Well-demarcated Margins Research Articles

AN ATYPICAL CASE OF BILATERAL CORNEAL OPACITY: WHAT ARE THE POSSIBLE DIAGNOSIS?

Introduction: Corneal opacity can be divided into inflammatory and noninflammatory entities. The clinical presentation and characteristics of a corneal opacity can often help reach a diagnosis. However, atypical cases are more challenging to diagnose. This report aims to explore an atypical case of corneal opacity and the diagnostic approach through its clinical presentation. Case Report: A thirty-seven-year-old female patient had a chief complaint of gradual blurry vision in both eyes and slowly growing whitish lesions one year prior. The patient recalled a history of bilateral eye redness two years ago. The anterior segment examination and AS-OCT revealed bilateral, smooth, oedematous pearly-white elevated opacity with well-demarcated margins at the center of the cornea, with epithelial depth. The diagnosis of corneal keloid was favored, with GDLD and SND as the differential diagnosis. In local anesthesia, the patient underwent superficial keratectomy and amniotic membrane transplantation of the right eye. On one month follow-up, the patient felt an improvement in her subjective complaints with a normal appearance of the cornea. Discussion: The atypical characteristics found in our case didn’t fit a single mold, as it shared features of post- injury hypertrophic scar, degenerative, and dystrophy. We diagnosed the patient with corneal keloid caused by suspicion of subclinical infection. Although GDLD and SND were still possible, the working diagnosis was enough to warrant a therapeutic surgical removal. Conclusion: Atypical presentations make diagnosis more challenging. However, despite improvements in diagnostic modalities, signs, and symptoms remain very helpful in reaching a working diagnosis.

Cytomorphologic features of thyroid nodules harboring thyroid adenoma-associated fusion: A single institutional review of 11 cases.

Thyroid adenoma-associated (THADA) fusions are being identified more frequently with increased preoperative molecular testing on indeterminate thyroid fine-needle aspirates (FNA). However, data on cytomorphologic features of THADA-fusion thyroid lesions are limited. We examined cytomorphologic features of a THADA-fusion thyroid FNA cohort with clinical, radiologic, and histologic data. Our THADA fusion FNA cohort included 11 specimens from 11 patients with a mean age and F:M ratio of 56.5 years and 2.7:1, respectively. Ten cases had FNA slides available for review and five cases had histopathology. Air-dried Diff-Quik and alcohol-fixed Papanicolaou smears, and formalin-fixed cell blocks were reviewed and findings were correlated with the matched resection, when available. Clinical and radiologic data were obtained from the medical record. THADA fusion thyroid lesions were hypoechoic or isoechoic (80%), solid (80%) with well-demarcated margins (100%) on ultrasound. Notable cytomorphologic features include crowded or prominent microfollicular groups (100%), scant colloid (91%), and mild nuclear atypia with nuclear grooves (100%), insignificant nuclear pleomorphism (100%), and without intranuclear pseudoinclusions (100%). All cases were classified as either atypia of undetermined significance (91%) or suspicious for follicular neoplasm (9%). Five resected cases were all low-risk lesions (benign and malignant) with no evidence of recurrence in the limited available follow-up. THADA-fusion thyroid FNAs show a crowded or prominent microfollicular pattern with mild nuclear atypia and without intranuclear pseudoinclusions, which overlaps with the cytomorphology of other RAS-like thyroid lesions. In our cohort, resected THADA lesions were low risk on histologic analysis.

MRI findings of epithelial–myoepithelial carcinoma of the parotid gland with radiologic–pathologic correlation

PurposeThis study aimed to describe the MRI findings of epithelial-myoepithelial carcinoma (EMC) of the parotid gland.Materials and methodsSeven patients (four males and three females) aged 40–86 years (mean age, 64 years) with histologically proven EMC of the parotid gland who underwent surgical resection after preoperative MRI were enrolled. MRI images were retrospectively reviewed and contrasted with pathological findings.ResultsFive patients (71%) had predominantly solid lesions, and two (29%) had predominantly cystic lesions. All seven lesions had well-demarcated margins and capsules without the invasion of adjacent structures. The capsules were incomplete in five lesions (71%) and complete in two (29%). Four lesions (57%) exhibited a multinodular structure with internal septa. Cystic components were observed in three lesions (43%). On T1-weighted images, the solid components were frequently homogeneous (5/7, 71%), and demonstrated isointensity in five lesions (71%) and hypointensity in two (29%) relative to the spinal cord. On T2-weighted images, the solid components were usually heterogeneous (6/7, 86%), and demonstrated hyperintensity in five lesions (71%) and isointensity in two (29%) relative to the spinal cord. The mean apparent diffusion coefficient value of the solid components was 0.967 × 10−3 mm2/s.ConclusionParotid gland EMCs usually appeared as predominantly solid lesions with well-demarcated margins and capsules. A multinodular structure with internal septa was characteristics of EMCs.

Successful surgical management of large conjunctival nevus in a 10-year-old child with resection and amniotic membrane transplantation

The purpose of this paper is to illustrate a case of large conjunctival nevus in a 10-year-old boy which was successfully treated with surgical excision and amniotic membrane transplant (AMT) reconstruction. The conjunctival nevus was initially noticed by the parents 1 year prior to presentation; they reported it had increased in size over the past 3 months. Slit-lamp examination revealed a pigmented conjunctival nevus measuring 5.5 mm vertically and 6.5 mm horizontally, with well-demarcated margins and presence of an intralesional cyst at the temporal bulbar conjunctiva, involving the limbus and encroaching onto the cornea. Complete resection of the conjunctival lesion and bulbar conjunctival reconstruction were performed. The histopathological examination showed conjunctival nevus. The wound healed well with vision of 6/6 and no recurrence. Surgical resection combined with AMT is a successful and an effective way to treat conjunctivalnevus.

Efficacy and Safety of Lyophilized Articular Cartilage Matrix as an Injectable Facial Filler.

To evaluate the efficacy and safety of an injectable lyophilized articular cartilage matrix (LACM) which is in the form of cartilage powder that may increase the convenience of use and become unaffected by donor site morbidity as a potential filler. The safety test was conducted using 20 rabbits with an intravascular embolization model. Commonly used commercial hyaluronic acid (HA), acellular dermal matrix (ADM), polymethyl methacrylate (PMMA), and polylactic acid (PLA) products were selected for comparison of efficacy and adverse effect of LACM. The efficacy test was performed using 30 mice subcutaneous buttock-injection model. Gross assessments of the changes in size of injected materials and histological examinations were conducted. Regarding the safety test, in one rabbit in the HA group, complete blurring occurred in the left eye, and necrosis of the posterior auricular artery was observed in one rabbit in the ADM group. In the ADM, severe ecchymosis around the injection sites was observed, and the bruises lasted longer than in the other groups. The LACM exhibited faster bruise resolution. Comparing the changes in size between weeks 4 and 12 in the mouse model, no significant changes in size were observed in the LACM (p = 0.359), HA (p = 0.421), and ADM (p = 0.097), but a significant change was observed in the PMMA (p = 0.001). In the histological examination, LACM exhibited well-demarcated margins with good biocompatibility. The LACM shows potential as a facial filler according to the in vivo safety and efficacy tests LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

CT and MR imaging findings of ocular adnexal mucosa-associated lymphoid tissue lymphoma associated with IgG4-related disease: multi-institutional case series.

To report CT and MR imaging findings of ocular adnexal mucosa-associated lymphoid tissue lymphoma associated with IgG4-related disease (IgG4-MALT lymphoma), a rare but clinically important complication of ocular adnexal IgG4-related disease. We retrospectively reviewed all cases of histologically confirmed ocular adnexal IgG4-related disease at three tertiary and one secondary referral centers, between February 2003 and December 2016. Seven cases of histopathologically diagnosed IgG4-MALT lymphoma were identified. CT and MR images were analyzed by consensus of two experienced head and neck radiologists. Lacrimal glands were the main site of involvement in all seven patients. The lesions typically showed well-demarcated margins, iso- to hyperattenuation on precontrast CT, T2 hypo- to isointensity, T1 isointensity, and homogenous internal architecture with homogenous enhancement pattern. Lesions were mostly hyperdense and isointense to normal extraocular muscles on postcontrast CT and MR images, respectively. Unlike in typical ocular adnexal IgG4-related disease, T2 isointensity and hyperattenuation on precontrast CT images were noted in some IgG4-MALT lymphoma cases. Although the findings may be nonspecific, the possibility of accompanying MALT lymphoma may need to be considered, when ocular adnexal lesions in patients clinically suspected of having IgG4-related disease are refractory to glucocorticoids and show T2 isointensity and hyperattenuation on precontrast CT for the optimal management of the patients. However, this is a case series of a very rare complication of ocular adnexal IgG4-related disease, and thus caution is warranted to generalize the conclusion.

Multidisciplinary approach for treatment of a dentigerous cyst \u2013 marsupialization, orthodontic treatment, and implant placement: a case report

BackgroundDentigerous cysts are common odontogenic cysts associated with unerupted teeth. We describe a previously unreported case of a multidisciplinary approach using surgical, orthodontic, and implant treatment to establish the occlusion for a patient with a maxillary dentigerous cyst.Case presentationAn 18-year-old Japanese woman visited our hospital with a chief complaint of gingival swelling in her anterior maxillary region, midline diastema, and tooth crowding. Her main symptom was this gingival swelling. A panoramic radiograph revealed a radiolucent area, 30 mm in diameter, round in shape, and with well-demarcated margins including the maxillary canine. Computed tomography revealed a cystic cavity filled with homogeneous fluid of the same density as water, and a distolingually inclined canine. Our clinical diagnosis was maxillary dentigerous cyst with an unerupted distolingually inclined canine. The selected treatment was marsupialization of the dentigerous cyst, followed by orthodontic traction of the unerupted canine, and simultaneous orthodontic treatment of the midline diastema and tooth crowding. The orthodontic traction failed because the canine did not erupt completely, and the canine was extracted. The treatment plan was then changed to implant treatment after the tooth crowding and midline diastema had been improved. Because the alveolar ridge width was inadequate, the implant was placed after a two-stage implant treatment; therefore, a satisfactory occlusion could be achieved. Our patient did not experience any complications, and the cyst has not recurred. A radiograph taken 7 years after marsupialization of the dentigerous cyst revealed that the cystic cavity had been replaced by new bone.ConclusionsIn general, orthodontic traction of an unerupted tooth after marsupialization should be the best option. However, if orthodontic traction fails, a multidisciplinary approach involving implant treatment may be necessary. We describe a case in which a multidisciplinary approach involving surgical, orthodontic, and implant treatment was used to establish a satisfactory occlusion for a patient with a dentigerous cyst.

Systematic review of giant gastric lipomas reported since 1980 and report of two new cases in a review of 117110 esophagogastroduodenoscopies.

AIMTo systematically review the syndrome of giant gastric lipomas, report 2 new illustrative cases.METHODSLiterature systematically reviewed using PubMed for publications since 1980 with following medical subject heading/keywords: (“giant lipoma”) AND (“gastric”) OR [(“lipoma”) and (“gastric”) and (“bleeding”)]. Two authors independently reviewed literature, and decided by consensus which articles to incorporate. Computerized review of pathology/endoscopy records at William Beaumont Hospitals, Royal Oak and Troy, Michigan, January 2005-December 2015, revealed 2 giant gastric lipomas among 117110 consecutive esophagogastroduodenoscopies (EGDs), which were thoroughly reviewed, including re-review of original endoscopic photographs, radiologic images, and pathologic slides.RESULTSGiant gastric lipomas are extremely rare: 32 cases reported since 1980, and 2 diagnosed among 117110 consecutive EGDs. Average patient age = 54.5 ± 17.0 years old (males = 22, females = 10). Maximal lipoma dimension averaged 7.9 cm ± 4.1 cm. Ulcerated mass occurred in 21 patients. Lipoma locations: antrum-17, body-and-antrum-4, antrum-intussuscepting-into-small-intestine-3, body-2, fundus-1, and unspecified-5. Intramural locations included submucosal-22, subserosal-2, and unspecified-8. Presentations included: acute upper gastrointestinal (UGI) bleeding-19, abdominal pain-5, nausea/vomiting-5, and asymptomatic-3. Symptoms among patients with UGI bleeding included: weakness/fatigue-6, abdominal pain-4, nausea/vomiting-4, early-satiety-3, dizziness-2, and other-1. Their hemoglobin on admission averaged 7.5 g/dL ± 2.8 g/dL. Patients with GI bleeding had significantly more frequently ulcers than other patients. EGD was extremely helpful diagnostically (n = 31 patients), based on characteristic endoscopic findings, including yellowish hue, well-demarcated margins, smooth overlying mucosa, and endoscopic cushion, tenting, or naked-fat signs. However, endoscopic mucosal biopsies were mostly non-diagnostic (11 of 12 non-diagnostic). Twenty (95%) of 21 abdominal CTs demonstrated characteristic findings of lipomas, including: well-circumscribed, submucosal, and homogeneous mass with attenuation of fat. Endoscopic-ultrasound showed characteristic findings in 4 (80%) of 5 cases: hyperechoic, well-localized, mass in gastric-wall-layer-3. Transabdominal ultrasound and UGI series were generally less helpful. All 32 patients underwent successful therapy without major complications or mortality, including: laparotomy and full-thickness gastric wall resection of tumor using various surgical reconstructions-26; laparotomy-and-enucleation-2; laparoscopic-transgastric-resection-2; endoscopic-mucosal-resection-1, and other-1. Two new illustrative patients are reported who presented with severe UGI bleeding from giant, ulcerated, gastric lipomas.CONCLUSIONThis systematic review may help standardize the endoscopic and radiologic evaluation and therapy of patients with this syndrome.

Abstract 1950: Whole genome microRNA profiling in functionally validated invasive GBM cells identifies a novel set of microRNAs driving GBM invasion

Abstract Glioblastoma multiforme (GBM) is the most malignant brain tumor that occurs in both adults and children. One of the key features that makes GBM particularly difficult to treat is the diffuse invasion of tumor cells into surrounding normal brain tissue. We hypothesize that direct comparison of matched invasive (GBMINV) and tumor core GBM cells (GBMTC) would facilitate the discovery of drivers of GBM invasion. However, GBMINV cells that have migrated deep into normal brain tissues are extremely difficult to obtain from patients as resection of normal human brain tissue can result in debilitating morbidities. To overcome this barrier, we utilized a panel of 6 pediatric patient tumor-derived orthotopic xenograft (PDOX) mouse models to isolate matched pairs of GBMTC cells from the visible tumor mass and GBMINV cells from the “normal” mouse brains. Global profiling of 768 human microRNA using a real-time PCR-based Taqman system identified 23 microRNAs were upregulated in the GBMINV cells in at least 5 of the 6 GBM models as compared with the matching GBMTC cells. Functional validation was performed by lentivirus-mediated silencing of miR-126, miR-487b and miR-369-5p, the top three overexpressed microRNA in the GBMINV cells. Compared with the untreated parental cells and tumor cells transduced with non-target control lentiviruses, silencing of miR-126, miR-487b or miR-369-5p suppressed GBMINV cell (both as neurosphere and monolayer) migration in vitro without affecting tumor proliferation and significantly inhibited the in vivo invasive growth of GBMINV cells, which were pre-enriched through 3 rounds of in vivo selections, into normal mouse brains. The depth of the invasive fronts were remarkably decreased/eliminated, exhibiting sharp, well-demarcated margins between tumor and normal mouse brain. To identify target genes of the 3 microRNAs, whole genome gene expression profiling from the same pairs of GBMINV and GBMTC cells was performed and identified a subset of genes suppressed by miR-126 (n = 74), miR-487b (n = 46) and miR-369-5p (n = 2) that occurred in at least 4 of the 6 pairs. Among them, RDX was inhibited by all three microRNAs, MANEA by miR-126 and miR-369, and a 32 genes (including PDK1, CREBZF, PRKAA2, TMF1 and HSPA13) by miR-126 and miR-487b. In conclusion, our novel strategy of utilizing functionally validated pairs of GBMINV and GBMTC cells has identified a set of microRNAs that are selectively over-expressed in GBMINV cells and allowed functionally confirmation of miR-126, miR-487b and miR-369-5p as drivers of GBM invasion. Citation Format: Lin Qi, Yu-lun Huang, Hua Mao, Mari Kogiso, Xiumei Zhao, Yuchen Du, Holly Lindsay, Xiaojun Yuan, Patricia Baxter, Jack Su, Chris Man, Laszlo Perlaky, Zhong Wang, You-Xing Zhou, Xiao-Nan Li. Whole genome microRNA profiling in functionally validated invasive GBM cells identifies a novel set of microRNAs driving GBM invasion. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1950.

CBIO-34MiR-126 AND miR-369-5p ARE DRIVERS OF GBM INVASION: AN IN VIVO STUDY IN PATIENT-TUMOR DERIVED ORTHOTOPIC XENOGRAFT MOUSE MODELS

We hypothesize that direct comparison of the matched invasive and tumor core GBM cells would facilitate the discovery of drivers of GBM invasion. However, GBM cells that infiltrate deep into brain tissues (GBMinv) are extremely difficult to obtain from patients. To overcome this barrier, we utilized a panel of 7 (1 adult and 6 pediatric) patient-tumor derived orthotopic xenograft (PDOX) mouse models to isolate matched GBMinv and GBMTC cells by cutting whole mouse brains into 10 slices (1 mm thick), followed by microscopic dissection of tumor mass (to harvest GBMTC cells) and the normal mouse brains (to harvest GBMinv cells), respectively. After the mouse cells were decontaminated through FACS, matched GBMinv and GBMTC cells were subjected to microRNA profiling using Taqman MicroRNA array (768 microRNAs). Compared with the GBMTC cells, 23 microRNAs were upregulated in the GBMinv cells in at least 5 of the 7 GBM models. Functional validation showed that silencing miR-126 and mir-369-5p, the top two overexpressed microRNA in GBMinv, did not significantly alter cell proliferation but suppressed tumor cell migration (both as neurospheres and as monolayer cultures) in vitro. To confirm their role as drivers of GBM invasion in vivo, purified GBMinv cells were transduced with lentiviruses (silencing miR-126 and mir-369-5p, respectively) and implanted into the brains of NOD/SCID mice. Compared with the untreated parental cells and tumor cells transduced with non-target control lentiviruses, silencing miR-126 or miR-369-5p significantly suppressed GBM invasion. Not only the areas but also the depth of the invasive front were remarkably decreased, exhibiting sharp or well-demarcated margins between tumor and mouse brains. In conclusion, we identified a set of microRNAs that are selectively over-expressed in the invasive front of GBM cells and functionally confirmed that miR-126 and miR-369-5p as drivers of GBM invasion.

Osteopetrosis - Classic Imaging Findings in the Spine.

A 27-year-old man presented to his primary care clinic with chronic, progressive mid to lower back pain. Neurologically, the patient was normal with no focal deficits. A radiographic examination of the thoracic and lumbar spine was performed [Table/Fig-1,​,2],2], demonstrating diffuse endplate sclerosis with a sharp delineation between the peripheral bony sclerosis and relative lucency of the central vertebral bodies, producing the characteristic “sandwich vertebrae” of osteopetrosis. In addition, several lumbar vertebrae demonstrated sclerosis along the inner margin of the remainder of the vertebral bodies, resulting in “bone within a bone” appearance, also characteristic of osteopetrosis. [Table/Fig-1]: Lower thoracic spine frontal view: diffuse vertebral endplate sclerosis with well-demarcated margins between the peripheral sclerotic and central relatively lucent bone, consistent with a “Sandwich vertebrae” appearance. The visualized ... [Table/Fig-2]: Lumbar spine lateral view: similar findings are demonstrated with both the “Sandwich vertebrae” and “bone within a bone” appearance Osteopetrosis is an inherited disease with a variety of genetic causes related to dysfunctional bone remodeling, which results in abnormally dense bones. Although dense, the involved bones are weakened and prone to pathologic fractures. There are many sub categories of osteopetrosis; however, they are largely divided into two main groups Autosomal recessive (ARO) and Autosomal dominant (ADO). The autosomal recessive subtype is typically severe, resulting in either fetal demise or discovered early in infancy with pathologic fractures, neurologic deficits, or bone marrow abnormalities. The autosomal dominant form of osteopetrosis (Albers-Schonberg disease), on the other hand, is less severe and often discovered in young to middle aged adults. Patients may be asymptomatic with incidental findings on radiographic examinations or present with fractures, scoliosis, arthritis, delayed healing, or osteomyelitis. There are two phenotypic variants of ADO. Subtype 1 (ADO1) is rare and secondary to a defect of the low density lipoprotein receptor 5 (LRP5), which results in increased uniform sclerosis [1]. This subtype primarily involves the cranium. Subtype 2 (ADO2) is far more common and secondary to a chloride channel 7 (CLCN7) deficiency [1]. Radiographically, ADO2 presents with “bone within a bone” pattern most often within the pelvis and long bones and less frequently within vertebrae, as well as the characteristic “sandwich vertebrae” appearance in the spine, as seen in this case [2]. Current treatment for ADO is primarily supportive, though, it is hypothesized that gene therapy may play a role in the future with an identifiable gene defect [3]. The “Sandwich vertebra” appearance, while classical for osteopetrosis, bears similarity to vertebral sclerosis patterns seen in other disease processes. Hyperparathyroidism is the primary differential consideration for this appearance in the spine, as both processes cause endplate sclerosis. In contrast to osteopetrosis, the demarcation between the peripheral sclerotic and central lucent bone is indistinct or smudgy with hyperparathyroidism; this pattern is colloquially referred to as the “Rugger-jersey” spine, which should be readily distinguished from the “sandwich vertebrae” appearance on imaging [4]. In radiographically equivocal cases, a clinical work-up for hyperparathyroidism establishes the correct diagnosis. Paget’s disease affects middle aged to elderly adults and may also result in endplate sclerosis, along with other characteristic imaging features. Plain radiographs demonstrate bony expansion with peripheral cortical and central trabecular thickening, resulting in a characteristic “picture frame” appearance of the vertebral bodies, as well as diffuse bony sclerosis [4,5]. This differs from the “bone within a bone” appearance of osteopetrosis, which typically lacks bony, cortical, or trabecular thickening. Patient age and imaging appearance are distinguishing features of Paget’s disease.

Imaging study of ossifying fibroma with associated aneurysmal bone cyst in the paranasal sinus

ObjectiveTo determine the CT and MR imaging features of ossifying fibroma with aneurysmal bone cyst of the paranasal sinus. Materials and methodsWe retrospectively reviewed 15 patients with histopathology-proven ossifying fibromas with aneurysmal bone cysts in the paranasal sinus. All 15 patients underwent CT and MR imaging. The following imaging features were reviewed: location, shape, margin, CT findings, and MR imaging appearances and time-intensity curve of dynamic contrast-enhanced MR imaging. ResultsOssifying fibromas occurred in the maxillary sinus in one patient, sphenoid sinus in 2, frontal sinus in 3, frontoethmoid sinuses in 3, and ethmoid sinus in 6 patients. Ossifying fibromas showed an elliptic-shape and aneurysmal bone cysts revealed a multicystic appearance, with well-demarcated margins. On unenhanced CT, ossifying fibromas appeared isodense to gray matter with scattered calcifications in nine, ground-glass appearance in 6 patients and aneurysmal bone cysts showed mixed density. Ossifying fibromas appeared isointense to gray matter in 12 and slightly hypointense in three patients on T1-weighted images, and isointense in 4 and hypointense in eleven patients on T2-weighted images, with moderate or marked enhancement after administration of contrast material. The time-intensity curves of eight ossifying fibromas exhibited a rapidly enhancing and rapid washout pattern. The intracystic components of aneurysmal bone cysts showed heterogeneous signal intensity on MR images, with fluid–fluid levels identified clearly by T2-weighted images, without enhancement. The periphery and septa of aneurysmal bone cysts appeared isointense on MR images, with marked enhancement. ConclusionsFluid–fluid levels within an elliptic-shape mass with scattered calcifications or ground-glass appearance is highly suggestive of this complicated entity in the paranasal sinus.

Differentiation of Chromophobe Renal Cell Carcinoma and Clear Cell Renal Cell Carcinoma by Using Helical CT

Background: The purpose of this study was to differentiate chromophobe renal cell carcinoma and clear cell renal cell carcinoma on helical CT. Methods: The CT images of 9 patients histopathologically proven to have chromophobe renal cell carcinoma and 20 patients with clear cell renal cell carcinoma were reviewed. The tumor sizes, margins, enhancement degrees and patterns, presence or absence of calcification, and tumor spread patterns (including perinephric changes, venous invasion, lymphadenopathy, and distant metastasis) were compared. Results: All the chromophobe renal cell carcinomas showed well-demarcated margins. Thechromophobe renal cell carcinomas showed milder enhancements than the clear cell renal cell carcinomas. The sensitivity and specificity for differentiating the chromophobe renal cell carcinoma from the clear cell renal cell carcinoma were 100 and 88%, respectively, when 101 Hounsfield units was used as the cut-off value in the corticomedullary phase, and 95 and 100% when a less-than-three-time enhancement change was used as a cut-off value in the corticomedullary phase (p 0.05). Conclusion: The CT findings of the chromophobe renal cell carcinomascompared to those of the clear cell renal cell carcinomas showed that there were mild enhancements in the corticomedullary phase, homogeneous enhancements, and well-demarcated margins.

US Findings after Irreversible Electroporation Ablation: Radiologic-Pathologic Correlation

To characterize ultrasonographic (US) findings after irreversible electroporation (IRE) to determine the utility of these findings in the accurate assessment of ablation margins. The institutional animal care and use committee approved the study. IRE ablation (n = 58) was performed in vivo in 16 pig livers by using two 18-gauge electroporation electrodes with 2-cm tip exposure, 1.5- or 2.0-cm interelectrode spacing, and an electroporation generator. Energy deposition was applied at 2250-3000 V (pulse length, 50-100 μsec; pulse repetition, 50-100). Ablations were performed under US guidance. Images were obtained during ablation and at defined intervals from 1 minute to 2 hours after the procedure. Zones of ablation were determined at gross and histopathologic examination of samples obtained from animals sacrificed 2-3 hours after IRE. Dimensions of the histologic necrosis zone and US findings were compared and subjected to statistical analysis, including a Student t test and multiple linear regression. Within 20-50 pulse repetitions of IRE energy, the ablation zone appeared as a hypoechoic area with well-demarcated margins. During the next 8-15 minutes, this zone decreased in size from 3.4 cm ± 0.5 to 2.5 cm ± 0.4 and became progressively more isoechoic. Subsequently, a peripheral hyperechoic rim measuring 2-7 mm (mean, 4 mm ± 1) surrounding the isoechoic zone developed 25-90 minutes (mean, 41 minutes ± 19) after IRE. The final length of the treatment zone, including the rim, increased to 3.3 cm ± 0.6. The final dimensions of the outer margin of this rim provided greatest accuracy (1.7 mm ± 0.2) and tightest correlation (r(2) = 0.89) with gross pathologic findings. Histologic examination demonstrated widened sinusoidal spaces that progressively filled with spatially distributed hemorrhagic infiltrate on a bed of hepatocytes with pyknotic nuclei throughout the treatment zone. US findings in the acute period after IRE are dynamic and evolve. The ablation zone can be best predicted by measuring the external hyperechoic rim that forms 90-120 minutes after ablation. This rim is possibly attributable to evolving hemorrhagic infiltration via widened sinusoids.

The feasibility and safety of transendocardial gene injection in canine using a multifunctional intracardiac echocardiography catheter

BackgroundTransendocardial gene delivery may expose patients to the risk of pericardial perfusion due to excessive needle injections. This study investigated the feasibility and safety of transendocardial gene injection using a newly developed multifunctional intracardiac echocardiography catheter. MethodsThis new system integrated intracardiac echocardiography, a retractable 29-G needle, and other accessories into a single catheter (10F) that could be delivered into the left ventricle via a retrograde aortic approach. In three canines, the catheter was used to inject 0.2ml of Evan's blue; six canines received myocardial injections of plasmid containing the EGFP transgene. In addition, two canines received transendocardial injections of a pAdTrace-bFGF plasmid. All canines receiving gene delivery were sacrificed after 3days. The hearts were harvested for gross, histological examination and gene expression assessment. ResultsThis catheter provided visual guidance for accurate needle-tip positioning within the target myocardium; the needle position was subsequently confirmed by microbubble infusion. No animal had pericardial effusion or sustained ventricular arrhythmia. Tissue staining showed well-demarcated margins within the target myocardium. In animals injected with pEGFP-N1, confocal microscopy demonstrated successful gene expression. In zones where pAdTrace-bFGF was injected, immunohistochemistry also showed positive staining. Compared to normal tissue (0.38±0.04), RT-PCR showed high levels of bFGF expression (0.63±0.02) in the target area (P<0.01). ConclusionsTransendocardial gene injection using a multifunctional intracardiac echocardiography catheter is feasible and could improve procedure-related safety which may provide a new strategy for transgene delivery in future.

Clinical implications of tumor cavitation following therapy with angiogenesis inhibitors in non-small cell lung cancer (NSCLC) patients

18034 Background: Angiogenesis inhibitors are being tested in patients with advanced cancer. We sought to determine the formation of tumor cavitation in NSCLC patients treated with antiangiogenic agents at MD Anderson Cancer Center. Methods: Retrospective analysis of all NSCLC cases treated with antiangiogenic agents in our institution between 6/1998 and 6/2005. Clinical data were retrieved from medical records, and chest-imaging findings were documented. Results: One hundred and twenty four patients were treated in 10 different trials. Twelve patients (9.7%, 6 men, 6 women, median age 56 years; cell type adenocarcinoma in 9 and squamous cell cancer in 3) developed tumor cavitation during the trial (median time to event 2 months). All patients had advanced lung cancer and failed previous chemotherapy. Tumor cavitation was found in 4 of 10 trials: 7/39 patients treated with bevacizumab (5 were treated in combination with erlotinib), 3/17 with ZD6474, and 2/23 with BAY43–9006. Median progression-free survival was similar between patients with (6 months) or without (4 months) cavitation. Stable disease was noted in 50% of patients who did and in 52% of patients who did not develop cavitation. Cavitation occurred in the primary tumor or metastases. Imaging characteristics did not significantly differ between tumors with or without cavitation: being proximal to subsegmental artery (66% vs 52%), having well-demarcated margins (66% vs 56%), and soft-tissue density (90% vs 85%). The frequency of adverse events (mild rash, neuropathy) of any grade was similar in patients with (42%) or without (51%) cavitation. One patient with cavitation developed hemoptysis and died. Conclusions: Development of tumor cavitation is not rare in lung cancer patients treated with antiangiogenic agents, but the clinical implications are minimal in most cases. No significant financial relationships to disclose.

MRI of postoperative maxillary cysts.

The purpose of this study is to review the MR characteristics of postoperative maxillary cysts (POMC). The MR findings in 24 patients with 38 surgically confirmed POMC were retrospectively reviewed. Of 32 cysts detected by MRI, 31 cysts (96.9%) were well demarcated. Nineteen cysts (59.4%) were smooth and the others (40.6%) were irregular. Thirty cysts (93.8%) had signal intensities ranging from that of muscle to that of subcutaneous fat on T1-weighted imaging. On T2-weighted imaging 16 homogeneous (50.0% and 5 inhomogeneous (15.6%) cysts showed signal intensities equal to or higher than subcutaneous fat. The peripheral rims of 11 ring-like cysts (34.4%) also showed signal intensities equal to or higher than subcutaneous fat on T2-weighted imaging. Nine patients (37.5%) had multiple cysts. Their characteristic high signal intensities or ring-like patterns on T2-weighted imaging and well-demarcated margins enabled them to be discriminated from other tumors of the maxillary sinus, such as carcinoma. MR imaging is useful for diagnosis of POMC.

Lugol staining pattern and histology of esophageal lesions.

To analyze the relationship between Lugol unstained areas and their histologic features, we applied the Lugol test to 24 specimens of resected esophagus. The staining patterns were graded into four types: grade I, hyperstaining; grade II, normal greenish brown staining; grade III, less intense staining; and grade IV, unstained. Most of the grade IV lesions were invasive carcinomas, carcinomas in situ, or severe dysplasia. The carcinomas in situ and the intraepithelial extension of the carcinomas, which were difficult to detect, were clearly shown as grade IV. On the other hand, moderate to mild dysplasia or atrophy showed grade III staining. Grade IV lesions showed well-demarcated sharp margins, whereas grade III lesions showed ill-demarcated dull margins. The grade III carcinomas, however, by the Lugol test, showed well-demarcated margins. Histologic evaluation disclosed that the staining intensity reflected well the thickness of the glycogen-containing cell layer in the lesion. The sharpness of the margin reflected the abrupt or gradual change from the glycogen-containing to non-containing cell layers. These findings suggest 1) the usefulness of the staining pattern of the Lugol test for the diagnosis of esophageal lesions such as squamous cell carcinoma and severe dysplasia, and 2) the usefulness of the Lugol test for precise delineation of the proximal resection line during surgery of esophageal carcinomas with unexpected wide extension.

Mesenchymal Hamartoma of the Liver

Mesenchymal hamartoma of the liver occurs almost exclusively in infancy and childhood, with approximately 140 total cases reported. We report the experience with 18 patients at the Childrens Hospital of Los Angeles (Calif) during the past 35 years. The charts of all patients with mesenchymal hamartoma were retrospectively reviewed. The mean age at presentation was 16 months. Thirteen patients were symptomatic, presenting with increasing abdominal distention. Physical examination revealed an abdominal mass or hepatomegaly. Ultrasonography and computed tomography were the most useful diagnostic tests. Fourteen patients underwent resection; 9 underwent hepatic resection and 5 underwent excision of the tumor only. One patient had marsupialization, 1 underwent a biopsy only, and 2 died of unrelated causes and the hamartoma was found incidentally at autopsy. In all instances, a large cystic mass with well-demarcated margins was found. Three patients were unavailable for follow-up and 13 patients were alive and well 1 month to 24 years (mean, 5 years) after diagnosis. Recurrence or malignant transformation was not noted. A presumptive diagnosis can be made preoperatively by normal laboratory values and a combination of ultrasonography and computed tomography. We recommend excision of the tumor in all patients once the diagnosis is made, with the expectation of complete recovery.