BRCA-associated Cancers: Role of Imaging in Screening, Diagnosis, and Management.

Harmful mutations of the BRCA tumor suppressor genes result in a greater lifetime risk for malignancy-breast and ovarian cancers in particular. An increased risk for male breast, fallopian tube, primary peritoneal, pancreatic, prostate, and colon cancers also has been reported. The BRCA gene is inherited in an autosomal dominant pattern and tends to be highly penetrant; thus, there is an increased incidence of these cancers in affected families. Compared with sporadic tumors, BRCA-associated malignancies have unique manifestations, clinical features, and pathologic profiles. Manifestation at an early patient age, high-grade tumors, and an aggressive clinical course are common features of BRCA-associated malignancies. Understanding the behavior of these cancers aids in identification of affected individuals and families, who can then make informed decisions regarding their future health. Enhanced screening, prophylactic surgery, and chemoprevention are options for managing cancer risk factors in these individuals. Imaging has an important role in the screening, evaluation, staging, and follow-up of BRCA-associated malignancies. Supplemental screening of BRCA mutation carriers often begins at an early age and is critical for early and accurate cancer diagnoses. The authors review the etiopathogenesis and imaging features of BRCA-associated malignancies, the importance of a multidisciplinary approach to determining the diagnosis, and the treatment of patients who have these mutations to improve their outcomes. © RSNA, 2017.

Effect of spatial resolution of T2-weighted imaging on diagnostic efficacy of MRI in detection of papilledema.

OBJECTIVE. Morphologic changes associated with papilledema may be masked by partial volume averaging effects in images obtained at a slice thickness greater than normal optic nerve thickness. We aimed to compare the diagnostic accuracy of high-resolution 3D T2-weighted imaging performed at submillimeter slice thickness with conventional T2-weighted imaging performed at 5-mm slice thickness for detection of papilledema. MATERIALS AND METHODS. Two blinded neuroradiologists evaluated conventional and high-resolution axial T2-weighted imaging across orbits from 25 patients with clinically proven papilledema and 66 control participants without papilledema. They graded optic nerve sheath distention and optic nerve head configuration, also making a binary determination for presence or absence of papilledema for each set of images. The diagnostic accuracy of each technique was assessed in terms of sensitivity, specificity, positive likelihood ratio, and interobserver agreement. These parameters were compared using the homogeneity of odds ratio and McNemar tests. RESULTS. High-resolution T2-weighted imaging was associated with higher sensitivity (83.3% vs 56.2%, p = 0.0072 for reader 1; 87.5% vs 54.2% for reader 2, p = 0.0001) but unchanged specificity. High-resolution T2-weighted imaging was significantly better than conventional T2-weighted imaging in detecting optic nerve head deformity in patients with papilledema, but there was no difference between two techniques in detection of optic nerve sheath distention. High-resolution imaging also enabled greater interobserver agreement (κ = 0.82) compared with conventional T2-weighted image (κ = 0.62). CONCLUSION. Improved visualization of the optic nerve head afforded by high-resolution T2-weighted imaging translates into better diagnostic performance of MRI in detection of papilledema, with higher sensitivity and interobserver reliability.

Hot spleen: hypervascular lesions of the spleen.

The differential diagnosis of splenic masses is broad and often hinges on the enhancement characteristics of the lesions. Most radiologists are familiar with the differential diagnosis of hypovascular lesions such as fungal infections, sarcoidosis/granulomatous disease, infarctions, and cysts. However, to our knowledge, there is no review article that presents the specific multimodality imaging features of vascular splenic lesions as a group. Vascular splenic lesions may be considered those that enhance more or similarly to the background splenic parenchyma. In this review, we illustrate the spectrum of imaging features of both benign and malignant vascular splenic lesions. The benign lesions include hemangiomas, hamartomas, and sclerosing angiomatoid nodular transformation of the spleen. The malignant lesions are divided into primary and metastatic lesions, ranging from lymphoma, angiosarcoma to pleomorphic sarcoma. While lymphoma and metastases may commonly present as hypoenhancing lesions relative to the background parenchyma, we are addressing them here as their appearance can be varied and hence deserve consideration. Littoral Cell angiomas are discussed separately, as they were originally considered benign, but recent studies have shown that they can have malignant potential.

Diagnostic yield of percutaneous image-guided tissue biopsy of focal hepatic lesions in cancer patients: ten percent are not metastases from the primary malignancy.

BACKGROUND: The diagnostic yield was evaluated of percutaneous image-guided tissue biopsy of hepatic lesions identified on computed tomography performed for staging of a primary malignancy, and it was determined how often the biopsy result was unexpectedly negative, benign, or secondary to a second unknown malignancy. METHODS: In a retrospective investigation from 1998 through 2008, 580 patients with primary malignancies had indeterminate focal hepatic lesions and underwent percutaneous image-guided biopsy; 369 patients had lesions in their liver at first cross-sectional imaging, performed for staging; 211 patients had a negative liver imaging study, followed by the subsequent appearance of at least 1 indeterminate suspicious lesion. The results of percutaneous image-guided tissue biopsies were compared with the histology of the primary malignancy. RESULTS: Liver biopsies were performed in 580 patients (288 men and 292 women; age, 25-92 years; mean age, 61 years). The most common primary malignancies were pancreatic (n = 96), breast (n = 85), melanoma (n = 57), esophageal (n = 51), lung (n = 47), colorectal (n = 37), and urothelial tumors (n = 26). Biopsy results were positive for malignancy in 528 (91%) cases. Among the positive biopsies, 29 (5%) cases had pathology results different from the primary tumor. Of the 52 biopsies negative for malignancy, 20 yielded a specific benign diagnosis, and 32 were nondiagnostic. CONCLUSIONS: If all liver lesions had been assumed to be metastases, as expected secondary to the known primary tumor, then the true or presumed alternate diagnosis would have been missed in 60 (10.3%) of the 580 cases. The authors did not attempt to determine whether actual clinical management changed based on these 60 liver biopsy results, so this number is an upper bound on management change. On the basis of these results, and given the minimal complication rate of liver biopsy, the authors suggest that liver biopsy should still be performed in the types of cases studied here, despite the finding that the vast majority of biopsies produced the expected result and presumably did not change patient management.

Imaging of carcinoid tumors: spectrum of findings with pathologic and clinical correlation.

Carcinoid tumors are primary malignant neoplasms that arise from neuroendocrine cells. These cells are located throughout the body, resulting in many possible locations for the development of carcinoid tumor. The most common primary location is the gastrointestinal tract, followed by respiratory and thymic carcinoids. The presentations of these tumors are variable depending on their location, aggressiveness, production of functional peptides, and tendency to invade or metastasize. Carcinoid tumors can be imaged by various modalities including gastrointestinal studies, ultrasound, computed tomography, and magnetic resonance imaging as well as nuclear medicine studies (radioactive octreotide). In this review, we illustrate the spectrum of imaging features of carcinoid tumors in various locations of the human body.

Training Nonradiologist Clinicians in Diagnostic Breast Ultrasound in Rural Rwanda: Impact on Knowledge and Skills.

OBJECTIVE: To assess the effectiveness of diagnostic breast ultrasound training provided for general practitioners and nurses in Rwanda via intensive in-person and subsequent online supervision and mentorship. METHODS: Four breast radiologists from Brigham and Women's Hospital trained two general practitioner physicians and five nurses in Rwanda over 9 total weeks of in-person training and 20 months of remote mentorship using electronic image review with emailed feedback. Independently recorded assessments were compared to calculate the sensitivity and specificity of trainee assessments, with radiologist assessments as the gold standard. We compared performance in the first versus second half of the training. RESULTS: Trainees' performance on written knowledge assessments improved after training (57.7% versus 98.1% correct, P = .03). Mean sensitivity of trainee-performed ultrasound for identifying a solid breast mass was 90.6% (SD 4.2%) in the first half of the training (period 1) and 94.0% (SD 6.7%) in period 2 (P = .32). Mean specificity was 94.7% (SD 5.4%) in period 1 and 100.0% (SD 0) in period 2 (P = .10). Mean sensitivity for identifying a medium- or high-suspicion solid mass increased from 79.2% (SD 11.0%) in period 1 to 96.3% (SD 6.4%) in period 2 (P = .03). Specificity was 84.4% (SD 15.0%) in period 1 and 96.7% (SD 5.8%) in period 2 (P = .31). DISCUSSION: Nonradiologist clinicians (doctors and nurses) in a rural sub-Saharan African hospital built strong skills in diagnostic breast ultrasound over 23 months of combined in-person training and remote mentorship. The sensitivity of trainees' assessments in identifying masses concerning for malignancy improved after sustained mentorship. Assessment of impact on patient care and outcomes is ongoing.

Murine Fig4 is dispensable for muscle development but required for muscle function.

BACKGROUND: Phosphatidylinositol phosphates (PIPs) are low-abundance phospholipids that participate in a range of cellular processes, including cell migration and membrane traffic. PIP levels and subcellular distribution are regulated by a series of lipid kinases and phosphatases. In skeletal muscle, PIPs and their enzymatic regulators serve critically important functions exemplified by mutations of the PIP phosphatase MTM1 in myotubular myopathy (MTM), a severe muscle disease characterized by impaired muscle structure and abnormal excitation-contraction coupling. FIG4 functions as a PIP phosphatase that participates in both the synthesis and breakdown of phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2). Mutation of FIG4 results in a severe neurodegenerative disorder in mice and a progressive peripheral polyneuropathy in humans. The effect of FIG4 mutation on skeletal muscle has yet to be examined. METHODS: Herein we characterize the impact of FIG4 on skeletal muscle development and function using the spontaneously occurring mouse mutant pale tremor (plt), a mouse line with a loss of function mutation in Fig4. RESULTS: In plt mice, we characterized abnormalities in skeletal muscle, including reduced muscle size and specific force generation. We also uncovered ultrastructural abnormalities and increased programmed cell death. Conversely, we detected no structural or functional abnormalities to suggest impairment of excitation-contraction coupling, a process previously shown to be influenced by PI(3,5)P2 levels. Conditional rescue of Fig4 mutation in neurons prevented overt muscle weakness and the development of obvious muscle abnormalities, suggesting that the changes observed in the plt mice were primarily related to denervation of skeletal muscle. On the basis of the ability of reduced FIG4 levels to rescue aspects of Mtmr2-dependent neuropathy, we evaluated the effect of Fig4 haploinsufficiency on the myopathy of Mtm1-knockout mice. Male mice with a compound Fig4+/-/Mtm1-/Y genotype displayed no improvements in muscle histology, muscle size or overall survival, indicating that FIG4 reduction does not ameliorate the Mtm1-knockout phenotype. CONCLUSIONS: Overall, these data indicate that loss of Fig4 impairs skeletal muscle function but does not significantly affect its structural development.

Diaphragmatic paralysis associated with neonatal brachial plexus palsy.

Phrenic nerve palsy can occur in the context of neonatal brachial plexus palsy, yet neither outcomes nor definitive treatment guidelines have been established. Diaphragmatic paralysis alone in the newborn results in significant respiratory sequelae and failure to thrive. Reviewing the available literature revealed little information about the incidence of phrenic nerve palsy associated with neonatal brachial plexus palsy, or whether outcomes are associated with the severity of the brachial plexus palsy. Of patients with brachial plexus palsy evaluated during 2005-2009 (n = 166) at our institution, a minority (2.4%; n = 4) had clinically significant diaphragmatic palsy. Of these, a majority (75%; n = 3) manifested respiratory complications sufficient to warrant diaphragmatic plication. The severity of brachial plexus palsy failed to correlate with severity of respiratory consequences. None of the patients underwent nerve repair or reconstruction. We suggest that diaphragmatic paralysis should not be overlooked during a brachial plexus examination, and diaphragmatic paralysis in the very young may require aggressive intervention before the treatment of brachial plexus palsy.