BRAF-Mutated Erdheim-Chester Disease: Profound Response to Vemurafenib Visualized With Serial Multimodality Imaging.

Erdheim-Chester disease (ECD) is an extremely rare and aggressive non-Langerhans histiocytic disorder. ECD typically presents with bone pain in middle-aged adults, although some patients present with multisystem disease involving the skeleton, central nervous system, cardiovascular system, lungs, and other disease sites. The etiology of ECD is currently unknown, but it is thought to be a reactive or neoplastic disorder. Recently, mutation of the BRAF gene has been found in >50% of ECD cases, and this gene has become a therapeutic target for patients with ECD. Vemurafenib, a BRAF inhibitor, has been approved by the FDA for treatment of ECD. This report presents an elderly male patient with an aggressive phenotype of ECD and highlights the utility of multimodality imaging in monitoring the clinical course and disease response to treatment with vemurafenib.

Computed Tomography Appearance of Surgically Resected Adrenal Hematomas.

OBJECTIVE: Adrenal hemorrhages arise as a result of a number of conditions and may exhibit a variety of appearances on computed tomography (CT). On occasion, patients will undergo adrenalectomy for treatment of a presumptive adrenal neoplasm that on surgical pathology is identified as an adrenal hemorrhage. We evaluated the CT appearance of surgically resected adrenal masses from our institution over a period of 15 years that ultimately proved to be adrenal hematomas. METHODS: A surgical pathology archive was queried for all cases of adrenal hemorrhage. Only cases with a corresponding diagnostic CT were included. Cases were excluded if an underlying adrenal mass was present. For the remaining cases, the CT appearances were evaluated by 2 radiologists quantitatively and qualitatively. RESULTS: Our search yielded 18 cases of adrenal hemorrhage, of which 5 cases had corresponding CT and no underlying secondary process within the adrenal. All of the adrenal hematomas in this series demonstrated an ovoid morphology and were well defined, with an average maximum diameter of 8.9 cm and highly variable attenuation on noncontrast CT (average attenuation range, 13.1-44.0 Hounsfield units [HU]). Four of the 5 lesions had degrees of peripheral enhancement that was either thin and somewhat uniform or heterogeneous and irregular. None of the lesions demonstrated invasion of the periadrenal fat or adjacent organs. CONCLUSIONS: Adrenal hematomas with a mass-like configuration offer a potential diagnostic dilemma for radiologists and surgeons. Although it is rare that an adrenal hemorrhage is surgically resected, awareness of the potential appearances of these lesions is important to spare patients from unnecessarily aggressive surgery.

Association of fine specificity and repertoire expansion of anticitrullinated peptide antibodies with rheumatoid arthritis associated interstitial lung disease.

BACKGROUND: Interstitial lung disease (ILD) is associated with high morbidity and mortality in rheumatoid arthritis (RA). Citrullinated proteins are observed in RA lung tissues; however, the association of specific anticitrullinated peptide antibodies (ACPA) with ILD in RA is unknown. METHODS: RA patients underwent multidetector CT (MDCT) of the chest, from which ILD features and a semiquantitative ILD Score (ILDS; range 0-32) were assessed. Anti-CCP (CCP2) and levels of a panel of antibodies against 17 citrullinated and four non-citrullinated peptides were assessed from concurrent serum samples using a custom Bio-Plex bead array. High level ACPA was defined as ≥the group 75th percentile. RESULTS: Among the 177 RA patients studied, median levels of CCP2 and all specific ACPAs were 46-273% higher among RA patients with versus those without ILD (all p values <0.05), and higher levels correlated with higher ILDS. In contrast, levels of non-citrullinated protein antibodies were not higher in those with ILD. RA patients had a median of 2 high level ACPA reactivities (range 0-16), with each high level ACPA associated, on average, with a 0.10 unit higher ILDS (p=0.001). This association remained significant after adjusting for characteristics associated with ILD (age, gender, current and former smoking, Disease Activity Score for 28 joints, current prednisone and leflunomide use). More high level ACPA were observed in those with versus without pulmonary function restriction or impaired diffusion. CONCLUSIONS: Our findings of a broader ACPA repertoire in RA ILD suggest a possible role for ACPA in the pathogenesis of ILD.

MDCT of adrenal masses: Can dual-phase enhancement patterns be used to differentiate adenoma and pheochromocytoma?

OBJECTIVE: The purpose of this study was to compare enhancement of adrenal adenomas and pheochromocytomas during dual-phase (arterial and venous phases) CT performed with currently used MDCT protocols with the goal of defining enhancement patterns predictive of pathologic findings. MATERIALS AND METHODS: Pathologically proven pheochromocytomas were retrospectively compared with adrenal adenomas. Inclusion criteria for adenomas, collected by searching the radiology database, were confirmatory adrenal CT (unenhanced with or without washout) and absence of clinical indicators of pheochromocytoma. A fellowship-trained attending radiologist blinded to the pathologic diagnosis reviewed existing images from dual-phase IV contrast-enhanced CT examinations to measure enhancement of adrenal lesions and characterize the appearance (homogeneous versus heterogeneous). Student t test analysis was performed to compare arterial and venous phase enhancement levels. RESULTS: The findings in 39 patients with 41 adenomas were compared with those in 10 patients with 12 pheochromocytomas. Mean arterial and venous enhancement of adenomas at 37 HU (-6 to 85 HU) and 60 HU (16-133 HU) was significantly lower than that of pheochromocytomas at 104 HU (42-190 HU) and 119 HU (61-195 HU) (p < 0.001). No adenoma was more than 85-HU enhancing in the arterial phase, and 58% of pheochromocytomas were more than 110-HU enhancing. Most adenomas (85%) were more enhancing in the venous phase. No adenoma was more enhancing in the arterial phase, but 25% (3/12) of pheochromocytomas were. Most (58%) pheochromocytomas were heterogeneous in appearance, compared with 22% of adenomas. CONCLUSION: For indeterminate adrenal masses identified at dual-phase IV contrast-enhanced CT, higher enhancement during the arterial phase, arterial phase enhancement levels greater than 110 HU, and lesion heterogeneity should prompt consideration of pheochromocytoma.

Serendipity in the diagnosis of pheochromocytoma.

OBJECTIVES: Pheochromocytomas are increasingly being discovered incidentally on imaging studies performed without clinical suspicion of the existence of an adrenal lesion. We aimed to determine the rate of diagnosis of adrenal pheochromocytoma as an incidental finding during a recent 7-year period. METHODS: We obtained the Department of Pathology database to study all the patients at our institution with newly diagnosed pheochromocytomas in the 7-year period from 2005 to 2011 to determine the clinical presentation and the means of diagnosis. RESULTS: In 40 (70.2%) of the 57 patients, an adrenal pheochromocytoma was detected in an imaging study performed without suspicion of an adrenal lesion. There were 13 chest computed tomography studies-8 to evaluate for possible pulmonary emboli. Other indications included abdominal pain or discomfort (n = 8), trauma (n = 3), abnormal liver function tests (n = 3), suspect renal artery stenosis (n = 3), hematuria (n = 2), colitis (n = 2), and 4 miscellaneous indications. DISCUSSION: Our study documents that the commonest current means of initial detection of pheochromocytoma is by serendipitous discovery. In 16 of our 40 patients with serendipitously discovered pheochromocytomas, there were no clinical symptoms of pheochromocytoma; these were true incidentalomas. More than two thirds of the new cases of pheochromocytoma were detected by serendipity (found during studies not performed to evaluate for pheochromocytoma), approximately one third were true incidentalomas (pheochromocytomas in patients without symptoms). CONCLUSIONS: In a 7-year period at a single institution, 40 patients, 70% of new cases of surgically proven pheochromocytoma, were initially detected by serendipity. Sixteen patients, 40% of those incidentally discovered represented true examples of "incidentalomas."

Small serotonin-producing neuroendocrine tumor of the pancreas associated with pancreatic duct obstruction.

OBJECTIVE: Pancreatic neuroendocrine tumors expressing serotonin (carcinoid tumors) account for a small portion of pancreatic neuroendocrine tumors. The purpose of this study was to describe cases of small serotonin-producing pancreatic neuroendocrine tumors associated with pancreatic duct obstruction. CONCLUSION: Serotonin produced by pancreatic neuroendocrine tumors can induce fibrosis and pancreatic duct obstruction. Pancreatic neuroendocrine tumors should be considered when CT shows a small hypervascular mass associated with upstream pancreatic duct dilatation or atrophy. Evidence of small pancreatic neuroendocrine tumors should be sought in cases of idiopathic pancreatic duct stenosis.

Pancreatic duct stenosis secondary to small endocrine neoplasms: a manifestation of serotonin production?

PURPOSE: To determine if serotonin production by pancreatic endocrine neoplasms is associated with the pancreatic duct stenosis seen in patients with stenosis that is out of proportion to the size of the tumors seen on computed tomographic images. MATERIALS AND METHODS: Institutional approval was obtained for this HIPAA-compliant study. Informed consent was waived. Clinical and radiologic findings in six patients were reviewed. Gross and histologic findings in the resected pancreata were also assessed. Formalin-fixed paraffin-embedded tumor sections were immunolabeled with antibodies to serotonin. Tissue microarrays constructed from 47 pancreatic endocrine neoplasms from the institutional tissue bank served as controls. Histologic and serotonin immunoreactivity findings were compared between the two groups. The Fisher exact test was used to compare serotonin immunoreactivity. RESULTS: Only one of the six study patients had a large dominant tumor (4 cm in the pancreatic head). All others were 2.5 cm or smaller. Four of the six pancreatic endocrine neoplasms with associated pancreatic duct stricture had prominent stromal fibrosis. Serotonin immunoreactivity was present in five (83%) patients, and this labeling was strong and diffuse in the four patients with prominent fibrosis. By contrast, stromal fibrosis was minimal in the nonimmunoreactive case. Only three (6%) of the 47 control pancreatic endocrine neoplasms were immunoreactive for serotonin (P < .01, Fisher exact test). CONCLUSION: These data suggest that serotonin produced by pancreatic endocrine neoplasms may be associated with local fibrosis and stenosis of the pancreatic duct. Clinicians should be aware that small pancreatic endocrine neoplasms can produce pancreatic duct stenosis resulting in ductal dilatation and/or upstream pancreatic atrophy out of proportion to the size of the tumor.

Focal fatty infiltration in the head of the pancreas: evaluation with multidetector computed tomography with multiplanar reformation imaging.

Fatty infiltration of the pancreas is generally a diffuse process; however, it may be unevenly distributed in the pancreas. Focal fatty infiltration of the pancreas is usually most prominent in the anterior aspect of the head of the pancreas and seen as a region of decreased attenuation on computed tomography and may simulate pancreatic neoplasm. We discuss and illustrate the various features of focal fatty infiltration of the pancreas on multidetector row helical computed tomography with multiplanar reformation images and show how this imaging modality helps to differentiate between focal fatty infiltration of the pancreas and actual pancreatic tumors.

The use of CT for screening: a national survey of radiologists' activities and attitudes.

PURPOSE: To investigate the activities, motivations, and attitudes of radiologists regarding specific computed tomographic (CT) screening examinations by using a survey. MATERIALS AND METHODS: All study activities were approved by the institutional review board. A self-administered, mailed survey was used to collect data on the practices and attitudes of U.S. radiologists regarding three CT screening tests--coronary artery calcium scoring (CACS), lung cancer screening CT, and whole-body screening CT. The survey was sent to 1000 diagnostic radiologists who were randomly sampled from the American Medical Association Physician Masterfile. RESULTS: A total of 398 (41.4%) of 961 eligible radiologists completed the survey. Among respondents, 33.6% reported reading CT screening studies, the most common being CACS (26.7%), followed by lung screening (19.2%) and whole-body screening (9.5%). Among respondents, 34.1% supported CACS and 29.9% supported lung CT screening for particular patients, while 1.9% supported whole-body CT screening. The most common reasons reported for reading CT screening studies were responses to requests from physicians (83.3%) or patients (75.0%), while fewer (40.8%) cited patient benefit from screening as a reason. CONCLUSION: A substantial proportion of a nationally representative sample of radiologists in the United States reads CT screening studies of the heart, lungs, and whole body and holds favorable attitudes toward CACS and lung CT screening. These attitudes may allow for the premature diffusion of new screening tests into practice before higher-level evidence demonstrates their benefits for population mortality.

Prevalence of unsuspected pancreatic cysts on MDCT.

OBJECTIVE: Current generation MDCT technology facilitates identification of small, nonenhancing lesions in the pancreas. The objective of this study was to determine the prevalence of findings of unsuspected pancreatic cysts on 16-MDCT in a population of adult outpatients imaged for disease unrelated to the pancreas. MATERIALS AND METHODS: Contrast-enhanced MDCT scans of the abdomen were reviewed from 2,832 consecutive examinations to identify pancreatic cysts. Patients with a history of pancreatic lesions or predisposing factors for pancreatic disease or who were referred for pancreatic CT were excluded. RESULTS: A total of 73 patients had pancreatic cysts, representing a prevalence of 2.6 per 100 patients (95% CI, 2.0-3.2). Cysts ranged in size from 2 to 38 mm (mean, 8.9 mm) and were solitary in 85% of cases. Analysis of demographic information showed a strong correlation between pancreatic cysts and age, with no cysts identified among patients under 40 years and a prevalence of 8.7 per 100 (95% CI, 4.6-12.9) in individuals from 80 to 89 years. After controlling for age, cysts were more common in individuals of the Asian race than all other race categories, with an odds ratio of 3.57 (95% CI, 1.05-12.13). There was no difference by sex in the prevalence of cysts (p = 0.527); however, cysts were on average 3.6 mm larger (p = 0.014) in men than women. CONCLUSION: In this outpatient population, the prevalence of unsuspected pancreatic cysts identified on 16-MDCT was 2.6%. Cyst presence strongly correlated with increasing age and the Asian race.

Lymphoplasmacytic sclerosing pancreatitis (autoimmune pancreatitis): evaluation with multidetector CT.

Lymphoplasmacytic sclerosing pancreatitis is a form of chronic pancreatitis characterized by a mixed inflammatory infiltrate that centers on the pancreatic ducts. It is a cause of benign pancreatic disease that can clinically mimic pancreatic cancer. Preoperative detection of lymphoplasmacytic sclerosing pancreatitis is important because patients usually respond to steroid therapy. Patients with lymphoplasmacytic sclerosing pancreatitis are often referred for computed tomography (CT) when they are suspected of having a pancreatic or biliary neoplasm; therefore, it is important to search for potential findings suggestive of lymphoplasmacytic sclerosing pancreatitis when typical findings of a pancreatic or biliary neoplasm are not found. Typical CT findings include diffuse or focal enlargement of the pancreas without dilatation of the main pancreatic duct. Focal enlargement is most commonly seen in the head of the pancreas, and the involved pancreas on contrast material-enhanced CT images may be iso-attenuating relative to the rest of the pancreas, or hypo-attenuating, especially during the early postcontrast phase. Thickening and contrast enhancement of the wall of the common bile duct and gallbladder may reflect inflammatory infiltrate and fibrosis associated with lymphoplasmacytic sclerosing pancreatitis. There are several features seen at CT that may help to differentiate lymphoplasmacytic sclerosing pancreatitis from pancreatic cancer, such as diffuse enlargement of the pancreas with minimal peripancreatic stranding in patients with obstructive jaundice, an absence of significant pancreatic atrophy, and an absence of significant main pancreatic duct dilatation. When these findings are encountered, clinical, other imaging, and serologic data should be evaluated.

Pulmonary artery measurements in pulmonary hypertension: the role of computed tomography.

PURPOSE: We studied the relationship between pulmonary artery diameter (PAD) as measured on computed tomography (CT) and pulmonary artery pressure (PAP) with the specific goal of assessing the reliability of various measurements on high-resolution chest CT as predictors of pulmonary hypertension (PH). MATERIALS AND METHODS: In a preliminary study we determined the method of measuring the main PAD (mPAD) that best correlated with PAP. Using this approach we measured mPAD on CT and correlated the data with PAP obtained from right heart catheterization in 298 patients with known PH and in 102 controls. Various metrics were analyzed for their specificity and sensitivity as screening measurements for PH. RESULTS: The mean PAD and mPAD/ascending aorta diameter (AAD) ratio were found to have the highest correlation with PAP (r=0.51 and 0.53, respectively; P<0.001). A threshold of mPAD>29.5 mm was found to be 70.8% sensitive and 79.4% specific for PH, and an mPAD threshold >31.5 mm had a sensitivity and specificity of 52.0% and 90.2%, respectively. An mPAD/AAD ratio >1 was found to be 70.8% sensitive and 76.5% specific for PH. There was no significant correlation between mPAD and body surface area or age (r=0.04 and 0.07, respectively). A strong statistically significant difference (P<0.0001) was found between mPAD and mPAD/AAD ratio between controls and the PH group. CONCLUSION: mPAD and mPAD/AAD ratio may be used to detect PH in patients of any age or with any body surface area.

Medical and surgical evaluation and treatment of adrenal incidentalomas.

INTRODUCTION: Adrenal incidentalomas are detected in approximately 4% of patients undergoing high-resolution abdominal imaging studies. The majority of adrenal incidentalomas are benign, but careful evaluation of all patients is warranted to be certain that primary adrenocortical carcinoma and functional adenomas are not missed. METHODS: The diagnostic approach in patients with adrenal incidentalomas should focus on two main questions: whether the lesion is malignant, and whether it is hormonally active. Radiological evaluation including noncontrast and contrast computed tomography attenuation values expressed in Hounsfield units is the best tool to differentiate between benign and malignant adrenal masses. All adrenal tumors with suspicious radiological findings, most functional tumors, and all tumors more than 4 cm in size that lack characteristic benign imaging features should be surgically excised. All patients should undergo hormonal evaluation for subclinical Cushing's syndrome and pheochromocytoma, and those with hypertension should also be evaluated for hyperaldosteronism. Combined 1-mg dexamethasone suppression test, plasma metanephrines, and aldosterone/plasma renin activity measurements (if hypertensive) are reasonable initial hormonal evaluations. RESULTS: Annual biochemical follow-up of most patients with adrenal incidentalomas, especially if the tumor is more than 3 cm in size, for up to 5 yr may be reasonable. Patients with adrenal masses less than 4 cm in size and a noncontrast attenuation value of more than 10 Hounsfield units should have a repeat computed tomography study in 3-6 months and then yearly for 2 yr. Adrenal tumors with indeterminate radiological features that grow to at least 0.8 cm over 3-12 months may be considered for surgical resection.

Small renal cell carcinomas: correlation of size with tumor stage, nuclear grade, and histologic subtype.

OBJECTIVE: Our goal was to correlate the size of renal cell carcinoma with tumor stage, nuclear grade, and histologic subtype in patients treated using partial or radical nephrectomy. MATERIALS AND METHODS: We retrospectively reviewed 213 consecutive renal cell carcinomas resected at our institution from 1995 through 1999. Three groups of lesions stratified by size (< or = 3 cm, > 3-5 cm, > 5 cm) were compared with regard to pathologic findings. Statistical significance was assessed using Fisher's exact test. RESULTS: Of 50 lesions 3 cm or smaller, 19 (38%) had extension outside the renal capsule (T3 or T4) and 14 (28%) were a high nuclear grade (Fuhrman grade 3 or 4). Lesions 3 cm or smaller and those greater than 3 cm to 5 cm did not differ statistically with regard to T stage or nuclear grade. Lesions larger than 5 cm showed a statistically higher T stage (p < 0.001) and nuclear grade (p = 0.001) than the other smaller lesions. More non-clear cell tumors were found in the two groups of smaller lesions (p = 0.105) but without statistical significance. The majority (58%) of the tumors were asymptomatic and had been detected incidentally on cross-sectional imaging. Lesions larger than 5 cm were significantly more likely to be symptomatic (p < 0.001). Seventy-nine percent of the tumors 3 cm or smaller were incidental, and these lesions did not differ significantly from the symptomatic lesions with regard to stage, grade, or histology. CONCLUSION: In our study population, renal cell carcinomas up to 3 cm, including asymptomatic lesions, showed a significant incidence of high nuclear grade and tumor extension beyond the renal capsule; these findings support aggressive management of small lesions. Symptomatic status was not an adequate discriminator to guide management. A longitudinal study is necessary to further evaluate the efficacy of current patterns of therapy.

Nephrogenic rests mimicking Wilms' tumor on CT.

Nephrogenic rests (NR) are persistent benign remnants of embryonic renal tissue. A small percentage of these may develop into Wilms' tumor (WT). Radiologic imaging is relied upon to differentiate between these entities, with the hallmark of malignant transformation being growth on serial imaging studies. There is, however, considerable overlap in their imaging characteristics. The authors present a case of two biopsy-proven NR in a 2-year-old girl with sporadic aniridia that were indistinguishable from WT on initial radiologic studies. One of the NR grew on serial imaging studies mimicking a WT, but after resection was confirmed to be a benign hyperplastic NR on pathologic examination.

Lymphoplasmacytic sclerosing pancreatitis with obstructive jaundice: CT and pathology features.

OBJECTIVE: The clinical presentation of lymphoplasmacytic sclerosing pancreatitis (LPSP) can be very similar to that of pancreatic cancer, with no statistically significant differences in the rates of abdominal pain, weight loss, jaundice, or levels of carcinoembryonic agent or cancer antigen 19-9. The purpose of this study is to describe and illustrate the CT features of LPSP presenting with obstructive jaundice and to correlate CT and pathology findings. MATERIALS AND METHODS: Five patients with LPSP were evaluated. Morphologic features of the pancreas on CT scans, including the size of the pancreas, presence or absence of a mass, segmental difference of contrast enhancement, pancreatic duct, major pancreatic vasculature, and biliary tract, were retrospectively evaluated and correlated with histopathology. The degree of contrast enhancement of the pancreas was compared in 10 patients without LPSP, who were scanned with the same protocol. RESULTS: CT scans showed diffuse (n = 2) or focal (n = 3) enlargement of the pancreatic head. The normal lobular appearance of the pancreas was effaced, and the gland appeared featureless in the involved region. Enlarged areas showed an enhancement pattern similar to that of the rest of the pancreas, and no segmental difference of contrast enhancement was identified. Pancreatic duct dilatation was not seen in any patient. Thickening and contrast enhancement of the common bile duct wall (n = 4) and gallbladder wall (n = 3) were observed and were pathologically correlated with inflammatory infiltrate and fibrosis of the common bile duct (n = 3) and gallbladder (n = 1). CONCLUSION: When these findings are encountered, further evaluation with serologic tests or biopsy may aid in the diagnosis of LPSP.