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BACKGROUND AND PURPOSE: To determine the ability of diffusion-weighted imaging (DWI) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to predict long-term response of brain metastases prior to and within 72 hours of stereotactic radiosurgery (SRS). METHODS: In this prospective pilot study, multiple b-value DWI and T1-weighted DCE-MRI were performed in patients with brain metastases before and within 72 hours following SRS. Diffusion-weighted (DW) images were analyzed using the monoexponential and intravoxel incoherent motion (IVIM) models. DCE-MRI data were analyzed using the extended Tofts pharmacokinetic model. The parameters obtained with these methods were correlated with brain metastasis outcomes according to modified Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) criteria. RESULTS: We included 25 lesions from 16 patients; 16 patients underwent pre-SRS MRI and 12/16 patients underwent both pre- and early (within 72 hours) post-SRS MRI. The perfusion fraction (f) derived from IVIM early post-SRS was higher in lesions demonstrating progressive disease than in lesions demonstrating stable disease, partial response, or complete response (q = 0.041). Pre-SRS extracellular extravascular volume fraction, v(e), and volume transfer coefficient, k(trans), derived from DCE-MRI were higher in non-responders versus responders (q = 0.041). CONCLUSIONS: Quantitative DWI and DCE-MRI are feasible imaging methods in the pre- and early (within 72 hours) post-SRS evaluation of brain metastases. DWI- and DCE-MRI-derived parameters demonstrated physiologic changes (tumor cellularity and vascularity) and offer potentially useful biomarkers that can predict treatment response. This allows for initiation of alternate therapies within an effective time window that may help prevent disease progression.

We examine the role of dynamic susceptibility contrast (DSC) magnetic resonance imaging (MRI) perfusion in differentiating pseudoprogression from progression in 20 consecutive patients with treated glioblastoma. MRI perfusion was performed, and relative cerebral blood volume (rCBV), relative peak height (rPH), and percent signal recovery (PSR) were measured. Pseudoprogression demonstrated lower median rCBV (P=.009) and rPH (P

Purpose: Blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) is an autosomal dominant complex eyelid malformation. The authors aim to offer an explanation for the lower eyelid malformation and propose a novel surgical approach to correct it. Methods: An observational and interventional case series of 10 consecutive, molecularly proven BPES patients who underwent surgical repair of the lower eyelid malformation. During surgery detailed anatomical examination and surgical repositioning of the medial canthal tendon was performed. All the patients were followed up regularly after the surgery and assessed for epiphora. Results: All patients exhibited a marked asymmetry in the attachment of the lower and upper eyelid to the medial canthal tendon, with the lower eyelid being much less attached. This resulted in an abnormal downward concavity with a temporal ectropion and a temporally displaced lower eyelid. Consequently, the inferior punctum was displaced temporally. All patients underwent a novel surgical technique to remediate this, namely, inserting a 4.0 nylon suture between the tarsal plate of the lower eyelid and the medial canthal tendon during telecanthus surgery. This simple additional surgical step corrected not only the position of the lower eyelid but also its abnormal downward concavity, the temporal ectropion and the lateral displacement of the inferior punctum. None of the authors' patients had lasting epiphora. Conclusion: Lateral displacement of the inferior punctum is an important hallmark in the diagnosis of BPES. The authors demonstrate an anatomical explanation for the complex lower eyelid malformation and also propose a novel surgical technique to correct this. During surgical repair of the telecanthus and blepharophimosis, specific attention should be paid to reattachment of the lower eyelid to the medial canthal tendon. This understanding improves clinical diagnosis and surgical treatment of BPES patients.

PURPOSE To evaluate the clinical and histopathologic characteristics of orbital hyalinizing spindle cell tumor with giant rosettes (HSCTGR). METHODS Interventional case series of 2 patients, aged 4 and 9 years referred to the Ocular Oncology Unit. Both patients presented with slowly progressive proptosis with dimness of vision in the second patient. CT was performed for both patients followed by excision of the masses. Histology was performed on tissue sections. RESULTS CT revealed a localized tumor in the first case and extensive mass extending to the optic canal in the second patient. Histologic analysis revealed features of HSCTGR with characteristic spindle-shaped cells with giant rosettes with hyalinized foci. Tumor cells were positive for vimentin in both cases and focal S100 positivity in first case. However, the second case showed a higher Ki-67 index compared to the first case, suggestive of moderately high proliferative activity. After excision, neither of the tumors demonstrated local recurrence, and both patients were without regional or distant metastases. Mean clinical follow-up was 12 months. CONCLUSIONS HSCTGR involving the orbit has not been previously reported in the literature. We report 2 cases of orbital presentation at a much younger age than has been shown in patients with this type of tumor in other areas of the body. Complete excision of this tumor with close follow-up is the preferred treatment. HSCTGR should be considered in the differential diagnosis of orbital fibrous tumor presenting as painless progressive proptosis.

Molecular and genetic testing is becoming increasingly relevant in GBM. We sought to determine whether dynamic susceptibility contrast (DSC) magnetic resonance imaging (MRI) perfusion imaging could predict EGFR-defined subtypes of GBM. We retrospectively identified 106 consecutive glioblastoma (GBM) patients with known EGFR gene amplification, and a subset of 65 patients who also had known EGFRvIII gene mutation status. All patients underwent T2* DSC MRI perfusion. DSC perfusion maps and T2* signal intensity time curves were evaluated, and the following measures of tumor perfusion were recorded: (1) maximum relative cerebral blood volume (rCBV), (2) relative peak height (rPH), and (3) percent signal recovery (PSR). The imaging metrics were correlated to EGFR gene amplification and EGFRvIII mutation status using univariate analyses. EGFR amplification was present in 44 (41.5 %) subjects and absent in 62 (58.5 %). Among the 65 subjects who had undergone EGFRvIII mutation transcript analysis, 18 subjects (27.7 %) tested positive for the EGFRvIII mutation, whereas 47 (72.3 %) did not. Higher median rCBV (3.31 versus 2.62, p = 0.01) and lower PSR (0.70 versus 0.78, p = 0.03) were associated with high levels of EGFR amplification. Higher median rPH (3.68 versus 2.76, p = 0.03) was associated with EGFRvIII mutation. DSC MRI perfusion may have a role in identifying patients with EGFR gene amplification and EGFRvIII gene mutation status, potential targets for individualized treatment protocols. Our results raise the need for further investigation for imaging biomarkers of genetically unique GBM subtypes.

BACKGROUND AND PURPOSE: Epidermal growth factor receptor amplification is a common molecular event in glioblastomas. The purpose of this study was to examine the potential usefulness of morphologic and diffusion MR imaging signs in the prediction of epidermal growth factor receptor gene amplification status in patients with glioblastoma. MATERIALS AND METHODS: We analyzed pretreatment MR imaging scans from 147 consecutive patients with newly diagnosed glioblastoma and correlated MR imaging features with tumor epidermal growth factor receptor amplification status. The following morphologic tumor MR imaging features were qualitatively assessed: 1) border sharpness, 2) cystic/necrotic change, 3) hemorrhage, 4) T2-isointense signal, 5) restricted water diffusion, 6) nodular enhancement, 7) subependymal enhancement, and 8) multifocal discontinuous enhancement. A total of 142 patients had DWI available for quantitative analysis. ADC maps were calculated, and the ADC mean , ADC min , ADC max , ADC ROI , and ADC ratio were measured. RESULTS: Epidermal growth factor receptor amplification was present in 60 patients (40.8%) and absent in 87 patients (59.2%). Restricted water diffusion correlated with epidermal growth factor receptor amplification ( P = .04), whereas the other 7 morphologic MR imaging signs did not ( P > .12). Quantitative DWI analysis found that all ADC measurements correlated with epidermal growth factor receptor amplification, with the highest correlations found with ADC ROI ( P = .0003) and ADC mean ( P = .0007). CONCLUSIONS: Our results suggest a role for diffusion MR imaging in the determination of epidermal growth factor receptor amplification status in glioblastoma. Additional work is necessary to confirm these results and isolate new imaging biomarkers capable of noninvasively characterizing the molecular status of these tumors.

Orbito-cranial foreign bodies present a treacherous situation that can escape detection. The only evidence of these foreign bodies may be the entry wound in the form of a small lid laceration. A two-year-old boy presented with right upper lid laceration following a fall two hours back. Analysis of the fluid around the wound revealed a beta-tracer protein (beta-TP) value of 33.5 mg/l suggestive of cerebrospinal fluid (CSF). Three-dimensional computed tomography (CT) scan revealed a foreign body measuring 4.2 cm x 0.8 cm passing from the orbital roof to the frontal lobe. The foreign body tract was explored through the eyelid laceration and a broken pencil was removed followed by dural patch graft. The patient developed no ocular or intracranial complications. Beta-TP, a highly specific marker of CSF is routinely used in screening patients of neurosurgery and otolaryngology with CSF leaks, however, its use has never been reported in ophthalmic literature based on an online PubMed search.

Dear Sir: It is with great interest that we read the recent investigation by Moon et al. [1] that assessed the value of preoperative imaging in the prediction of methyl-guanine methyl transferase (MGMT) promoter methylation status in 24 patients with high-grade gliomas. By evaluating preoperative computed tomography (CT), conventional magnetic resonance (MR) imaging, perfusion MR imaging, and diffusion tensor imaging (DTI), they found that MGMT promoter methylation was associated with ill-defined tumor margins, lower CT attenuation, higher apparent diffusion coefficient (ADC), and lower fractional anisotropy (FA). The remainder of the qualitative conventional MR imaging measures (ring versus nodular tumor enhancement, presence of a cystic portion, and heterogeneity of the signal intensity on the T2-weighted images) as well as perfusion MR imaging (as assessed by relative cerebral blood volume) were not found to be different between groups. Their results are relevant given the recently described prognostic significance of MGMT promoter methylation status in the survival of patients with high-grade gliomas [2, 3]. An imaging biomarker for MGMT methylation could serve as a surrogate for histopathology in those cases where pathology sampling is suboptimal, or could be of value if future preoperative treatment regimens are developed and based on presumed MGMT status. However, a major confounding factor in that study is the fact that both WHO grade III tumors and grade IV tumors were included, with a relatively small number of patients in each group. WHO grade III and IV tumors are a highly heterogeneous group in terms of histological findings, biological behavior, and radiographic characteristics. In that study, a total of 57.1% of grade III tumors were methylated versus only 41.1% in the grade IV tumors. Although this difference has not reached statistical significance, likely reflecting small sample sizes, the possibility that radiographic differences found between the methylated and unmethylated groups could at least in part reflect differences in histological grade cannot be excluded. The radiographic differences among the different types of malignant gliomas such as anaplastic oligodendrogliomas, grade III astrocytomas, and glioblastomas have been well described and cannot be ignored. The distribution of the different radiographic parameters according to tumor type and grade was not provided in that paper. We would like to take this opportunity to report our experience with attempting to find MR imaging parameters that may predict MGMT promoter methylation status. We examined the preoperative MR imaging of patients with malignant glioma treated at our institution and who had the MGMT promoter methylation status determined. To improve the homogeneity of the sample, we restricted the analysis to patients with glioblastomas (WHO grade IV tumors). The cohort of 77 patients all underwent preoperative conventional MR imaging with standard sequences (axial diffusion, T1-weighted, T2-weighted, FLAIR, gradient-echo or susceptibility-weighted, and triplanar post-gadolinium T1-weighted images). We qualitatively assessed, by consensus of experienced neuroradiologists (6 and 11 years experience), the following signs: (1) enhancing border sharpness; (2) cystic/necrotic change; (3) hemorrhage; (4) T2-isointense signal; (5) diffusion restriction; (6) nodular enhancement; (7) subependymal enhancement; and (8) multifocal discontinuous enhancement. In addition, 49 of the 77 patients had T2* dynamic susceptibility contrast perfusion-weighted MR imaging, where rCBV was recorded using maximal region-of-interest (ROI) technique (in a fashion similar to the manner described by Moon et al. [1]) as well as additional perfusion metrics including peak height (PH), relative peak height (rPH), and percentage signal recovery (PSR). Similar to Moon et al. [1], we found that 31 of our 77 patients (40.2%) had methylation of the MGMT promoter, compared with 46 (59.8%) with unmethylated MGMT promoter. Despite measuring additional perfusion metrics such as PH, rPH, and PSR, we also found MR perfusion-weighted imaging to have no value in predicting MGMT promoter methylation, with p values ranging from 0.66 to 0.87 (Table 1). Table 1 Relationship between perfusion metric and MGMT methylation status However, none of our conventional MR imaging signs was significantly associated with MGMT methylation promoter status, with p values ranging from 0.14 to 0.97 (Table 2). Moon et al. [1] found that ill-defined tumor margins were associated with methylation of the MGMT promoter, which could be potentially explained by the fact that some lower-grade tumors tend to have ill-defined margins and have higher frequency of MGMT promoter methylation. Moon’s findings also disagree with a study performed by Drabcyz et al. [4] in 59 patients, which found that ring enhancement was highly associated with unmethylated MGMT promoter status (p=0.006) and in an elegant texture analysis found T2-weighted texture features to be important (p

Marcus Gunn jaw winking synkinesis (MGJWS) occurs due to an aberrant innervation of the levator palpebrae superioris muscle by a branch of the motor division of the trigeminal nerve that supplies the muscles of mastication. MGJWS is mostly unilateral occurring in isolation and is less frequently associated with ocular or systemic abnormalities. Although MGJWS is mostly unilateral, few bilateral cases have been reported. Here we describe a rare case of bilateral MGJWS in an 18 year-old male patient with asymmetric bilateral ptosis and monocular elevation deficiency in the right eye.

Objective: To examine the potential utility of conventional MRI signs in differentiating pseudoprogression (PsP) from early progression (EP). Methods: This retrospective study reviewed initial postradiotherapy MRI scans of 321 patients with glioblastoma undergoing chemotherapy and radiotherapy. A total of 93 patients were found to have new or increased enhancing mass lesions, raising the possibility of PsP. Final diagnosis of PsP or EP was established upon review of surgical specimens from a second resection or by clinical and radiologic follow-up. A total of 11 MRI signs potentially helpful in the differentiation between PsP and EP were examined on the initial post-RT MRI and were correlated with the final diagnosis through χ2 or Fisher exact test. Results: Sixty-three (67.7%) of the 93 patients had EP, of which 22 (34.9%) were diagnosed by pathology. Thirty patients (32.3%) had PsP; 6 (16.7% of the 30) were diagnosed by pathology. Subependymal enhancement was predictive for EP (p = 0.001) with 38.1% sensitivity, 93.3% specificity, and 41.8% negative predictive value. The other 10 signs had no predictive value (p = 0.06–1.0). Conclusions: Conventional MRI signs have limited utility in diagnosing PsP in patients with recently treated glioblastomas and worsening enhancing lesions. We did not find a sign with a high negative predictive value for PsP that would have been the most useful for the clinical physician. When present, subependymal spread of the enhancing lesion is a useful MRI marker in identifying EP rather than PsP.

T cell/histiocyte-rich large B-cell lymphoma (THRBCL) is an uncommon morphologic variant of diffuse large B-cell lymphoma characterized by a minor population of neoplastic B cells existing in a background of predominant reactive T lymphocytes. Diagnosis of this entity is occasionally difficult and would require careful immunohistochemical analysis of the tumor cells, as it may appear similar to other lymphoid diseases, such as nodular lymphocyte-predominant Hodgkin lymphoma, classical Hodgkin lymphoma, and peripheral T-cell lymphoma. The authors report a case of 37-year-old man who presented with a slowly growing, painless proptosis of the right eye with a well-defined mass in the posterosuperior aspect of globe. An incisional biopsy of the mass was performed. Histopathologic examination and immunohistochemical analysis revealed the diagnosis of THRBCL. To the best of the authors' knowledge, this is the first case of primary THRBCL occurring in the orbit.

Primary extraskeletal osteosarcoma (EOS) is an extremely rare malignancy. In this report, the clinical course of a 32-year-old man presenting with proptoses is described. Medical history included Hirschsprung disease (HD), horseshoe kidney, azoospermia, and vertebral anomalies. Imaging of the orbit showed an oval, well-defined heterogeneous mass adjacent to the lateral wall of the orbit. The patient underwent a lateral orbitotomy and complete excision of the mass. The mass was not attached to the bone. Histopathologic and immunohistochemical examination confirmed the diagnosis of an EOS. The patient received chemotherapy and radiotherapy and is free of the disease 3 years after the diagnosis. Genetic screening showed no mutations for both the RET proto-oncogene for HD and the p53 tumor suppressor gene for osteosarcoma.

A 14-year-old boy presented with intractable diplopia for 10 days following an assault. A thorough history revealed that he was unaware of any penetrating injury. However, imaging demonstrated a radiolucent foreign body between the globe and the orbital floor. On surgical exploration, it was found to be the proximal part of a ball point pen. Its removal resulted in complete resolution of diplopia. Thorough clinical and radiological examination is recommended when a foreign body is suspected in pediatric patients. Prompt diagnosis will aid in early intervention and prevention of long-term complications.

Atypical fibroxanthoma is an uncommon neoplasm of the superficial soft tissue that occurs in actinically damaged skin of elderly patients. It is characterized by a pleomorphic histologic appearance but has a generally favorable clinical course. These lesions are usually small in size and rarely occur on the eyelid. The authors present an unusual case of neglected giant atypical fibroxanthoma of the eyelid in an elderly patient.

Objective: To study the basis of defective levator palpebrae superioris (LPS) function in blepharophimosis-ptosis-epicanthus inversus syndrome (BPES), an autosomal dominant eyelid malformation sometimes associated with ovarian dysfunction. Methods: Eight patients with molecularly proved BPES underwent high-resolution surface-coil 3-T magnetic resonance imaging before surgical intervention. The features of LPS muscle and adjoining connective tissue were compared with an age-matched control subject. During LPS resection for ptosis repair, detailed anatomic examination of the LPS was performed. Histopathologic characteristics were compared with normal control samples from a cadaver and a patient with simple severe congenital ptosis. Results: The most striking feature shown on magnetic resonance imaging was the thin, long anterior part of the LPS. During the operation, this consisted of a disorganized, thin, long aponeurosis. However, in the posterior part of the LPS, there was an organized thick structure suggestive of a muscle belly. Histopathologic examination revealed posteriorly well-formed striated muscle fibers in all patients with BPES but not in the control sample from the patient with simple severe congenital ptosis. These striated muscle fibers were comparable to those of the normal control tissue but were more intermixed with collagenous tissue and little fatty degeneration. Conclusions: The presence of striated muscle fibers in LPS of patients with BPES contrasts with the fatty degeneration in patients with simple severe congenital ptosis. To our knowledge, this is the first study providing novel insights into the pathogenesis of the eyelid malformation in BPES through extensive imaging, anatomic study, and histopathologic testing in a unique cohort of patients with molecularly proved BPES.

Traumatic subperiosteal hematoma (SpH) usually presents late, after the initial trauma. It is generally seen in young males. Computed tomography is the best mode of imaging and helps to rule out orbital fracture or associated subdural hematoma. We present the clinical features and management of four patients seen at the orbit clinic with SpH. Management is based on time of presentation, visual acuity and any communicating bleed. The prognosis of traumatic SpH is excellent if treated with an individualized patient approach.