The presence of large focal lesions is a strong independent prognostic factor in multiple myeloma.

Spatial intratumor heterogeneity is frequently seen in multiple myeloma (MM) and poses a significant challenge for risk classifiers, which rely on tumor samples from the iliac crest. Because biopsy-based assessment of multiple skeletal sites is difficult, alternative strategies for risk stratification are required. Recently, the size of focal lesions (FLs) was shown to be a surrogate marker for spatial heterogeneity, suggesting that data from medical imaging could be used to improve risk stratification approaches. Here, we investigated the prognostic value of FL size in 404 transplant-eligible, newly diagnosed MM patients. Using diffusion-weighted magnetic resonance imaging with background suppression, we identified the presence of multiple large FLs as a strong prognostic factor. Patients with at least 3 large FLs with a product of the perpendicular diameters >5 cm2 were associated with poor progression-free survival (PFS) and overall survival (OS; median, 2.3 and 3.6 years, respectively). This pattern, seen in 13.8% of patients, was independent of the Revised International Staging System (RISS), gene expression profiling (GEP)-based risk score, gain(1q), or extramedullary disease (hazard ratio, 2.7 and 2.2 for PFS and OS in multivariate analysis, respectively). The number of FLs lost its negative impact on outcome after adjusting for FL size. In conclusion, the presence of at least 3 large FL is a feature of high risk, which can be used to refine the diagnosis of this type of disease behavior and as an entry criterion for risk-stratified trials.

Low expression of hexokinase-2 is associated with false-negative FDG-positron emission tomography in multiple myeloma.

18F-Fluorodeoxyglucose (FDG)-positron emission tomography (PET) and diffusion-weighted magnetic resonance imaging with background signal suppression (DWIBS) are 2 powerful functional imaging modalities in the evaluation of malignant plasma cell (PC) disease multiple myeloma (MM). Preliminary observations have suggested that MM patients with extensive disease according to DWIBS may be reported as being disease-free on FDG-PET ("PET false-negative"). The aim of this study was to describe the proportion of PET false-negativity in a representative set of 227 newly diagnosed MM patients with simultaneous assessment of FDG-PET and DWIBS, and to identify tumor-intrinsic features associated with this pattern. We found the incidence of PET false-negativity to be 11%. Neither tumor load-associated parameters, such as degree of bone marrow PC infiltration, nor the PC proliferation rate were associated with this subset. However, the gene coding for hexokinase-2, which catalyzes the first step of glycolysis, was significantly lower expressed in PET false-negative cases (5.3-fold change, P < .001) which provides a mechanistic explanation for this feature. In conclusion, we demonstrate a relevant number of patients with FDG-PET false-negative MM and a strong association between hexokinase-2 expression and this negativity: a finding which may also be relevant for clinical imaging of other hematological cancers.

PRES and Epilepsy: A Potential Long-Term Consequence of a "Reversible" Syndrome.

Epilepsy is very rarely attributed to posterior reversible encephalopathy syndrome (PRES). We report the case of a previously healthy 21-year-old who developed epilepsy with mesial temporal sclerosis following an episode of PRES related to a complicated Cesarean delivery. Neuroimaging at the time of PRES and 3 months after revealed the development of unilateral hippocampal volume loss following resolution of acute PRES-related brain edema. We discuss the incidence and importance of "non-reversible" sequelae of PRES and their implications for patient care.

Characterization of Thyroid Nodules by 4-Dimensional Computed Tomography: Initial Experience.

OBJECTIVE: We aimed to evaluate the use of 4-dimensional computed tomography (4DCT) for characterization of thyroid nodules. METHODS: Our study drew from 100 consecutive patients with primary hyperparathyroidism who underwent 4D parathyroid CT imaging for adenoma localization. Included subjects had tissue sampling of a thyroid nodule within 3 months of 4DCT. RESULTS: Twenty subjects (18 women and 2 men) had thyroid nodules that were pathologically confirmed. Precontrast nodule attenuation was significantly lower in malignant nodules when compared with benign nodules (36 vs 61 HU, P = 0.05). Arterial phase and delayed phase nodule attenuations were not significantly different in malignant and benign nodules (128 vs 144 HU, P = 0.7; 74 vs 98 HU, P = 0.3). CONCLUSIONS: Our initial experience with a small group of patients was unable to support the use of 4DCT for characterizing thyroid nodules; however, precontrast nodule attenuation was significantly lower in malignant nodules when compared with benign nodules.

Root Cause Analysis: An Examination of Odontogenic Origins of Acute Maxillary Sinusitis in Both Immunocompetent & Immunocompromised Patients.

BACKGROUND AND PURPOSE: Dental and periodontal diseases represent important but often overlooked causes of acute sinusitis. Our goal was to examine the prevalence of potential odontogenic sources of acute maxillary sinusitis according to immune status and their associations with sinusitis. MATERIALS AND METHODS: A retrospective review of maxillofacial computed tomography studies from 2013 to 2014 was performed. Each maxillary sinus and its ipsilateral dentition were evaluated for findings of acute sinusitis and dental/periodontal disease. RESULTS: Eighty-four patients (24 immunocompetent, 60 immunocompromised) had 171 maxillary sinuses that met inclusion criteria for acute maxillary sinusitis. Inspection of dentition revealed oroantral fistula in 1%, periapical lucencies in 16%, and projecting tooth root(s) in 71% of cases. Immunocompromised patients were more likely to have bilateral sinusitis than immunocompetent patients (67% vs 33%, P = 0.005). A paired case-control analysis in a subset of patients with unilateral maxillary sinusitis (n = 39) showed a higher prevalence of periapical lucency in association with sinuses that had an air fluid level-29% of sinuses with a fluid level had periapical lucency compared with 12% without sinus fluid (P = 0.033). CONCLUSIONS: Potential odontogenic sources of acute maxillary sinusitis are highly prevalent in both immunocompetent and immunocompromised patients, although the 2 patient populations demonstrate no difference in the prevalence of these potential odontogenic sources. Periapical lucencies were found to be associated with an ipsilateral sinus fluid level. Increased awareness of the importance of dental and periodontal diseases as key components of maxillofacial computed tomography interpretation would facilitate a more appropriate and timely treatment.

Features of infratentorial-predominant posterior reversible encephalopathy syndrome.

Posterior reversible encephalopathy syndrome (PRES) is a neurotoxic process that typically occurs in the setting of immune dysregulation. In contrast to the characteristic pattern involving parieto-occipital and posterior frontal regions, predominant involvement of the infratentorial brain occurs in a minority of PRES patients. We examined six patients with infratentorial predominant posterior reversible encephalopathy syndrome (IPPRES) relative to those with typical PRES in terms of clinical factors of toxicity and outcomes. We review the current understanding of PRES pathophysiology. An institutional database of PRES patients was created through an IRB-approved search of the electronic record from 2007 to 2012. MR images were reviewed and classified by two neuro radiologists. Clinical data including laboratory data, blood pressure, and discharge outcome were collected through review of existing electronic medical records. Characteristics of the two groups were compared. Six cases among 80 PRES patients displayed an atypical distribution of signal abnormality predominantly involving the infratentorial brain. In IPPRES patients, signal abnormalities within the supratentorial brain, when present, showed a predominantly central distribution rather than the typical peripheral distribution. IPPRES patients showed higher rates of extreme hypertension, renal dysfunction, abnormal serum calcium, and abnormal serum magnesium relative to typical PRES patients. Outcomes were similar between the two groups. In our small series, IPPRES differs from typical PRES patients not only in the distribution of imaging abnormalities but also in rates of extreme hypertension and several laboratory indices. Despite these differences, clinical outcome in the IPPRES group was similar to that of typical PRES.

Lithium toxicity and PRES: a novel association.

We report two cases of posterior reversible encephalopathy syndrome (PRES) occurring in association with supra-therapeutic serum lithium levels. Although the neurologic manifestations of lithium toxicity are well known, this is, to our knowledge, the first report describing a link between lithium toxicity and PRES. We discuss the current understanding of the pathogenesis of PRES and suggest mechanisms by which lithium may play a role in its development.

Elevation of serum lactate dehydrogenase at posterior reversible encephalopathy syndrome onset in chemotherapy-treated cancer patients.

The pathophysiology of posterior reversible encephalopathy syndrome (PRES) is incompletely understood; however, an underlying state of immune dysregulation and endothelial dysfunction has been proposed. We examined alterations of serum lactate dehydrogenase (LDH), a marker of endothelial dysfunction, relative to the development of PRES in patients receiving chemotherapy. A retrospective Institutional Review Board approved database of 88 PRES patients was examined. PRES diagnosis was confirmed by congruent clinical diagnosis and MRI. Clinical features at presentation were recorded. Serum LDH values were collected at three time points: prior to, at the time of, and following PRES diagnosis. Student's t-test was employed. LDH values were available during the course of treatment in 12 patients (nine women; mean age 57.8 years [range 33-75 years]). Chemotherapy-associated PRES patients were more likely to be normotensive (25%) versus the non-chemotherapy group (9%). LDH levels at the time of PRES diagnosis were higher than those before and after (p=0.0263), with a mean difference of 114.8 international units/L. Mean time intervals between LDH measurement prior to and following PRES diagnosis were 44.8 days and 51.4 days, respectively. Mean elapsed time between last chemotherapy administration and PRES onset was 11.1days. In conclusion, serum LDH, a marker of endothelial dysfunction, shows statistically significant elevation at the onset of PRES toxicity in cancer patients receiving chemotherapy. Our findings support a systemic process characterized by endothelial injury/dysfunction as a factor, if not the prime event, in the pathophysiology of PRES.

ACR appropriateness criteria sinonasal disease.

Sinonasal imaging is performed in 2 major clinical scenarios: inflammatory rhinosinusitis or suspected mass lesion. Rhinosinusitis affects more than 16% of the US population annually. It poses an immense economic burden, accounting for more than 26 million outpatient visits annually and costing more than $4.3 billion annually in direct medical expenses. Most cases of uncomplicated acute and subacute rhinosinusitis are diagnosed clinically and should not require any imaging procedure. CT of the sinuses without contrast is the imaging method of choice in patients with recurrent acute sinusitis or chronic sinusitis. Sinusitis cannot be diagnosed on the basis of imaging findings alone. CT scan findings should be interpreted in conjunction with clinical and endoscopic findings. MRI is currently used for evaluation of sinus disease as a complementary study in cases of aggressive sinus infection with ocular/intracranial complications, potential invasive fungal sinusitis in immunocompromised patients or in the evaluation of a sinonasal mass. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.

Hemiparkinsonism after unilateral traumatic midbrain hemorrhage in a young woman.

The relationship between head trauma and parkinsonism has been debated since James Parkinson's first description of the shaking palsy in the late 19th century. We observed in our outpatient clinic a young woman in whom hemiparkinsonism developed within 3 weeks of sustaining closed head trauma with loss of consciousness. The patient had a discrete unilateral midbrain hemorrhage on head MRI which involved the contralateral substantia nigra. The condition responded well to carbidopa/levodopa. This patient is a convincing example of posttraumatic midbrain hemorrhage causing parkinsonism.

Rosette-forming glioneuronal tumor of the fourth ventricle.

We present a case of a 22-year-old asymptomatic female whose CT study (performed following trauma) incidentally discovered a posterior fossa mass. The lesion was further evaluated with a MRI study, and (following discussion with the patient and her family) elective surgical resection of the lesion was performed. On pathology, histological evaluation revealed a diagnosis of rosette-forming glioneuronal tumor of the fourth ventricle. RGNT of the fourth ventricle or posterior fossa should always be considered in the differential diagnosis of infratentorial lesions, especially in young adults.

Standard and novel imaging methods for multiple myeloma: correlates with prognostic laboratory variables including gene expression profiling data.

Multiple myeloma causes major morbidity resulting from osteolytic lesions that can be detected by metastatic bone surveys. Magnetic resonance imaging and positron emission tomography can detect bone marrow focal lesions long before development of osteolytic lesions. Using data from patients enrolled in Total Therapy 3 for newly diagnosed myeloma (n=303), we analyzed associations of these imaging techniques with baseline standard laboratory variables assessed before initiating treatment. Of 270 patients with complete imaging data, 245 also had gene expression profiling data. Osteolytic lesions detected on metastatic bone surveys correlated with focal lesions detected by magnetic resonance imaging and positron emission tomography, although, in two-way comparisons, focal lesion counts based on both magnetic resonance imaging and positron emission tomography tended to be greater than those based on metastatic bone survey. Higher numbers of focal lesions detected by magnetic resonance imaging and positron emission tomography were positively linked to high serum concentrations of C-reactive protein, gene-expression-profiling-defined high risk, and the proliferation molecular subgroup. Positron emission tomography focal lesion maximum standardized unit values were significantly correlated with gene-expression-profiling-defined high risk and higher numbers of focal lesions detected by positron emission tomography. Interestingly, four genes associated with high-risk disease (related to cell cycle and metabolism) were linked to counts of focal lesions detected by magnetic resonance imaging and positron emission tomography. Collectively, our results demonstrate significant associations of all three imaging techniques with tumor burden and, especially, disease aggressiveness captured by gene-expression-profiling-risk designation. (Clinicaltrials.gov identifier: NCT00081939).

ACR Appropriateness Criteria(®) myelopathy.

Myelopathy is a problem that requires imaging to distinguish among numerous specifically treatable causes. The first priority is to determine mechanical stability after trauma. Next, it is crucial to distinguish intrinsic disease from extrinsic compression-for example, by epidural abscess. Osteophytes or disc extrusions and metastatic compression are the most common causes of extrinsic lesions. Imaging approaches rely on clinical features such as pain, fever, trauma, and pattern of progression. CT is preferred initially in acute trauma and MRI in all other circumstances. Contrast-enhanced MRI is added when tumor or infection is suspected or with slow or stepwise progression, especially when pain is not prominent. Vascular imaging is used when arteriovenous malformation, fistula, or occlusive disease is suspected. Because the treatment of myelopathy is often complex, treatment planning may require more than one imaging study or sequential examination to assess interval change. The ACR Appropriateness Criteria(®) are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.

Curtains.

A 55-year-old immunocompetent man presented with headache, nausea, progressive bilateral upper lid ptosis, and diplopia. Examination showed bilateral asymmetric upper lid ptosis with limited adduction and elevation of both eyes. Cranial magnetic resonance imaging revealed enhancing intra-axial and extra-axial midbrain lesions. Blood and cerebrospinal fluid were positive for cryptococcal antigen and cerebrospinal fluid fungal cultures grew Cryptococcus neoformans. Treatment with liposomal amphotericin B and flucytosine resulted in complete resolution of his neurological deficits and lesions on neuroimaging. Patients with cryptococcal meningitis may rarely present with bilateral cranial nerve III dysfunction.

ACR Appropriateness Criteria® on cerebrovascular disease.

Stroke is the sudden onset of focal neurologic symptoms due to ischemia or hemorrhage in the brain. Current FDA-approved clinical treatment of acute ischemic stroke involves the use of the intravenous thrombolytic agent recombinant tissue plasminogen activator given <3 hours after symptom onset, following the exclusion of intracerebral hemorrhage by a noncontrast CT scan. Advanced MRI, CT, and other techniques may confirm the stroke diagnosis and subtype, demonstrate lesion location, identify vascular occlusion, and guide other management decisions but, within the first 3 hours after ictus, should not delay or be used to withhold recombinant tissue plasminogen activator therapy after the exclusion of acute hemorrhage on noncontrast CT scans. MR diffusion-weighted imaging is highly sensitive and specific for acute cerebral ischemia and, when combined with perfusion-weighted imaging, may be used to identify potentially salvageable ischemic tissue, especially in the period >3 hours after symptom onset. Advanced CT perfusion methods improve sensitivity to acute ischemia and are increasingly used with CT angiography to evaluate acute stroke as a supplement to noncontrast CT. The ACR Appropriateness Criteria(®) are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.

Endolymphatic sac tumor.

Endolymphatic sac tumor is an uncommon, locally aggressive tumor. The tumor is located in the medial and posterior petrosal bone region and may involve the dura. A hypervascular tumor involving the endolymphatic sac with destructive changes, it involves the bone and may show reactive new bone formation. Diagnosis is based on clinical, radiological, and pathological correlation. We present a case of endolymphatic sac tumor in a 24-year-old female who presented with a chief complaint of hearing loss.

Ectopic pituitary adenoma in persistent craniopharyngeal canal: case report and literature review.

An ectopic location of pituitary adenoma is rare. Nasopharyngeal location of ectopic pituitary adenoma has been attributed to remnants of the Rathke pouch. We describe an interesting case of ectopic pituitary adenoma in the setting of partially persistent craniopharyngeal canal. Embryological basis of ectopic pituitary adenoma and craniopharyngeal canal have been discussed.