Distribution and Rate of Myxoid Liposarcoma Spine Metastases: Impact on Surveillance Imaging.

BACKGROUND: Myxoid liposarcoma (LPS) has a unique tendency to spread to extrapulmonary sites, including osseous sites such as the spine, and adjacent sites such as the paraspinous tissue. No clear consensus exists to guide the approach to imaging in these patients. OBJECTIVE: The aim of this study was to investigate the rate and distribution of spine metastases in patients with myxoid LPS and detection modality. METHODS: Records of all patients with myxoid LPS evaluated at our sarcoma center were retrospectively reviewed. Disease patterns and imaging modality utilization were analyzed. RESULTS: Between 2000 and 2020, 164 patients with myxoid LPS were identified. The majority (n = 148, 90%) presented with localized disease, with half (n = 82, 50%) of all patients developing metastases or recurrence during their disease course. With a median follow-up of 69.2 months, spine/paraspinous metastases developed in 38 patients (23%), of whom 35 (92%) already had synchronous, non-spine metastases. Spine disease was only visible on magnetic resonance imaging (MRI), as opposed to other imaging modalities, for over one-quarter of patients with spine metastases (n = 10). For patients with metastatic disease, spine metastases were associated with worse median overall survival (2.1 vs. 8.7 years, p < 0.001). CONCLUSION: Spine metastases occurred in nearly one-quarter of patients with myxoid LPS and represented an advanced disease state, as they primarily presented in the setting of synchronous, non-spine metastases, and were associated with worse overall survival. Routine surveillance with spine MRI in patients with localized disease likely provides no benefit but may be considered in those with known metastatic disease.

Primary Clear Cell Sarcoma of Bone: Clinicopathologic Study of a Rare Presentation.

Clear cell sarcoma (CCS) is an uncommon malignant mesenchymal neoplasm of young adults with a predilection for tendons and aponeuroses of distal extremities, a distinctive nested growth pattern, melanocytic differentiation, and usually an EWSR1::ATF1 fusion. Distinction from melanoma can be challenging but is critical for clinical management. Rare cases of primary bone CCS have been reported. The purpose of this study was to evaluate the clinicopathologic features of a series of primary bone CCS. Three cases of primary bone CCS were identified out of 140 CCS diagnosed between 2010 and 2021. Two patients were female, and 1 patient was male; ages were 19, 47, and 61 years. All tumors arose in the long bones of the extremities (femur, humerus, fibula). Two tumors also involved regional lymph nodes at presentation. Two showed characteristic histologic features, in the form of nests and fascicles of uniform epithelioid to spindle cells with prominent nucleoli and pale eosinophilic to clear cytoplasm; 1 tumor showed sheet-like growth, unusual focal pleomorphism, and more notable nuclear atypia. By immunohistochemistry, S100 protein was positive in 2/3 cases, SOX10 in 3/3, HMB-45 in 2/3, MiTF in 2/2, and melan A in 1/3. All cases were confirmed to harbor EWSR1 rearrangement and EWSR1::ATF1 fusion or t(12;22). On follow-up, all 3 patients developed metastases and died of disease, 5, 18, and 21 months after diagnosis. In summary, CCS rarely presents in the skeleton. At such locations, distinction from metastatic melanoma is particularly challenging. Clinical and pathologic features are similar to conventional CCS of soft tissue. Primary bone CCS may pursue an aggressive clinical course.

Differentiating leiomyosarcoma from leiomyoma: in support of an MR imaging predictive scoring system.

PURPOSE: The purpose of this study was to determine the Magnetic Resonance (MR) imaging features that best differentiate leiomyosarcoma (LMS) from leiomyoma, and to explore a scoring system to preoperatively identify those at highest risk of having LMS. METHODS: Our Institutional Review Board approved this retrospective HIPAA-compliant study with a waiver for written informed consent. Institutional Research Patient Data Registry identified patients with histopathologically-proven LMS (n = 19) or leiomyoma (n = 25) and a pelvic MRI within six months prior to surgery. Qualitative differentiating MRI features were selected based on prior publications and clinical experience. Patient and MRI characteristics for leiomyomas versus LMS were compared using Wilcoxon rank-sum tests or Fisher's exact tests and using a basic classification tree. Hypothesis testing was two-tailed, with a p value < 0.001 used to determine inclusion of variables into an MR imaging predictive (MRP) score. Diagnostic performance [sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV)] of the MRP in diagnosis of LMS used all possible scores as cutoffs. RESULTS: Seven out of 15 MRI features were found to have an association with LMS. The final MRP scores ranged from 0 to 7: a score of 0-3 was associated with 100% NPV for LMS, and a MRP score of 6-7 with 100% PPV for LMS. CONCLUSION: Seven qualitative MR imaging features, extracted from a standard MR imaging protocol, allow differentiation of LMS from leiomyoma. An exploratory risk stratification MRP score can be used to determine the likelihood of LMS being present.

A Review of the Spectrum of Imaging Manifestations of Epithelioid Hemangioendothelioma.

OBJECTIVE. The purpose of this article is to review the spectrum of imaging manifestations of epithelioid hemangioendothelioma across different organ systems and briefly describe its current treatment strategies. CONCLUSION. Epithelioid hemangioendothelioma is a rare, locally invasive neoplasm with metastatic potential. Although most commonly occurring in liver, lungs, and bones, it can also present at multiple other sites. Because of its nonspecific clinical and imaging manifestations, it is often misdiagnosed. The possibility of epithelioid hemangioendothelioma must be considered in the presence of a slowly growing mass that invades adjacent structures. Imaging can help plan percutaneous biopsy, detect sites of disease, and identify poor prognostic factors.

Imaging of Waldenström Macroglobulinemia: A Comprehensive Review for the Radiologist in the Era of Personalized Medicine.

OBJECTIVE. We describe the range of organ systems involved and the spectrum of imaging findings seen in Waldenström macroglobulinemia (WM). CONCLUSION. Although imaging is not mandatory in the initial workup of a patient with WM, a multimodality imaging approach can lead toward the diagnosis of a lymphoproliferative disorder, establish the tumor burden, identify sites of involvement, and thus explain the clinical presentation, help in determining prognosis and monitoring response to therapy, and help identify treatment-induced toxicity.

Focal Liver Uptake on FDG PET/CT Without CT Correlate: Utility of MRI in the Evaluation of Patients With Known Malignancy.

OBJECTIVE. The purpose of this study was to determine the significance and utility of MRI in evaluation of focal hepatic uptake on FDG PET/CT without a CT correlate in patients with known malignancy. MATERIALS AND METHODS. In this retrospective study, we identified 36 of 1851 patients between 2005 and 2012 with known malignancy (19 women, 17 men; mean age, 56.1 years old) who had focal hepatic uptake on FDG PET/CT without a CT correlate and follow-up MRI within 100 days for assessment of uptake. Two radiologists reviewed the FDG PET/CT images together, reached consensus about presence of focal hepatic uptake, and measured maximum standardized uptake value (SUVmax) of the focal uptake and background liver. MR images were then reviewed to identify any correlate. Follow-up imaging and histopathologic data were reviewed to confirm or refute metastasis. Statistical correlation between intensity of FDG uptake and presence of focal lesions on MRI was performed. RESULTS. Fifty sites of focal hepatic uptake without CT correlate were identified. The median SUVmax was 4.1 (range, 2.1-10.1), whereas the ratio of median SUVmax of the hepatic lesion to that of normal parenchyma was 1.3 (range, 0.98-2.6). MRI confirmed focal lesions in 26 of 50 sites (52%). Seventy-seven percent of cases of hepatic uptake with an MRI correlate (20/26) were confirmed as metastatic disease (six cases at histopathology). Therefore, 40% of cases of hepatic uptake without a CT correlate (20/50) were metastases. We found no statistically significant difference in the SUVmax of hepatic lesions and SUVmax ratio between the groups with and without an MRI correlate (median SUVmax = 3.85 vs 4.2, p = 0.5; SUVmax ratio = 1.32 vs 1.31, p = 0.97) as well as between the groups with the final diagnosis of benign lesions and metastasis (SUVmax = 4.05 vs 3.95, p = 0.64; SUVmax ratio = 1.31 vs 1.32, p = 0.91). CONCLUSION. More than half of the cases of focal hepatic uptake on PET/CT without a CT correlate had an MRI correlate in our study, and more than 75% of these lesions were metastases, regardless of SUVmax.

Multimodality imaging of indolent B cell lymphoma from diagnosis to transformation: what every radiologist should know.

Indolent B cell lymphomas are a group of lymphoid malignancies characterized by their potential to undergo histologic transformation to aggressive lymphomas. While different subtypes of indolent B cell lymphomas demonstrate specific clinical and imaging features, histologic transformation can be suspected on cross-sectional imaging when disproportionate lymph node enlargement or new focal lesions in extranodal organs are seen. On PET/CT, transformed indolent lymphoma may show new or increased nodal FDG avidity or new FDG-avid lesions in different organs. In this article, we will (1) review the imaging features of different subtypes of indolent B cell lymphomas, (2) discuss the imaging features of histologic transformation, and (3) propose a diagnostic algorithm for transformed indolent lymphoma. The purpose of this review is to familiarize radiologists with the spectrum of clinical and imaging features of indolent B cell lymphomas and to define the role of imaging in raising concern for transformation and in guiding biopsy for confirmation.

Value of hepatocellular phase imaging after intravenous gadoxetate disodium for assessing hepatic metastases from gastroenteropancreatic neuroendocrine tumors: comparison with other MRI pulse sequences and with extracellular agent.

OBJECTIVE: To compare hepatocellular phase imaging after intravenous gadoxetate disodium with other MRI pulse sequences and with extracellular agent for assessing hepatic metastases from gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN). MATERIALS AND METHODS: In this IRB-approved, HIPAA-compliant retrospective study, we included 30 patients (15 women, mean age: 58 years, range 44-77 years) with GEP-NEN metastatic to the liver, who underwent MRI with gadoxetate disodium. Six MRI sequences were reviewed by two radiologists to score tumor-liver interface (TLI) on a 5-point scale, to assess lesion detectability in different liver segments (divided into 3 zones/patient), and to measure lesion size. Contrast-to-noise ratio (CNR) was calculated on each sequence. In 19 patients, lesion size and CNR on dynamic imaging with gadopentetate dimeglumine was compared with hepatocellular phase. Wilcoxon signed-rank test was used to compare TLI scores, lesion size, and median CNR, using Bonferroni correction for multiple testing. Interobserver agreement for TLI was analyzed using Krippendorff's alpha, and for lesion size using concordance correlation coefficient (CCC) and mean relative difference. RESULTS: Hepatocellular phase had the best TLI (mean TLI for reader 1 = 1.2, reader 2 = 1.3) compared to all other sequences (p < 0.0001) with excellent interobserver agreement (Krippendorff's alpha = 1.0), maximum lesion detectability (61/90 zones), highest interobserver agreement for lesion measurement (CCC 0.9875 and smallest mean relative difference - 1.567%), and highest median CNR (31.2, p < 0.008). Hepatocellular phase also had the highest CNR when compared with gadopentetate imaging. CONCLUSION: Hepatocellular phase imaging offers significant advantages for assessment of hepatic metastasis in GEP-NEN, and should be routinely considered for follow-up of these patients.

Gastroenteropancreatic neuroendocrine tumors: impact of consistent contrast agent selection on radiologists' confidence in hepatic lesion assessment on restaging MRIs.

PURPOSE: To evaluate the impact of contrast agent selection on radiologists' confidence in assessing liver lesions on follow-up magnetic resonance imaging (MRI) studies in patients with neuroendocrine tumors. METHODS: This Institutional Review Board-approved, retrospective study performed at a tertiary cancer center and a quaternary care urban academic hospital included all 694 follow-up abdominal MRI studies from 179 patients with gastroenteropancreatic neuroendocrine tumor performed from 01/01/2010 to 05/31/2015. Primary outcome measure was radiologists' confidence in assessing liver lesions on follow-up MRI. MRI reports were reviewed to abstract radiologists' confidence, classified as "equivocal" if any equivocal connotation (mention of limitation due to differences in contrast agent or follow-up recommendation with specific contrast agent) was present; or "unequivocal" if a precise, confident comparison to prior was documented without the use of ambiguous terms. A fellowship-trained radiologist separately evaluated 100 randomly selected reports and images to calculate interobserver agreement with the report classification (equivocal vs. unequivocal) and with the original MRI report, respectively. Chi-square test was used to compare the proportion of equivocal reports when "same" or "different" contrast agent was used for successive examinations. RESULTS: Rates of equivocal reports were higher when different contrast agents were used for successive examinations compared to examinations with same contrast agent (13.2% [21/159] vs. 1.8% [10/535]; p < 0.0001). There was very good interobserver agreement for assessment of radiologist confidence (κ = 0.92 for report review, κ = 0.82 for image review). CONCLUSIONS: Consistent use of contrast agent for follow-up MRIs allows more confident assessment of liver lesions in patients with neuroendocrine tumors.

Screening with whole-body magnetic resonance imaging in pediatric subjects with Li-Fraumeni syndrome: A single institution pilot study.

BACKGROUND: Li-Fraumeni syndrome (LFS) is an autosomal dominant hereditary cancer syndrome associated with germline mutations in the TP53 gene and a high risk of childhood-onset malignancies. Cancer surveillance is challenging in pediatric mutation carriers given the anatomic spectrum of malignancies and young age of onset. Whole-body magnetic resonance imaging (WB-MRI) may provide an acceptable method for early cancer detection. PROCEDURE: We conducted a prospective feasibility pilot study of pediatric subjects (age < 18 years) with LFS to determine return rates for annual WB-MRI scan. Secondary objectives included characterization of incident cancers (and how they were detected). RESULTS: Forty-five WB-MRI scans in 20 subjects were performed over 5 years; two patients enrolled without subsequently undergoing scans. Eighty-nine percent of participants scanned (95% confidence interval: 67-99%) returned for second examinations. Fifty-five percent of participants required general anesthesia, which was well tolerated in all cases. Six patients required dedicated follow-up imaging. One participant required biopsy of a detected brain lesion; pathology demonstrated reactive gliosis. Another participant, with prior choroid plexus carcinoma, had a new brain lesion detected on clinical follow-up MRI not seen on WB-MRI 6 months prior. All other participants remain well (median: 3 years, range: 0.08-4 years). CONCLUSIONS: WB-MRI in pediatric subjects is a well-tolerated approach to cancer surveillance despite the need for general anesthesia in some patients. A large multicenter trial would determine true test characteristics and efficacy of this approach for early cancer detection in children at high cancer risk.

Computer-Aided Diagnosis of Ground-Glass Opacity Nodules Using Open-Source Software for Quantifying Tumor Heterogeneity.

OBJECTIVE: The purposes of this study are to develop quantitative imaging biomarkers obtained from high-resolution CTs for classifying ground-glass nodules (GGNs) into atypical adenomatous hyperplasia (AAH), adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), and invasive adenocarcinoma (IAC); to evaluate the utility of contrast enhancement for differential diagnosis; and to develop and validate a support vector machine (SVM) to predict the GGN type. MATERIALS AND METHODS: The heterogeneity of 248 GGNs was quantified using custom software. Statistical analysis with a univariate Kruskal-Wallis test was performed to evaluate metrics for significant differences among the four GGN groups. The heterogeneity metrics were used to train a SVM to learn and predict the lesion type. RESULTS: Fifty of 57 and 51 of 57 heterogeneity metrics showed statistically significant differences among the four GGN groups on unenhanced and contrast-enhanced CT scans, respectively. The SVM predicted lesion type with greater accuracy than did three expert radiologists. The accuracy of classifying the GGNs into the four groups on the basis of the SVM algorithm was 70.9%, whereas the accuracy of the radiologists was 39.6%. The accuracy of SVM in classifying the AIS and MIA nodules was 73.1%, and the accuracy of the radiologists was 35.7%. For indolent versus invasive lesions, the accuracy of the SVM was 88.1%, and the accuracy of the radiologists was 60.8%. We found that contrast enhancement does not significantly improve the differential diagnosis of GGNs. CONCLUSION: Compared with the GGN classification done by the three radiologists, the SVM trained regarding all the heterogeneity metrics showed significantly higher accuracy in classifying the lesions into the four groups, differentiating between AIS and MIA and between indolent and invasive lesions. Contrast enhancement did not improve the differential diagnosis of GGNs.

Biliary and pancreatic complications of molecular targeted therapies in cancer imaging.

The purpose of this review is to familiarize radiologists with the different imaging manifestations of biliary and pancreatic toxicity of molecular targeted therapies. The advent of molecular targeted therapies for cancer treatment has prompted radiologists to be familiar with these new molecules, their patterns of response, and their class-specific toxicities. While liver and bowel toxicities have been extensively reported in literature, less is known about the pathogenesis and imaging of toxicity involving the pancreatobiliary system. Biliary and pancreatic toxicity of molecular targeted therapies present with variable manifestations and varying degrees of severity, from asymptomatic liver function tests elevation to acute pancreatitis or cholecystitis. Management of these conditions depends on the clinical scenario and the severity of the findings. In this article, we will (1) present the various classes of molecular targeted therapies most commonly associated with biliary and pancreatic toxicity; (2) illustrate imaging findings of drug-associated biliary and pancreatic injuries and their possible differential diagnosis; and (3) provide a guide for management of these conditions.

Molecular Targeted Therapy in Modern Oncology: Imaging Assessment of Treatment Response and Toxicities.

Oncology is a rapidly evolving field with a shift toward personalized cancer treatment. The use of therapies targeted to the molecular features of individual tumors and the tumor microenvironment has become much more common. In this review, anti-angiogenic and other molecular targeted therapies are discussed, with a focus on typical and atypical response patterns and imaging manifestations of drug toxicities.

Diffuse Large B-Cell Lymphoma in the Era of Precision Oncology: How Imaging Is Helpful.

Diffuse large B cell lymphoma (DLBCL) is the most common histological subtype of Non-Hodgkin's lymphoma. As treatments continues to evolve, so do imaging strategies, and positron emission tomography (PET) has emerged as the most important imaging tool to guide oncologists in the diagnosis, staging, response assessment, relapse/recurrence detection,and therapeutic decision making of DLBCL. Other imaging modalities including magnetic resonance imaging (MRI), computed tomography (CT), ultrasound, and conventional radiography are also used in the evaluation of lymphoma. MRI is useful for nervous system and musculoskeletal system involvement and is emerging as a radiation free alternative to PET/CT. This article provides a comprehensive review of both the functional and morphological imaging modalities, available in the management of DLBCL.

Evolving Cancer Classification in the Era of Personalized Medicine: A Primer for Radiologists.

Traditionally tumors were classified based on anatomic location but now specific genetic mutations in cancers are leading to treatment of tumors with molecular targeted therapies. This has led to a paradigm shift in the classification and treatment of cancer. Tumors treated with molecular targeted therapies often show morphological changes rather than change in size and are associated with class specific and drug specific toxicities, different from those encountered with conventional chemotherapeutic agents. It is important for the radiologists to be familiar with the new cancer classification and the various treatment strategies employed, in order to effectively communicate and participate in the multi-disciplinary care. In this paper we will focus on lung cancer as a prototype of the new molecular classification.

Update on Gastrointestinal Stromal Tumors for Radiologists.

The management of gastrointestinal stromal tumors (GISTs) has evolved significantly in the last two decades due to better understanding of their biologic behavior as well as development of molecular targeted therapies. GISTs with exon 11 mutation respond to imatinib whereas GISTs with exon 9 or succinate dehydrogenase subunit mutations do not. Risk stratification models have enabled stratifying GISTs according to risk of recurrence and choosing patients who may benefit from adjuvant therapy. Assessing response to targeted therapies in GIST using conventional response criteria has several potential pitfalls leading to search for alternate response criteria based on changes in tumor attenuation, volume, metabolic and functional parameters. Surveillance of patients with GIST in the adjuvant setting is important for timely detection of recurrences.

Current Concepts in Non-Gastrointestinal Stromal Tumor Soft Tissue Sarcomas: A Primer for Radiologists.

Non-gastrointestinal stromal tumor (GIST) soft tissue sarcomas (STSs) are a heterogeneous group of neoplasms whose classification and management continues to evolve with better understanding of their biologic behavior. The 2013 World Health Organization (WHO) has revised their classification based on new immunohistochemical and cytogenetic data. In this article, we will provide a brief overview of the revised WHO classification of soft tissue tumors, discuss in detail the radiology and management of the two most common adult non-GIST STS, namely liposarcoma and leiomyosarcoma, and review some of the emerging histology-driven targeted therapies in non-GIST STS, focusing on the role of the radiologist.

MRI Findings in Patients With Leukemia and Positive CSF Cytology: A Single-Institution 5-Year Experience.

OBJECTIVE: The purposes of this study were to describe the spectrum of MRI findings and determine the prognostic role of MRI in adults with acute leukemia with positive CSF cytology. MATERIALS AND METHODS: In this retrospective study of 34 patients (19 women, 15 men; mean age, 51 years; range, 18-72 years) treated for CNS leukemia between 2006 and 2011, 31 (91%) contrast-enhanced brain and 14 (41%) spine MRI studies were reviewed by two radiologists to note patterns of enhancement. Interobserver agreement and correlation of enhancement with outcome were analyzed. RESULTS: MRI showed abnormal findings in 25 patients (74%). Pachymeningeal enhancement (n = 9/31, 29%), leptomeningeal enhancement (n = 6/31, 19%), cranial nerve enhancement (n = 9/31, 29%), masslike enhancement (n = 3/31, 10%), and spinal meningeal enhancement (n = 10/14, 71%) were identified. There was strong interobserver agreement (κ = 0.906). Survival rates were shorter to a statistically significant degree with pachymeningeal enhancement (median, 7 months; interquartile range [IQR], 5-8 months versus median, 26 months; IQR, 15 months to not reached; p = 0.004) and two or more sites of enhancement (median, 8 months; IQR, 3-13 months versus median, 19 months; IQR, 9 months to not reached; p = 0.046). CONCLUSION: Brain or spine MRI examinations (or both) showed abnormal findings in nearly three-fourths of adults with acute leukemia with positive CSF cytology who were imaged for neurologic symptoms. Pachymeningeal enhancement and two or more sites of brain involvement were associated with shorter survival.