Familiarity with the clinical, pathologic, and cross-sectional imaging features of pulmonary and extrapulmonary sarcoidosis can help suggest the diagnosis and guide optimal patient care. Sarcoidosis is a multisystem granulomatous disorder characterized by development of noncaseating granulomas in various organs. Although the etiology of this condition is unclear, environmental and genetic factors may be substantial in its pathogenesis. Clinical features are often nonspecific, and imaging is essential to diagnosis. Abnormalities may be seen on chest radiographs in more than 90% of patients with thoracic sarcoidosis. Symmetric hilar and mediastinal adenopathy and pulmonary micronodules in a perilymphatic distribution are characteristic features of sarcoidosis. Irreversible pulmonary fibrosis may be seen in 25% of patients with the disease. Although sarcoidosis commonly involves the lungs, it can affect virtually any organ in the body. Computed tomography (CT), magnetic resonance imaging, and positron emission tomography/CT are useful in the diagnosis of extrapulmonary sarcoidosis, but imaging features may overlap with those of other conditions. Familiarity with the spectrum of multimodality...

Recurrent, metastatic mesenchymal myxoid tumors of the gynecologic tract present a management challenge as there is minimal evidence to guide systemic therapy. Such tumors also present a diagnostic dilemma, as myxoid features are observed in leiomyosarcomas, inflammatory myofibroblastic tumors (IMT), and mesenchymal myxoid tumors. Comprehensive genomic profiling was performed in the course of clinical care on a case of a recurrent, metastatic myxoid uterine malignancy (initially diagnosed as smooth muscle tumor of uncertain malignant potential (STUMP)), to guide identify targeted therapeutic options. To our knowledge, this case represents the first report of clinical response to targeted therapy in a tumor harboring a DCTN1-ALK fusion protein. Hybridization capture of 315 cancer-related genes plus introns from 28 genes often rearranged or altered in cancer was applied to >50 ng of DNA extracted from this sample and sequenced to high, uniform coverage. Therapy was given in the context of a phase I clinical trial ClinicalTrials.gov Identifier: ( NCT01548144 ). Immunostains showed diffuse positivity for ALK1 expression and comprehensive genomic profiling identified an in frame DCTN1-ALK gene fusion. The diagnosis of STUMP was revised to that of an IMT with myxoid features. The patient was enrolled in a clinical trial and treated with an anaplastic lymphoma kinase (ALK) inhibitor (crizotinib/Xalkori®) and a multikinase VEGF inhibitor (pazopanib/Votrient®). The patient experienced an ongoing partial response (6+ months) by response evaluation criteria in solid tumors (RECIST) 1.1 criteria. For myxoid tumors of the gynecologic tract, comprehensive genomic profiling can identify clinical relevant genomic alterations that both direct treatment targeted therapy and help discriminate between similar diagnostic entities.

The authors provide an updated review of the molecular cytogenetics and clinical features of von Hippel–Lindau syndrome and discuss the multimodality imaging features of the numerous benign and malignant tumors that can occur in this genetic condition. Von Hippel–Lindau syndrome (VHL) is an autosomal-dominant hereditary tumor disease that arises owing to germline mutations in the VHL gene, located on the short arm of chromosome 3. Patients with VHL may develop multiple benign and malignant tumors involving various organ systems, including retinal hemangioblastomas (HBs), central nervous system (CNS) HBs, endolymphatic sac tumors, pancreatic neuroendocrine tumors, pancreatic cystadenomas, pancreatic cysts, clear cell renal cell carcinomas, renal cysts, pheochromocytomas, paragangliomas, and epididymal and broad ligament cystadenomas. The VHL/hypoxia-inducible factor pathway is believed to play a key role in the pathogenesis of VHL-related tumors. The diagnosis of VHL can be made clinically when the characteristic clinical history and findings have manifested, such as the presence of two or more CNS HBs. Genetic testing for heterozygous germline VHL mutation may also be used to confirm the diagnosis of VHL. Imaging plays an important role in the diagnosis...