Pembrolizumab: first experience with recurrent primary central nervous system (CNS) tumors.

Patients with progressive primary brain tumors (PBT) are attracted to promising new treatments, even prior to convincing data. Anti-PD1 immunotherapies have been in the spotlight since publication of groundbreaking results for metastatic melanoma with pembrolizumab (PBL). Our objective was to report on the response and toxicity of PBL in patients with advanced PBT. We retrospectively reviewed the charts of 22 patients (17 adults and 5 children) with recurrent central nervous system tumors treated with PBL. We analyzed prior antineoplastic therapies, steroid usage, and outcomes. Patients received a median of two neoplastic therapies prior to PBL, and a median of three infusions of PBL in adults and four in children. Twelve patients (9 adults and 3 children) started PBL on steroids (median dose in adults 4 mg; range 2-8, and in children 1.5 mg, range 0.5-4) and five patients received steroids later during PBL treatment. Twelve patients (10 adults and 2 children) received concomitant bevacizumab with PBL. Side effects were minimal. All patients showed progressive tumor growth during therapy. Median OS from the start of PBL was 2.6 months in adults and 3.2 months in children. Two GB patients underwent tumor resection following treatment with PBL. Tumor-lymphocytic response in these cases was unremarkable, and PD-L1 immuno-staining was negative. In this series of 22 patients with recurrent primary brain tumors, PBL showed no clinical or histologic efficacy. We do not recommend further use of PBL for recurrent PBT unless convincing prospective clinical trial data are published.

Supratentorial calcified pseudotumour: experience of a single institution and review of the literature.

BACKGROUND: Calcified pseudotumours (CPTs) are rarely found in the central nervous system (CNS). Information on supratentorial CPT is limited. We add our experience treating three supratentorial CPTs. Clinical presentation, pathological findings and clinical course are discussed, and a literature review is provided. METHOD: Between September 2011 and December 2012, three patients (age range 33-60 years) were diagnosed with symptomatic supratentorial CPTs, for which they underwent resection. Their clinical, radiological, and surgical data were retrospectively retrieved from their medical records and reported. RESULTS: Symptoms at presentation included headache (n = 1), blurred vision (n = 1), and cognitive decline (n = 1). One tumour was in the left frontal lobe very close to the convexity surface, and the other two were in the midline adjacent to the corpus callosum. Radiological features included a calcified mass on computerised tomography (n = 3), a hypointense (n = 2) or hyperintense (n = 1) signal on T2 and a rim of enhancement with some non-homogenous lesional enhancement on T1-gadolinium (Gd) sequences on magnetic resonance imaging (n = 2). Two patients underwent gross total resection and had an uneventful postoperative course. The third underwent partial removal due to the tumour's adherence to adjacent vascular structures and suffered postoperative complications. On pathology, all lesions had low cellularity fibrovascular tissue mixed with lobules of a haematoxylinophilic, chondromyxoid-like matrix surrounded at its periphery by a variable layer of palisading spindle, epithelioid or multinucleated giant cells. All three CPTs had focal inflammatory infiltrates and variable degrees of metaplastic calcification and ossification. CONCLUSIONS: Surgical removal is recommended for benign intracranial CPTs that are symptomatic, are associated with brain oedema, or show tumour growth. Stable and asymptomatic CPTs can be followed.

Spontaneous bleeding into a suprasellar cavernous angioma of a neonate: case report and literature review.

INTRODUCTION: Cavernous angiomas (CA) are congenital intraparenchymal vascular malformations that contain sinusoidal spaces lined by a single-layer endothelium, separated by collagenous stroma with no intervening brain parenchyma. Despite the congenital origin of CA, they rarely present in the neonatal and prenatal period. In this paper, we present a case report of a neonatal suprasellar CA that presented with a bleed. We also present a literature review focusing on specific features of intracranial CA in the neonatal and fetal age groups. CASE REPORT: A 27-day-old neonate presented with a left eye ptosis for 2 days, followed by a generalized seizure. A head computed tomography revealed a suprasellar hematoma with intraventricular and subarachnoid extension. Brain magnetic resonance imaging revealed hemorrhages of various ages. Magnetic resonance angiography did not reveal any vascular malformation. Surgical exploration of the suprasellar mass revealed a capsulated dense hematoma. Postoperatively, the neonate was weaned of artificial ventilation over a protracted period and remained hemiparetic with signs of third nerve palsy. Pathology revealed a CA. CA presenting as a suprasellar bleed with subarachnoid and intraventricular extension is very rare especially among neonates. To the best of our knowledge, 20 cases of CA have been reported in the neonatal and fetal period in the English literature. Neonatal CA in general and suprasellar location in particular are extremely rare lesions. Neonatal/fetal CA seems to present more aggressively and have a worse prognosis compared to those presenting at a later age.

Gliomatosis cerebri presenting as idiopathic intracranial hypertension in a child.

We present a rare case of a diffuse anaplastic astrocytoma (gliomatosis configuration) in a child, which was misdiagnosed as pseudotumor cerebri following initially normal CT of the brain and elevated opening pressure on lumbar puncture with normal cerebrospinal composition.

Micro-RNA Expression Patterns Predict Metastatic Spread in Solid Pseudopapillary Neoplasms of the Pancreas.

Solid pseudopapillary neoplasm (SPN) of pancreas is a rare pancreatic neoplasm with a low metastatic potential. Up to 10% of patients with localized disease at presentation will develop systemic metastases, usually in the peritoneum or the liver. Due to the rarity of SPNs and the overall excellent prognosis, reliable prognostic factors to predict malignant biological behavior remain undetermined. Therefore, we aimed to define clinical, histological, and microRNA patterns that are associated with metastatic disease. We conducted a retrospective single center study on all patients operated for SPN of pancreas between 1995 and 2018. Clinical and pathological data were collected, and expression patterns of 2,578 human microRNAs were analyzed using microRNA array (Affimetrix 4.1) in normal pancreases (NPs), localized tumors (LTs), and metastatic tumors (MTs). The diagnosis of SPN was confirmed in 35 patients who included 28 females and 3 males, with a mean age of 33.8 ± 13.9 years. The only clinical factor associated with metastases was tumor size (mean tumor size 5.20 ± 3.78 in LT vs. 8.13± 1.03 in MT, p < 0.012). Microscopic features of malignancy were not associated with metastases, nor were immunohistochemical stains, including the proliferative index KI67. Higher expressions of miR-184, miR-10a, and miR-887, and lower expressions of miR-375, miR-217, and miR-200c were observed in metastatic tissues on microarray, and validated by real-time polymerase chain reaction. Hierarchal clustering demonstrated that the microRNA expression pattern of MTs was significantly different from that of LTs. The only clinical factor associated with metastases of SPN of pancreas was tumor size. Histological features and immunohistological staining were not predictive of metastases. A panel of six microRNAs was differentially expressed in MTs, and these findings could potentially be used to predict tumor behavior. Validation of these results is needed in larger series.

Mature teratoma splitting the brainstem in a newborn: case report.

Mature teratomas (MTs) of the posterior fossa are extremely rare. The authors present a case of a prenatal diagnosis of an MT splitting the brainstem. Representative images as well as the clinical and surgical course are presented. Literature regarding "split brainstem" and MT of the posterior fossa is discussed.

Compound nevus with congenital features and balloon cell changes--an immunohistochemical study.

Balloon cell nevi and balloon cell changes in nevi have rarely been reported in the literature. We describe a compound nevus showing focal balloon cell changes in a 20-year-old man. The melanocytic nature of the balloon cells is confirmed by an immunohistochemical study. The findings are compared with those in balloon cell melanomas.

Surgery for Recurrent High-Grade Glioma After Treatment with Bevacizumab.

BACKGROUND: Bevacizumab (BVZ) is an antiangiogenic agent approved by the Food and Drug Administration that is used for the treatment of recurrent glioblastoma. Complications related to impaired healing may adversely affect patients resected for recurrent high-grade glioma (HGG) after treatment with BVZ. OBJECTIVE: To examine the complication rate, outcome, and tumor vasculature in patients resected for recurrent HGG after treatment with BVZ. METHODS: Data were reviewed retrospectively from patients undergoing surgery for recurrent HGG after treatment with BVZ. Results were compared with a control group of recurrently operated BVZ-naïve HGG. Tumor samples and magnetic resonance imaging scans were analyzed. RESULTS: Fifteen patients underwent HGG resection after progression after BVZ. Forty-four BVZ-naïve patients who underwent surgeries for tumor recurrence were included as controls. Median time from BVZ treatment to surgery was 30 days (2-107). Median overall survival from time of tumor diagnosis was 21.0 months (12-83.0), and median survival from post-BVZ surgery was 5.0 months (2.0-19.0), compared with 8.1 months in BVZ-naïve controls measured from time of their last reoperation. Five of the 15 patients survived 6 or more months after post-BVZ surgery. Nine patients developed postsurgical complications requiring intervention. Complication rates for surgery after BVZ treatment were 66.7% compared with 38.6% in the control group (P = 0.077). We did not see overt changes in histopathology or immunohistochemistry staining; however, tumor vasculature in tumors resected after treatment with BVZ showed a significant decrease in mean vessel density. CONCLUSIONS: Surgery for recurrent HGG may be feasible in a select group of patients. Mean tumor vessel density may be decreased after treatment with BVZ.

Huge hemispheric intraparenchymal cyst caused by Taenia multiceps in a child. Case report.

The authors report an unusual case of a huge intraparenchymal cyst in a 4-year-old girl caused by Taenia multiceps infection. After surgical removal of the cyst, the child recovered completely. Brain infestation by coenurus is a rare disease, mainly reported in Africa, with a few case reports from patients in developed countries. Humans, especially young children, become intermediate hosts by ingesting eggs passed in the excrement of a definitive host, usually carnivores. In such cases, high mortality and morbidity rates have been reported. These rates decreased after the introduction of the modem neuroradiological techniques of computed tomography and magnetic resonance imaging.

Diagnosing necrotic meningioma: a distinctive imaging pattern in diffusion MRI and MR spectroscopy.

The differential diagnosis of necrotic meningiomas includes brain abscess and malignant neoplasms. We report and discuss hereby the work-up of two patients diagnosed with necrotic meningioma using diffusion-weighted imaging, magnetic resonance spectroscopy, resective surgery, and histopathology. The purpose of the present article is to add to the scant literature on the use of advanced imaging modalities in the routine investigation of brain lesions and their utility in arriving at the final diagnosis.

Acute generalized exanthematous pustulosis following a spider bite: report of 3 cases.

Acute generalized exanthematous pustulosis (AGEP) is a rare severe cutaneous adverse reaction caused mostly by drugs. Three of 22 AGEP cases (13.6%), recruited by us as part of two prospective multinational studies, occurred 24 to 48 hours after a spider bite. We suggest that a spider bite is a possible trigger for AGEP.

Risk factors for incomplete excision of squamous cell carcinomas.

OBJECTIVE: The aim of this study was to identify risk factors for incomplete excision of squamous cell carcinomas (SCCs). PATIENTS AND METHODS: A cross-sectional study of 369 patients who underwent a primary excision of SCCs was performed within an outpatient and a hospital plastic surgery department setting. RESULTS: Incomplete excision occurred in 25 of 369 primary excisions of SCC (6.8%). Location of the tumors on the forehead, temples, peri-auricular region, ears, cheeks, nose, lips or neck was significantly associated with incomplete excision of the tumors. In particular, high incomplete excision proportions were observed for tumors located on the ears (16.7%), neck (16.7%), temples (11.1%), nose (10.8%) or lips (7.1%). Incomplete excision of SCC was associated with the setting of the operation in the hospital as compared to ambulatory settings (p = 0.046) and was inversely associated with the specimen thickness (p = 0.002). There was no statistically significant association between incomplete excision of SCC and gender, age, clinical appearance of the lesion (suspected SCC vs other diagnoses), differentiation pattern, diameter of the tumor, length or width of the excised specimen, solar changes or ulceration. CONCLUSION: We recommend that in patients with SCCs located in the forehead, temples, periauricular region, ears, cheeks, nose, lips or neck surgeons should commence particular surgical measures to avoid inadequate excisions of the tumors. In particular, surgeons should use wider excisional margins in tumors located in the embryonic fusion planes (e.g. eyelids and naso-labial folds).

Characterization of malignant melanoma using vibrational spectroscopy.

Malignant melanoma, a malignant neoplasm of epidermal melanocytes is the third most common skin cancer. In many cases, melanoma develops from nevus, which is considered as the nonmalignant stage. Fourier transform infrared microspectroscopy (FTIR-MSP), which is based on characteristic molecular vibrational spectra of cells, was used to investigate spectral differences between melanoma, nevus, and the corresponding normal epidermis. In the present work, FTIR-MSP was performed on formalin-fixed biopsies of melanoma and nevi along with the adjoining histologically normal epidermis to understand the biochemical variations from the epidermis and identify suitable parameters for differentiation of nevi from melanoma. The comparative analysis of various parameters calculated from the spectral data of the normal epidermis and the abnormal regions showed that the changes in the nucleic acids was a significant indicator of the abnormal nature of the tissues. The RNA/DNA ratio was decreased in case of both melanoma and nevus compared to the epidermis. The amide II/amide I ratio was greater for nevus and melanoma compared to the epidermis. In contrast to other organs, the analysis of carbohydrates was not found as a suitable indicator in case of malignant melanoma. Shifts in band wave number were found to be a major distinguishing feature between the melanoma and compound nevi. The present study helps in the identification of spectral features suitable for distinction of melanoma from nevus that appear similar even in FTIR spectral features and thus can pave the way for development of in vivo screening systems based on these diagnostic markers.

Central nervous system manifestation of IgG4-related disease.

IMPORTANCE: IgG4-related disease (IgG4-RD) is characterized by an inflammatory reaction rich in IgG4-positive plasma cells. Head and brain involvement is rare in IgG4-RD, and brain parenchyma involvement has never been reported. OBSERVATION: A man in his mid-50s with multiorgan IgG4-RD developed progressive spastic hemiparesis and dementia. Magnetic resonance imaging of the brain revealed several cortical and subcortical lesions. Pathologic findings in the brain were consistent with IgG4-related central nervous system involvement. The patient was treated with high-dose corticosteroids followed by rituximab, and his cognitive and motor functions improved significantly. CONCLUSIONS AND RELEVANCE: IgG4-RD should be considered in patients with unusual neurologic manifestations suggestive of autoimmune disease.

Tumor location and IDH1 mutation may predict intraoperative seizures during awake craniotomy.

OBJECT: Intraoperative seizures during awake craniotomy may interfere with patients' ability to cooperate throughout the procedure, and it may affect their outcome. The authors have assessed the occurrence of intraoperative seizures during awake craniotomy in regard to tumor location and the isocitrate dehydrogenase 1 (IDH1) status of the tumor. METHODS: Data were collected in 137 consecutive patients who underwent awake craniotomy for removal of a brain tumor. The authors performed a retrospective analysis of the incidence of seizures based on the tumor location and its IDH1 mutation status, and then compared the groups for clinical variables and surgical outcome parameters. RESULTS: Tumor location was strongly associated with the occurrence of intraoperative seizures. Eleven patients (73%) with tumor located in the supplementary motor area (SMA) experienced intraoperative seizures, compared with 17 (13.9%) with tumors in the other three non-SMA brain regions (p < 0.0001). Interestingly, there was no significant association between history of seizures and tumor location (p = 0.44). Most of the patients (63.6%) with tumor in the SMA region harbored an IDH1 mutation compared with those who had tumors in non-SMA regions. Thirty-one of 52 patients (60%) with a preoperative history of seizures had an IDH1 mutation (p = 0.02), and 15 of 22 patients (68.2%) who experienced intraoperative seizures had an IDH1 mutation (p = 0.03). In a multivariate analysis, tumor location was found as a significant predictor of intraoperative seizures (p = 0.002), and a trend toward IDH1 mutation as such a predictor was found as well (p = 0.06). Intraoperative seizures were not associated with worse outcome. CONCLUSIONS: Patients with tumors located in the SMA are more prone to develop intraoperative seizures during awake craniotomy compared with patients who have a tumor in non-SMA frontal areas and other brain regions. The IDH1 mutation was more common in SMA region tumors compared with other brain regions, and may be an additional risk factor for the occurrence of intraoperative seizures.

Development of a novel animal burn model using radiant heat in rats and swine.

OBJECTIVES: The objective was to develop a novel animal model of burns in rats and pigs. METHODS: The model uses heat that is delivered via a radiant heater with an opening of 5 cm by 5 cm, set at 400 degrees C, for 20 seconds. An advantage of this model is that the heating source does not come into direct contact with the animal, and the heat dispersion surrounding its center is very constant. The device was evaluated in 40 rats and seven pigs. With rats, three to four burns were created on each rat, resulting in a burn covering a total body surface area of 30% to 50%. In pigs, 16 burns were created on each animal. RESULTS: In rats, infliction of burns resulted in mortality rates of 0%-50% depending on the size of the burns and the rats. In pigs, the burns reepithelialized within approximately 3 weeks and resulted in hourglass contracted scars in two of three burns within 1 month. CONCLUSIONS: The authors describe a novel animal burn model that utilizes radiant heat to create consistent burns that maximizes safety to the investigators and animals.

Histological assessment of tangentially excised burn eschars.

BACKGROUND: The burn eschar serves as a medium for bacterial growth and a source of local and systemic infection. To prevent or minimize these complications, it is important to debride the eschar as early as possible. OBJECTIVE: To identify the presence of viable skin within the excisions by examining tangentially excised burn eschars. METHODS: A total of 146 samples of burned human tissue were removed during 54 routine sharp tangential excision procedures (using dermatomes). The samples were histologically examined to identify the relative thickness of the dead, intermediate and viable layers. RESULTS: The mean (± SD) thickness of the excised samples was 1.7±1.1 mm. The sacrificed viable tissue (mean thickness 0.7±0.8 mm) occupied 41.2% of the entire thickness of the excision. In 32 biopsies (21.8%; 95% CI 16.0 to 29.3), the excision did not reach viable skin. Only eight biopsies (5.4%; 95% CI 2.8 to 10.1) contained all of the necrotic tissue without removing viable tissue. CONCLUSIONS: The thickness of a single tangentially excised layer of eschar is not much greater than the actual thickness of the entire skin and often contains viable tissue. Because surgical debridement is insufficiently selective, more selective means of debriding burn eschars should be explored.