Single Large Lesion Research Articles

Breast Conservation Project: Clinical Outcomes of Extreme Oncoplastic Breast-Conserving Therapy Versus Mastectomy for Large and Multiple Lesions.

Patients with multiple or large malignant breast lesions are classically considered mastectomy candidates, but extreme oncoplastic breast-conservation surgery (eOBCS) has become an alternative approach. There is a paucity of outcomes data comparing eOBCS with mastectomy. We reviewed our prospectively maintained, single-institution database. We included patients with non-metastatic breast cancer with multiple ipsilateral or single large (≥ 5cm) malignant breast lesions identified preoperatively who underwent either eOBCS or mastectomy. Patient demographics, clinicopathologic features, and surgical, oncologic, and cosmetic outcomes were evaluated. Seventy-six (88%) patients underwent eOBCS and 10 (12%) underwent mastectomy. Median follow-up was 24.8months. Mastectomy patients had larger lesions than eOBCS patients (median 70mm vs. 32.5mm; p = 0.06). Six (60%) index mastectomy patients underwent at least one additional surgery. For eOBCS patients, 34 (44%) required re-excision, 7 of whom underwent more than one subsequent surgery to obtain negative margins, and 6 (7.9%) ultimately underwent mastectomy. For patients undergoing additional surgery (n = 40), median time between index and final operation was 315days for mastectomy versus 21days for eOBCS patients (p < 0.001). Mastectomy patients more frequently experienced complications (p = 0.001) and underwent cosmetic revision (p < 0.001). There was no difference in cosmetic scores, and eOBCS patients reported less pain (p = 0.009). There were two local and three distant recurrences in the eOBCS cohort and one distant recurrence in the mastectomy group. Breast conservation was attainable in over 90% of eOBCS patients. Increased postoperative complications and discomfort and longer duration of surgical treatment in mastectomy patients without oncologic superiority should drive informed patient discussions.

Wide Local Excision versus Simple Vulvectomy in Vulval Intraepithelial Neoplasia 3: Case Report and Literature Review

Vulvar intraepithelial neoplasia is a premalignant lesion of the vulva. Women with vulvar cervical intraepithelial neoplasia 3 are at high risk of recurrence and vulvar carcinoma. They warrant a surgical management for the same reason. It may be either ablative or excisional, sometimes can be a combination of both. The decision for wide local excision or simple vulvectomy depends on clinical factors. Case: We present a case of a 67-year-old lady who presented with vulvar itching and a large black vulvar lesion involving the fourchette area, with HPV 16 positive. Initially, there was a doubt of melanoma, but vulval biopsy was suggestive of high-grade squamous intraepithelial lesion (HSIL) (vulval intraepithelial neoplasia 3 [VIN 3]). As it was a single large lesion, the initial plan was wide local excision but as the lesion was large and occupying almost half of the vulva, the decision of simple vulvectomy was taken. A wide local excision would have resulted in vulvar asymmetry and since there was a big lesion, chances of satellite lesions over the vulva were there; decision was made for simple vulvectomy. In this case report, we will review the literature on the surgical management of VIN 3. Conclusion: Treatment is recommended for all vulvar HSIL because of the potential for invasion. Simple vulvectomy is an easy procedure, with less hospital stay, less blood loss, and least recurrence rates. It is a suitable treatment option for multifocal and large lesions of the vulva.

Hepatocellular Carcinoma in Non-Fibrotic Liver: A Narrative Review.

Hepatocellular carcinoma (HCC) in a non-fibrotic liver (F0) is considered to be rare, and there is a marked paucity of studies in the literature on this HCC type. A review of the literature shows some important clinical and tumor characteristics: (a) it occurs mainly in young female and elder male patients; (b) clinically, under normal hepatic function, alpha-fetoprotein level is often normal, and there are no risk factors; (c) associated with metabolic disease; (d) macroscopically, single large lesions are noted; and (e) microscopically, the lesions are well-differentiated and encapsulated. Radiological imaging results are straightforward, showing arterial hyperenhancement and later wash-out. The combined use of B-mode and contrast-enhanced (CE) ultrasound (US) is the most reliable and cost-effective diagnostic method. Few peri-and post-operative complications are noted and 5-year survival is not inferior to patients with HCC on fibrosis liver despite the lesion's large size. Most clinicians believe that HCC is unlikely to occur if patients have no symptoms and normal hepatic function. Although detailed clinical data are very limited, we expect that this review will help to improve the clinical management of HCC in non-fibrotic livers.

Metabolic bulk volume from FDG PET as an independent predictor of progression-free survival in follicular lymphoma.

Total metabolic tumor volume (TMTV) in 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) predicts patient outcome in follicular lymphoma (FL); however, it requires laborious segmentation of all lesions. We investigated the prognostic value of the metabolic bulk volume (MBV) obtained from the single largest lesion. Pretreatment FDG PET/computed tomography (CT) scans of 201 patients were analyzed for TMTV and MBV using a 41% maximum standardized uptake value (SUVmax) threshold. During a median follow-up of 3.2 years, 54 events, including 14 deaths, occurred. Optimal cut-offs were 121.1 cm3 for TMTV and 24.8 cm3 for MBV. Univariable predictors of progression-free survival (PFS) included a high Follicular Lymphoma International Prognostic Index 2 (FLIPI2) score, TMTV, and MBV. In the multivariable analysis, high TMTV and MBV were independent predictors of worse PFS (P =0.015 and 0.033). Furthermore, in a sub-group with FLIP2 scores of 0-2 (n = 132), high MBV could identify patients with worse PFS (P = 0.007). . Readily measurable MBV is useful for stratifying risk in FL patients.

Solitary pityriasis versicolor an uncommon presentation as a large single patch Report of three cases and review of unusual clinical forms

Pityriasis versicolor (PV) is a common disease, easy recognizable, that usually affects the trunk and upper limbs with multiple rounded scaly lesions which can vary in color from case to case. However, infrequent localizations have been reported, as well as diverse unusual clinical presentations, including atrophic, hyperkeratotic, annular, or inverse forms, among other. We describe 3 cases presenting with a single large lesion in the neck, which can hinder the diagnosis. No description of this form was found neither in large series of PV, nor in extensive reviews. This solitary variety would be just another atypical clinical presentation of PV. Clinicians should be aware of this variety in order to avoid unnecessary studies.

Metabolic bulk volume predicts survival in a homogeneous cohort of stage II/III diffuse large B-cell lymphoma patients undergoing R-CHOP treatment.

Accurate risk stratification can improve lymphoma management, but current volumetric 18F-fluorodeoxyglucose (FDG) indicators require time-consuming segmentation of all lesions in the body. Herein, we investigated the prognostic values of readily obtainable metabolic bulk volume (MBV) and bulky lesion glycolysis (BLG) that measure the single largest lesion. The study subjects were a homogeneous cohort of 242 newly diagnosed stage II or III diffuse large B-cell lymphoma (DLBCL) patients who underwent first-line R-CHOP treatment. Baseline PET/CT was retrospectively analyzed for maximum transverse diameter (MTD), total metabolic tumor volume (TMTV), total lesion glycolysis (TLG), MBV, and BLG. Volumes were drawn using 30% SUVmax as threshold. Kaplan-Meier survival analysis and the Cox proportional hazards model assessed the ability to predict overall survival (OS) and progression-free survival (PFS). During a median follow-up period of 5.4 years (maximum of 12.7 years), events occurred in 85 patients, including progression, relapse, and death (65 deaths occurred at a median of 17.6 months). Receiver operating characteristic (ROC) analysis identified an optimal TMTV of 112 cm3, MBV of 88 cm3, TLG of 950, and BLG of 750 for discerning events. Patients with high MBV were more likely to have stage III disease; worse ECOG performance; higher IPI risk score; increased LDH; and high SUVmax, MTD, TMTV, TLG, and BLG. Kaplan-Meier survival analysis showed that high TMTV (p = 0.005 and < 0.001), MBV (both p < 0.001), TLG (p < 0.001 and 0.008), and BLG (p = 0.018 and 0.049) were associated with significantly worse OS and PFS. On Cox multivariate analysis, older age (> 60 years; HR, 2.74; 95% CI, 1.58-4.75; p < 0.001) and high MBV (HR, 2.74; 95% CI, 1.05-6.54; p = 0.023) were independent predictors of worse OS. Older age (hazard ratio [HR], 2.90; 95% CI, 1.74-4.82; p < 0.001) and high MBV (HR, 2.36; 95% CI, 1.15-6.54; p = 0.032) were also independent predictors of worse PFS. Furthermore, among subjects ≤60 years, high MBV remained the only significant independent predictor of worse OS (HR, 4.269; 95% CI, 1.03-17.76; p = 0.046) and PFS (HR, 6.047; 95% CI, 1.73-21.11; p = 0.005). Among subjects with stage III disease, only greater age (HR, 2.540; 95% CI, 1.22-5.30; p = 0.013) and high MBV (HR, 6.476; 95% CI, 1.20-31.9; p = 0.030) were significantly associated with worse OS, while greater age was the only independent predictor of worse PFS (HR, 6.145; 95% CI, 1.10-4.17; p = 0.024). MBV easily obtained from the single largest lesion may provide a clinically useful FDG volumetric prognostic indicator in stage II/III DLBCL patients treated with R-CHOP.

Ultrasound-based sensors for respiratory motion assessment in multimodality PET imaging

Breathing motion can displace internal organs by up to several cm; as such, it is a primary factor limiting image quality in medical imaging. Motion can also complicate matters when trying to fuse images from different modalities, acquired at different locations and/or on different days. Currently available devices for monitoring breathing motion often do so indirectly, by detecting changes in the outline of the torso rather than the internal motion itself, and these devices are often fixed to floors, ceilings or walls, and thus cannot accompany patients from one location to another. We have developed small ultrasound-based sensors, referred to as ‘organ configuration motion’ (OCM) sensors, that attach to the skin and provide rich motion-sensitive information. In the present work we tested the ability of OCM sensors to enable respiratory gating during in vivo PET imaging. A motion phantom involving an FDG solution was assembled, and two cancer patients scheduled for a clinical PET/CT exam were recruited for this study. OCM signals were used to help reconstruct phantom and in vivo data into time series of motion-resolved images. As expected, the motion-resolved images captured the underlying motion. In Patient #1, a single large lesion proved to be mostly stationary through the breathing cycle. However, in Patient #2, several small lesions were mobile during breathing, and our proposed new approach captured their breathing-related displacements. In summary, a relatively inexpensive hardware solution was developed here for respiration monitoring. Because the proposed sensors attach to the skin, as opposed to walls or ceilings, they can accompany patients from one procedure to the next, potentially allowing data gathered in different places and at different times to be combined and compared in ways that account for breathing motion.

Neurocysticercosis in a Japanese woman with lung cancer who repeatedly visited endemic countries

BackgroundTaenia solium, present in most developing countries, infects many individuals and may result in their death. Neurocysticercosis (NCC) develops after invasion of the brain by parasitic larvae. It is the most common parasitic disease of the human central nervous system. On imaging scans it can be similar to brain tumors. We report a patient with a metastatic brain tumor and NCC. The co-presence of NCC was diagnosed based on specific neuroimaging- and epidemiologic findings.Case presentationA 36-year-old non-smoking Japanese woman with a history of non-small-cell lung cancer had undergone resection of the lower lobe followed by cytotoxic chemotherapy 2 years before apparently suffering recurrence. A positron emission computed tomography (PET) scan incidentally revealed multiple intracranial cold spots exhibiting differences in their shape and size. On brain magnetic resonance imaging (MRI) scans we observed many different patterns of peripheral edema and gadolinium-enhancing effects. As she had often visited Latin America and Southeast Asia and had eaten raw pork and Kimchi, we suspected that the brain lesions were due to NCC rather than metastatic brain tumors. However, serum immunoblotting assay and DNA analysis were negative for T. solium. Rather than performing resection, we administered albendazole (ABZ) and dexamethasone because her earlier cytotoxic chemotherapy had elicited severe pancytopenia. Except for a single large lesion in the left frontal lobe, this treatment resulted in a significant reduction in the size of these lesions and a decrease in perilesional edema. She underwent resection of the residual lesion 10 months later. Histology revealed it to be a metastatic tumor. Polymerase chain reaction (PCR) assay for NCC was negative. In the course of 11-months follow-up there has been no recurrence.ConclusionThis is the first presentation of NCC in a Japanese woman with a metastatic brain tumor. NCC was incidentally discovered on PET scans and, based on her travel history and epidemiological findings; it was diagnosed and successfully treated with ABZ. NCC is endemic in most developing countries and as visits to such countries have increased, NCC must be ruled out in patients with multiple cystic nodular brain lesions.

851 Giant Oncocytoma In A Solitary Kidney: A Case Report on Balancing Surgical Resection Against Surveillance

Abstract Renal oncocytomas are benign kidney neoplasms that are typically small, unilaterally localised (95%) and challenging to differentiate on cross-sectional imaging, hence requiring surgical intervention. We herein present the extremely rare case of a patient with giant, bilateral oncocytomas and oncocytosis, and chronic kidney disease (CKD) and discuss the associated treatment challenges. A 61-year-old male with no past medical history presented with CKD (eGFR of 32ml/min). On investigation, cross sectional imaging revealed bilateral, multifocal, solid and vascular renal lesions. The largest lesion measuring 115mm x 102mm was situated in the right kidney, with multiple lesions noted in the left kidney, measuring up to 44mm. He subsequently underwent a right radical nephrectomy and histopathological analysis reported oncocytosis of the background kidney. The largest left sided renal lesion was biopsied, also confirmatory of benign oncocytoma. eGFR after surgery was 26ml/min. Following patient-centric consultations, further surgical intervention for the left sided renal lesions was declined, aiming to avoid renal replacement therapy (RRT). He has remained on active surveillance with biannual scans for 6 years. The lesions in his remaining kidney have since grown and coalesced into a single large lesion, with axial dimensions in the most recent MRI scan of 104mm x 306mm. He has progressed to stage IV CKD (eGFR 16ml/min), but still currently without need of RRT. This case study underscores both the significance of shared decision making in urology and surgery. Ultimately, the most significant skill lies in knowing when to not operate, especially when presented with the rarest of cases.

The application of neonate lung ultrasound in congenital pulmonary airway malformation

Objective To analyze the characteristics of lung ultrasound (LUS) in congenital pulmonary airway malformation (CPAM), and to compare the difference of image characteristics between LUS and chest X-ray(CXR) and evaluate the value of neonate LUS in CPAM. Methods From June 2017 to October 2018, the characteristics of LUS and CXR of 32 neonates who were diagnosed with CPAM by prenatal ultrasound and postnatal chest CT were analyzed retrospectively, and the difference of their direct signs and indirect signs were compared. Results Among 32 CPAM cases, 10 cases (31.25%) showed a single large cystic lesions and 3 cases with consolidation, 4 cases (12.5%) characterized by multiple hypoechoic lesions and 3 cases with consolidation, 16 cases (50%) showed consolidation with or without intensiveaerated bronchus sign or dendritic air-filled bronchi, 2 cases (6.25%) only characterized by dense B-line. The non-characteristic sonographic findings including pleural line was not smooth and not clear; A-line decreased or disappeared, dense B-lines were observed. The ability of LUS in measuring the size of CPAM was limited.Among 32 CPAM cases, 10 cases (31.25%) showed large cystic hypoechoic lesions and 22 cases (68.75%) showed small cystic hypoechoic lesions by CT scan. In this group, there were 11 cases(34.4%) with normal CXR. There was no significant differences of the direct signs (including single large cystic lesions and multiple hypoechoic lesions) between LUS and CXR (P=0.80), however the indirect signs of LUS were more obvious than CXR, with significant difference(P=0.001). Conclusions The neonatal LUS findings of CPAM is multiple, it can be used as a preliminary qualitative screening method.The diagnosis value of indirect sign of LUS is superior to CXR. Key words: Ultrasonography; Lungs; Congenital pulmonary airway malformation; Computed tomography; Chest X-ray

Determinants of infarction patterns in posterior cerebral circulation

Background Ischemic stroke is defined as focal or global neurological dysfunction lasting longer than 24 h or leading to death that is caused by vascular insult, either stricture or occlusion of a specific vascular territory. Aim of the study This study aimed to determine the relationship between different risk factors and different infarction patterns in posterior circulation such single small lacunar lesion, single large lesion, and multiple scattered lesions. Patients and methods This study included 60 patients recruited from the stroke unit of Ain Shams University and El Sahel Teaching Hospitals during the period from April to October 2018 with the diagnosis of posterior circulation ischemic stroke. The study population was divided into three groups according to the infarction pattern. Infarction patterns were categorized into a single small lacunar lesion (20 patients) (group I), a single large lesion (20 patients) (group II), and multiple scattered lesions (20 patients) (group III). Results There was no significant difference between the three groups in the presence of vascular risk factors such as hypertension (P = 0.153), diabetes (P = 0.317), dyslipidemia (P = 0.420), presence of cardiac diseases (P = 0.180), and smoking (P = 0.931). The only significant difference in terms of vascular risk factors was atrial fibrillation (AF). AF was present in six patients in group II and six patients in group III, and not present in group I patients (P = 0.024). Conclusion Different vascular risk factors such as hypertension, diabetes, dyslipidemia, and smoking are present in all infarction patterns of posterior cerebral circulation, either single or multiple infarctions, and there were no significant differences in the presence of these vascular risk factors in relation to the type of the vascular lesion. AF and significant vertebrobasilar stenosis were mostly associated with large and multiple infarct lesion patterns. Small-vessel disease was the most common stroke etiology for a single small lacunar lesion, whereas large artery atherosclerosis was mostly present in a single large lesion and multiple lesions. Strict control of vascular risk factors is highly recommended in all infarction patterns of posterior circulation.

Infarction Patterns in Posterior Cerebral Circulation: Etiology and Prognosis

Study Objectives: About a quarter of strokes and transient ischemic attacks occur in the vertebrobasilar distribution. Vertebrobasilar stroke is particularly prone to devastating consequences especially brain stem infarctions due to damage of the regional brain tissues that contain vital centers, and is associated with high rates of death and disability. Study Design: This was across sectional observational prospective hospital-based study conducted on 60 patients with first-ever acute posterior circulation ischemic stroke. The aim of the current study was to determine the relationship between different risk factors and different infarction patterns in posterior circulation; single small lacunar lesion, single large lesion, or multiple scattered lesions. Diagnosis of ischemic stroke and stroke subtypes were defined using the Trial of ORG 10,172 in Acute Stroke Treatment (TOAST) criteria as well as clinical and brain imaging features. Stroke severity using National Institutes of Health Stroke Scale (NIHSS) score was done on admission, after 24 hours from admission, and at 7 days from onset of symptoms. The patients functional status was assessed by modified Rankin scale (mRS) done on admission and on discharge from hospital and at 7-day follow up from onset of symptoms. Patients were classified according to infarction patterns into a single small lacunar lesion (group I), a single large lesion (group II), and multiple scattered lesions (group III) 20 patients in each group. Results: There was no significant difference between the three groups as regard the presence of vascular risk factors and the only significant difference as regard vascular risk factors was atrial fibrillation (AF). There was significant difference between the three groups as regard the occurrence of previous transient ischemic attacks (TIA). There was significant difference between the three groups as regard NIHSS score on admission, after 24 hours, and at 7 days from admission. There were significant differences between the three groups as regard mRS score at discharge and at 7-day follow up from the onset of symptoms and the degree of improvement from admission to discharge. There was significant difference between the three groups as regard volume of infarction in Brain magnetic resonance imaging (MRI). Group II and group III patients had larger volumes of infarction when compared to group I patients. There was no significant difference between the three groups as regard presence of significant intracranial stenosis in magnetic resonance angiography (MRA). There was significant difference between the three groups as regard stroke etiology. It was found that largeartery atherosclerosis (LAA) was the most common stroke etiology in posterior circulation being present in (53.3%) of the patient group and was common in group II and III in contrast to group I patients. Conclusions: Different vascular risk factors such as hypertension, diabetes, dyslipidemia, and smoking are present in all infarction patterns of posterior circulation ischemic stroke either single or multiple infarctions. However, AF and significant vertebrobasilar stenosis were mostly associated with large and multiple infarct lesion patterns. Small vessel disease was the most common stroke etiology for single small lacunar lesion while large artery atherosclerosis was associated with single large lesion and multiple lesions in the posterior circulation. Early MRI and MRA help in define type and prognosis of posterior circulation infarcts. Early diagnosis and control of potentially modifiable risk factors and comorbid conditions are an important aspect in the early management of patients with infarction in the posterior circulation.

Primary Hepatic Mixed Acinar-Neuroendocrine Tumor: A Rare Case of a Liver Mass

Extra-pancreatic primary acinar cell carcinomas (ACC) are rare and have been reported in the stomach, jejunum, colon and liver. Of the seven hepatic cases reported, most presented with abdominal pain, a liver mass and no pancreatic involvement. This case is one among the unusual cases reported. A 67-year-old lady with past history of chronic hepatitis B infection presented with progressively worsening abdominal pain. Lab workup revealed an elevated lipase (3532 U/L), a normal liver function test, AFP and CA19-9. Abdominal ultrasound and CT showed an 11cm by 8cm heterogeneously enhancing mass in the right hepatic lobe with central enhancement [Figure 1] and no involvement of the pancreas or the biliary tree. Histopathology of the mass revealed atypical proliferation of neoplastic cells with pseudo-glandular formation and occasional prominent nucleoli [Figure 2a]. The cells stained positive for pancytokeratin, CK7, chromogranin, synaptophysin [Figure 2b] and trypsin; and negative for Hep-Par 1 [Figure 3], monoclonal CEA and CA19-9. The histologic features and immunophenotype were consistent with mixed acinar-neuroendocrine tumor. Surveillance MRI and endoscopic ultrasound (EUS) did not demonstrate a pancreatic mass leading to a diagnosis of primary hepatic ACC. It was determined that the tumor was not surgically resectable due to vascular proximity and the patient was referred to an oncologist for systemic chemotherapy. Patients with rare primary hepatic ACC usually present with abdominal pain with normal to low elevations of AFP and CA19-9. A para-neoplastic syndrome causing lipase hyper-secretion as seen in this patient has been mentioned in the literature. CT scan usually shows a single large hypo-enhancing lesion with areas of necrosis or multiple smaller solid lesions. Histopathology reveals typical tumor cells with immmuno-histochemistry demonstrating positivity for trypsin and chymotrypsin for acinar differentiation; synaptophysin for neuroendocrine differentiation. Multiple theories including presence of common progenitor cells showing aberrant pancreatic differentiation or occurrence of heterotopic or metaplastic pancreatic tissue among liver tissue has been implicated in the etio-pathogenesis. This case highlights the occurrence of a rare tumor and that it should be considered in the differential when a vascular tumor is detected in an otherwise healthy liver with normal tumor markers.2320_A Figure 1. shows axial and sagittal sections of Abdominal CT scan demonstrating the extent of the tumor2320_B Figure 2. (a) shows pseudo-glandular formation and prominent nucleoli on H and E stain and Figure 2 (b) shows tumor cells staining positive for synaptophysin2320_C Figure 3. Figure 3 shows islands of normal hepatic tissue with negative staining for Hep-Par 1

Incidental endoscopic findings of a rare gastric neuroendocrine carcinoma concurrent with an uncommon primary duodenal adenocarcinoma: A case report

Gastric neuroendocrine tumors (NETs) are rare gastric tumors. They are often found during esophagogastroduodenoscopy (EGD) as multiple small intramucosa polyps or as a single large polypoid lesion. Gastric NETs are difficult to distinguish from gastric adenocarcinoma or lymphoma. NETs are uncommon tumors, usually poorly differentiated and highly malignant. They are typically accompanied by vascular invasion and metastasis and have an extremely poor prognosis. Here, we reported an NET of the stomach concurrent with primary duodenal adenocarcinoma. A 56‐year‐old woman had underlying adenocarcinoma of the lung and received regular chemotherapy. Because of upper abdomen discomfort, EGD was performed, which showed diffuse multiple polypoid lesions over the stomach and another protruding mass over the posterior wall of the duodenal bulb. Abdomen computed tomography and the pathological report confirmed the above diagnosis.

Lung Ultrasound Findings in Congenital Pulmonary Airway Malformation.

Congenital pulmonary airway malformation (CPAM) is a group of rare congenital malformations of the lung and airways. Lung ultrasound (LU) is increasingly used to diagnose neonatal respiratory diseases since it is quick, easy to learn, and radiation-free, but no formal data exist for congenital lung malformations. We aimed to describe LU findings in CPAM neonates needing neonatal intensive care unit (NICU) admission and to compare them with a control population. A retrospective review of CPAM cases from three tertiary academic NICUs over 3 years (2014-2016) identified five patients with CPAM who had undergone LU examination. LU was compared with chest radiograms and computed tomography (CT) scans that were used as references. CPAM lesions were easily identified and corresponded well with CT scans; they varied from a single large cystic lesion, multiple hypoechoic lesions, and/or consolidation. The first two LU findings have not been described in other respiratory conditions and were not found in controls. We provide the first description of LU findings in neonates with CPAM. LU may be used to confirm antenatally diagnosed CPAM and to suspect CPAM in infants with respiratory distress if cystic lung lesions are revealed. Further studies are necessary to define the place of LU in the management of CPAM.

Evidence for Seroprevalence in Human Localized Cutaneous Leishmaniasis Caused by Leishmania donovani in Sri Lanka.

Visceral leishmaniasis (VL) is considered as a major health threat in the Indian subcontinent. Leishmania donovani, a usually visceralizing species, causes cutaneous leishmaniasis (CL) in Sri Lanka. However, visceralizing potential of the local L. donovani is not yet fully understood. This project studied the seroprevalence of local CL by using an in-house ELISA. An IgG-based ELISA using crude Leishmania antigen (Ag) was developed and validated. A total of 50 laboratory confirmed cases of locally acquired CL were examined using the newly developed ELISA. According to the optimized ELISA, seroprevalence of anti-Leishmania IgG antibodies in the study group was 34.0% (n = 17/50). Majority of seropositive individuals were males (n = 13/17), representing 76%. Nearly half of the seropositive individuals were young adults (20–40 years, n = 9/17, 53%). Higher proportions of single lesions, large lesions, and nodular lesions were associated with a seroconversion. A proportion of local L. donovani infections leading to CL have the ability to raise an antibody response in the host. This may indicate early systemic involvement as one possibility. Study of a large number of patients with adequate follow-up would be useful.

Outcome Evaluation of Patients with Limited Brain Metastasis From Malignant Melanoma, Treated with Surgery, Radiation Therapy, and Targeted Therapy.

The incidence of brain metastases from melanoma is increasing. Several effective treatment options are now available but what can be considered the optimal therapeutic strategy is not yet defined. We evaluated the outcome of patients with brain metastatic melanoma in terms of local control rate, brain distant progression, and overall survival. The present retrospective study includes only patients with limited brain metastases (≤4) who underwent surgery plus stereotactic radiosurgery (SRS), or SRS alone. Surgical resection was performed in patients with good Karnofsky performance score, single large brain lesions, controlled extracranial disease, and SRS alone in all other cases. Supramargical resection was performed in all patients. The prescribed radiotherapy doses were 24 Gy/1 fraction and 30 Gy in 3-5 fractions for lesions >2.5 cm. Clinical outcome was evaluated by brain magnetic resonance imaging performed 2 months after radiotherapy and then every 3 months. From April 2011 to October 2015, 53 patients were treated. The median age was 54 years (range, 29-82 years). Most of patients had 1-2 brain metastases (86.8%). Twelve patients (22.6%) underwent surgical resection followed by SRS on the tumor bed, and 41 (77.4%) received SRS alone. The median follow-up time was 20.9 months (range, 5.7-61.3 months). The median, 1-, 2-, 3-year overall survival were 11.8 months, 47.2%, 28%, and 21.8%, respectively. Factors recorded as influencing survival were the number of brain metastases, the melanoma-specific graded prognostic assessment score, and BRAF mutated status. Our data identifier a subset of patients with a more favorable outcome who could take advantage of a more aggressive local approach followed by targeted therapy.

Abstract P1-06-06: Evidence for tumor heterogeneity and clonal evolution during invasive progression of breast cancer

Abstract Purpose: Intratumoral heterogeneity is well recognized to be an important driver of treatment resistance and metastasis. We undertook this N of one study to measure the degree of heterogeneity in a single large preinvasive lesion with an invasive component to determine the relationship between tumor heterogeneity, spatial distribution, clonal evolution, and invasive progression. Methods: We identified a patient with extensive DCIS measuring 7.5 cm, associated with 1.5 cm of an invasive component. We segregated the tumor sample into 32 unique blocks with precise geospatial localization; invasive cancer was identified in 3 of 32 blocks. NGS libraries were made from FFPE derived DNA (20-40ng) for full exome sequencing and hybridization to a 4.8 million element SNP array. All data were analyzed and a phylogentic tree was constructed. Results: The sequence data was analyzed with Platypus[1] and 3922 somatic mutation sites were found in total. These sites were concatenated into one sequence for each sample. Then a Neighbor-Joining tree was built with a Jukes-Cantor model and 1000 bootstrap replicates using FastME 2.0[2], to assess the reliability of the tree (Figure 1). Phylogenetic analysis revealed that invasive cancer evolved twice, independently. Dense sampling allowed reconstruction of the temporal order of mutations that accumulated in the cell lineage of the invasive cancers. Furthermore, the phylogeny revealed that distant regions may be closely genetically related, the oldest parts of the tumor were in the interior of the tumor, and that the invasive tumors evolved near the oldest parts of the tumor, rather than at the expanding front. Conclusions: Extensive sampling and sequencing of a single tumor yields important insights about tumor heterogeneity and tumor progression for DCIS to invasive cancer. Foci of invasion were geospatially associated with preinvasive regions of progressively higher mutational load. 1. Rimmer A, Phan H, Mathieson I, Iqbal Z, Twigg SR, Wilkie AO, McVean G, Lunter G, Consortium W: Integrating mapping-, assembly-and haplotype-based approaches for calling variants in clinical sequencing applications. Nature genetics 2014, 46(8):912-918. 2. Lefort V, Desper R, Gascuel O: FastME 2.0: a comprehensive, accurate, and fast distance-based phylogeny inference program. Molecular biology and evolution 2015:msv150. Citation Format: Ding Y, Marks JR, King LM, Hall AH, Mardis ER, Rodrigo AG, Maley CC, Hwang E-S. Evidence for tumor heterogeneity and clonal evolution during invasive progression of breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P1-06-06.

Myelinoclastic diffuse sclerosis (Schilder's disease)

Schilder's myelinoclastic diffuse sclerosis is a rare sporadic demyelinating disease that usually affects children between 5 and 14 years old. The disease often mimics intracranial neoplasm or abscess. We report a 9-year-old girl with Schilder's disease who presented with sudden onset of right hemiparesis. Brain magnetic resonance imaging (MRI) showed a single large tumefactive white matter lesion. A diagnosis of Schilder's disease was based on clinical features and MRI findings. The patient showed dramatic clinical improvement and significant regression of the lesion in response to high-dose intravenous methyl prednisolone.

A Young Woman with Sudden Hemiparesis

Abstract: Stroke related to cerebral vasospasm may have the same appearance that ischemic stroke of other causes. The correct diagnosis is critical to avoid inappropriate treatments as thombolysis and anticoaglant therapy. In this case, a previous young healthy woman presented with acute onset of right-sided hemiplegia and expressive aphasia. Interpretation of Magnetic Resonance Images was challenging: acute ischemia, severe vasospasm, no signs of subarachnoid hemorrhage or intra-arterial thrombi, no evidence of cervical artery dissection. Cerebral angiography allowed to conclude that a ruptured small aneurysm was responsible for stroke, related to a spasm at the 7th day of aneurysm rupture concomitant of neck pain. The predictive MRI signs and the factors that contributed for the good outcome of a symptomatic vasospasm are discussed Case Presentation; A 30-year-old woman, without risk factors, presented with acute onset of right-sided deficit and expressive aphasia for potential thrombolysis.The interpretation of MRI was challenging. Various MRI findings help determine the etiology of stroke. A previously healthy 30-year-old woman presented to the stroke center for potential thrombolysis. She had presented sharp neck pain one week ago and neurological examination was unremarkable. She awoke at 8 am with right motor deficit. On arrival, 4 hours later, she was mutic with a Glasgow Coma Scale score of 15. She was normotensive (110/75 mmHg) with right-sided hemiplegia. Electrocardiogram did not demonstrate any arrthymia or other abnormality Emergent magnetic resonance imaging (MRI) of the brain displayed on diffusion-weighted imaging MRI (DWI) (Figure 1) and apparent coefficient diffusion map, (within 4 hours from onset), an acute ischemic stroke in the superficial territory of left middle cerebral artery (MCA), with normal fluid attenuated inversion recovery (FLAIR) except vessel hyperintensities (FVHs) proximal and distal to the sylvian fissure (Figures 2 and 3). T2* did not reveal any thrombus or hemorrhage. The presence of hyperintensity on DWI without corresponding hyperintensity on FLAIR, called “DWI-FLAIR mismatch indicate that the patient is likely within the time window for thrombolysis, Magnetic resonance angiography (MRA) visualized a severe vasospasm of the left terminal internal carotid artery and left MCA (M1 segment) (Figure 4). Intracranial and extracranial MRA was otherwise unremarkable, especially no dissection of the left carotid artery was identified, as also demonstrated by three-dimensional black blood (3D CUBE) T1 sequence. Diagnosis: Aneurysm rupture presenting as delayed ischemic stroke related to severe vasospasm Discussion: The interpretation of this imaging is challenging. Various MRI findings help determine the etiology of stroke and patient selection for acute ischemic stroke treatment (thrombolysis) [1]. The most common mechanisms of stroke in young population are cardioembolism and patent foramen ovale, and dissection of the cervical arteries. The first cause can be suspected when patients present acute multiple territorial lesions or a single large cortical and subcortical lesion on DWI and patent foramen ovale, another source of cardioembolism, usually causes small cortical lesions in vertebro-basilar territory. The presence of hypointense signals with blooming artifacts in the arterial system on T2* sequence (susceptible vessel sign) assess the presence of intra-arterial thrombi, usually associated with cardioembolic stroke. In this unusual presentation of stroke in a young patient without any risk factor, the absence of visualization of intra-arterial thrombus on T2* sequence and of carotid artery dissection (mural hematoma) on dedicated 3D CUBE sequence and the presence of a long spasm allow to conclude that a ruptured aneurysm was responsible for stroke, related to the spasm that occurred at the 7th day of rupture contemporary of neck pain. Seven days after the aneurysm rupture, a subarachnoid hemorrhage could not be identified on CT, nor on FLAIR and T2* MRI sequences : even if FLAIR sequence is more sensitive than CT and over a longer time period, the patient underwent MRI to late for examination at the 7th day [2]. Cerebral angiography identified a small aneurysm of the left anterior choroidal artery (Figure 5). Patients with DWI-FLAIR mismatch are likely to be within the time of adequate treatment. Endovascular treatment was performed using mechanical angioplasty and coiling. At 3-month follow-up, the patient was asymptomatic and MRA was normal (Figure 6). FHVs are imaging markers of both occlusion or narrowing when proximal to the ischemic core and of collateral system when distal. When present outside the ischemic core, they are associated with good outcome [3]. In the present case, the presence of collateral flow objective by FHV, an early treatment and the absence of risk factors contributed for the good outcome of a symptomatic vasospasm [4,5].