Targeting Hypoxia-Inducible Factor-1α for the Management of Hepatocellular Carcinoma.

Hypoxia-inducible factor 1 alpha (HIF-1α) is a transcription factor that regulates the cellular response to hypoxia and is upregulated in all types of solid tumor, leading to tumor angiogenesis, growth, and resistance to therapy. Hepatocellular carcinoma (HCC) is a highly vascular tumor, as well as a hypoxic tumor, due to the liver being a relatively hypoxic environment compared to other organs. Trans-arterial chemoembolization (TACE) and trans-arterial embolization (TAE) are locoregional therapies that are part of the treatment guidelines for HCC but can also exacerbate hypoxia in tumors, as seen with HIF-1α upregulation post-hepatic embolization. Hypoxia-activated prodrugs (HAPs) are a novel class of anticancer agent that are selectively activated under hypoxic conditions, potentially allowing for the targeted treatment of hypoxic HCC. Early studies targeting hypoxia show promising results; however, further research is needed to understand the effects of HAPs in combination with embolization in the treatment of HCC. This review aims to summarize current knowledge on the role of hypoxia and HIF-1α in HCC, as well as the potential of HAPs and liver-directed embolization.

Anatomic and Functional Imaging of Immunoglobulin G4-related Disease and Its Mimics.

Immunoglobulin G4 (IgG4)-related disease (IgG4-RD) is an immune-mediated fibrosclerosing disease with tumefactive lesions infiltrated by IgG4-positive plasma cells. Initially described as autoimmune pancreatitis, IgG4-RD is now recognized as a discrete entity and is found to affect virtually any organ in the body. Common extrapancreatic sites include the biliary tree, salivary glands, periorbital tissue, lungs, kidneys, lymph nodes, aorta, retroperitoneum, and thyroid gland. Diagnosis-which relies on histopathologic, serologic, and radiologic features-can be challenging with the disease underdiagnosed, as IgG4-RD often mimics malignancy, infectious processes, or other immune-mediated conditions. Patients may present with signs of compression of nearby structures due to mass effect or with organ failure when the disease is left untreated. The clinical course is complex, with single- or multiorgan involvement and metachronous or synchronous occurrence of lesions. IgG4-RD responds well to glucocorticoid therapy, disease-modifying antirheumatic drugs, and B-cell-depleting biologic agents; prompt diagnosis is important to avoid delay in treatment and unnecessary pharmacologic or surgical intervention. While imaging features may not be specific for IgG4-RD, functional whole-body imaging with fluorine 18-fluorodeoxyglucose PET/CT is a useful adjunct for localizing extrapancreatic sites for biopsy, monitoring therapeutic response, and demonstrating disease relapse. The authors describe the pancreatic and extrapancreatic sites of involvement in IgG4-RD, with imaging features and patterns to aid in distinguishing IgG4-RD from its mimics through a multimodality approach with emphasis on functional imaging evaluation. ©RSNA, 2023 Quiz questions in the supplemental material and the slide presentation from the RSNA Annual Meeting are available for this article.

Interventional Management of Acquired Lymphatic Disorders.

The lymphatic system is a complex network of tissues, vessels, and channels found throughout the body that assists in fluid balance and immunologic function. When the lymphatic system is disrupted related to idiopathic, iatrogenic, or traumatic disorders, lymphatic leaks can result in substantial morbidity and/or mortality. The diagnosis and management of these leaks is challenging. Modern advances in lymphatic imaging and interventional techniques have made radiology critical in the multidisciplinary management of these disorders. The authors provide a review of conventional and clinically relevant variant lymphatic anatomy and recent advances in diagnostic techniques such as MR lymphangiography. A detailed summary of technical factors related to percutaneous lymphangiography and lymphatic intervention is presented, including transpedal and transnodal lymphangiography. Traditional transabdominal access and retrograde access to the central lymph nodes and thoracic duct embolization techniques are outlined. Newer techniques including transhepatic lymphangiography and thoracic duct stent placement are also detailed. For both diagnostic and interventional radiologists, an understanding of lymphatic anatomy and modern diagnostic and interventional techniques is vital to the appropriate treatment of patients with acquired lymphatic disorders. ©RSNA, 2022.

PET/CT of delayed uterine leiomyoma metastasizing to lung and femur.

Benign metastasizing leiomyomas are benign disseminated extra-uterine tumors in patients with prior history of uterine leiomyomas and may occur years after hysterectomy. The lung is mostly affected, with less common occurrence in the brain, heart, spine, retroperitoneum, and bone. The authors present the role of 18F-FDG PET/CT in the metabolic staging and post-surgical monitoring of a patient with lung and femoral involvement.

Histiocytosis and Neoplasms of Macrophage-Dendritic Cell Lineages: Multimodality Imaging with Emphasis on PET/CT.

Histiocytosis is a rare inflammatory process characterized by pathologic infiltration and accumulation of cells derived from the monocytic lineage in normal tissue. It encompasses more than 100 different subtypes of disorders that were recently classified into five main groups: (a) Langerhans-related histiocytosis, (b) Rosai-Dorfman histiocytosis, (c) cutaneous and mucocutaneous histiocytosis, (d) malignant histiocytosis, and (e) hemophagocytic lymphohistiocytosis and macrophage activation syndrome. Langerhans cell histiocytosis is the most common histiocytic disorder. Less common types include Erdheim-Chester disease, Rosai-Dorfman disease, adult and juvenile xanthogranuloma, necrobiotic xanthogranuloma, histiocytic sarcoma, interdigitating dendritic cell sarcoma, Langerhans cell sarcoma, and hemophagocytic lymphohistiocytosis. Although the pathogenesis of these disorders may be attributable to mutations in the oncogenic driver, recent discoveries have shown that inflammation and fibrosis secondary to mutated histiocytes, rather than a proliferative cell mechanism, result in manifestation of the disease. Diagnosis, which relies on a multidisciplinary approach, is challenging and often delayed because clinical findings are nonspecific and may mimic malignant processes at radiologic evaluation. Compared with conventional imaging, PET/CT allows detection of the increased metabolic activity in histiocytes. Diagnostic algorithms for histiocytic disorders should include functional imaging with fluorine 18 (18F) fluorodeoxyglucose (FDG) PET/CT, which provides a comprehensive whole-body evaluation of their potential involvement with multiple organ systems and allows monitoring of therapeutic response. The most recent revised classification, pathophysiologic and clinical manifestations, sites of involvement, and imaging features of histiocytosis are described in this review and a multimodality approach is used, with emphasis on 18F-FDG PET/CT evaluation. ©RSNA, 2021.