, the radiologist's roles are to confirm the imaging features of schwannoma and exclude appropriate differential considerations. The characteristic imaging features of CN schwannomas reflect their slow growth as benign neoplasms and include circumscribed margins, displacement of local structures, and smooth expansion of osseous foramina. These neoplasms exhibit various degrees of solid enhancement, often with internal cystic spaces on magnetic resonance (MR) and computed tomographic (CT) images and heterogeneous high signal intensity specifically on T2-weighted MR images. Clinical and/or imaging evidence of end-organ compromise of the involved CN may exist and aid in the identification of the nerve of origin. With a detailed understanding of the course of the CNs, the diagnostic features of CN schwannomas, and the correlation between these data and the associated clinical presentations of these tumors, the radiologist can have a key role in the diagnosis of CN schwannomas and the treatment planning for affected patients. (©)RSNA, 2016.

Temporal patterns of 18 F-fluorodeoxyglucose positron emission tomography/computed tomography sinonasal uptake after treatment of sinonasal malignancy.

BACKGROUND: Current guidelines have identified 10 to 12 weeks posttreatment as the ideal time-point for improved diagnostic accuracy of positron emission tomography/computed tomography (PET/CT) for deep tissue sites of the head and neck. After treatment, the sinonasal skull base is predisposed to prolonged inflammation that may render this time-point inappropriate for initial posttreatment imaging surveillance for sinonasal malignancies. The purpose of this study is to evaluate temporal trends in 18 F-fluorodeoxyglucose (18 FDG) sinonasal uptake after treatment for sinonasal malignancies to better elucidate the optimal time-point for initial PET/CT posttreatment evaluation in this patient population. METHODS: A retrospective analysis of all successfully treated and non-locally recurrent sinonasal malignancies over a 15-year study period (2000 to 2015) was performed at our institution. Posttreatment 18 FDG PET/CT standardized uptake value data were collected and compared between various time-points (2 to 4 months, 5 to 12 months, 5 to 24 months, and 13 to 24 months) using an independent-samples t test. RESULTS: A statistically significant difference was noted between the posttreatment time windows 2 to 4 and 5 to 12 months (p = 0.048) as well as 2 to 4 and 5 to 24 months (p = 0.02). A trend toward significance was seen when comparing 2 to 4 and 13 to 24 months (p = 0.083). CONCLUSION: Our analysis of PET/CT in patients previously treated for sinonasal malignancy suggests that the posttreatment sinonasal skull base is characterized by a prolonged period of hypermetabolism that endures beyond the period previously described for deep tissue sites of the head and neck. These findings prompt a reevaluation of the previously described 10- to 12-week cutoff point for initial posttreatment PET/CT for head and neck squamous cell carcinoma as applied to sinonasal malignancies.

Endoscopy versus imaging: Analysis of surveillance methods in sinonasal malignancy.

BACKGROUND: The purpose of this study was to assess the utility of imaging and endoscopy in posttreatment surveillance of sinonasal malignancies. METHODS: We conducted a retrospective analysis of primary sinonasal malignancies diagnosed between 2000 and 2014. Posttreatment surveillance included nasal endoscopy and imaging (MRI, CT, and positron emission tomography [PET]/CT). Positive predictive value (PPV), negative predictive value (NPV), specificity, and sensitivity were calculated for each modality and compared. RESULTS: One hundred nine sinonasal malignancies were identified with 30 recurrences. Endoscopy showed a sensitivity and specificity of 24% and 89%, respectively, whereas imaging was 76% and 90%, respectively. Identifying suspicious symptoms significantly improved the PPV of both endoscopy and imaging. MRI demonstrates the highest PPV when compared with other imaging modalities. CONCLUSION: Both modalities are necessary in posttreatment surveillance. MRI shows the highest PPV, whereas endoscopy trends toward a higher specificity. PET/CT scans have a high false-positive rate and should be reserved for tumors with a high propensity for distant metastases. © 2016 Wiley Periodicals, Inc. Head Neck 38:1229-1233, 2016.

US-guided Biopsy of Neck Lesions: The Head and Neck Neuroradiologist's Perspective.

Ultrasonographically (US) guided percutaneous biopsy of a neck lesion is a cost-effective, safe, and diagnostically effective procedure without radiation exposure. The benefit of real-time visualization of the needle location allows for instantaneous maneuvering of the needle trajectory for safe and accurate tissue sampling with short procedural time. Effective US-guided biopsy requires technical experience, strong clinical acumen, and skillful biopsy technique. A neuroradiologist's knowledge of head and neck anatomy and pathology allows correlation with cross-sectional imaging and enhances the understanding of US imaging evaluation. Familiarity with a spectrum of neck surgeries and reconstructions and expertise in imaging evaluation of the treated neck are invaluable in accurate identification of the target for biopsy in patients with treatment-related altered anatomy using US guidance. After thyroid nodules, the common adult neck masses are lymphadenopathy, head and neck cancer, salivary neoplasms, nerve sheath tumors, and inflammatory and infectious pseudomasses. Diagnostic expertise in the imaging characteristics of these individual pathologic conditions and their differential diagnoses also play an important role in choosing the biopsy technique and in procuring an adequate sample for diagnosis, including material for ancillary laboratory testing. Using an anatomic zone approach, this article illustrates the practical considerations in patient selection, the methodical analysis of preprocedure cross-sectional imaging and its correlation with real-time US evaluation, general principles for optimizing US instrumentation, and biopsy technique. In skillful hands, the versatility and portability of US make it the valuable modality for histologic sampling of superficial head and neck lesions. Online supplemental material is available for this article.