Single-Cell Sequencing Illuminates Thymic Development: An Updated Framework for Understanding Thymic Epithelial Tumors.

Thymic epithelial tumors (TETs) are rare tumors for which treatment options are limited. The ongoing need for improved systemic therapies reflects a limited understanding of tumor biology as well as the normal thymus. The essential role of the thymus in adaptive immunity is largely effected by its epithelial compartment, which directs thymocyte (T-cell) differentiation and immunologic self-tolerance. With aging, the thymus undergoes involution whereby epithelial tissue is replaced by adipose and other connective tissue, decreasing immature T-cell production. Against this natural drive toward involution, a fraction of thymuses will instead undergo oncologic transformation, leading to the formation of TETs, including thymoma and thymic carcinoma. The rarity of these tumors restricts investigation of the mechanisms of tumorigenesis and development of rational treatment options. To this end, the development of technologies which allow deep molecular profiling of individual tumor cells permits a new window through which to view normal thymic development and contrast the malignant changes that result in oncogenic transformation. In this review, we describe the findings of recent illuminating studies on the diversity of cell types within the epithelial compartment through thymic differentiation and aging. We contextualize these findings around important unanswered questions regarding the spectrum of known somatic tumor alterations, cell of origin, and tumor heterogeneity. The perspectives informed by single-cell molecular profiling offer new approaches to clinical and basic investigation of thymic epithelial tumors, with the potential to accelerate development of improved therapeutic strategies to address ongoing unmet needs in these rare tumors.

Anastomosing haemangioma of the mediastinum: Clinicopathological series with radiological and genetic characterisation.

AIMS: Anastomosing haemangiomas are benign tumours with anastomosing vascular channels that may mimic angiosarcoma. While anastomosing haemangiomas have been described in diverse locations, particularly the abdominal/paraspinal region, data on anastomosing haemangiomas in the mediastinum remain limited. We report the clinicopathological, radiological and molecular characteristics of the largest single-institutional series of mediastinal anastomosing haemangiomas. METHODS AND RESULTS: In our pathology archives in 2011-23, we reviewed all vascular lesions involving the mediastinum and identified seven anastomosing haemangiomas. Clinical information was abstracted from medical charts; available radiological imaging was reviewed. Targeted DNA-based next-generation sequencing (447 genes, including GNAQ and GNA11) was performed on five cases. The seven patients included five women and two men, with an age range of 55-77 (median = 72) years. Of the six tumours with available radiology, two each were in the prevascular, visceral and paravertebral mediastinum, with lobulated peripheral enhancement in all tumours examined with contrast enhancement. Six patients underwent tumour resection; one patient received proton radiotherapy. Microscopically, each tumour was solitary and characterised by anastomosing capillary-sized vessels lined by hobnail endothelial cells. Fibrin microthrombi, hyaline globules and extramedullary haematopoiesis were common. In the five tumours analysed by next-generation sequencing, GNAQ p.Q209P was identified in one tumour; no additional reportable alterations were identified in the remaining cases. No recurrence was noted in the four patients with available follow-up of 3-58 (median = 9.5) months after resection. CONCLUSION: While mediastinal anastomosing haemangiomas can microscopically mimic angiosarcoma, awareness of this entity and radiological correlation may help to circumvent this diagnostic pitfall.

Intralesional microbleeding in resected thymic cysts indeterminate on imaging.

Background: The propensity of thymic cysts to mimic solid thymic epithelial tumors (TETs) on computed tomography (CT), on account of attenuation values greater than water and thickened or calcified walls, can lead to non-therapeutic thymectomy. These lesions can fluctuate in volume, CT attenuation, and magnetic resonance imaging (MRI) signal over time. We hypothesized that spontaneous hemorrhage and resorption may contribute to their variable appearance over time. Methods: Completely excised thymic cysts were identified retrospectively over a 20-year period by their pathologic diagnosis. Cysts were excluded if they did not have available presurgical imaging, were not prevascular, were located within or contained an enhancing mass by imaging, or were of non-thymic origin upon microscopic review. Histopathological analysis of all available resected thymic cyst material and radiologic analysis of the cysts on pre-operative imaging were performed. Results: Upon application of exclusion criteria, we identified 18 thymic cysts from the initial 85 mediastinal cystic specimens. Most cysts were unilocular (11/15, 73%), showed turbid-to-semisolid, hemorrhagic fluid (10/12, 83%) and showed histopathological findings suggestive of intralesional microbleeding (14/18, 78%), remodeling (8/18, 44%), pathological wound healing/scarring of the capsule (16/18, 89%), and fat necrosis in the surrounding thymic tissue (12/18, 67%). On CT, 6/17 (35%) cysts demonstrated wall calcification. Sixty-five percent (11/17) had attenuation values ≥20 Hounsfield units (HU). Two of the 4 cysts imaged by MRI were T1-isointense, one was mixed hyper- and isointense, and one T1-hypointense to muscle, with iso- and hyperintensity indicating hemorrhagic or proteinaceous content. Twenty-five percent (1/4) of cyst walls imaged by MRI were T1/T2-hypointense, indicating presence of calcification, hemosiderin, and/or fibrosis. Conclusions: Resected thymic cysts in this cohort often showed features suggestive of intralesional microbleeding, inflammation, and fibrosis, which may explain their appearance and behavior over time on CT and MRI.

Longitudinal CT and MRI Characteristics of Unilocular Thymic Cysts.

Background Isoattenuating and hyperattenuating thymic cysts at CT are often misinterpreted as lymphadenopathy or thymic epithelial neoplasms. Purpose To evaluate the longitudinal change in thymic cyst appearance at CT and MRI. Materials and Methods All chest MRI studies showing thymic cysts between July 2008 and December 2019, identified from a retrospective search of a quality assurance database, were included in this study if initial CT depicted a thymic lesion, the patient was referred for follow-up MRI for characterization, and the baseline (ie, index) MRI indicated a cystic lesion. Follow-up CT scans and/or MRI scans were identified through July 2020. Thymic cyst characteristics, such as size, location, and morphologic features, as well as CT and MRI characteristics, were recorded. Change in size, attenuation, and T1-weighted MRI signal was assessed longitudinally. Descriptive statistics of longitudinal change were tabulated. Results A total of 244 chest MRI studies in 140 patients with 142 unique cysts and 392 CT examinations (636 total examinations and 645 thymic cysts-nine examinations with two cysts each) were evaluated. The median follow-up duration was 2.2 years. Thirty-three patients with 34 unique cysts (34 of 142 cysts [24%]) underwent imaging follow-up for more than 5 years. Thymic cysts followed up for more than 5 years were most commonly saccular (189 of 274 cysts [69% axially]) and retrosternal (14 of 34 cysts [41%]). Craniocaudal dimension was larger than transverse and anteroposterior dimensions in 223 of 274 cysts (81%). Mean thymic cyst attenuation was 25 HU (range, 15-100 HU). Five of 31 cysts (16%) exhibited wall calcification. The median cyst wall thickness was 2.0 mm (range, 0.9-3.0 mm). Most thymic cysts changed in volume (31 of 34 cysts [91%]), CT attenuation (15 of 35 cysts [43%]), and T1-weighted MRI signal (12 of 18 cysts [67%]) over time. None developed mural irregularity, nodularity, or septations. Conclusion Unilocular thymic cysts, defined at index MRI, never developed irregular wall thickening, mural nodularity, or septations that would raise concern for malignant transformation. However, these cysts showed mural calcification and change in size, CT attenuation, and MRI signal over more than 5 years of follow-up. © RSNA, 2021 Online supplemental material is available for this article.

ACR Appropriateness Criteria® Imaging of Mediastinal Masses.

Mediastinal masses can present with symptoms, signs, and syndromes or incidentally. Selecting the appropriate diagnostic imaging study for mediastinal mass evaluation requires awareness of the strengths and weaknesses of the various imaging modalities with regard to tissue characterization, soft tissue contrast, and surveillance. This publication expounds on the differences between chest radiography, CT, PET/CT, ultrasound, and MRI in terms of their ability to decipher and surveil mediastinal masses. Making the optimal imaging choice can yield diagnostic specificity, avert unnecessary biopsy and surgery, guide the interventionist when necessary, and serve as a means of surveillance for probably benign, but indeterminate mediastinal masses. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

Imaging Assessment of Visceral Pleural Surface Invasion by Lung Cancer: Comparison of CT and Contrast-Enhanced Radial T1-Weighted Gradient Echo 3-Tesla MRI.

OBJECTIVE: To compare the diagnostic performance of contrast-enhanced radial T1-weighted gradient-echo 3-tesla (3T) magnetic resonance imaging (MRI) and computed tomography (CT) for the detection of visceral pleural surface invasion (VPSI). Visceral pleural invasion by non-small-cell lung cancer (NSCLC) can be classified into two types: PL1 (without VPSI), invasion of the elastic layer of the visceral pleura without reaching the visceral pleural surface, and PL2 (with VPSI), full invasion of the visceral pleura. MATERIALS AND METHODS: Thirty-three patients with pathologically confirmed VPSI by NSCLC were retrospectively reviewed. Multidetector CT and contrast-enhanced 3T MRI with a free-breathing radial three-dimensional fat-suppressed volumetric interpolated breath-hold examination (VIBE) pulse sequence were compared in terms of the length of contact, angle of mass margin, and arch distance-to-maximum tumor diameter ratio. Supplemental evaluation of the tumor-pleura interface (smooth versus irregular) could only be performed with MRI (not discernible on CT). RESULTS: At the tumor-pleura interface, radial VIBE MRI revealed a smooth margin in 20 of 21 patients without VPSI and an irregular margin in 10 of 12 patients with VPSI, yielding an accuracy, sensitivity, specificity, positive predictive value, negative predictive value, and F-score for VPSI detection of 91%, 83%, 95%, 91%, 91%, and 87%, respectively. The McNemar test and receiver operating characteristics curve analysis revealed no significant differences between the diagnostic accuracies of CT and MRI for evaluating the contact length, angle of mass margin, or arch distance-to-maximum tumor diameter ratio as predictors of VPSI. CONCLUSION: The diagnostic performance of contrast-enhanced radial T1-weighted gradient-echo 3T MRI and CT were equal in terms of the contact length, angle of mass margin, and arch distance-to-maximum tumor diameter ratio. The advantage of MRI is its clear depiction of the tumor-pleura interface margin, facilitating VPSI detection.

Added Value of Magnetic Resonance Imaging for the Evaluation of Mediastinal Lesions.

The high soft tissue contrast and tissue characterization properties of magnetic resonance imaging allow further characterization of indeterminate mediastinal lesions on chest radiography and computed tomography, increasing diagnostic specificity, preventing unnecessary intervention, and guiding intervention or surgery when needed. The combination of its higher soft tissue contrast and ability to image dynamically during free breathing, without ionizing radiation exposure, allows more thorough and readily appreciable assessment of a lesion's invasiveness and assessment of phrenic nerve involvement, with significant implications for prognostic clinical staging and surgical management.

Direct and indirect CT imaging features of esophago-airway fistula in adults.

BACKGROUND: Esophago-airway fistula (EAF) is an abnormal connection between the esophagus and the trachea or a major bronchus. While contrast esophagography remains the primary radiographic tool for the diagnosis of EAF, computed tomography (CT) is often employed in its evaluation. A systematic analysis of CT findings of EAF in adults has not been previously published. The goal of our study is to determine the direct and indirect CT findings of EAF in adults. METHODS: We identified patients with EAF detected on CT at our institution between January 1, 2001 and December 31, 2019, with endoscopic or surgical confirmation. We collected patient clinicopathologic characteristics and assessed CTs for direct and indirect imaging features of EAF in these patients. RESULTS: Twenty-six patients (median age: 56 years; range, 25-79 years; F=13, 50% and M=13, 50%) with confirmed EAF were identified. Half of the patients had an underlying malignancy. On CT, a direct connection between the esophagus and the airway was identified in most cases (22/26; 85%). Common indirect CT findings of EAF included esophageal wall thickening (21/26, 81%), mediastinal fatty stranding (21/26, 81%), airway wall thickening (20/26, 77%), fluid or debris within the airways (17/26, 65%), and focal or diffuse esophageal dilation with air (17/26, 65%). Mediastinal fluid collections were infrequently seen (4/26, 15%), but findings of aspiration or other pneumonia were common (19/26, 73%). CONCLUSIONS: CT plays an essential role in both the primary and secondary evaluation of adult EAF resulting from both malignant and benign etiologies. CT may be the first diagnostic exam to suggest and detect the presence of EAF and may precede clinical suspicion, and it can detect a subset of fistulas not demonstrated on esophagography. There are several direct and indirect imaging findings on CT that can help in the detection of EAF.

ACR Appropriateness Criteria® Occupational Lung Diseases.

Ordering the appropriate diagnostic imaging for occupational lung disease requires a firm understanding of the relationship between occupational exposure and expected lower respiratory track manifestation. Where particular inorganic dust exposures typically lead to nodular and interstitial lung disease, other occupational exposures may lead to isolated small airway obstruction. Certain workplace exposures, like asbestos, increase the risk of malignancy, but also produce pulmonary findings that mimic malignancy. This publication aims to delineate the common and special considerations associated with occupational lung disease to assist the ordering physician in selecting the most appropriate imaging study, while still stressing the importance of a multidisciplinary approach. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

Distribution of Mediastinal Lesions Across Multi-Institutional, International, Radiology Databases.

INTRODUCTION: Mediastinal lesions are uncommon; studies on their distribution are, in general, small and from a single institution. Furthermore, these studies are usually based on pathology or surgical databases and, therefore, miss many lesions that did not undergo biopsy or resection. Our aim was to identify the distribution of lesions in the mediastinum in a large international, multi-institutional cohort. METHODS: At each participating institution, a standardized retrospective radiology database search was performed for interpretations of computed tomography, positron emission tomography-computed tomography, and magnetic resonance imaging scans including any of the following terms: "mediastinal nodule," "mediastinal lesion," "mediastinal mass," or "mediastinal abnormality" (2011-2014). Standardized data were collected. Statistical analysis was performed. RESULTS: Among 3308 cases, thymomas (27.8%), benign mediastinal cysts (20.0%), and lymphomas (16.1%) were most common. The distribution of lesions varied among mediastinal compartments; thymomas (38.3%), benign cysts (16.8%), and neurogenic tumors (53.9%) were the most common lesions in the prevascular, visceral, and paravertebral mediastinum, respectively (p < 0.001). Mediastinal compartment was associated with age; patients with paravertebral lesions were the youngest (p < 0.0001). Mediastinal lesions differed by continent or country, with benign cysts being the most common mediastinal lesions in the People's Republic of China, thymomas in Europe, and lymphomas in North America and Israel (p < 0.001). Benign cysts, thymic carcinomas, and metastases were more often seen in larger hospitals, whereas lymphomas and thymic hyperplasia occurred more often in smaller hospitals (p < 0.01). CONCLUSIONS: Our study confirmed that the spectrum and frequency of mediastinal lesions depend on mediastinal compartment and age. This information provides helpful demographic data and is important when considering the differential diagnosis of a mediastinal lesion.

ACR Appropriateness Criteria® Acute Respiratory Illness in Immunocompromised Patients.

The immunocompromised patient with an acute respiratory illness (ARI) may present with fever, chills, weight loss, cough, shortness of breath, or chest pain. The number of immunocompromised patients continues to rise with medical advances including solid organ and stem cell transplantation, chemotherapy, and immunomodulatory therapy, along with the continued presence of human immunodeficiency virus and acquired immunodeficiency syndrome. Given the myriad of pathogens that can infect immunocompromised individuals, identifying the specific organism or organisms causing the lung disease can be elusive. Moreover, immunocompromised patients often receive prophylactic or empiric antimicrobial therapy, further complicating diagnostic evaluation. Noninfectious causes for ARI should also be considered, including pulmonary edema, drug-induced lung disease, atelectasis, malignancy, radiation-induced lung disease, pulmonary hemorrhage, diffuse alveolar damage, organizing pneumonia, lung transplant rejection, and pulmonary thromboembolic disease. As many immunocompromised patients with ARI progress along a rapid and potentially fatal course, timely selection of appropriate imaging is of great importance in this setting. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking, or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

ACR Appropriateness Criteria® Noninvasive Clinical Staging of Primary Lung Cancer.

Lung cancer is the leading cause of cancer-related deaths in both men and women. The major risk factor for lung cancer is personal tobacco smoking, particularly for small-cell lung cancer (SCLC) and squamous cell lung cancers, but other significant risk factors include exposure to secondhand smoke, environmental radon, occupational exposures, and air pollution. Education and socioeconomic status affect both incidence and outcomes. Non-small-cell lung cancer (NSCLC), including adenocarcinoma, squamous cell carcinoma, and large cell carcinoma, comprises about 85% of lung cancers. SCLC accounts for approximately 13% to 15% of cases. Prognosis is directly related to stage at presentation. NSCLC is staged using the eighth edition of the tumor-node-metastasis (TNM) criteria of the American Joint Committee on Cancer. For SCLC the eighth edition of TNM staging is recommended to be used in conjunction with the modified Veterans Administration Lung Study Group classification system distinguishing limited stage from extensive stage SCLC. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

Quantitative Thoracic Magnetic Resonance Criteria for the Differentiation of Cysts from Solid Masses in the Anterior Mediastinum.

OBJECTIVE: To evaluate quantitative magnetic resonance imaging (MRI) parameters for differentiation of cysts from and solid masses in the anterior mediastinum. MATERIALS AND METHODS: The development dataset included 18 patients from two institutions with pathologically-proven cysts (n = 6) and solid masses (n = 12) in the anterior mediastinum. We measured the maximum diameter, normalized T1 and T2 signal intensity (nT1 and nT2), normalized apparent diffusion coefficient (nADC), and relative enhancement ratio (RER) of each lesion. RERs were obtained by non-rigid registration and subtraction of precontrast and postcontrast T1-weighted images. Differentiation criteria between cysts and solid masses were identified based on receiver operating characteristics analysis. For validation, two separate datasets were utilized: 15 patients with 8 cysts and 7 solid masses from another institution (validation dataset 1); and 11 patients with clinically diagnosed cysts stable for more than two years (validation dataset 2). Sensitivity and specificity were calculated from the validation datasets. RESULTS: nT2, nADC, and RER significantly differed between cysts and solid masses (p = 0.032, 0.013, and < 0.001, respectively). The following criteria differentiated cysts from solid masses: RER < 26.1%; nADC > 0.63; nT2 > 0.39. In validation dataset 1, the sensitivity of the RER, nADC, and nT2 criteria was 87.5%, 100%, and 75.0%, and the specificity was 100%, 40.0%, and 57.4%, respectively. In validation dataset 2, the sensitivity of the RER, nADC, and nT2 criteria was 90.9%, 90.9%, and 72.7%, respectively. CONCLUSION: Quantitative MRI criteria using nT2, nADC, and particularly RER can assist differentiation of cysts from solid masses in the anterior mediastinum.

Clinical TNM staging of thymic epithelial malignancies.

The International Thymic Malignancy Interest Group (ITMIG) and the International Association for the Study of Lung Cancer (IASLC) formed the Thymic Domain of the Staging and Prognostic Factors Committee (TD-SPFC) to develop the first stage classification system for thymic epithelial tumors (TETs) which was published in the TNM Classification of Malignant Tumours issued by the American Joint Committee on Cancer (AJCC) and the Union for International Cancer Control (UICC), now in 8th edition. This system was developed from evidence-based analysis of the large ITMIG database of TETs, in conjunction with expert opinion. Until its publication in December 2017, there had been no universally accepted, standard means of classifying these tumors, although Masaoka-Koga staging system had most closely approached this standard. This brief article will summarize this new stage classification system for TETs, highlighting its differences with Masaoka-Koga and relevant next goals.

Cystic mediastinal masses and the role of MRI.

While some cystic masses can be definitively diagnosed on CT, others remain indeterminate. Because of its intrinsic superior soft tissue resolution, MR is an important tool in the evaluation of select mediastinal masses that are incompletely characterized on CT. This review describes how non-vascular MR provides greater diagnostic precision in the evaluation of indeterminate cystic mediastinal masses on CT. It also emphasizes key MR pulse sequences for optimal evaluation of problematic mediastinal masses.

Primary Paratracheal Leiomyoma: Increased Preoperative Diagnostic Specificity With Magnetic Resonance Imaging.

We report the case of a 47-year-old woman whose primary mediastinal leiomyoma was incidentally found during evaluation of her persistent cough. The preoperative diagnosis of mediastinal leiomyoma is challenging because of its rarity and indeterminate features on chest radiography, computed tomography (CT), and positron emission tomography-CT. We highlight how magnetic resonance imaging can substantially contribute to mediastinal mass characterization and diagnostic specificity.

What's New in 10 Years? A Revised Cardiothoracic Curriculum for Diagnostic Radiology Residency with Goals and Objectives Related to General Competencies.

This is a cardiothoracic curriculum document for radiology residents meant to serve not only as a study guide for radiology residents but also as a teaching and curriculum reference for radiology educators and radiology residency program directors. This document represents a revision of a cardiothoracic radiology resident curriculum that was published 10 years ago in Academic Radiology. The sections that have been significantly revised, expanded, or added are (1) lung cancer screening, (2) lung cancer genomic profiling, (3) lung adenocarcinoma revised nomenclature, (4) lung biopsy technique, (5) nonvascular thoracic magnetic resonance, (6) updates to the idiopathic interstitial pneumonias, (7) cardiac computed tomography updates, (8) cardiac magnetic resonance updates, and (9) new and emerging techniques in cardiothoracic imaging. This curriculum was written and endorsed by the Education Committee of the Society of Thoracic Radiology. This curriculum operates in conjunction with the Accreditation Council for Graduate Medical Education (ACGME) milestones project that serves as a framework for semiannual evaluation of resident physicians as they progress through their training in an ACGME-accredited residency or fellowship programs. This cardiothoracic curriculum document is meant to serve not only as a more detailed guide for radiology trainees, educators, and program directors but also complementary to and guided by the ACGME milestones.